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Harpole Jr., David Harold

Overview:

A. Non-small cell lung cancer
1. Evaluation of serum and tissue molecular biologic markers of recurrence in patients with a localize non-small cell lung cancer.
2. Molecular biologic staging of lymph nodes in patients with non-small cell lung cancer.
3. The evaluation of the clonality of metastatic tumors in patients with non-small cell lung cancer.

B. Clinical research activities
1. Creation of a prospective database for the Duke Thoracic Oncology Program.
2. A cost and satisfaction evaluation of thoracoscopy and open thoracotomy in patients.
3. Development of risk associated models of morbidity in patients undergoing general thoracic surgery procedures: The VA Cooperative Surgical Risk Study
4. A member of the Duke Gastrointestinal Malignancy Research Committee, developing esophageal cancer treatment protocols and outcome studies.

Positions:

Professor of Surgery

Surgery, Cardiovascular and Thoracic Surgery
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1984

M.D. — University of Virginia

Instructor Of Surgery, Surgery

Harvard University

Grants:

Translational Research in Surgical Oncology

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
January 01, 2002
End Date
August 31, 2021

myPlan Lung Cancer Test and Prediction of Chemotherapy Benefit

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
Myriad Genetics, Inc.
Role
Principal Investigator
Start Date
March 03, 2016
End Date
March 02, 2021

Lung Squamous Cell Carcinoma: Validation of Molecular Signatures of Prognosis

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
University of Colorado - Denver
Role
Principal Investigator
Start Date
July 09, 2012
End Date
May 30, 2017

GSK2302032A Antigen-Specific cancer Immunotherapeutic as adjuvant therapy in patients with Non-Small Cell Lung Cancer

Administered By
Duke Cancer Institute
AwardedBy
GlaxoSmithKline
Role
Principal Investigator
Start Date
October 01, 2013
End Date
March 19, 2015

IPA - Joshi

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
Veterans Administration Medical Center
Role
Principal Investigator
Start Date
November 01, 2011
End Date
October 31, 2013

IPA - Debbie Conlon

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
Durham Veterans Affairs Medical Center
Role
Principal Investigator
Start Date
September 16, 2012
End Date
September 15, 2013

Validating Molecular Signature Risk Models of NSCLC

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 21, 2006
End Date
July 31, 2012

Refining and Validating Genomic Signatures in Lung Cancer

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 14, 2009
End Date
December 31, 2010

Prospective Validation of Genomic Signatures of Chemosensitivity in NSCLC

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
January 01, 2009
End Date
November 30, 2010

Semiparametric ROC Curve Regression for Cancer Screening Studies

Administered By
Biostatistics & Bioinformatics
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
September 27, 2007
End Date
August 31, 2010

Tissue and Serum Indicators of Lung Cancer

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1996
End Date
August 31, 2002

Tissue And Serum Indicators Of Lung Cancer Recurrence

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 1996
End Date
August 31, 1999
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Publications:

Reply to D.A. Palma

Authors
Yang, CFJ; Chan, DY; D'Amico, TA; Berry, MF; Harpole, DH
MLA Citation
Yang, CFJ, Chan, DY, D'Amico, TA, Berry, MF, and Harpole, DH. "Reply to D.A. Palma." Journal of Clinical Oncology 35.5 (February 10, 2017): 572-. (Letter)
Source
scopus
Published In
Journal of Clinical Oncology
Volume
35
Issue
5
Publish Date
2017
Start Page
572
DOI
10.1200/JCO.2016.70.2787

The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma: An Analysis of 1991 Patients.

This study examined the association of extent of lung resection, pathologic nodal evaluation, and survival for patients with clinical stage I (cT1-2N0M0) adenocarcinoma with lepidic histologic features in the National Cancer Data Base.The association between extent of surgical resection and long-term survival for patients in the National Cancer Data Base with clinical stage I lepidic adenocarcinoma who underwent lobectomy or sublobar resection was evaluated using Kaplan-Meier and Cox proportional hazards regression analyses.Of the 1991 patients with cT1-2N0M0 lepidic adenocarcinoma who met the study criteria, 1544 underwent lobectomy and 447 underwent sublobar resection. Patients treated with sublobar resection were older, more likely to be female, and had higher Charlson/Deyo comorbidity scores, but they had smaller tumors and lower T status. Of the patients treated with lobectomy, 6% (n = 92) were upstaged because of positive nodal disease, with a median of seven lymph nodes sampled (interquartile range 4-10). In an analysis of the entire cohort, lobectomy was associated with a significant survival advantage over sublobar resection in univariate analysis (median survival 9.2 versus 7.5 years, p = 0.022, 5-year survival 70.5% versus 67.8%) and after multivariable adjustment (hazard ratio = 0.81, 95% confidence interval: 0.68-0.95, p = 0.011). However, lobectomy was no longer independently associated with improved survival when compared with sublobar resection (hazard ratio = 0.99, 95% confidence interval: 0.77-1.27, p = 0.905) in a multivariable analysis of a subset of patients in which only those patients who had undergone a sublobar resection including lymph node sampling were compared with patients treated with lobectomy.Surgeons treating patients with stage I lung adenocarcinoma with lepidic features should cautiously utilize sublobar resection rather than lobectomy, and they must always perform adequate pathologic lymph node evaluation.

Authors
Cox, ML; Yang, C-FJ; Speicher, PJ; Anderson, KL; Fitch, ZW; Gu, L; Davis, RP; Wang, X; D'Amico, TA; Hartwig, MG; Harpole, DH; Berry, MF
MLA Citation
Cox, ML, Yang, C-FJ, Speicher, PJ, Anderson, KL, Fitch, ZW, Gu, L, Davis, RP, Wang, X, D'Amico, TA, Hartwig, MG, Harpole, DH, and Berry, MF. "The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma: An Analysis of 1991 Patients." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (January 7, 2017).
PMID
28082103
Source
epmc
Published In
Journal of Thoracic Oncology
Publish Date
2017
DOI
10.1016/j.jtho.2017.01.003

Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer.

Patients with limited metastases, oligometastases (OMs), might have improved outcomes compared with patients with widespread distant metastases (DMs). The incidence and behavior of OMs from non-small-cell lung cancer (NSCLC) need further characterization.The medical records of patients who had undergone surgery for stage I-III NSCLC from 1995 to 2009 were retrospectively reviewed. All information pertaining to development of the first metastatic progression was recorded and analyzed. Patients with DMs were categorized into OMs (1-3 lesions potentially amenable to local therapy) and DM subgroups.Of 1719 patients reviewed, 368 (21%) developed DMs with a median follow-up period of 39 months. A single lesion was diagnosed in 115 patients (31%) and 69 (19%) had 2 to 3 lesions (50% oligometastatic). The median survival from the DM diagnosis for oligometastatic and diffuse DM was 12.4 and 6.1 months, respectively (hazard ratio, 0.54; 95% confidence interval, 0.42-0.68; P < .001). Patients with a single metastasis had the longest median survival at 14.7 months. Younger age, OM, the use of chemotherapy for the primary tumor, and DM detection by surveillance imaging were independently associated with improved survival.DMs and OMs are common in surgically managed NSCLC. Overall survival appears to be prolonged with OM.

Authors
Torok, JA; Gu, L; Tandberg, DJ; Wang, X; Harpole, DH; Kelsey, CR; Salama, JK
MLA Citation
Torok, JA, Gu, L, Tandberg, DJ, Wang, X, Harpole, DH, Kelsey, CR, and Salama, JK. "Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer." Clinical lung cancer 18.1 (January 2017): e57-e70.
PMID
27477488
Source
epmc
Published In
Clinical lung cancer
Volume
18
Issue
1
Publish Date
2017
Start Page
e57
End Page
e70
DOI
10.1016/j.cllc.2016.06.011

Reply to T.-H. Wang et al.

Authors
Yang, C-FJ; Chan, DY; Wang, X; D'Amico, TA; Harpole, DH; Berry, MF
MLA Citation
Yang, C-FJ, Chan, DY, Wang, X, D'Amico, TA, Harpole, DH, and Berry, MF. "Reply to T.-H. Wang et al." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35.1 (January 2017): 118-120.
PMID
28034078
Source
epmc
Published In
Journal of Clinical Oncology
Volume
35
Issue
1
Publish Date
2017
Start Page
118
End Page
120

A Risk Score to Assist Selecting Lobectomy Versus Sublobar Resection for Early Stage Non-Small Cell Lung Cancer.

The long-term survival benefit of lobectomy over sublobar resection for early-stage non-small cell lung cancer must be weighed against a potentially increased risk of perioperative mortality. The objective of the current study was to create a risk score to identify patients with favorable short-term outcomes following lobectomy.The 2005-2012 American College of Surgeons National Surgical Quality Improvement Program database was queried for patients undergoing a lobectomy or sublobar resection (either segmentectomy or wedge resection) for lung cancer. A multivariable logistic regression model was utilized to determine factors associated with 30-day mortality among the lobectomy group and to develop an associated risk score to predict perioperative mortality.Of the 5,749 patients who met study criteria, 4,424 (77%) underwent lobectomy, 1,098 (19%) underwent wedge resection, and 227 (4%) underwent segmentectomy. Age, chronic obstructive pulmonary disease, previous cerebrovascular event, functional status, recent smoking status, and surgical approach (minimally invasive versus open) were utilized to develop the risk score. Patients with a risk score of 5 or lower had no significant difference in perioperative mortality by surgical procedure. Patients with a risk score greater than 5 had significantly higher perioperative mortality after lobectomy (4.9%) as compared to segmentectomy (3.6%) or wedge resection (0.8%, p < 0.01).In this study, we have developed a risk model that predicts relative operative mortality from a sublobar resection as compared to a lobectomy. Among patients with a risk score of 5 or less, lobectomy confers no additional perioperative risk over sublobar resection.

Authors
Gulack, BC; Jeffrey Yang, C-F; Speicher, PJ; Yerokun, BA; Tong, BC; Onaitis, MW; D'Amico, TA; Harpole, DH; Hartwig, MG; Berry, MF
MLA Citation
Gulack, BC, Jeffrey Yang, C-F, Speicher, PJ, Yerokun, BA, Tong, BC, Onaitis, MW, D'Amico, TA, Harpole, DH, Hartwig, MG, and Berry, MF. "A Risk Score to Assist Selecting Lobectomy Versus Sublobar Resection for Early Stage Non-Small Cell Lung Cancer." The Annals of thoracic surgery 102.6 (December 2016): 1814-1820.
PMID
27592602
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
102
Issue
6
Publish Date
2016
Start Page
1814
End Page
1820
DOI
10.1016/j.athoracsur.2016.06.032

Reply to D.A. Palma.

Authors
Yang, C-FJ; Chan, DY; D'Amico, TA; Berry, MF; Harpole, DH
MLA Citation
Yang, C-FJ, Chan, DY, D'Amico, TA, Berry, MF, and Harpole, DH. "Reply to D.A. Palma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology (November 21, 2016): JCO2016702787-.
PMID
27870575
Source
epmc
Published In
Journal of Clinical Oncology
Publish Date
2016
Start Page
JCO2016702787

Outcomes of Major Lung Resection After Induction Therapy for Non-Small Cell Lung Cancer in Elderly Patients.

This study analyzes the impact of age on perioperative outcomes and long-term survival of patients undergoing surgery after induction chemotherapy for non-small cell lung cancer.Short- and long-term outcomes of patients with non-small cell lung cancer who were at least 70 years and received induction chemotherapy followed by major lung resection (lobectomy or pneumonectomy) from 1996 to 2012 were assessed using multivariable logistic regression, Kaplan-Meier, and Cox proportional hazard analysis. The outcomes of these elderly patients were compared with those of patients younger than 70 years who underwent the same treatment from 1996 to 2012.Of the 317 patients who met the study criteria, 53 patients were at least 70 years. The median age was 74 years (range, 70 to 82 years) in the elderly group, and induction chemoradiation was used in 24 (45%) patients. Thirty-day mortality was similar between the younger (n = 12) and elderly (n = 3) patients (5% versus 6%; p = 0.52). There were no significant differences in the incidence of postoperative complications between younger and elderly patients (49% versus 57%; p = 0.30). Patients younger than 70 years had a median overall survival (30 months; 95% confidence interval [CI], 24 to 43) and a 5-year survival (39%; 95% CI, 33 to 45) that was not significantly different from patients at least 70 years (median overall survival, 30 months; 95% CI, 18 to 68; and 5-year overall survival, 36%; 95% CI, 21 to 51). However, there was a trend toward worse survival in the elderly group after multivariable adjustment (hazard ratio, 1.43; 95% CI, 0.97 to 2.12; p = 0.071).Major lung resection after induction chemotherapy can be performed with acceptable short- and long-term results in appropriately selected patients at least 70 years, with outcomes that are comparable to those of younger patients.

Authors
Yang, C-FJ; Mayne, NR; Wang, H; Meyerhoff, RR; Hirji, S; Tong, BC; Hartwig, M; Harpole, D; D'Amico, TA; Berry, M
MLA Citation
Yang, C-FJ, Mayne, NR, Wang, H, Meyerhoff, RR, Hirji, S, Tong, BC, Hartwig, M, Harpole, D, D'Amico, TA, and Berry, M. "Outcomes of Major Lung Resection After Induction Therapy for Non-Small Cell Lung Cancer in Elderly Patients." The Annals of thoracic surgery 102.3 (September 2016): 962-970.
PMID
27234579
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
102
Issue
3
Publish Date
2016
Start Page
962
End Page
970
DOI
10.1016/j.athoracsur.2016.03.088

Impact of Age on Long-Term Outcomes of Surgery for Malignant Pleural Mesothelioma.

Although malignant pleural mesothelioma (MPM) is generally a disease associated with more advanced age, the association of age, treatment, and outcomes has not been well-characterized. We evaluated the impact of age on outcomes in patients with MPM to provide data for use in the treatment selection process for elderly patients with potentially resectable disease.Overall survival (OS) of patients younger than 70 and 70 years or older with Stage I to III MPM who underwent cancer-directed surgery or nonoperative management in the Surveillance, Epidemiology, and End Results database (2004-2010) was evaluated using multivariable Cox proportional hazard models and propensity score-matched analysis.Cancer-directed surgery was used in 284 of 879 (32%) patients who met inclusion criteria, and was associated with improved OS in multivariable analysis (hazard ratio, 0.71; P = .001). Cancer-directed surgery was used much less commonly in patients 70 years and older compared with patients younger than 70 years (22% [109/497] vs. 46% [175/382]; P < .001), but patients 70 years and older had improved 1-year (59.4% vs. 37.9%) and 3-year (15.4% vs. 8.0%) OS compared with nonoperative management. The benefit of surgery in patients 70 years and older was observed even after propensity score-matched analysis was used to control for selection bias.Surgical treatment is associated with improved survival compared with nonoperative management for both patients younger than 70 years and patients aged 70 years or older.

Authors
Yang, C-FJ; Yan, BW; Meyerhoff, RR; Saud, SM; Gulack, BC; Speicher, PJ; Hartwig, MG; D'Amico, TA; Harpole, DH; Berry, MF
MLA Citation
Yang, C-FJ, Yan, BW, Meyerhoff, RR, Saud, SM, Gulack, BC, Speicher, PJ, Hartwig, MG, D'Amico, TA, Harpole, DH, and Berry, MF. "Impact of Age on Long-Term Outcomes of Surgery for Malignant Pleural Mesothelioma." Clinical lung cancer 17.5 (September 2016): 419-426.
PMID
27236386
Source
epmc
Published In
Clinical lung cancer
Volume
17
Issue
5
Publish Date
2016
Start Page
419
End Page
426
DOI
10.1016/j.cllc.2016.03.002

Induction Chemotherapy is Not Superior to a Surgery-First Strategy for Clinical N1 Non-Small Cell Lung Cancer.

Guidelines recommend primary surgical resection for non-small cell lung cancer (NSCLC) patients with clinical N1 disease and adjuvant chemotherapy if nodal disease is confirmed after resection. We tested the hypothesis that induction chemotherapy for clinical N1 (cN1) disease improves survival.Patients treated with lobectomy or pneumonectomy for cT1-3 N1 M0 NSCLC from 2006 to 2011 in the National Cancer Data Base were stratified by treatment strategy: surgery first vs induction chemotherapy. Propensity scores were developed and matched with a 2:1 nearest neighbor algorithm. Survival analyses using Kaplan-Meier methods were performed on the unadjusted and propensity-matched cohorts.A total of 5,364 cN1 patients were identified for inclusion, of which 565 (10.5%) were treated with induction chemotherapy. Clinical nodal staging was accurate in 68.6% (n = 3,292) of patients treated with surgical resection first, whereas 16.3% (n = 780) were pN0 and 10.7% (n = 514) were pN2-3. Adjuvant chemotherapy was given to 60.9% of the surgery-first patients who were pN1-3 after resection. Before adjustment, patients treated with induction chemotherapy were younger, with lower comorbidity burden, were more likely to be treated at an academic center and to have private insurance (all p < 0.001), but were significantly more likely to have T3 tumors (28.7% vs 9.9%, p < 0.001) and to require pneumonectomy (23.5% vs 18.5%, p = 0.005). The unadjusted and propensity-matched analyses found no differences in short-term outcomes or survival between groups.Induction chemotherapy for cN1 NSCLC is not associated with improved survival. This finding supports the currently recommended treatment paradigm of surgery first for cN1 NSCLC.

Authors
Speicher, PJ; Fitch, ZW; Gulack, BC; Yang, C-FJ; Tong, BC; Harpole, DH; D'Amico, TA; Berry, MF; Hartwig, MG
MLA Citation
Speicher, PJ, Fitch, ZW, Gulack, BC, Yang, C-FJ, Tong, BC, Harpole, DH, D'Amico, TA, Berry, MF, and Hartwig, MG. "Induction Chemotherapy is Not Superior to a Surgery-First Strategy for Clinical N1 Non-Small Cell Lung Cancer." The Annals of thoracic surgery 102.3 (September 2016): 884-894.
PMID
27476819
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
102
Issue
3
Publish Date
2016
Start Page
884
End Page
894
DOI
10.1016/j.athoracsur.2016.05.065

Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer: A Population-Based Analysis.

The objective of this study was to evaluate outcomes of minimally invasive approaches to esophagectomy using population-level data.Multivariable regression modeling was used to determine predictors associated with the use of minimally invasive approaches for patients in the National Cancer Data Base who underwent resection of middle and distal clinical T13N03M0 esophageal cancers from 2010 to 2012. Perioperative outcomes and 3-year survival were compared between propensity-matched groups of patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE) or open esophagectomy (OE). A subgroup analysis was performed to evaluate the impact of using robotic-assisted operations as part of the minimally invasive approach.Among 4,266 patients included, 1,308 (30.6%) underwent MIE. It was more likely to be used in patients treated at academic (adjusted odds ratio [OR], 10.1; 95% confidence interval [CI], 4.2-33.1) or comprehensive cancer facilities (adjusted OR, 6.4; 95% CI, 2.6-21.1). Compared with propensity-matched patients who underwent OE, patients who underwent MIE had significantly more lymph nodes examined (15 versus 13; p = 0.016) and shorter hospital lengths of stay (10 days versus 11 days; p = 0.046) but similar resection margin positivity, readmission, and 30-day mortality (all p > 0.05). Survival was similar between the matched groups at 3 years for both adenocarcinoma and squamous cell carcinoma (p > 0.05). Compared with MIE without robotic assistance, use of a robotic approach was not associated with any significant differences in perioperative outcomes (p > 0.05).The use of minimally invasive techniques to perform esophagectomy for esophageal cancer is associated with modestly improved perioperative outcomes without compromising survival.

Authors
Yerokun, BA; Sun, Z; Jeffrey Yang, C-F; Gulack, BC; Speicher, PJ; Adam, MA; D'Amico, TA; Onaitis, MW; Harpole, DH; Berry, MF; Hartwig, MG
MLA Citation
Yerokun, BA, Sun, Z, Jeffrey Yang, C-F, Gulack, BC, Speicher, PJ, Adam, MA, D'Amico, TA, Onaitis, MW, Harpole, DH, Berry, MF, and Hartwig, MG. "Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer: A Population-Based Analysis." The Annals of thoracic surgery 102.2 (August 2016): 416-423.
PMID
27157326
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
102
Issue
2
Publish Date
2016
Start Page
416
End Page
423
DOI
10.1016/j.athoracsur.2016.02.078

Long-term survival following open versus thoracoscopic lobectomy after preoperative chemotherapy for non-small cell lung cancer.

Video-assisted thoracoscopic (VATS) lobectomy is increasingly accepted for the management of early-stage non-small cell lung cancer (NSCLC), but its role for locally advanced cancers has not been as well characterized. We compared outcomes of patients who received induction therapy followed by lobectomy, via VATS or thoracotomy.Perioperative complications and long-term survival of all patients with NSCLC who received induction chemotherapy (ICT) (with or without induction radiation therapy) followed by lobectomy from 1996-2012 were assessed using Kaplan-Meier and Cox proportional hazard analysis. Propensity score-matched comparisons were used to assess the potential impact of selection bias.From 1996 to 2012, 272 patients met inclusion criteria and underwent lobectomy after ICT: 69 (25%) by VATS and 203 (75%) by thoracotomy. An 'intent-to-treat' analysis was performed. Compared with thoracotomy patients, VATS patients had a higher clinical stage, were older, had greater body mass index, and were more likely to have coronary disease and chronic obstructive pulmonary disease. Induction radiation was used more commonly in thoracotomy patients [VATS 28% (n = 19) vs open 72% (n = 146), P < 0.001]. Thirty-day mortality was similar between the VATS [3% (n = 2)] and open [4% (n = 8)] groups (P = 0.69). Seven (10%) of the VATS cases were converted to thoracotomy due to difficulty in dissection from fibrotic tissue and adhesions (n = 5) or bleeding (n = 2); none of these conversions led to perioperative deaths. In univariate analysis, VATS patients had improved 3-year survival compared with thoracotomy (61% vs 43%, P = 0.010). In multivariable analysis, the VATS approach showed a trend towards improved survival, but this did not reach statistical significance (hazard ratio, 0.56; 95% confidence interval, 0.32-1.01; P = 0.053). Moreover, a propensity score-matched analysis balancing patient characteristics demonstrated that the VATS approach had similar survival to an open approach (P = 0.56).VATS lobectomy in patients treated with induction therapy for locally advanced NSCLC is feasible and effective and does not appear to compromise oncologic outcomes.

Authors
Yang, C-FJ; Meyerhoff, RR; Mayne, NR; Singhapricha, T; Toomey, CB; Speicher, PJ; Hartwig, MG; Tong, BC; Onaitis, MW; Harpole, DH; D'Amico, TA; Berry, MF
MLA Citation
Yang, C-FJ, Meyerhoff, RR, Mayne, NR, Singhapricha, T, Toomey, CB, Speicher, PJ, Hartwig, MG, Tong, BC, Onaitis, MW, Harpole, DH, D'Amico, TA, and Berry, MF. "Long-term survival following open versus thoracoscopic lobectomy after preoperative chemotherapy for non-small cell lung cancer." European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 49.6 (June 2016): 1615-1623.
PMID
26719408
Source
epmc
Published In
European Journal of Cardio-Thoracic Surgery
Volume
49
Issue
6
Publish Date
2016
Start Page
1615
End Page
1623
DOI
10.1093/ejcts/ezv428

Impact of patient selection and treatment strategies on outcomes after lobectomy for biopsy-proven stage IIIA pN2 non-small cell lung cancer.

We evaluated the impact of patient selection and treatment strategies on long-term outcomes of patients who had lobectomy after induction therapy for stage IIIA pN2 non-small cell lung cancer (NSCLC).The impact of various patient selection, induction therapy and operative strategies on survival of patients with biopsy-proven stage IIIA pN2 NSCLC who received induction chemotherapy ± radiation followed by lobectomy from 1995 to 2012 was assessed using Cox proportional hazards analysis.From 1995 to 2012, 111 patients had lobectomy for stage IIIA pN2 NSCLC after chemotherapy ± radiation with an overall 5-year survival of 39%. The use of induction chemoradiation decreased over time; from 1996 to 2007, 46/65 (71%) patients underwent induction chemoradiation, whereas from 2007 to 2012, 36/46 (78%) patients underwent induction chemotherapy. The use of video-assisted thoracoscopic surgery (VATS) increased over the time period of the study, from 0/26 (0%) in 1996-2001, to 4/39 (10%) in 2002-07 to 33/46 (72%) in 2008-12. Compared with patients given induction chemotherapy alone, patients given additional induction radiation were more likely to have complete pathologic response (30 vs 11%, P = 0.01) but had worse 5-year survival in univariable analysis (31 vs 48%, log-rank P = 0.021). Patients who underwent pathologic mediastinal restaging following induction therapy but prior to resection had an improved overall survival compared with patients who did not undergo pathologic mediastinal restaging {5-year survival: 45.2 [95% confidence interval (CI): 33.9-55.9] vs 13.9% (95% CI: 2.5-34.7); log-rank, P = 0.004}. In multivariable analysis, the particular induction therapy strategy and the surgical approach used, as well as the extent of mediastinal disease were not important predictors of survival. However, pathologic mediastinal restaging was associated with improved survival (HR 0.39; 95% CI: 0.21-0.72; P = 0.003).For patients with stage IIIA pN2 NSCLC, the VATS approach or the addition of radiation to induction therapy can be selectively employed without compromising survival. The strategy of assessing response to induction therapy with pathologic mediastinal restaging allows one to select appropriate patients for complete resection and is associated with a 5-year overall survival of 39% in this population.

Authors
Yang, C-FJ; Adil, SM; Anderson, KL; Meyerhoff, RR; Turley, RS; Hartwig, MG; Harpole, DH; Tong, BC; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Yang, C-FJ, Adil, SM, Anderson, KL, Meyerhoff, RR, Turley, RS, Hartwig, MG, Harpole, DH, Tong, BC, Onaitis, MW, D'Amico, TA, and Berry, MF. "Impact of patient selection and treatment strategies on outcomes after lobectomy for biopsy-proven stage IIIA pN2 non-small cell lung cancer." European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 49.6 (June 2016): 1607-1613.
PMID
26719403
Source
epmc
Published In
European Journal of Cardio-Thoracic Surgery
Volume
49
Issue
6
Publish Date
2016
Start Page
1607
End Page
1613
DOI
10.1093/ejcts/ezv431

The Integrated Comprehensive Care Program: A Novel Home Care Initiative After Major Thoracic Surgery.

Authors
Harpole, DH
MLA Citation
Harpole, DH. "The Integrated Comprehensive Care Program: A Novel Home Care Initiative After Major Thoracic Surgery." Seminars in thoracic and cardiovascular surgery 28.2 (June 2016): 582-584.
PMID
28043481
Source
epmc
Published In
Seminars in Thoracic and Cardiovascular Surgery
Volume
28
Issue
2
Publish Date
2016
Start Page
582
End Page
584
DOI
10.1053/j.semtcvs.2016.05.005

Detection of Occult Micrometastases in Patients With Clinical Stage I Non-Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance).

Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM.Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen.Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity.NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.

Authors
Martin, LW; D'Cunha, J; Wang, X; Herzan, D; Gu, L; Abraham, N; Demmy, TL; Detterbeck, FC; Groth, SS; Harpole, DH; Krasna, MJ; Kernstine, K; Kohman, LJ; Patterson, GA; Sugarbaker, DJ; Vollmer, RT; Maddaus, MA; Kratzke, RA
MLA Citation
Martin, LW, D'Cunha, J, Wang, X, Herzan, D, Gu, L, Abraham, N, Demmy, TL, Detterbeck, FC, Groth, SS, Harpole, DH, Krasna, MJ, Kernstine, K, Kohman, LJ, Patterson, GA, Sugarbaker, DJ, Vollmer, RT, Maddaus, MA, and Kratzke, RA. "Detection of Occult Micrometastases in Patients With Clinical Stage I Non-Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.13 (May 2016): 1484-1491.
PMID
26926677
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
13
Publish Date
2016
Start Page
1484
End Page
1491
DOI
10.1200/jco.2015.63.4543

Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer.

Data on optimal adjuvant therapy after complete resection of small-cell lung cancer (SCLC) are limited, and in particular, there have been no studies evaluating the role of adjuvant chemotherapy, with or without prophylactic cranial irradiation, relative to no adjuvant therapy for stage T1-2N0M0 SCLC. This National Cancer Data Base analysis was performed to determine the potential benefits of adjuvant chemotherapy with and without prophylactic cranial irradiation in patients who undergo complete resection for early-stage small-cell lung cancer.Overall survival of patients with pathologic T1-2N0M0 SCLC who underwent complete resection in the National Cancer Data Base from 2003 to 2011, stratified by adjuvant therapy regimen, was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Patients treated with induction therapy and those who died within 30 days of surgery were excluded from analysis.Of 1,574 patients who had pT1-2N0M0 SCLC during the study period, 954 patients (61%) underwent complete R0 resection with a 5-year survival of 47%. Adjuvant therapy was administered to 59% of patients (n = 566), including chemotherapy alone (n = 354), chemoradiation (n = 190, including 99 patients who underwent cranial irradiation), and radiation alone (n = 22). Compared with surgery alone, adjuvant chemotherapy with or without radiation was associated with significantly improved survival. In addition, multivariable Cox modeling demonstrated that treatment with adjuvant chemotherapy (hazard ratio [HR], 0.78; 95% CI, 0.63 to 0.95) or chemotherapy with radiation directed at the brain (HR, 0.52; 95% CI, 0.36 to 0.75) was associated with improved survival when compared with no adjuvant therapy.Patients with pT1-2N0M0 SCLC treated with surgical resection alone have worse outcomes than those who undergo resection with adjuvant chemotherapy alone or chemotherapy with cranial irradiation.

Authors
Yang, C-FJ; Chan, DY; Speicher, PJ; Gulack, BC; Wang, X; Hartwig, MG; Onaitis, MW; Tong, BC; D'Amico, TA; Berry, MF; Harpole, DH
MLA Citation
Yang, C-FJ, Chan, DY, Speicher, PJ, Gulack, BC, Wang, X, Hartwig, MG, Onaitis, MW, Tong, BC, D'Amico, TA, Berry, MF, and Harpole, DH. "Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.10 (April 2016): 1057-1064.
PMID
26786925
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
10
Publish Date
2016
Start Page
1057
End Page
1064
DOI
10.1200/jco.2015.63.8171

Use and Outcomes of Minimally Invasive Lobectomy for Stage I Non-Small Cell Lung Cancer in the National Cancer Data Base.

Previous studies have raised concerns that video-assisted thoracoscopic (VATS) lobectomy may compromise nodal evaluation. The advantages or limitations of robotic lobectomy have not been thoroughly evaluated.Perioperative outcomes and survival of patients who underwent open versus minimally-invasive surgery (MIS [VATS and robotic]) lobectomy and VATS versus robotic lobectomy for clinical T1-2, N0 non-small cell lung cancer from 2010 to 2012 in the National Cancer Data Base were evaluated using propensity score matching.Of 30,040 lobectomies, 7,824 were VATS and 2,025 were robotic. After propensity score matching, when compared with the open approach (n = 9,390), MIS (n = 9,390) was found to have increased 30-day readmission rates (5% versus 4%, p < 0.01), shorter median hospital length of stay (5 versus 6 days, p < 0.01), and improved 2-year survival (87% versus 86%, p = 0.04). There were no significant differences in nodal upstaging and 30-day mortality between the two groups. After propensity score matching, when compared with the robotic group (n = 1,938), VATS (n = 1,938) was not significantly different from robotics with regard to nodal upstaging, 30-day mortality, and 2-year survival.In this population-based analysis, MIS (VATS and robotic) lobectomy was used in the minority of patients for stage I non-small cell lung cancer. MIS lobectomy was associated with shorter length of hospital stay and was not associated with increased perioperative mortality, compromised nodal evaluation, or reduced short-term survival when compared with the open approach. These results suggest the need for broader implementation of MIS techniques.

Authors
Yang, C-FJ; Sun, Z; Speicher, PJ; Saud, SM; Gulack, BC; Hartwig, MG; Harpole, DH; Onaitis, MW; Tong, BC; D'Amico, TA; Berry, MF
MLA Citation
Yang, C-FJ, Sun, Z, Speicher, PJ, Saud, SM, Gulack, BC, Hartwig, MG, Harpole, DH, Onaitis, MW, Tong, BC, D'Amico, TA, and Berry, MF. "Use and Outcomes of Minimally Invasive Lobectomy for Stage I Non-Small Cell Lung Cancer in the National Cancer Data Base." The Annals of thoracic surgery 101.3 (March 2016): 1037-1042.
PMID
26822346
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
101
Issue
3
Publish Date
2016
Start Page
1037
End Page
1042
DOI
10.1016/j.athoracsur.2015.11.018

The Biology of Pulmonary Metastasis.

The process of metastasis relies on a series of stochastic and sequential steps, with selective pressure exerted on a large number of genetically volatile cancer cells to produce a very small fraction of tumor cells with the ability to navigate the transition from primary tumor cell to end-organ metastasis. This process is intricately determined by cell-microenvironment interactions, the mechanistic understanding of which is steadily increasing. The continued elucidation of pathways that govern these interactions offers potential therapeutic options to patients with advanced disease.

Authors
Scott, CD; Harpole, DH
MLA Citation
Scott, CD, and Harpole, DH. "The Biology of Pulmonary Metastasis." Thoracic surgery clinics 26.1 (February 2016): 1-6.
PMID
26611504
Source
epmc
Published In
Thoracic Surgery Clinics
Volume
26
Issue
1
Publish Date
2016
Start Page
1
End Page
6
DOI
10.1016/j.thorsurg.2015.09.001

Adding radiation to induction chemotherapy does not improve survival of patients with operable clinical N2 non-small cell lung cancer.

Radiotherapy is commonly used in induction regimens for patients with non-small cell lung cancer with operable mediastinal nodal disease, although evidence has not shown a benefit over induction chemotherapy alone. We compared outcomes between induction chemotherapy and induction chemoradiation using the National Cancer Data Base.Induction radiation use and survival of patients who underwent lobectomy or pneumonectomy after induction chemotherapy for clinical T1-3N2M0 non-small cell lung cancer in the National Cancer Data Base from 2003 to 2006 were assessed using logistic regression, general linear regression, Kaplan-Meier, and Cox proportional hazard analysis.Of 1362 patients who met study criteria, 834 (61%) underwent induction chemoradiation and 528 (39%) underwent induction chemotherapy. Lobectomy was performed in 82% of patients (n = 1111), and pneumonectomy was performed in 18% of patients (n = 251). Pneumonectomy was performed more often after induction chemoradiation than after induction chemotherapy (20% vs 16%, P = .04). Downstaging from N2 to N0/N1 was more common with induction chemoradiation compared with induction chemotherapy (58% vs 46%, P < .01), but 5-year survival of patients receiving induction chemoradiation and patients receiving induction chemotherapy was similar in unadjusted analysis (41% vs 41%, P = .41). In multivariable analysis, the addition of radiation to induction chemotherapy also was not associated with a survival benefit (hazard ratio, 1.03; 95% confidence interval, 0.89-1.18; P = .73).Induction chemoradiation is used in the majority of patients with non-small cell lung cancer with N2 disease who undergo induction therapy before surgical resection, but it is not associated with improved survival compared with induction chemotherapy.

Authors
Yang, C-FJ; Gulack, BC; Gu, L; Speicher, PJ; Wang, X; Harpole, DH; Onaitis, MW; D'Amico, TA; Berry, MF; Hartwig, MG
MLA Citation
Yang, C-FJ, Gulack, BC, Gu, L, Speicher, PJ, Wang, X, Harpole, DH, Onaitis, MW, D'Amico, TA, Berry, MF, and Hartwig, MG. "Adding radiation to induction chemotherapy does not improve survival of patients with operable clinical N2 non-small cell lung cancer." The Journal of thoracic and cardiovascular surgery 150.6 (December 2015): 1484-1492.
PMID
26259994
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
150
Issue
6
Publish Date
2015
Start Page
1484
End Page
1492
DOI
10.1016/j.jtcvs.2015.06.062

A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo.

The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3 protein is expressed on the surface of tumor cells but not in normal adult tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo across multiple PDX models. Serial transplantation experiments executed with limiting dilutions of cells provided functional evidence confirming that the lack of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and responses were observed in PDX models initiated from patients with both limited and extensive-stage disease and were independent of their sensitivity to standard-of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3-expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class ADC for the treatment of high-grade pulmonary neuroendocrine tumors.

Authors
Saunders, LR; Bankovich, AJ; Anderson, WC; Aujay, MA; Bheddah, S; Black, K; Desai, R; Escarpe, PA; Hampl, J; Laysang, A; Liu, D; Lopez-Molina, J; Milton, M; Park, A; Pysz, MA; Shao, H; Slingerland, B; Torgov, M; Williams, SA; Foord, O; Howard, P; Jassem, J; Badzio, A; Czapiewski, P; Harpole, DH; Dowlati, A; Massion, PP; Travis, WD; Pietanza, MC; Poirier, JT; Rudin, CM; Stull, RA; Dylla, SJ
MLA Citation
Saunders, LR, Bankovich, AJ, Anderson, WC, Aujay, MA, Bheddah, S, Black, K, Desai, R, Escarpe, PA, Hampl, J, Laysang, A, Liu, D, Lopez-Molina, J, Milton, M, Park, A, Pysz, MA, Shao, H, Slingerland, B, Torgov, M, Williams, SA, Foord, O, Howard, P, Jassem, J, Badzio, A, Czapiewski, P, Harpole, DH, Dowlati, A, Massion, PP, Travis, WD, Pietanza, MC, Poirier, JT, Rudin, CM, Stull, RA, and Dylla, SJ. "A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo." Science translational medicine 7.302 (August 2015): 302ra136-.
PMID
26311731
Source
epmc
Published In
Science Translational Medicine
Volume
7
Issue
302
Publish Date
2015
Start Page
302ra136
DOI
10.1126/scitranslmed.aac9459

Impact of Pulmonary Function Measurements on Long-Term Survival After Lobectomy for Stage I Non-Small Cell Lung Cancer.

Pulmonary function tests predict respiratory complications after lobectomy. We evaluated the impact of pulmonary function measurements on long-term survival after lobectomy for stage I non-small cell lung cancer.The relationship between percent predicted forced expiratory volume in 1 second (FEV1) and percent predicted diffusing capacity of the lung for carbon monoxide (Dlco) and overall survival for patients who underwent lobectomy without induction therapy for stage I (T1-2N0M0) non-small cell lung cancer from 1996 to 2012 was evaluated using the Kaplan-Meier approach and a multivariable Cox proportional hazard model.During the study period, 972 patients (mean Dlco 76 ± 21, mean FEV1 73 ± 21) met inclusion criteria. Perioperative mortality was 2.6% (n = 25). The 5-year survival of the entire cohort was 60.1%, with a median follow-up of 43 months. The 5-year survival for patients with percent predicted FEV1 stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.1%, 59.3%, 52.5%, and 53.4%, respectively. The 5-year survival for patients with percent predicted Dlco stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.2%, 63.4%, 44.2%, and 33.1%, respectively. In multivariable survival analysis, both larger tumor size (hazard ratio 1.15, p = 0.01) and lower Dlco (hazard ratio 0.986, p < 0.0001) were significant predictors of worse survival. The association of FEV1 and survival was not statistically significant (p = 0.18).Survival after lobectomy for patients with stage I non-small cell lung cancer is impacted by lower Dlco, which can be used in the risk and benefit assessment when choosing therapy.

Authors
Berry, MF; Jeffrey Yang, C-F; Hartwig, MG; Tong, BC; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Jeffrey Yang, C-F, Hartwig, MG, Tong, BC, Harpole, DH, D'Amico, TA, and Onaitis, MW. "Impact of Pulmonary Function Measurements on Long-Term Survival After Lobectomy for Stage I Non-Small Cell Lung Cancer." The Annals of thoracic surgery 100.1 (July 2015): 271-276.
PMID
25986099
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
100
Issue
1
Publish Date
2015
Start Page
271
End Page
276
DOI
10.1016/j.athoracsur.2015.02.076

Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database.

This study was conducted to determine how malignant pleural mesothelioma (MPM) histology was associated with the use of surgery and survival.Overall survival of patients with stage I-III epithelioid, sarcomatoid, and biphasic MPM in the Surveillance, Epidemiology, and End Results database from 2004-2010 was evaluated using multivariate Cox proportional hazards models.Of 1183 patients who met inclusion criteria, histologic subtype was epithelioid in 811 patients (69%), biphasic in 148 patients (12%), and sarcomatoid in 224 patients (19%). Median survival was 14 mo in the epithelioid group, 10 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). Cancer-directed surgery was used more often in patients with epithelioid (37%, 299/811) and biphasic (44%, 65/148) histologies as compared with patients with sarcomatoid histology (26%, 58/224; P < 0.01). Among patients who underwent surgery, median survival was 19 mo in the epithelioid group, 12 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). In multivariate analysis, surgery was associated with improved survival in the epithelioid group (hazard ratio [HR] 0.72; P < 0.01) but not in biphasic (HR 0.73; P = 0.19) or sarcomatoid (HR 0.79; P = 0.18) groups.Cancer-directed surgery is associated with significantly improved survival for MPM patients with epithelioid histology, but patients with sarcomatoid and biphasic histologies have poor prognoses that may not be favored by operative treatment. The specific histology should be identified before treatment, so that surgery can be offered to patients with epithelioid histology, as these patients are most likely to benefit.

Authors
Meyerhoff, RR; Yang, C-FJ; Speicher, PJ; Gulack, BC; Hartwig, MG; D'Amico, TA; Harpole, DH; Berry, MF
MLA Citation
Meyerhoff, RR, Yang, C-FJ, Speicher, PJ, Gulack, BC, Hartwig, MG, D'Amico, TA, Harpole, DH, and Berry, MF. "Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database." The Journal of surgical research 196.1 (June 2015): 23-32.
PMID
25791825
Source
epmc
Published In
Journal of Surgical Research
Volume
196
Issue
1
Publish Date
2015
Start Page
23
End Page
32
DOI
10.1016/j.jss.2015.01.043

Long-Term Outcomes of Lobectomy for Non-Small Cell Lung Cancer After Definitive Radiation Treatment.

Salvage surgical resection for non-small cell lung cancer (NSCLC) patients initially treated with definitive chemotherapy and radiotherapy can be performed safely, but the long-term benefits are not well characterized.Perioperative complications and long-term survival of all patients with NSCLC who received curative-intent definitive radiotherapy, with or without chemotherapy, followed by lobectomy from 1995 to 2012 were evaluated.During the study period, 31 patients met the inclusion criteria. Clinical stage distribution was stage I in 2 (6%), stage II in 5 (16%), stage IIIA in 15 (48%), stage IIIB in 5 (16%), stage IV in 3 (10%), and unknown in 1 (3%). The reasons surgical resection was initially not considered were: patients deemed medically inoperable (5 [16%]); extent of disease was considered unresectable (21 [68%]); small cell lung cancer misdiagnosis (1 [3%]), and unknown (4 [13%]). Definitive therapy was irradiation alone in 2 (6%), concurrent chemoradiotherapy in 28 (90%), and sequential chemoradiotherapy in 1 (3%). The median radiation dose was 60 Gy. Patients were subsequently referred for resection because of obvious local relapse, medical tolerance of surgical intervention, or posttherapy imaging suggesting residual disease. The median time from radiation to lobectomy was 17.7 weeks. There were no perioperative deaths, and morbidity occurred in 15 patients (48%). None of the 3 patients with residual pathologic nodal disease survived longer than 37 months, but the 5-year survival of pN0 patients was 36%. Patients who underwent lobectomy for obvious relapse (n = 3) also did poorly, with a median overall survival of 9 months.Lobectomy after definitive radiotherapy can be done safely and is associated with reasonable long-term survival, particularly when patients do not have residual nodal disease.

Authors
Yang, C-FJ; Meyerhoff, RR; Stephens, SJ; Singhapricha, T; Toomey, CB; Anderson, KL; Kelsey, C; Harpole, D; D'Amico, TA; Berry, MF
MLA Citation
Yang, C-FJ, Meyerhoff, RR, Stephens, SJ, Singhapricha, T, Toomey, CB, Anderson, KL, Kelsey, C, Harpole, D, D'Amico, TA, and Berry, MF. "Long-Term Outcomes of Lobectomy for Non-Small Cell Lung Cancer After Definitive Radiation Treatment." The Annals of thoracic surgery 99.6 (June 2015): 1914-1920.
PMID
25886806
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
99
Issue
6
Publish Date
2015
Start Page
1914
End Page
1920
DOI
10.1016/j.athoracsur.2015.01.064

Value of circulating insulin-like growth factor-associated proteins for the detection of stage I non-small cell lung cancer Discussion

Authors
Burt, B; Kubasiak, ; Harpole, DH
MLA Citation
Burt, B, Kubasiak, , and Harpole, DH. "Value of circulating insulin-like growth factor-associated proteins for the detection of stage I non-small cell lung cancer Discussion." JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 149.3 (March 2015): 734-+.
Source
wos-lite
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
149
Issue
3
Publish Date
2015
Start Page
734
End Page
+

The Society of Thoracic Surgeons practice guidelines on the role of multimodality treatment for cancer of the esophagus and gastroesophageal junction.

Authors
Little, AG; Lerut, AE; Harpole, DH; Hofstetter, WL; Mitchell, JD; Altorki, NK; Krasna, MJ
MLA Citation
Little, AG, Lerut, AE, Harpole, DH, Hofstetter, WL, Mitchell, JD, Altorki, NK, and Krasna, MJ. "The Society of Thoracic Surgeons practice guidelines on the role of multimodality treatment for cancer of the esophagus and gastroesophageal junction." The Annals of thoracic surgery 98.5 (November 2014): 1880-1885.
PMID
25262396
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
98
Issue
5
Publish Date
2014
Start Page
1880
End Page
1885
DOI
10.1016/j.athoracsur.2014.07.069

Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction Discussion

Authors
Rao, V; Kindi, A; Jr, HDH; Rosengart, TK
MLA Citation
Rao, V, Kindi, A, Jr, HDH, and Rosengart, TK. "Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction Discussion." JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 148.5 (November 2014): 2323-2324.
Source
wos-lite
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
148
Issue
5
Publish Date
2014
Start Page
2323
End Page
2324

Abstract 1904: RNA expression based screening of ALK gene fusion from formalin fixed non-small cell lung cancer samples

Authors
Maddula, K; Joshi, M-B; Modur, V; Harpole, DH
MLA Citation
Maddula, K, Joshi, M-B, Modur, V, and Harpole, DH. "Abstract 1904: RNA expression based screening of ALK gene fusion from formalin fixed non-small cell lung cancer samples." October 1, 2014.
Source
crossref
Published In
Cancer Research
Volume
74
Issue
19 Supplement
Publish Date
2014
Start Page
1904
End Page
1904
DOI
10.1158/1538-7445.AM2014-1904

Thoracoscopic left upper lobectomy in patients with internal mammary artery coronary bypass grafts.

This study examined outcomes of a technique for performing thoracoscopic left upper lobectomy (LUL) in patients with a previous left internal mammary artery (LIMA) coronary artery bypass graft, where a small wedge of lung parenchyma adjacent to the graft is left to avoid injury.All patients undergoing thoracoscopic LUL from 1999 to 2010 at a single institution were reviewed. Perioperative morbidity, cancer recurrence, and long-term survival were compared between patients who had (LIMA group) or did not have (control group) a previous LIMA graft.During the study period, 290 patients underwent thoracoscopic LUL; 14 (5%) had previous LIMA grafts. There was no perioperative mortality in the LIMA group versus 4 (1%) in the control group (p = 0.65). One patient (7%) in the LIMA group required conversion to thoracotomy, which was similar to the control group (n = 16, 6%; p = 0.83). Overall perioperative morbidity was also not different between the groups (LIMA 36% [5 of 14] versus control 29% [81 of 276], p = 0.61). No patient in the LIMA group had perioperative cardiac ischemia. For patients with lung cancer, 5-year survival (LIMA 50% vs control 63%, p = 0.23) and cancer recurrence rates (LIMA 27% (3 of 11) versus control 15% (36 of 242), p = 0.27) were not different between the groups. Only 1 LIMA recurrence was local, and it was not related to the parenchyma left on the LIMA graft.Thoracoscopic LUL can be performed safely in patients with LIMA bypass grafts. Leaving lung parenchyma on the graft may prevent injury and does not compromise oncologic outcomes in appropriately selected patients.

Authors
Shah, AA; Worni, M; Onaitis, MW; Balderson, SS; Harpole, DH; D'Amico, TA; Berry, MF
MLA Citation
Shah, AA, Worni, M, Onaitis, MW, Balderson, SS, Harpole, DH, D'Amico, TA, and Berry, MF. "Thoracoscopic left upper lobectomy in patients with internal mammary artery coronary bypass grafts." The Annals of thoracic surgery 98.4 (October 2014): 1207-1212.
PMID
25110335
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
98
Issue
4
Publish Date
2014
Start Page
1207
End Page
1212
DOI
10.1016/j.athoracsur.2014.05.068

Consensus report of a joint NCI thoracic malignancies steering committee: FDA workshop on strategies for integrating biomarkers into clinical development of new therapies for lung cancer leading to the inception of "master protocols" in lung cancer.

On February 2, 2012, the National Cancer Institute (NCI) sponsored a 2-day workshop with the NCI Thoracic Malignancies Steering Committee and the Food and Drug Administration to bring together leading academicians, clinicians, industry and government representatives to identify challenges and potential solutions in the clinical development of novel targeted therapies for lung cancer. Measures of success are rapidly evolving from a scientific and regulatory perspective and the objectives of this workshop were to achieve initial consensus on a high priority biomarker-driven clinical trial designed to rapidly assess the activity of targeted agents in molecularly defined lung cancer subsets and to facilitate generation of data leading to approval of these new therapies. Additionally, the meeting focused on identification of the barriers to conduct such a trial and the development of strategies to overcome those barriers. The "Lung Master Protocols" recently launched by NCI were the direct outcome of this workshop.

Authors
Malik, SM; Pazdur, R; Abrams, JS; Socinski, MA; Sause, WT; Harpole, DH; Welch, JJ; Korn, EL; Ullmann, CD; Hirsch, FR
MLA Citation
Malik, SM, Pazdur, R, Abrams, JS, Socinski, MA, Sause, WT, Harpole, DH, Welch, JJ, Korn, EL, Ullmann, CD, and Hirsch, FR. "Consensus report of a joint NCI thoracic malignancies steering committee: FDA workshop on strategies for integrating biomarkers into clinical development of new therapies for lung cancer leading to the inception of "master protocols" in lung cancer." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 9.10 (October 2014): 1443-1448.
PMID
25521397
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
9
Issue
10
Publish Date
2014
Start Page
1443
End Page
1448
DOI
10.1097/jto.0000000000000314

Outcomes after pneumonectomy for benign disease: the impact of urgent resection.

Pneumonectomy for benign disease is often complicated by inflammatory processes that obscure operative planes. We reviewed our experience to evaluate the impact of requiring urgent or emergent pneumonectomy on outcomes.All pneumonectomies for benign conditions from 1997 to 2012 at a single institution were retrospectively reviewed. Mortality was assessed using multivariable logistic regression that included laterality, age, and surgery status, which was emergent if performed within 24 hours of initial evaluation, urgent if performed after 24 hours but within the same hospital stay, and otherwise elective.Among 42 pneumonectomies, completion pneumonectomy after previous ipsilateral lung resection was performed in 14 patients (33%). Resection was elective in 22 patients (52%), urgent in 12 (28%), and emergent in 8 (19%). The most common indication was for necrotic lung (n = 12; 29%). Muscle flaps were used in 26 patients (62%). Perioperative mortality for the entire cohort was 29% (n = 12) and was significantly higher when surgery was urgent (5 of 12; 42%) or emergent (5 of 8; 62.5%) compared with elective (2 of 22; 9.1%) (p = 0.03). Requiring urgent or emergent surgery remained a significant predictor of mortality in multivariable analysis (odds ratio 10.4, p = 0.01).Pneumonectomy for benign disease has significant risk for mortality, particularly when not performed electively. Although surgery cannot be planned in the setting of trauma or some situations of acute infection, patients known to have conditions that are likely to require pneumonectomy should be considered for surgery earlier in their disease course, before developing an acute problem that requires urgent or emergent resection.

Authors
Klapper, J; Hirji, S; Hartwig, MG; D'Amico, TA; Harpole, DH; Onaitis, MW; Berry, MF
MLA Citation
Klapper, J, Hirji, S, Hartwig, MG, D'Amico, TA, Harpole, DH, Onaitis, MW, and Berry, MF. "Outcomes after pneumonectomy for benign disease: the impact of urgent resection." Journal of the American College of Surgeons 219.3 (September 2014): 518-524.
PMID
24862885
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
219
Issue
3
Publish Date
2014
Start Page
518
End Page
524
DOI
10.1016/j.jamcollsurg.2014.01.062

Sex differences in early outcomes after lung cancer resection: analysis of the Society of Thoracic Surgeons General Thoracic Database.

Women with lung cancer have superior long-term survival outcomes compared with men, independent of stage. The cause of this disparity is unknown. For patients undergoing lung cancer resection, these survival differences could be due, in part, to relatively better perioperative outcomes for women. This study was undertaken to determine differences in perioperative outcomes after lung cancer surgery on the basis of sex.The Society of Thoracic Surgeons' General Thoracic Database was queried for all patients undergoing resection of lung cancer between 2002 and 2010. Postoperative complications were analyzed with respect to sex. Univariable analysis was performed, followed by multivariable modeling to determine significant risk factors for postoperative morbidity and mortality.A total of 34,188 patients (16,643 men and 17,545 women) were considered. Univariable analysis demonstrated statistically significant differences in postoperative complications favoring women in all categories of postoperative complications. Women also had lower in-hospital and 30-day mortality (odds ratio, 0.56; 95% confidence interval, 0.44-0.71; P < .001). Multivariable analysis demonstrated that several preoperative conditions independently predicted 30-day mortality: male sex, increasing age, lower diffusion capacity, renal insufficiency, preoperative radiation therapy, cancer stage, extent of resection, and thoracotomy as surgical approach. Coronary artery disease was an independent predictor of mortality in women but not in men. Thoracotomy as the surgical approach and preoperative radiation therapy were predictive of mortality for men but not for women. Postoperative prolonged air leak and empyema predicted mortality in men but not in women.Women have lower postoperative morbidity and mortality after lung cancer surgery. Some risk factors are sex-specific with regard to mortality. Further study is warranted to determine the cause of these differences and to determine their effect on survival.

Authors
Tong, BC; Kosinski, AS; Burfeind, WR; Onaitis, MW; Berry, MF; Harpole, DH; D'Amico, TA
MLA Citation
Tong, BC, Kosinski, AS, Burfeind, WR, Onaitis, MW, Berry, MF, Harpole, DH, and D'Amico, TA. "Sex differences in early outcomes after lung cancer resection: analysis of the Society of Thoracic Surgeons General Thoracic Database." The Journal of thoracic and cardiovascular surgery 148.1 (July 2014): 13-18.
PMID
24726742
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
148
Issue
1
Publish Date
2014
Start Page
13
End Page
18
DOI
10.1016/j.jtcvs.2014.03.012

Patient Genotypes Impact Survival After Surgery for Isolated Congenital Heart Disease DISCUSSION

Authors
Coles, JG; Kim, M; Mckeown, P; Harpole, DH; Backer, CL
MLA Citation
Coles, JG, Kim, M, Mckeown, P, Harpole, DH, and Backer, CL. "Patient Genotypes Impact Survival After Surgery for Isolated Congenital Heart Disease DISCUSSION." ANNALS OF THORACIC SURGERY 98.1 (July 2014): 110-111.
Source
wos-lite
Published In
The Annals of Thoracic Surgery
Volume
98
Issue
1
Publish Date
2014
Start Page
110
End Page
111

Differential prognostic significance of extralobar and intralobar nodal metastases in patients with surgically resected stage II non-small cell lung cancer.

We sought to determine the prognostic significance of extralobar nodal metastases versus intralobar nodal metastases in patients with lung cancer and pathologic stage N1 disease.A retrospective review of a prospectively maintained lung resection database identified 230 patients with pathologic stage II, N1 non-small cell lung cancer from 1997 to 2011. The surgical pathology reports were reviewed to identify the involved N1 stations. The outcome variables included recurrence and death. Univariate and multivariate analyses were performed using the R statistical software package.A total of 122 patients had extralobar nodal metastases (level 10 or 11); 108 patients were identified with intralobar nodal disease (levels 12-14). The median follow-up was 111 months. The baseline characteristics were similar in both groups. No significant differences were noted in the surgical approach, anatomic resections performed, or adjuvant therapy rates between the 2 groups. Overall, 80 patients developed recurrence during follow-up: 33 (30%) of 108 in the intralobar and 47 (38%) of 122 in the extralobar cohort. The median overall survival was 46.9 months for the intralobar cohort and 24.4 months for the extralobar cohort (P < .001). In a multivariate Cox proportional hazard model that included the presence of extralobar nodal disease, age, tumor size, tumor histologic type, and number of positive lymph nodes, extralobar nodal disease independently predicted both recurrence-free and overall survival (hazard ratio, 1.96; 95% confidence interval, 1.36-2.81; P = .001).In patients who underwent surgical resection for stage II non-small cell lung cancer, the presence of extralobar nodal metastases at level 10 or 11 predicted significantly poorer outcomes than did nodal metastases at stations 12 to 14. This finding has prognostic importance and implications for adjuvant therapy and surveillance strategies for patients within the heterogeneous stage II (N1) category.

Authors
Haney, JC; Hanna, JM; Berry, MF; Harpole, DH; D'Amico, TA; Tong, BC; Onaitis, MW
MLA Citation
Haney, JC, Hanna, JM, Berry, MF, Harpole, DH, D'Amico, TA, Tong, BC, and Onaitis, MW. "Differential prognostic significance of extralobar and intralobar nodal metastases in patients with surgically resected stage II non-small cell lung cancer." The Journal of thoracic and cardiovascular surgery 147.4 (April 2014): 1164-1168.
PMID
24507984
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
147
Issue
4
Publish Date
2014
Start Page
1164
End Page
1168
DOI
10.1016/j.jtcvs.2013.12.015

Accuracy of fluorodeoxyglucose-positron emission tomography within the clinical practice of the American College of Surgeons Oncology Group Z4031 trial to diagnose clinical stage I non-small cell lung cancer.

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is recommended for diagnosis and staging of non-small cell lung cancer (NSCLC). Meta-analyses of FDG-PET diagnostic accuracy demonstrated sensitivity of 96% and specificity of 78% but were performed in select centers, introducing potential bias. This study evaluates the accuracy of FDG-PET to diagnose NSCLC and examines differences across enrolling sites in the national American College of Surgeons Oncology Group (ACOSOG) Z4031 trial.Between 2004 and 2006, 959 eligible patients with clinical stage I (cT1-2 N0 M0) known or suspected NSCLC were enrolled in the Z4031 trial, and with a baseline FDG-PET available for 682. Final diagnosis was determined by pathologic examination. FDG-PET avidity was categorized into avid or not avid by radiologist description or reported maximum standard uptake value. FDG-PET diagnostic accuracy was calculated for the entire cohort. Accuracy differences based on preoperative size and by enrolling site were examined.Preoperative FDG-PET results were available for 682 participants enrolled at 51 sites in 39 cities. Lung cancer prevalence was 83%. FDG-PET sensitivity was 82% (95% confidence interval, 79 to 85) and specificity was 31% (95% confidence interval, 23% to 40%). Positive and negative predictive values were 85% and 26%, respectively. Accuracy improved with lesion size. Of 80 false-positive scans, 69% were granulomas. False-negative scans occurred in 101 patients, with adenocarcinoma being the most frequent (64%), and 11 were 10 mm or less. The sensitivity varied from 68% to 91% (p=0.03), and the specificity ranged from 15% to 44% (p=0.72) across cities with more than 25 participants.In a national surgical population with clinical stage I NSCLC, FDG-PET to diagnose lung cancer performed poorly compared with published studies.

Authors
Grogan, EL; Deppen, SA; Ballman, KV; Andrade, GM; Verdial, FC; Aldrich, MC; Chen, CL; Decker, PA; Harpole, DH; Cerfolio, RJ; Keenan, RJ; Jones, DR; D'Amico, TA; Shrager, JB; Meyers, BF; Putnam, JB
MLA Citation
Grogan, EL, Deppen, SA, Ballman, KV, Andrade, GM, Verdial, FC, Aldrich, MC, Chen, CL, Decker, PA, Harpole, DH, Cerfolio, RJ, Keenan, RJ, Jones, DR, D'Amico, TA, Shrager, JB, Meyers, BF, and Putnam, JB. "Accuracy of fluorodeoxyglucose-positron emission tomography within the clinical practice of the American College of Surgeons Oncology Group Z4031 trial to diagnose clinical stage I non-small cell lung cancer." The Annals of thoracic surgery 97.4 (April 2014): 1142-1148.
PMID
24576597
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
97
Issue
4
Publish Date
2014
Start Page
1142
End Page
1148
DOI
10.1016/j.athoracsur.2013.12.043

Sleeve lobectomy for non-small cell lung cancer with N1 nodal disease does not compromise survival.

BACKGROUND: We evaluated if sleeve lobectomy had worse survival compared with pneumonectomy for non-small cell lung cancer (NSCLC) with N1 disease, which may be a risk factor for locoregional recurrence. METHODS: Patients who underwent pneumonectomy or sleeve lobectomy without induction treatment for T2-3 N1 M0 NSCLC at a single institution from 1999 to 2011 were reviewed. Survival distribution was estimated with the Kaplan-Meier method, and multivariable Cox proportional hazards regression was used to evaluate the effect of resection extent on survival. RESULTS: During the study period, 87 patients underwent pneumonectomy (52 [60%]) or sleeve lobectomy (35 [40%]) for T2-3 N1 M0 NSCLC. Pneumonectomy and sleeve lobectomy patients had similar mean ages (60.9 ± 10.7 vs 63.5 ± 12.7 years, p = 0.30), gender distribution (69.2% [36 of 52] vs 60.0% [21 of 35] male, p = 0.37), mean forced expiratory volume in 1 second (66.3 ± 15.9 vs 63.5 ± 17.6, p = 0.47), stage (61.5% [32 of 52] vs 62.9% [22 of 35] stage II, p = 0.90), and tumor grade (51.9% [27 of 52] vs 31.4% [11 of 35] well/moderately differentiated, p = 0.17). Postoperative mortality (3.8% [2 of 52] vs 5.7% [2 of 35], p = 0.68) and median (interquartile range) length of stay (5 [4 to 7] vs 5 [4 to 7] days, p = 0.68) were similar between the two groups. The 3-year survival after pneumonectomy (46.8% [95% CI, 31.8% to 60.4%]) and sleeve lobectomy (65.2% [95% CI, 45.5% to 79.3%]) was not significantly different (p = 0.23). In multivariable survival analysis that included resection extent, age, stage, and grade, only increasing age predicted worse survival (hazard ratio, 1.03/year; p = 0.03). CONCLUSIONS: Performing sleeve lobectomy instead of pneumonectomy for NSCLC with N1 nodal disease does not compromise long-term survival.

Authors
Berry, MF; Worni, M; Wang, X; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Worni, M, Wang, X, Harpole, DH, D'Amico, TA, and Onaitis, MW. "Sleeve lobectomy for non-small cell lung cancer with N1 nodal disease does not compromise survival." Ann Thorac Surg 97.1 (January 2014): 230-235.
PMID
24206972
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
97
Issue
1
Publish Date
2014
Start Page
230
End Page
235
DOI
10.1016/j.athoracsur.2013.09.016

Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB Protocol 39803.

OBJECTIVE: Accurate pathologic restaging of N2 stations after neoadjuvant therapy in stage IIIA (N2) non-small cell lung cancer is needed. METHODS: A prospective multi-institutional trial was designed to judge the feasibility of videothoracoscopy to restage the ipsilateral nodes in mediastinoscopy-proven stage IIIA (N2) non-small cell lung cancer after 2 cycles of platinum-based chemotherapy and/or 40 Gy or more of radiotherapy. The goals included biopsy of 3 negative N2 node stations or to identify 1 positive N2 node or pleural carcinomatosis. RESULTS: Ten institutions accrued 68 subjects. Of the 68 subjects, 46 (68%) underwent radiotherapy and 66 (97%) underwent chemotherapy. Videothoracoscopy successfully met the prestudy feasibility in 27 patients (40%): 3 negative stations confirmed at thoracotomy in 7, persistent stage N2 disease in 16, and pleural carcinomatosis in 4. In 20 procedures (29%), no N2 disease was found, 3 stations were not biopsied because of unanticipated nodal obliteration. Thus, 47 videothoracoscopy procedures (69%, 95% confidence interval, 57%-80%) restaged the mediastinum. Videothoracoscopy was unsuccessful in 21 patients (31%) because the procedure had to be aborted (n = 11) or because of false-negative stations (n = 10). Of the 21 failures, 15 were right-sided, and 10 had a positive 4R node. The sensitivity of videothoracoscopy was 67% (95% confidence interval, 47%-83%), and the negative predictive value was 73% (95% confidence interval, 56%-86%) if patients with obliterated nodal tissue were included. The sensitivity was 83% (95% confidence interval, 63%-95%) and the negative predictive value was 64% (95% confidence interval, 31%-89%) if those patients were excluded. The specificity was 100%. One death occurred after thoracotomy. CONCLUSIONS: Videothoracoscopy restaging was "feasible" in this prospective multi-institutional trial and provided pathologic specimens of the ipsilateral nodes. Videothoracoscopy restaging was limited by radiation and the 4R nodal station.

Authors
Jaklitsch, MT; Gu, L; Demmy, T; Harpole, DH; D'Amico, TA; McKenna, RJ; Krasna, MJ; Kohman, LJ; Swanson, SJ; DeCamp, MM; Wang, X; Barry, S; Sugarbaker, DJ; CALGB Thoracic Surgeons,
MLA Citation
Jaklitsch, MT, Gu, L, Demmy, T, Harpole, DH, D'Amico, TA, McKenna, RJ, Krasna, MJ, Kohman, LJ, Swanson, SJ, DeCamp, MM, Wang, X, Barry, S, Sugarbaker, DJ, and CALGB Thoracic Surgeons, . "Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB Protocol 39803." J Thorac Cardiovasc Surg 146.1 (July 2013): 9-16.
PMID
23768804
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
146
Issue
1
Publish Date
2013
Start Page
9
End Page
16
DOI
10.1016/j.jtcvs.2012.12.069

Abstract LB-296: FDG-PET avidity negatively impacts survival in pStage I NSCLC in the ACOSOG Z4031 trial.

Authors
Grogan, EL; Deppen, SA; Chen, H; Ballman, KV; Verdial, FC; Aldrich, MC; Decker, PA; Harpole, DH; Cerfolio, RJ; Keenan, RJ; Jones, DR; D'Amico, TA; Shrager, JB; Meyers, BF; Putnam, JB
MLA Citation
Grogan, EL, Deppen, SA, Chen, H, Ballman, KV, Verdial, FC, Aldrich, MC, Decker, PA, Harpole, DH, Cerfolio, RJ, Keenan, RJ, Jones, DR, D'Amico, TA, Shrager, JB, Meyers, BF, and Putnam, JB. "Abstract LB-296: FDG-PET avidity negatively impacts survival in pStage I NSCLC in the ACOSOG Z4031 trial." April 15, 2013.
Source
crossref
Published In
Cancer Research
Volume
73
Issue
8 Supplement
Publish Date
2013
Start Page
LB-296
End Page
LB-296
DOI
10.1158/1538-7445.AM2013-LB-296

Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non-small cell lung cancer: Results from Cancer and Leukemia Group B 159902

Objective: Previous studies suggest that cytologic analysis of cells obtained by lavage of the pleural surfaces at the time of resection of non-small cell lung cancer can identify patients at risk for recurrence. Because telomerase gene expression has been associated with worse outcome in non-small cell lung cancer, we hypothesized that identification of cells obtained from pleural lavage that express telomerase would identify patients at risk for recurrent disease. Methods: Patients with presumed non-small cell lung cancer underwent thoracotomy with curative intent. Cells obtained by lavage of the pleural surfaces were analyzed for telomerase catalytic subunit human telomerase reverse transcriptase mRNA expression using reverse transcriptase polymerase chain reaction. Results: A total of 194 patients with stage I/II non-small cell lung cancer had adequate samples, and median follow-up was 60 months (17-91 months). By using Cox models, no statistical differences were found between human telomerase reverse transcriptase-negative and positive patients in disease-free survival (hazard ratio, 1.28; 95% confidence interval, 0.85-1.94; log-rank test, P =.2349) or overall survival (hazard ratio, 1.13; 95% confidence interval, 0.72-1.79; log-rank test, P =.5912) Conclusions: Detection of human telomerase reverse transcriptase in cells obtained from pleural lavage of patients with stage I/II non-small cell lung cancer does not identify patients at risk for recurrent disease. © 2013 by The American Association for Thoracic Surgery.

Authors
Boylan, AM; Wang, XF; Ko, R; Watson, PM; Gu, L; Harpole, D; Bueno, R; Kelly, R; Kohman, L; Kratzke, R
MLA Citation
Boylan, AM, Wang, XF, Ko, R, Watson, PM, Gu, L, Harpole, D, Bueno, R, Kelly, R, Kohman, L, and Kratzke, R. "Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non-small cell lung cancer: Results from Cancer and Leukemia Group B 159902." Journal of Thoracic and Cardiovascular Surgery 146.1 (2013): 206-211.
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
146
Issue
1
Publish Date
2013
Start Page
206
End Page
211
DOI
10.1016/j.jtcvs.2012.08.059

Neighborhood-level socioeconomic determinants impact outcomes in nonsmall cell lung cancer patients in the Southeastern United States.

BACKGROUND: Studies examining the impact of lower socioeconomic status (SES) on the outcomes of patients with nonsmall cell lung cancer (NSCLC) are inconsistent. The objective of this study was to clearly elucidate the association between SES, education, and clinical outcomes among patients with NSCLC. METHODS: The study population was derived from a consecutive, retrospective cohort of patients with NSCLC who received treatment within the Duke Health System between 1995 and 2007. SES determinants were based on the individual's census tract and corresponding 2000 Census data. Determinants included the percentage of the population living below poverty, the median household income, and the percentages of residents with at least a high school diploma and at least a bachelor's degree. The SES and educational variables were divided into quartiles. Statistical comparisons were performed using the 25th and 75th percentiles. RESULTS: Individuals who resided in areas with a low median household income or in which a high percentage of residents were living below the poverty line had a shorter cancer-specific 6-year survival than individuals who resided in converse areas (P = .0167 and P = .0067, respectively). Those living in areas in which a higher percentage of residents achieved a high school diploma had improved disease outcomes compared with those living in areas in which a lower percentage attained a high school diploma (P = .0033). A survival advantage also was observed for inhabitants of areas in which a higher percentage of residents attained a bachelor's degree (P = .0455). CONCLUSIONS: Low SES was identified as an independent prognostic factor for poor survival in patients with both early and advanced stage NSCLC. Patients who lived in areas with high poverty levels, low median incomes, and low education levels had worse mortality.

Authors
Erhunmwunsee, L; Joshi, M-BM; Conlon, DH; Harpole, DH
MLA Citation
Erhunmwunsee, L, Joshi, M-BM, Conlon, DH, and Harpole, DH. "Neighborhood-level socioeconomic determinants impact outcomes in nonsmall cell lung cancer patients in the Southeastern United States." Cancer 118.20 (October 15, 2012): 5117-5123.
PMID
22392287
Source
pubmed
Published In
Cancer
Volume
118
Issue
20
Publish Date
2012
Start Page
5117
End Page
5123
DOI
10.1002/cncr.26185

Pathologic complete response of a malignant peripheral nerve sheath tumor in the lung treated with neoadjuvant Ifosfamide and radiation therapy.

Authors
Cuneo, KC; Riedel, RF; Dodd, LG; Harpole, DH; Kirsch, DG
MLA Citation
Cuneo, KC, Riedel, RF, Dodd, LG, Harpole, DH, and Kirsch, DG. "Pathologic complete response of a malignant peripheral nerve sheath tumor in the lung treated with neoadjuvant Ifosfamide and radiation therapy." J Clin Oncol 30.28 (October 1, 2012): e291-e293.
PMID
22869889
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
30
Issue
28
Publish Date
2012
Start Page
e291
End Page
e293
DOI
10.1200/JCO.2012.42.8797

Thoracoscopic lobectomy has increasing benefit in patients with poor pulmonary function: a Society of Thoracic Surgeons Database analysis.

OBJECTIVE: Using a national database, we asked whether video-assisted thoracoscopic surgery (VATS) lobectomy is beneficial in high-risk pulmonary patients. BACKGROUND: Single-institution series demonstrated benefit of VATS lobectomy over lobectomy via thoracotomy in poor pulmonary function patients [FEV1 (forced expiratory volume in 1 second) or DLCO (diffusion capacity of the lung to carbon monoxide) <60% predicted]. METHODS: The STS General Thoracic Database was queried for patients having undergone lobectomy by either thoracotomy or VATS between 2000 and 2010. Postoperative pulmonary complications included those defined by the STS database. RESULTS: In the STS database, 12,970 patients underwent lobectomy (thoracotomy, n = 8439; VATS, n = 4531) and met inclusion criteria. The overall rate of pulmonary complications was 21.7% (1832/8439) and 17.8% (806/4531) in patients undergoing lobectomy with thoracotomy and VATS, respectively (P < 0.0001). In a multivariable model of pulmonary complications, thoracotomy approach (OR = 1.25, P < 0.001), decreasing FEV1% predicted (OR = 1.01 per unit, P < 0.001) and DLCO% predicted (OR = 1.01 per unit, P < 0.001), and increasing age (1.02 per year, P < 0.001) independently predicted pulmonary complications. When examining pulmonary complications in patients with FEV1 less than 60% predicted, thoracotomy patients have markedly increased pulmonary complications when compared with VATS patients (P = 0.023). No significant difference is noted with FEV1 more than 60% predicted. CONCLUSIONS: Poor pulmonary function predicts respiratory complications regardless of approach. Respiratory complications increase at a significantly greater rate in lobectomy patients with poor pulmonary function after thoracotomy compared with VATS. Planned surgical approach should be considered while determining whether a high-risk patient is an appropriate resection candidate.

Authors
Ceppa, DP; Kosinski, AS; Berry, MF; Tong, BC; Harpole, DH; Mitchell, JD; D'Amico, TA; Onaitis, MW
MLA Citation
Ceppa, DP, Kosinski, AS, Berry, MF, Tong, BC, Harpole, DH, Mitchell, JD, D'Amico, TA, and Onaitis, MW. "Thoracoscopic lobectomy has increasing benefit in patients with poor pulmonary function: a Society of Thoracic Surgeons Database analysis." Ann Surg 256.3 (September 2012): 487-493.
PMID
22868367
Source
pubmed
Published In
Annals of Surgery
Volume
256
Issue
3
Publish Date
2012
Start Page
487
End Page
493
DOI
10.1097/SLA.0b013e318265819c

Effect of increasing experience on dosimetric and clinical outcomes in the management of malignant pleural mesothelioma with intensity-modulated radiation therapy.

PURPOSE: To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity was graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method. RESULTS: Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P<.01) and lung V5 (volume receiving 5 Gy or more; P<.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated. CONCLUSIONS: With increasing experience, target volume coverage improved and dose to the contralateral lung decreased. Rates of pulmonary toxicity were relatively low. However, both local and distant control rates remained suboptimal.

Authors
Patel, PR; Yoo, S; Broadwater, G; Marks, LB; Miles, EF; D'Amico, TA; Harpole, D; Kelsey, CR
MLA Citation
Patel, PR, Yoo, S, Broadwater, G, Marks, LB, Miles, EF, D'Amico, TA, Harpole, D, and Kelsey, CR. "Effect of increasing experience on dosimetric and clinical outcomes in the management of malignant pleural mesothelioma with intensity-modulated radiation therapy." Int J Radiat Oncol Biol Phys 83.1 (May 1, 2012): 362-368.
PMID
22516382
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
83
Issue
1
Publish Date
2012
Start Page
362
End Page
368
DOI
10.1016/j.ijrobp.2011.11.057

Outcomes after surgical management of synchronous bilateral primary lung cancers.

BACKGROUND: Distinguishing between synchronous primary lung cancers and metastatic disease in patients with bilateral lung masses is often difficult. The objective of this study is to examine outcomes associated with a strategy of performing staged bilateral resections in patients without N2 disease based on invasive mediastinal staging and without distant metastases. METHODS: Patients undergoing resections of bilateral synchronous primary lung cancer at our institution between 1997 and 2010 were reviewed. Perioperative complications were graded according to National Cancer Institute guidelines. Survival was estimated using the Kaplan-Meier method and compared using a log-rank test. End points included overall survival, disease-free survival, operative death, cancer recurrence, and postoperative complications. RESULTS: Resections of bilateral synchronous primary lung cancers were performed in 47 patients. Forty-five patients (96%) had at least a unilateral thoracoscopic approach; 28 (60%) had bilateral thoracoscopic approaches. The median postresection length of stay was 3 days. Thirteen patients (28%) had a postoperative complication; only 3 (6%) were grade 3 or higher. There was 1 perioperative death (2%). Eleven patients received adjuvant therapy; only 3 patients in whom adjuvant therapy was indicated did not receive the recommended treatment. The overall 3-year survival was 35%. Survival of patients whose bilateral tumors had identical histology did not differ from patients whose histology was different (p = 0.57). Three-year disease-free survival was 24%. CONCLUSIONS: Aggressive surgical treatment of apparent synchronous bilateral primary lung cancer can be performed with low morbidity. Most patients tolerate the bilateral surgeries and adjuvant therapy. Overall survival is sufficiently high to support this aggressive approach.

Authors
Shah, AA; Barfield, ME; Kelsey, CR; Onaitis, MW; Tong, B; Harpole, D; D'Amico, TA; Berry, MF
MLA Citation
Shah, AA, Barfield, ME, Kelsey, CR, Onaitis, MW, Tong, B, Harpole, D, D'Amico, TA, and Berry, MF. "Outcomes after surgical management of synchronous bilateral primary lung cancers." Ann Thorac Surg 93.4 (April 2012): 1055-1060.
PMID
22381451
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
93
Issue
4
Publish Date
2012
Start Page
1055
End Page
1060
DOI
10.1016/j.athoracsur.2011.12.070

Feasibility of hybrid thoracoscopic lobectomy and en-bloc chest wall resection.

OBJECTIVES: Lobectomy with an en-bloc chest wall resection is an effective but potentially morbid treatment of lung cancer invading the chest wall. Minimally invasive approaches to lobectomy have reduced morbidity compared with thoracotomy for early stage lung cancer, but there is insufficient evidence regarding the feasibility of hybrid thoracoscopic lobectomy chest wall resection. We reviewed our experience with an en-bloc chest wall resection and lobectomy to evaluate the outcomes of a hybrid approach using thoracoscopic lobectomy combined with the chest wall resection where rib spreading is avoided. METHODS: All patients who underwent lobectomy and en-bloc chest wall resection with ribs for primary non-small cell lung cancer from January 2000 to July 2010 were reviewed. Starting in April 2003, a hybrid approach was introduced where thoracoscopic techniques were utilized to accomplish the pulmonary resection and a limited counter incision was used to perform the en-bloc resection of the chest wall, avoiding scapular mobilization and rib spreading. Preoperative, perioperative and outcome variables were assessed using the standard descriptive statistics. RESULTS: During the study period, 105 patients underwent en-bloc lobectomy and chest wall resection, including 93 patients with resection via thoracotomy and 12 patients with resection via the hybrid thoracoscopic approach. Complete resection was achieved in all patients in both groups. Tumour size and the extent of resection were similar in the two groups. There were no conversions and no perioperative mortality in the hybrid group. Post-operative outcomes were similar, although patients who underwent the hybrid approach had a shorter length of stay (P = 0.03). CONCLUSIONS: A hybrid approach that combines thoracoscopic lobectomy and chest wall resection is feasible and effective in selected patients. The use of a limited counter incision without rib spreading does not compromise oncologic efficacy. Further experience is needed to determine if this approach provides any advantage in outcomes, including post-operative morbidity.

Authors
Berry, MF; Onaitis, MW; Tong, BC; Balderson, SS; Harpole, DH; D'Amico, TA
MLA Citation
Berry, MF, Onaitis, MW, Tong, BC, Balderson, SS, Harpole, DH, and D'Amico, TA. "Feasibility of hybrid thoracoscopic lobectomy and en-bloc chest wall resection." Eur J Cardiothorac Surg 41.4 (April 2012): 888-892.
PMID
22219441
Source
pubmed
Published In
European Journal of Cardio-Thoracic Surgery
Volume
41
Issue
4
Publish Date
2012
Start Page
888
End Page
892
DOI
10.1093/ejcts/ezr150

Molecular prognostication of lung cancer

Authors
Tong, BC; Harpole, DH
MLA Citation
Tong, BC, and Harpole, DH. "Molecular prognostication of lung cancer." Principles and Practice of Lung Cancer: The Official Reference Text of the International Association for the Study of Lung Cancer (IASLC): Fourth Edition. February 13, 2012. 147-162.
Source
scopus
Publish Date
2012
Start Page
147
End Page
162

Molecular markers for incidence, prognosis, and response to therapy.

Lung cancer is the most common malignancy in the United States and worldwide. In 2011, it is estimated that more than 221,000 people in the United States will be diagnosed with cancer of the lung and bronchus. For patients with early-stage disease, 5-year survival approaches only 50%. Recent advances using molecular, genetic, and proteomic profiling of lung tumors have enabled refining the prognosis for patients with non-small cell lung cancer. With targeted therapies, there is an opportunity to enhance long-term survival. This article discusses several key molecular markers used in the prognostication and treatment of non-small cell lung cancer.

Authors
Tong, BC; Harpole, DH
MLA Citation
Tong, BC, and Harpole, DH. "Molecular markers for incidence, prognosis, and response to therapy." Surg Oncol Clin N Am 21.1 (January 2012): 161-175.
PMID
22098838
Source
pubmed
Published In
Surgical Oncology Clinics of North America
Volume
21
Issue
1
Publish Date
2012
Start Page
161
End Page
175
DOI
10.1016/j.soc.2011.09.007

Perioperative management of patients on clopidogrel (Plavix) undergoing major lung resection.

BACKGROUND: Management of patients requiring antiplatelet therapy with clopidogrel (Plavix) and major lung resection must balance the risks of bleeding and cardiovascular events. We reviewed our experience with patients treated with clopidogrel perioperatively to examine outcomes, including results of a new strategy for high-risk patients. METHODS: Patients who underwent major lung resection and received perioperative clopidogrel between January 2005 and September 2010 were reviewed. Initially, clopidogrel management consisted of discontinuation approximately 5 days before surgery and resumption immediately after surgery. After July 2010, high-risk patients (drug-eluting coronary stent placement within prior year or previous coronary event after clopidogrel discontinuation) were admitted 2 to 3 days preoperatively and bridged with the intravenous glycoprotein IIb/IIIa receptor inhibitor eptifibatide (Integrilin) according to a multidisciplinary cardiology/anesthesiology/thoracic surgery protocol. Outcomes were compared with control patients (matched for preoperative risk factors and extent of pulmonary resection) who did not receive perioperative clopidogrel. RESULTS: Fifty-four patients who had major lung resection between January 2005 and September 2010 and received clopidogrel perioperatively were matched with 108 control subjects. Both groups had similar mortality, postoperative length of stay, and no differences in the rates of perioperative transfusions, reoperations for bleeding, myocardial infarctions, and strokes. Seven of the 54 clopidogrel patients were admitted preoperatively for an eptifibatide bridge. Two of these patients received perioperative transfusions, but there were no deaths, reoperations, myocardial infarctions, or stroke. CONCLUSIONS: Patients taking clopidogrel can safely undergo major lung resection. Treatment with an eptifibatide bridge may minimize the risk of cardiovascular events in higher risk patients.

Authors
Ceppa, DP; Welsby, IJ; Wang, TY; Onaitis, MW; Tong, BC; Harpole, DH; D'Amico, TA; Berry, MF
MLA Citation
Ceppa, DP, Welsby, IJ, Wang, TY, Onaitis, MW, Tong, BC, Harpole, DH, D'Amico, TA, and Berry, MF. "Perioperative management of patients on clopidogrel (Plavix) undergoing major lung resection." Ann Thorac Surg 92.6 (December 2011): 1971-1976.
PMID
21978871
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
92
Issue
6
Publish Date
2011
Start Page
1971
End Page
1976
DOI
10.1016/j.athoracsur.2011.07.052

A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery.

PURPOSE: We hypothesized that patients who received ketamine during thoracic surgery would benefit from suppression of the inflammatory cascade, represented by lower interleukin (IL)-6 and C-reactive protein (CRP) plasma levels. METHODS: This study was a randomized, double blind, placebo controlled clinical trial of ketamine in patients undergoing thoracic surgery. The setting was a single university teaching hospital. Forty patients who presented to the preoperative clinic prior to thoracic surgery (20 control, 20 treatment) were randomized to receive either a 0.5 mg/kg ketamine bolus or an equivalent volume of normal saline intravenously prior to chest wall incision. Plasma samples taken prior to induction of anesthesia and at 24 h following surgery were assayed for IL-6 and CRP levels. Verbal pain scores were reported at 4 and 24 h following surgery and at discharge. RESULTS: IL-6 plasma levels did not differ significantly at 24 h for patients receiving ketamine (245 ± 287 pg/ml, mean ± SD) compared to patients who received placebo (269 ± 210 pg/ml), p = 0.39. Additionally, CRP levels at 24 h were not significantly different (8.8 ± 4.5 mg/dl for ketamine, 9.3 ± 5.6 mg/dl for placebo patients), p = 0.37. Finally, verbal pain scores were not significantly different between patient groups at 4 or 24 h, or at discharge. CONCLUSIONS: These findings suggest that the routine use of a single dose of ketamine prior to chest wall incision is not effective at reducing pain or inflammation in thoracic surgery patients at 24 h postoperatively.

Authors
D'Alonzo, RC; Bennett-Guerrero, E; Podgoreanu, M; D'Amico, TA; Harpole, DH; Shaw, AD
MLA Citation
D'Alonzo, RC, Bennett-Guerrero, E, Podgoreanu, M, D'Amico, TA, Harpole, DH, and Shaw, AD. "A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery." J Anesth 25.5 (October 2011): 672-678.
PMID
21809148
Source
pubmed
Published In
Journal of Anesthesia
Volume
25
Issue
5
Publish Date
2011
Start Page
672
End Page
678
DOI
10.1007/s00540-011-1206-4

NEIGHBORHOOD-LEVEL SOCIOECONOMIC (SES) DETERMINANTS NEGATIVELY IMPACT TREATMENT DECISIONS AMONG NON-SMALL CELL LUNG CANCER PATIENTS IN THE SOUTHEASTERN UNITED STATES

Authors
Joshi, MM; Erhunmwunsee, L; Conlon, DH; Harpole, DH
MLA Citation
Joshi, MM, Erhunmwunsee, L, Conlon, DH, and Harpole, DH. "NEIGHBORHOOD-LEVEL SOCIOECONOMIC (SES) DETERMINANTS NEGATIVELY IMPACT TREATMENT DECISIONS AMONG NON-SMALL CELL LUNG CANCER PATIENTS IN THE SOUTHEASTERN UNITED STATES." June 2011.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
6
Issue
6
Publish Date
2011
Start Page
S327
End Page
S328

Utility of a simple algorithm to grade diastolic dysfunction and predict outcome after coronary artery bypass graft surgery.

BACKGROUND: Inclusion of a measure of left ventricular diastolic dysfunction (LVDD) may improve risk prediction after cardiac surgery. Current LVDD grading guidelines rely on echocardiographic variables that are not always available or aligned to allow grading. We hypothesized that a simplified algorithm involving fewer variables would enable more patients to be assigned a LVDD grade compared with a comprehensive algorithm, and also be valid in identifying patients at risk of long-term major adverse cardiac events (MACE). METHODS: Intraoperative transesophageal echocardiography data were gathered on 905 patients undergoing coronary artery bypass graft surgery, including flow and tissue Doppler-based measurements. Two algorithms were constructed to categorize LVDD: a comprehensive four-variable algorithm, A, was compared with a simplified version, B, with only two variables-transmitral early flow velocity and early mitral annular tissue velocity-for ease of grading and association with MACE. RESULTS: Using algorithm A, only 563 patients (62%) could be graded, whereas 895 patients (99%) received a grade with algorithm B. Over the median follow-up period of 1,468 days, Cox modeling showed that LVDD was significantly associated with MACE when graded with algorithm B (p=0.013), but not algorithm A (p=0.79). Patients with the highest incidence of MACE could not be graded with algorithm A. CONCLUSIONS: We found that an LVDD algorithm with fewer variables enabled grading of a significantly greater number of coronary artery bypass graft patients, and was valid, as evidenced by worsening grades being associated with MACE. This simplified algorithm could be extended to similar populations as a valid method of characterizing LVDD.

Authors
Swaminathan, M; Nicoara, A; Phillips-Bute, BG; Aeschlimann, N; Milano, CA; Mackensen, GB; Podgoreanu, MV; Velazquez, EJ; Stafford-Smith, M; Mathew, JP; Cardiothoracic Anesthesia Research Endeavors (CARE) Group,
MLA Citation
Swaminathan, M, Nicoara, A, Phillips-Bute, BG, Aeschlimann, N, Milano, CA, Mackensen, GB, Podgoreanu, MV, Velazquez, EJ, Stafford-Smith, M, Mathew, JP, and Cardiothoracic Anesthesia Research Endeavors (CARE) Group, . "Utility of a simple algorithm to grade diastolic dysfunction and predict outcome after coronary artery bypass graft surgery." Ann Thorac Surg 91.6 (June 2011): 1844-1850.
PMID
21492828
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
91
Issue
6
Publish Date
2011
Start Page
1844
End Page
1850
DOI
10.1016/j.athoracsur.2011.02.008

A model for morbidity after lung resection in octogenarians.

OBJECTIVE: Age is an important risk factor for morbidity after lung resection. This study was performed to identify specific risk factors for complications after lung resection in octogenarians. METHODS: A prospective database containing patients aged 80 years or older, who underwent lung resection at a single institution between January 2000 and June 2009, was reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed. Morbidity was measured as a patient having any perioperative event as defined by the Society of Thoracic Surgeons General Thoracic Surgery Database. A multivariable risk model for morbidity was developed using a panel of established preoperative and operative variables. Survival was calculated using the Kaplan-Meier method. RESULTS: During the study period, 193 patients aged 80 years or older (median age 82 years) underwent lung resection: wedge resection in 77, segmentectomy in 13, lobectomy in 96, bilobectomy in four, and pneumonectomy in three. Resection was accomplished via thoracoscopy in 149 patients (77%). Operative mortality was 3.6% (seven patients) and morbidity was 46% (89 patients). A total of 181 (94%) patients were discharged directly home. Postoperative events included atrial arrhythmia in 38 patients (20%), prolonged air leak in 24 patients (12%), postoperative transfusion in 22 patients (11%), delirium in 16 patients (8%), need for bronchoscopy in 14 patients (7%), and pneumonia in 10 patients (5%). Significant predictors of morbidity by multivariable analysis included resection greater than wedge (odds ratio 2.98, p=0.006), thoracotomy as operative approach (odds ratio 2.6, p=0.03), and % predicted forced expiratory volume in 1s (odds ratio 1.28 for each 10% decrement, p=0.01). CONCLUSIONS: Octogenarians can undergo lung resection with low mortality. Extent of resection, use of a thoracotomy, and impaired lung function increase the risk of complications. Careful evaluation is necessary to select the most appropriate approach in octogenarians being considered for lung resection.

Authors
Berry, MF; Onaitis, MW; Tong, BC; Harpole, DH; D'Amico, TA
MLA Citation
Berry, MF, Onaitis, MW, Tong, BC, Harpole, DH, and D'Amico, TA. "A model for morbidity after lung resection in octogenarians." Eur J Cardiothorac Surg 39.6 (June 2011): 989-994.
PMID
21276728
Source
pubmed
Published In
European Journal of Cardio-Thoracic Surgery
Volume
39
Issue
6
Publish Date
2011
Start Page
989
End Page
994
DOI
10.1016/j.ejcts.2010.09.038

PERSISTENT N2 DISEASE AFTER NEOADJUVANT CHEMOTHERAPY-NOW WHAT?

Authors
Higgins, KA; Ready, NE; D'amico, TA; Onaitis, MW; Crawford, J; Clough, R; Berry, MF; Yoo, D; Harpole, DH; Dunphy, F; Kelsey, CR
MLA Citation
Higgins, KA, Ready, NE, D'amico, TA, Onaitis, MW, Crawford, J, Clough, R, Berry, MF, Yoo, D, Harpole, DH, Dunphy, F, and Kelsey, CR. "PERSISTENT N2 DISEASE AFTER NEOADJUVANT CHEMOTHERAPY-NOW WHAT?." June 2011.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
6
Issue
6
Publish Date
2011
Start Page
S1572
End Page
S1572

Lung Volume Reduction Surgery Using the NETT Selection Criteria DISCUSSION

Authors
Jr, HDH; Swanson, SJ; Ginsburg, D; Turna, A; Jr, DMM
MLA Citation
Jr, HDH, Swanson, SJ, Ginsburg, D, Turna, A, and Jr, DMM. "Lung Volume Reduction Surgery Using the NETT Selection Criteria DISCUSSION." ANNALS OF THORACIC SURGERY 91.5 (May 2011): 1561-1561.
Source
wos-lite
Published In
The Annals of Thoracic Surgery
Volume
91
Issue
5
Publish Date
2011
Start Page
1561
End Page
1561

A 10-gene progenitor cell signature predicts poor prognosis in lung adenocarcinoma.

BACKGROUND: One aspect of the cancer stem cell hypothesis is that patients with tumors that exhibit stem-like phenotypes have poor prognoses. Distal epithelial progenitors from lungs early in development demonstrate both self-renewal and potential to differentiate into all bronchial and alveolar epithelial cell types. By contrast, late progenitors are only able to produce alveolar cells. We sought to create a lung-specific progenitor cell signature for possible prognosis prediction in human lung cancer. METHODS: A transgenic mouse was created in which embryonic distal epithelial progenitor cells express green fluorescent protein when tamoxifen is administered. Lung progenitor cells were harvested after tamoxifen injection at either embryonic day 11.5 (E11.5) or 17.5 (E17.5). The RNA extracted from these cells was hybridized to Affymetrix 430.2 mouse chips (Affymetrix, Santa Clara, CA). A genomic signature was created by comparing the cell types using L1 logistic regression and applied to transcriptome datasets of resected patients from our tumor bank and the National Institutes of Health Director's Challenge Consortium. RESULTS: When a 10-gene genomic signature was applied to resected human adenocarcinoma datasets, tumors that were transcriptionally similar to the early progenitors had a significantly worse prognosis than those similar to the late progenitors. Using a Cox model in which age and stage were included, the predicted score from the logistic regression model was an independent predictor of survival. CONCLUSIONS: A lung progenitor cell signature predicts poor prognosis in lung adenocarcinoma. Modulation of these genes or their signaling pathways may be effective therapeutic strategies in the future.

Authors
Onaitis, M; D'Amico, TA; Clark, CP; Guinney, J; Harpole, DH; Rawlins, EL
MLA Citation
Onaitis, M, D'Amico, TA, Clark, CP, Guinney, J, Harpole, DH, and Rawlins, EL. "A 10-gene progenitor cell signature predicts poor prognosis in lung adenocarcinoma." Ann Thorac Surg 91.4 (April 2011): 1046-1050.
PMID
21353202
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
91
Issue
4
Publish Date
2011
Start Page
1046
End Page
1050
DOI
10.1016/j.athoracsur.2010.12.054

Retraction: A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2006;355:570-80.

To the Editor: We would like to retract our article, "A Genomic Strategy to Refine Prognosis in Early-Stage Non-Small-Cell Lung Cancer,"(1) which was published in the Journal on August 10, 2006. Using a sample set from a study by the American College of Surgeons Oncology Group (ACOSOG) and a collection of samples from a study by the Cancer and Leukemia Group B (CALGB), we have tried and failed to reproduce results supporting the validation of the lung metagene model described in the article. We deeply regret the effect of this action on the work of other investigators.

Authors
Potti, A; Mukherjee, S; Petersen, R; Dressman, HK; Bild, A; Koontz, J; Kratzke, R; Watson, MA; Kelley, M; Ginsburg, GS; West, M; Harpole, DH; Nevins, JR
MLA Citation
Potti, A, Mukherjee, S, Petersen, R, Dressman, HK, Bild, A, Koontz, J, Kratzke, R, Watson, MA, Kelley, M, Ginsburg, GS, West, M, Harpole, DH, and Nevins, JR. "Retraction: A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2006;355:570-80." N Engl J Med 364.12 (March 24, 2011): 1176-.
PMID
21366430
Source
pubmed
Published In
The New England journal of medicine
Volume
364
Issue
12
Publish Date
2011
Start Page
1176
DOI
10.1056/NEJMc1101915

Retraction: Genomic signatures to guide the use of chemotherapeutics.

Authors
Potti, A; Dressman, HK; Bild, A; Riedel, RF; Chan, G; Sayer, R; Cragun, J; Cottrill, H; Kelley, MJ; Petersen, R; Harpole, D; Marks, J; Berchuck, A; Ginsburg, GS; Febbo, P; Lancaster, J; Nevins, JR
MLA Citation
Potti, A, Dressman, HK, Bild, A, Riedel, RF, Chan, G, Sayer, R, Cragun, J, Cottrill, H, Kelley, MJ, Petersen, R, Harpole, D, Marks, J, Berchuck, A, Ginsburg, GS, Febbo, P, Lancaster, J, and Nevins, JR. "Retraction: Genomic signatures to guide the use of chemotherapeutics." Nat Med 17.1 (January 2011): 135-.
PMID
21217686
Source
pubmed
Published In
Nature Medicine
Volume
17
Issue
1
Publish Date
2011
Start Page
135
DOI
10.1038/nm0111-135

A comprehensive evaluation for aspiration after esophagectomy reduces the incidence of postoperative pneumonia

Authors
Berry, MF; Atkins, Z; Tong, BC; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Atkins, Z, Tong, BC, Harpole, DH, D'Amico, TA, and Onaitis, MW. "A comprehensive evaluation for aspiration after esophagectomy reduces the incidence of postoperative pneumonia." Dysphagia 26.3 (2011): 326--.
Source
scival
Published In
Dysphagia
Volume
26
Issue
3
Publish Date
2011
Start Page
326-
DOI
10.1007/s00455-011-9343-3

A comprehensive evaluation for aspiration after esophagectomy reduces the incidence of postoperative pneumonia.

OBJECTIVE: This study assesses the effect of using a comprehensive swallowing evaluation before starting oral feedings on aspiration detection and pneumonia occurrence after esophagectomy. METHODS: The records of all patients undergoing esophagectomy between January 1996 and June 2009 were reviewed. Multivariable logistic regression analysis assessed the effect of preoperative and operative variables on the incidence of aspiration and pneumonia. Separate analyses were performed on patients before (early era, 1996-2002) and after (later era, 2003-2009) a rigorous swallowing evaluation was used routinely before starting oral feedings. RESULTS: During the study period, 799 patients (379 from the early era and 420 from the later era) underwent esophagectomy; 30-day mortality was 3.5% (28 patients). Cervical anastomoses were performed in 76% of patients in the later era compared with 40% of patients in the early era. Overall, 96 (12%) patients had evidence of aspiration postoperatively, and the pneumonia incidence was 14% (113 patients). Age (odds ratio, 1.05 per year; P < .0001) and later era (odds ratio, 1.90; P = .0001) predicted aspiration in all patients in a multivariable model. In the early era, cervical anastomosis and aspiration independently predicted pneumonia. With a comprehensive swallowing evaluation in the later era, the detected incidence of aspiration increased (16% vs 7%, P < .0001), whereas the incidence of pneumonia decreased (11% vs 18%, P = .004) compared with the early era, such that neither anastomotic location nor aspiration predicted pneumonia in the later era. CONCLUSIONS: Esophagectomy is often associated with occult aspiration. A comprehensive swallowing evaluation for aspiration before initiating oral feedings significantly decreases the occurrence of pneumonia.

Authors
Berry, MF; Atkins, BZ; Tong, BC; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Atkins, BZ, Tong, BC, Harpole, DH, D'Amico, TA, and Onaitis, MW. "A comprehensive evaluation for aspiration after esophagectomy reduces the incidence of postoperative pneumonia." J Thorac Cardiovasc Surg 140.6 (December 2010): 1266-1271.
PMID
20884018
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
140
Issue
6
Publish Date
2010
Start Page
1266
End Page
1271
DOI
10.1016/j.jtcvs.2010.08.038

Systematic Classification of Morbidity and Mortality After Thoracic Surgery DISCUSSION

Authors
Swanson, SJ; Seely, ; Harpole, DH; Block, MI
MLA Citation
Swanson, SJ, Seely, , Harpole, DH, and Block, MI. "Systematic Classification of Morbidity and Mortality After Thoracic Surgery DISCUSSION." ANNALS OF THORACIC SURGERY 90.3 (September 2010): 942-942.
Source
wos-lite
Published In
The Annals of Thoracic Surgery
Volume
90
Issue
3
Publish Date
2010
Start Page
942
End Page
942

Pathologic T0N1 Esophageal Cancer After Neoadjuvant Therapy and Surgery: An Orphan Status DISCUSSION

Authors
Krasna, MJ; Kim, ; Harpole, DH; Schipper, PH; Low, DE
MLA Citation
Krasna, MJ, Kim, , Harpole, DH, Schipper, PH, and Low, DE. "Pathologic T0N1 Esophageal Cancer After Neoadjuvant Therapy and Surgery: An Orphan Status DISCUSSION." ANNALS OF THORACIC SURGERY 90.3 (September 2010): 890-891.
Source
wos-lite
Published In
The Annals of Thoracic Surgery
Volume
90
Issue
3
Publish Date
2010
Start Page
890
End Page
891

Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.

BACKGROUND: Atrial fibrillation is responsible for significant morbidity after lung cancer surgery, and preoperative and perioperative risk factors are not well described. METHODS: The Society of Thoracic Surgeons (STS) database was queried for all lobectomy and pneumonectomy patients with a diagnosis of lung cancer. A multivariable logistic regression model was developed to predict the risk of atrial arrhythmia as a function of preoperative and perioperative factors. Generalized estimating equations methodology was used to account for correlation among observations from the same institution. Missing data were handled using the method of chained equations with 10 randomly imputed data sets. RESULTS: A total of 13,906 patients who underwent resection for lung cancer at participating institutions had complete information for postoperative atrial arrhythmia, of whom 1,755 (12.6%) experienced the outcome. Multivariable logistic analysis indentified increasing age, increasing extent of operation, male sex, nonblack race, and stage II or greater tumors as predictors of postoperative atrial fibrillation. CONCLUSIONS: Analysis of the STS database has identified five variables that predict postoperative atrial fibrillation. This predictive model may be useful to develop strategies for risk stratification, prophylaxis, and treatment.

Authors
Onaitis, M; D'Amico, T; Zhao, Y; O'Brien, S; Harpole, D
MLA Citation
Onaitis, M, D'Amico, T, Zhao, Y, O'Brien, S, and Harpole, D. "Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database." Ann Thorac Surg 90.2 (August 2010): 368-374.
PMID
20667313
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
90
Issue
2
Publish Date
2010
Start Page
368
End Page
374
DOI
10.1016/j.athoracsur.2010.03.100

A cost-minimisation analysis of lobectomy: thoracoscopic versus posterolateral thoracotomy.

OBJECTIVE: Recent evidence suggests that lobectomy performed either through thoracoscopy (TL) or via a posterolateral thoracotomy (PLT) produces equivalent oncologic outcomes in appropriately selected patients. Advantages of thoracoscopic lobectomy include decreased postoperative pain, shorter length of stay, fewer postoperative complications and better compliance with adjuvant chemotherapy. This study evaluates the costs associated with lobectomy performed thoracoscopically or via thoracotomy. METHODS: This is a retrospective analysis of actual costing and prospectively collected health-related quality of life (QOL) outcomes. Between 2002 and 2004, 113 patients underwent lobectomy (PLT: n=37; TL: n=76) and completed QOL assessments both preoperatively and 1-year postoperatively. Actual fixed and variable direct costs from the preoperative, hospitalisation and 30-day postoperative phases were captured using a T1 cost accounting system and were combined with actual professional collections. Cost-utility analysis was performed by transforming a global QOL measurement to an estimate of utility and calculating a quality-adjusted life year (QALY) for each patient. RESULTS: Baseline characteristics were similar in the two groups. Total costs (USD) were significantly greater for the strategy of PLT (USD 12,119) than for TL (USD 10,084; p=0.0012). Even when only stage I and II lung cancers were included (n=32 PLT, n=69 TL), total costs for PLT were still higher than that for TL (USD 11,998 vs USD 10,120; p=0.005). The mean QALY for the PLT group was 0.74+/-0.22 and for the TL group was 0.72+/-0.18 (p=0.68). CONCLUSIONS: In this retrospective analysis, TL was significantly less expensive than PLT from the preoperative evaluation through 30 days postoperatively, with overall savings of approximately USD 2000 per patient. In light of equivalent QALY outcomes, this cost-utility analysis supports increased adoption of TL as a cost-minimisation strategy. The use of TL for the 50,000 lobectomies performed in the United States each year would represent a savings of approximately USD 100 million.

Authors
Burfeind, WR; Jaik, NP; Villamizar, N; Toloza, EM; Harpole, DH; D'Amico, TA
MLA Citation
Burfeind, WR, Jaik, NP, Villamizar, N, Toloza, EM, Harpole, DH, and D'Amico, TA. "A cost-minimisation analysis of lobectomy: thoracoscopic versus posterolateral thoracotomy." Eur J Cardiothorac Surg 37.4 (April 2010): 827-832.
PMID
19939695
Source
pubmed
Published In
European Journal of Cardio-Thoracic Surgery
Volume
37
Issue
4
Publish Date
2010
Start Page
827
End Page
832
DOI
10.1016/j.ejcts.2009.10.017

Pulmonary function tests do not predict pulmonary complications after thoracoscopic lobectomy.

BACKGROUND: Pulmonary function tests predict respiratory complications and mortality after lung resection through thoracotomy. We sought to determine the impact of pulmonary function tests upon complications after thoracoscopic lobectomy. METHODS: A model for morbidity, including published preoperative risk factors and surgical approach, was developed by multivariable logistic regression. All patients who underwent lobectomy for primary lung cancer between December 1999 and October 2007 with preoperative forced expiratory volume in 1 second (FEV1) or diffusion capacity to carbon monoxide (Dlco) 60% or less predicted were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Pulmonary complications were defined as atelectasis requiring bronchoscopy, pneumonia, reintubation, and tracheostomy. RESULTS: During the study period, 340 patients (median age 67) with Dlco or FEV1 60% or less (mean % predicted FEV1, 55+/-1; mean % predicted Dlco, 61+/-1) underwent lobectomy (173 thoracoscopy, 167 thoracotomy). Operative mortality was 5% (17 patients) and overall morbidity was 48% (164 patients). At least one pulmonary complication occurred in 57 patients (17%). Significant predictors of pulmonary complications by multivariable analysis for all patients included Dlco (odds ratio 1.03, p=0.003), FEV1 (odds ratio 1.04, p=0.003), and thoracotomy as surgical approach (odds ratio 3.46, p=0.0007). When patients were analyzed according to operative approach, Dlco and FEV1 remained significant predictors of pulmonary morbidity for patients undergoing thoracotomy but not thoracoscopy. CONCLUSIONS: In patients with impaired pulmonary function, preoperative pulmonary function tests are predictors of pulmonary complications when lobectomy for lung cancer is performed through thoracotomy but not through thoracoscopy.

Authors
Berry, MF; Villamizar-Ortiz, NR; Tong, BC; Burfeind, WR; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Villamizar-Ortiz, NR, Tong, BC, Burfeind, WR, Harpole, DH, D'Amico, TA, and Onaitis, MW. "Pulmonary function tests do not predict pulmonary complications after thoracoscopic lobectomy." Ann Thorac Surg 89.4 (April 2010): 1044-1051.
PMID
20338305
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
89
Issue
4
Publish Date
2010
Start Page
1044
End Page
1051
DOI
10.1016/j.athoracsur.2009.12.065

Thoracoscopic lobectomy is associated with lower morbidity than open lobectomy: a propensity-matched analysis from the STS database.

BACKGROUND: Several single-institution series have demonstrated that compared with open thoracotomy, video-assisted thoracoscopic lobectomy may be associated with fewer postoperative complications. In the absence of randomized trials, we queried the Society of Thoracic Surgeons database to compare postoperative mortality and morbidity following open and video-assisted thoracoscopic lobectomy. A propensity-matched analysis using a large national database may enable a more comprehensive comparison of postoperative outcomes. METHODS: All patients having lobectomy as the primary procedure via thoracoscopy or thoracotomy were identified in the Society of Thoracic Surgeons database from 2002 to 2007. After exclusions, 6323 patients were identified: 5042 having thoracotomy, 1281 having thoracoscopy. A propensity analysis was performed, incorporating preoperative variables, and the incidence of postoperative complications was compared. RESULTS: Matching based on propensity scores produced 1281 patients in each group for analysis of postoperative outcomes. After video-assisted thoracoscopic lobectomy, 945 patients (73.8%) had no complications, compared with 847 patients (65.3%) who had lobectomy via thoracotomy (P < .0001). Compared with open lobectomy, video-assisted thoracoscopic lobectomy was associated with a lower incidence of arrhythmias [n = 93 (7.3%) vs 147 (11.5%); P = .0004], reintubation [n = 18 (1.4%) vs 40 (3.1%); P = .0046], and blood transfusion [n = 31 (2.4%) vs n = 60 (4.7%); P = .0028], as well as a shorter length of stay (4.0 vs 6.0 days; P < .0001) and chest tube duration (3.0 vs 4.0 days; P < .0001). There was no difference in operative mortality between the 2 groups. CONCLUSIONS: Video-assisted thoracoscopic lobectomy is associated with a lower incidence of complications compared with lobectomy via thoracotomy. For appropriate candidates, video-assisted thoracoscopic lobectomy may be the preferred strategy for appropriately selected patients with lung cancer.

Authors
Paul, S; Altorki, NK; Sheng, S; Lee, PC; Harpole, DH; Onaitis, MW; Stiles, BM; Port, JL; D'Amico, TA
MLA Citation
Paul, S, Altorki, NK, Sheng, S, Lee, PC, Harpole, DH, Onaitis, MW, Stiles, BM, Port, JL, and D'Amico, TA. "Thoracoscopic lobectomy is associated with lower morbidity than open lobectomy: a propensity-matched analysis from the STS database." J Thorac Cardiovasc Surg 139.2 (February 2010): 366-378.
PMID
20106398
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
139
Issue
2
Publish Date
2010
Start Page
366
End Page
378
DOI
10.1016/j.jtcvs.2009.08.026

Outcomes of video-assisted thoracoscopic decortication.

BACKGROUND: Video-assisted thoracoscopic surgical decortication (VATSD) is widely used for treatment of early empyema and hemothorax, but conversion to open thoracotomy for decortication (OD) is more frequent in the setting of complex, chronic empyema. This study compared indications for and outcomes associated with VATSD and OD. METHODS: The outcomes of 420 consecutive patients undergoing VATSD or OD for benign conditions from 1996 to 2006 were reviewed and compared with respect to baseline characteristics, preoperative management, and operative and postoperative course. Patients were analyzed on an intention-to-treat basis. RESULTS: The cohort consisted of 326 VATSD and 94 OD patients. The conversion rate from VATSD to OD was 11.4%. The operative time and median in-hospital length of stay were shorter for the VATSD group: 97 vs 155 minutes (p < 0.001), and 15 vs 21 days (p = 0.03), respectively. The median postoperative length of stay was 7 days for the VATSD group vs 10 days for the OD group (p < 0.001). Significantly fewer postoperative complications occurred in the VATSD group in the following categories: atelectasis, prolonged air leak, reintubation, ventilator dependence, need for tracheostomy, blood transfusion, sepsis, and 30-day mortality. CONCLUSIONS: Thoracoscopic decortication for empyema, complex pleural effusion, and hemothorax yields results that are at least equivalent to open decortication. Patients undergoing VATSD have fewer postoperative complications. The conversion and reoperation rates are low, suggesting that a thoracoscopic approach is an effective and reasonable first option for most patients with complex pleural effusions and empyema.

Authors
Tong, BC; Hanna, J; Toloza, EM; Onaitis, MW; D'Amico, TA; Harpole, DH; Burfeind, WR
MLA Citation
Tong, BC, Hanna, J, Toloza, EM, Onaitis, MW, D'Amico, TA, Harpole, DH, and Burfeind, WR. "Outcomes of video-assisted thoracoscopic decortication." Ann Thorac Surg 89.1 (January 2010): 220-225.
PMID
20103240
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
89
Issue
1
Publish Date
2010
Start Page
220
End Page
225
DOI
10.1016/j.athoracsur.2009.09.021

Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer (Journal of Clinical Oncology (2007) 25, (4350-4357))

Authors
Hsu, DS; Balakumaran, BS; Acharya, CR; Vlahovic, V; Walters, KS; Garman, K; Anders, C; Riedel, RF; Lancaster, J; Harpole, D; al, E
MLA Citation
Hsu, DS, Balakumaran, BS, Acharya, CR, Vlahovic, V, Walters, KS, Garman, K, Anders, C, Riedel, RF, Lancaster, J, Harpole, D, and al, E. "Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer (Journal of Clinical Oncology (2007) 25, (4350-4357))." Journal of Clinical Oncology 28.35 (2010): 5229--.
Source
scival
Published In
Journal of Clinical Oncology
Volume
28
Issue
35
Publish Date
2010
Start Page
5229-
DOI
10.1200/JCO.2010.33.7311

Discussion

Authors
Krasna, MJ; Harpole, DH; Schipper, PH; Low, DE
MLA Citation
Krasna, MJ, Harpole, DH, Schipper, PH, and Low, DE. "Discussion." Annals of Thoracic Surgery 90.3 (2010): 890-891.
Source
scival
Published In
The Annals of Thoracic Surgery
Volume
90
Issue
3
Publish Date
2010
Start Page
890
End Page
891
DOI
10.1016/j.athoracsur.2010.03.116

Discussion

Authors
Swanson, SJ; Harpole, DH; Block, MI
MLA Citation
Swanson, SJ, Harpole, DH, and Block, MI. "Discussion." Annals of Thoracic Surgery 90.3 (2010): 942--.
Source
scival
Published In
The Annals of Thoracic Surgery
Volume
90
Issue
3
Publish Date
2010
Start Page
942-
DOI
10.1016/j.athoracsur.2010.05.014

Discussion

Authors
Harpole, DH; Poullis, MP; Decamp, MM; Murthy, SC
MLA Citation
Harpole, DH, Poullis, MP, Decamp, MM, and Murthy, SC. "Discussion." Annals of Thoracic Surgery 90.2 (2010): 382--.
Source
scival
Published In
The Annals of Thoracic Surgery
Volume
90
Issue
2
Publish Date
2010
Start Page
382-
DOI
10.1016/j.athoracsur.2010.04.100

The Effect of Increasing Experience with Intensity Modulated Radiation Therapy for Resected Malignant Pleural Mesothelioma

Authors
Patel, PR; Yoo, S; Marks, L; Miles, E; D'Amico, TA; Harpole, DH; Kelsey, C
MLA Citation
Patel, PR, Yoo, S, Marks, L, Miles, E, D'Amico, TA, Harpole, DH, and Kelsey, C. "The Effect of Increasing Experience with Intensity Modulated Radiation Therapy for Resected Malignant Pleural Mesothelioma." 2010.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S505
End Page
S506

Risk factors for morbidity after lobectomy for lung cancer in elderly patients.

BACKGROUND: Studies evaluating risk factors for complications after lobectomy in elderly patients have not adequately analyzed the effect of using minimally invasive approaches. METHODS: A model for morbidity including published preoperative risk factors and surgical approach was developed by multivariable logistic regression. All patients aged 70 years or older who underwent lobectomy for primary lung cancer without chest wall resection or airway procedure between December 1999 and October 2007 at a single institution were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Morbidity was measured as a patient having any perioperative complication. The impact of bias in the selection of surgical approach was assessed using propensity scoring. RESULTS: During the study period, 338 patients older than 70 years (mean age, 75.7 +/- 0.2) underwent lobectomy (219 thoracoscopy, 119 thoracotomy). Operative mortality was 3.8% (13 patients) and morbidity was 47% (159 patients). Patients with at least one complication had increased length of stay (8.3 +/- 0.6 versus 3.8 +/- 0.1 days; p < 0.0001) and mortality (6.9% [11 of 159] versus 1.1% [2 of 179]; p = 0.008). Significant predictors of morbidity by multivariable analysis included age (odds ratio, 1.09 per year; p = 0.01) and thoracotomy as surgical approach (odds ratio, 2.21; p = 0.004). Thoracotomy remained a significant predictor of morbidity when the propensity to undergo thoracoscopy was considered (odds ratio, 4.9; p= 0.002). CONCLUSIONS: Patients older than 70 years of age can undergo lobectomy for lung cancer with low morbidity and mortality. Advanced age and the use of a thoracotomy increased the risk of complications in this patient population.

Authors
Berry, MF; Hanna, J; Tong, BC; Burfeind, WR; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Hanna, J, Tong, BC, Burfeind, WR, Harpole, DH, D'Amico, TA, and Onaitis, MW. "Risk factors for morbidity after lobectomy for lung cancer in elderly patients." Ann Thorac Surg 88.4 (October 2009): 1093-1099.
PMID
19766786
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
88
Issue
4
Publish Date
2009
Start Page
1093
End Page
1099
DOI
10.1016/j.athoracsur.2009.06.012

Measurement of gene expression biomarkers by qNPA (TM) from archived NSCLC FFPE: prognosis of 5-year survival

Authors
Joshi, M-BM; Seligmann, B; Harpole, DH
MLA Citation
Joshi, M-BM, Seligmann, B, and Harpole, DH. "Measurement of gene expression biomarkers by qNPA (TM) from archived NSCLC FFPE: prognosis of 5-year survival." September 2009.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S502
End Page
S502

KRAS mutation analysis in non-small cell lung cancer (NSCLC) versus colorectal cancer (CRC): implications for EGFR-directed therapies

Authors
Mack, PC; Gandara, DR; Omori, A; Grimminger, PP; Lenz, H-J; Joshi, M-BM; Harpole, DH; Danenberg, KD
MLA Citation
Mack, PC, Gandara, DR, Omori, A, Grimminger, PP, Lenz, H-J, Joshi, M-BM, Harpole, DH, and Danenberg, KD. "KRAS mutation analysis in non-small cell lung cancer (NSCLC) versus colorectal cancer (CRC): implications for EGFR-directed therapies." September 2009.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S350
End Page
S350

Socioeconomic status predicts outcomes from NSCLC

Authors
Erhunmwunsee, L; Stinnett, SS; Harpole, DH
MLA Citation
Erhunmwunsee, L, Stinnett, SS, and Harpole, DH. "Socioeconomic status predicts outcomes from NSCLC." September 2009.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S310
End Page
S311

Ribonucleotide reductase (RRM1) expression in non-small cell lung cancer (NSCLC): implications for personalizing gemcitabine-based therapy

Authors
Gandara, DR; Mack, PC; Omori, A; Grimminger, P; Joshi, M-BM; Harpole, DH; Danenberg, KD
MLA Citation
Gandara, DR, Mack, PC, Omori, A, Grimminger, P, Joshi, M-BM, Harpole, DH, and Danenberg, KD. "Ribonucleotide reductase (RRM1) expression in non-small cell lung cancer (NSCLC): implications for personalizing gemcitabine-based therapy." September 2009.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S401
End Page
S402

Thymidylate synthase (TS) RNA expression in non-small cell lung cancer (NSCLC): implications for personalizing pemetrexed therapy

Authors
Gandara, DR; Mack, PC; Omori, A; Grimminger, P; Lara, PN; Joshi, M-BM; Harpole, DH; Danenberg, KD
MLA Citation
Gandara, DR, Mack, PC, Omori, A, Grimminger, P, Lara, PN, Joshi, M-BM, Harpole, DH, and Danenberg, KD. "Thymidylate synthase (TS) RNA expression in non-small cell lung cancer (NSCLC): implications for personalizing pemetrexed therapy." September 2009.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9
Publish Date
2009
Start Page
S400
End Page
S400

Thoracoscopic lobectomy is associated with lower morbidity compared with thoracotomy.

OBJECTIVES: Advantages of thoracoscopic lobectomy include less postoperative pain, shorter hospitalization, and improved delivery of adjuvant chemotherapy. The incidence of postoperative complications has not been thoroughly assessed. This study analyzes morbidity after lobectomy to compare the thoracoscopic approach and thoracotomy. METHODS: By using a prospective database, the outcomes of patients who underwent lobectomy from 1999-2009 were analyzed with respect to postoperative complications. Propensity-matched groups were analyzed based on preoperative variables and stage. RESULTS: Of the 1079 patients in the study, 697 underwent thoracoscopic lobectomy, and 382 underwent lobectomy by means of thoracotomy. In the overall analysis thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (P = .01), atelectasis (P = .0001), prolonged air leak (P = .0004), transfusion (P = .0001), pneumonia (P = .001), sepsis (P = .008), renal failure (P = .003), and death (P = .003). In the propensity-matched analysis based on preoperative variables, when comparing 284 patients in each group, 196 (69%) patients who underwent thoracoscopic lobectomy had no complications versus 144 (51%) patients who underwent thoracotomy (P = .0001). In addition, thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (13% vs 21%, P = .01), less atelectasis (5% vs 12%, P = .006), fewer prolonged air leaks (13% vs 19%, P = .05), fewer transfusions (4% vs 13%, P = .002), less pneumonia (5% vs 10%, P = .05), less renal failure (1.4% vs 5%, P = .02), shorter chest tube duration (median of 3 vs 4 days, P < .0001), and shorter length of hospital stay (median of 4 vs 5 days, P < .0001). CONCLUSIONS: Thoracoscopic lobectomy is associated with a lower incidence of major complications, including atrial fibrillation, compared with lobectomy by means of thoracotomy. The underlying factors responsible for this advantage should be analyzed to improve the safety and outcomes of other thoracic procedures.

Authors
Villamizar, NR; Darrabie, MD; Burfeind, WR; Petersen, RP; Onaitis, MW; Toloza, E; Harpole, DH; D'Amico, TA
MLA Citation
Villamizar, NR, Darrabie, MD, Burfeind, WR, Petersen, RP, Onaitis, MW, Toloza, E, Harpole, DH, and D'Amico, TA. "Thoracoscopic lobectomy is associated with lower morbidity compared with thoracotomy." J Thorac Cardiovasc Surg 138.2 (August 2009): 419-425.
PMID
19619789
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
138
Issue
2
Publish Date
2009
Start Page
419
End Page
425
DOI
10.1016/j.jtcvs.2009.04.026

Prognostic factors for recurrence after pulmonary resection of colorectal cancer metastases.

BACKGROUND: This study was undertaken to review a large series of resections of colorectal pulmonary metastases in the era of modern chemotherapy. METHODS: A retrospective chart review of prospectively maintained thoracic surgery databases identified 378 patients who underwent pulmonary resection for colorectal cancer metastases with curative intent from 1998 to 2007. RESULTS: The primary site of disease was rectum (52%), left colon (26%), right colon (16%), and unknown (6%). Before thoracic recurrence, 166 patients (44%) had previously undergone resection of extrathoracic metastases. Median disease-free interval (DFI) was 24 months from the time of the primary operation. The number of metastatic deposits resected was one in 60%, two in 20%, three in 10%, and four or more in 10%. Chemotherapy was administered to 87 patients (23%) before resection and to 169 patients (45%) after resection. Three-year recurrence-free survival was 28%, and 3-year overall survival was 78%. Multivariable analysis revealed age younger than 65 years, female sex, DFI less than 1 year, and number of metastases greater than three as independent predictors of recurrence. Of 44 patients with three or more lesions and less than 1 year DFI, none was cured by operation. By contrast, recurrence-free survival was 49% at 3 years for those with one lesion and DFI greater than 1 year. CONCLUSIONS: Age younger than 65 years, female sex, DFI less than 1 year, and number of metastases greater than three predict recurrence. Medical management alone should be considered standard for patients who have both three or more pulmonary metastases and less than 1 year DFI.

Authors
Onaitis, MW; Petersen, RP; Haney, JC; Saltz, L; Park, B; Flores, R; Rizk, N; Bains, MS; Dycoco, J; D'Amico, TA; Harpole, DH; Kemeny, N; Rusch, VW; Downey, R
MLA Citation
Onaitis, MW, Petersen, RP, Haney, JC, Saltz, L, Park, B, Flores, R, Rizk, N, Bains, MS, Dycoco, J, D'Amico, TA, Harpole, DH, Kemeny, N, Rusch, VW, and Downey, R. "Prognostic factors for recurrence after pulmonary resection of colorectal cancer metastases." Ann Thorac Surg 87.6 (June 2009): 1684-1688.
PMID
19463577
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
87
Issue
6
Publish Date
2009
Start Page
1684
End Page
1688
DOI
10.1016/j.athoracsur.2009.03.034

Measurement of gene expression biomarkers by qNPA from archived NSCLC FFPE: Prognosis of 5-year survival.

11098 Background: There are vast archives of formalin fixed paraffin-embedded (FFPE) tissue samples that are clinically annotated offering great research potential. However, the technology currently available to assess gene expression is limited to fresh, frozen, tissue. Recently, a method for measuring gene expression from FFPE using the quantitative Nuclease Protection Assay (qNPA) has been published in a model of diffuse large B-cell lymphoma. It was demonstrated that identical results were obtained from small amounts of FFPE as from matched frozen tissue, or from freshly fixed versus 18 year archived FFPE.This study used the qNPA assay to measure gene expression in archived FFPE primary tumor samples of patients with stage 1 NSCLC for whom the survival outcomes are known (n=86). HTG lysis buffer is added to the sample; nuclease protection probes that are complementary to the mRNA of interest are then added to the solution. The probes hybridize to all RNA, soluble and cross-linked. After hybridization, S1 nuclease was added and destroys all nonspecific, single strand nucleic acid, producing a stoichiometric amount of target-mRNA to probe duplexes. Base hydrolysis releases the probe from these duplexes. Probes were transferred to a programmed ArrayPlate, detection linker added, and both probes and detection linkers were captured onto the array. The ArrayPlate was washed, HRP-labeled detection probe added, incubated, washed, and chemiluminescent substrate was added. Finally, the ArrayPlate was imaged, to measure the expression of each gene in all the wells.Mantel-Cox analysis indicates that the detection of increased expression of G-CSF (p = 0.07; H.R. =1.904; 95% CI=0.9003-4.028) and Leptin (p=0.09; H.R. =1.910; 95% CI=0.9299-3.924) individually suggest an improved survival. Age, gender and T size were found to not be significant in this data set.These results suggest an improved survival advantage in patients with an elevated native GCSF level in stage 1 NSCLC that is consistent with the survival benefits associated with the prophylactic treatment of GCSF for chemosensitivity in stage III or IV NSCLC patients. These results are currently being assessed using a larger cohort. [Table: see text].

Authors
Joshi, MM; Seligmann, B; Sabalos, C; Harpole, DH
MLA Citation
Joshi, MM, Seligmann, B, Sabalos, C, and Harpole, DH. "Measurement of gene expression biomarkers by qNPA from archived NSCLC FFPE: Prognosis of 5-year survival." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27.15_suppl (May 2009): 11098-.
PMID
27963124
Source
epmc
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
11098

Stage I NSCLC: elucidating the prognostic factors.

Authors
Pham, D; Harpole, DH
MLA Citation
Pham, D, and Harpole, DH. "Stage I NSCLC: elucidating the prognostic factors." Thorax 64.3 (March 2009): 185-186.
PMID
19252015
Source
pubmed
Published In
Thorax
Volume
64
Issue
3
Publish Date
2009
Start Page
185
End Page
186
DOI
10.1136/thx.2008.105965

CT metrics of airway disease and emphysema in severe COPD

Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of -950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = -0.28, p = 0.0001) and SRWA (r = -0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = -0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = -5.2, p = 0.009; β = -2.6, p = 0.008, respectively) and %LAA-950 (β = -10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. © 2009 American College of Chest Physicians.

Authors
Kim, WJ; Silverman, EK; Hoffman, E; Criner, GJ; Mosenifar, Z; Sciurba, FC; Make, BJ; Carey, V; Estépar, RSJ; Diaz, A; Reilly, JJ; Martinez, FJ; Washko, GR; Fishman, AP; Bozzarello, BA; Al-Amin, A; Katz, M; Wheeler, C; Baker, E; Barnard, P; Cagle, P; Carter, J; Chatziioannou, S; Conejo-Gonzales, K; Dubose, K; Haddad, J; Hicks, D; Kleiman, N; Milburn-Barnes, M; Nguyen, C; Reardon, M; Reeves-Viets, J; Sax, S; Sharafkhaneh, A; Wilson, O; Young, C; Espada, R; Butanda, R; Ellisor, M; Fox, P; Hale, K et al.
MLA Citation
Kim, WJ, Silverman, EK, Hoffman, E, Criner, GJ, Mosenifar, Z, Sciurba, FC, Make, BJ, Carey, V, Estépar, RSJ, Diaz, A, Reilly, JJ, Martinez, FJ, Washko, GR, Fishman, AP, Bozzarello, BA, Al-Amin, A, Katz, M, Wheeler, C, Baker, E, Barnard, P, Cagle, P, Carter, J, Chatziioannou, S, Conejo-Gonzales, K, Dubose, K, Haddad, J, Hicks, D, Kleiman, N, Milburn-Barnes, M, Nguyen, C, Reardon, M, Reeves-Viets, J, Sax, S, Sharafkhaneh, A, Wilson, O, Young, C, Espada, R, Butanda, R, Ellisor, M, Fox, P, and Hale, K et al. "CT metrics of airway disease and emphysema in severe COPD." Chest 136.2 (2009): 396-404.
PMID
19411295
Source
scival
Published In
Chest
Volume
136
Issue
2
Publish Date
2009
Start Page
396
End Page
404
DOI
10.1378/chest.08-2858

Histologic considerations for individualized systemic therapy approaches for the management of non-small cell lung cancer

Over the past 5 to 10 years, we have reached a treatment plateau using standard platinum-based doublets in an unselected population of patients with advanced non-small cell lung cancer (NSCLC). Recent studies have focused on improving patient outcomes with new chemotherapeutic or targeted agents, as well as on individualizing therapy on the basis of patient characteristics such as tumor histology and biomarker analysis. This article summarizes recent data on histologic response determinants to chemotherapy and targeted therapy, with particular attention to the importance of standardized tissue collection, handling, storage, and analysis techniques, in order to best apply the results of tumor analysis to patient-care decisions. Such decisions are related to both improving patient safety and optimizing efficacy with standard chemotherapy as well as newer targeted therapy agents. This entails a change from a generalized approach in treating patients with NSCLC to an individualized strategy based on tumor histology. © 2009 American College of Chest Physicians.

Authors
West, H; Harpole, D; Travis, W
MLA Citation
West, H, Harpole, D, and Travis, W. "Histologic considerations for individualized systemic therapy approaches for the management of non-small cell lung cancer." Chest 136.4 (2009): 1112-1118.
PMID
19809052
Source
scival
Published In
Chest
Volume
136
Issue
4
Publish Date
2009
Start Page
1112
End Page
1118
DOI
10.1378/chest.08-2484

Molecular analysis-based treatment strategies for the management of non-small cell lung cancer

Even with the introduction of targeted agents and the establishment of multiple lines of therapy, the median survival for patients with advanced non-small cell lung cancer (NSCLC) does not considerably extend beyond 1 year. Emerging research suggests that clinical characteristics alone are insufficient for selecting patients for therapies that may confer significant survival benefit. The discovery of predictive and prognostic molecular markers such as gene mutations in EGFR and KRAS as well as high tumor expression levels of DNA repair pathway components ribonucleotide reductase subunit 1 and excision repair cross-complementing group 1 has sparked an interest in the development of individualized therapy as a strategy for increasing survival in patients with NSCLC. Techniques to analyze molecular biomarkers, such as immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction, and, more recently, gene microarray techniques, are being investigated for their potential to accurately predict an individual patient's response to therapy. Many prospective trials are still needed to clarify and confirm the utility of molecular biomarkers for guiding treatment selection, and continued participation in clinical trials is critical for the development of tools to provide customized treatment plans for patients with NSCLC. © 2009 International Association for the Study of Lung Cancer.

Authors
West, H; Lilenbaum, R; Harpole, D; Wozniak, A; Sequist, L
MLA Citation
West, H, Lilenbaum, R, Harpole, D, Wozniak, A, and Sequist, L. "Molecular analysis-based treatment strategies for the management of non-small cell lung cancer." Journal of Thoracic Oncology 4.9 SUPPL. 2 (2009): S1029-S1039.
PMID
19704347
Source
scival
Published In
Journal of Thoracic Oncology
Volume
4
Issue
9 SUPPL. 2
Publish Date
2009
Start Page
S1029
End Page
S1039
DOI
10.1097/JTO.0b013e3181b27170

Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study.

BACKGROUND: A feasibility study examining the effects of supervised aerobic exercise training on cardiopulmonary and quality of life (QOL) endpoints among postsurgical nonsmall cell lung cancer (NSCLC) patients was conducted. METHODS: Using a single-group design, 20 patients with stage I-IIIB NSCLC performed 3 aerobic cycle ergometry sessions per week at 60% to 100% of peak workload for 14 weeks. Peak oxygen consumption (VO(2peak)) was assessed using an incremental exercise test. QOL and fatigue were assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale. RESULTS: Nineteen patients completed the study. Intention-to-treat analysis indicated that VO(2peak) increased 1.1 mL/kg(-1)/min(-1) (95% confidence interval [CI], -0.3-2.5; P = .109) and peak workload increased 9 W (95% CI, 3-14; P = .003), whereas FACT-L increased 10 points (95% CI, -1-22; P = .071) and fatigue decreased 7 points (95% CI; -1 to -17; P = .029) from baseline to postintervention. Per protocol analyses indicated greater improvements in cardiopulmonary and QOL endpoints among patients not receiving adjuvant chemotherapy. CONCLUSIONS: This pilot study provided proof of principle that supervised aerobic training is safe and feasible for postsurgical NSCLC patients. Aerobic exercise training is also associated with significant improvements in QOL and select cardiopulmonary endpoints, particularly among patients not receiving chemotherapy. Larger randomized trials are warranted.

Authors
Jones, LW; Eves, ND; Peterson, BL; Garst, J; Crawford, J; West, MJ; Mabe, S; Harpole, D; Kraus, WE; Douglas, PS
MLA Citation
Jones, LW, Eves, ND, Peterson, BL, Garst, J, Crawford, J, West, MJ, Mabe, S, Harpole, D, Kraus, WE, and Douglas, PS. "Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study." Cancer 113.12 (December 15, 2008): 3430-3439.
PMID
18988290
Source
pubmed
Published In
Cancer
Volume
113
Issue
12
Publish Date
2008
Start Page
3430
End Page
3439
DOI
10.1002/cncr.23967

Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups.

PURPOSE: Adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC) is now accepted on the basis of several randomized clinical trials (RCTs) that demonstrated improved survival. Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB disease is unclear. This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC. PATIENTS AND METHODS: Within 4 to 8 weeks of resection, patients were randomly assigned to adjuvant chemotherapy or observation. Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy. Chemotherapy consisted of paclitaxel 200 mg/m(2) intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was overall survival. RESULTS: Three hundred-forty-four patients were randomly assigned. Median follow-up was 74 months. Groups were well-balanced with regard to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were the predominant toxicity; there were no treatment-related deaths. Survival was not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P = .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors > or = 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P = .043). CONCLUSION: Because a significant survival advantage was not observed across the entire cohort, adjuvant chemotherapy should not be considered standard care in stage IB NSCLC. Given the magnitude of observed survival differences, CALGB 9633 was underpowered to detect small but clinically meaningful improvements. A statistically significant survival advantage for patients who had tumors > or = 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.

Authors
Strauss, GM; Herndon, JE; Maddaus, MA; Johnstone, DW; Johnson, EA; Harpole, DH; Gillenwater, HH; Watson, DM; Sugarbaker, DJ; Schilsky, RL; Vokes, EE; Green, MR
MLA Citation
Strauss, GM, Herndon, JE, Maddaus, MA, Johnstone, DW, Johnson, EA, Harpole, DH, Gillenwater, HH, Watson, DM, Sugarbaker, DJ, Schilsky, RL, Vokes, EE, and Green, MR. "Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups." J Clin Oncol 26.31 (November 1, 2008): 5043-5051.
PMID
18809614
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
31
Publish Date
2008
Start Page
5043
End Page
5051
DOI
10.1200/JCO.2008.16.4855

Quality of life outcomes are equivalent after lobectomy in the elderly.

OBJECTIVE: Prospective analyses of quality of life in elderly patients after lobectomy are limited, yet surgeons often recommend suboptimal therapy to these patients on the basis of the belief that lobectomy is poorly tolerated. Surgical decision making in elderly patients with lung cancer is better informed when the benefits to survival and quality of life after lobectomy are understood. METHODS: By using a validated quality of life instrument, 422 patients were prospectively assessed preoperatively and 3, 6, and 12 months after lobectomy. Outcomes were analyzed with respect to age (group 1: < 70 years and group 2: > or = 70 years). The outcome domains of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, global health, and pain in the chest were analyzed using a mixed model. The trend in quality of life was determined according to age. The Kaplan-Meier method was used for analysis of overall survival. RESULTS: The mean age was 60.1 years in group 1 (N = 256) and 74.7 years in group 2 (N = 166). Baseline demographics and quality of life were similar except that group 2 had better emotional functioning scores and worse pain in the chest scores. Postoperatively, both groups demonstrated significant decreases in quality of life at 3 months. However, at 6 and 12 months, all domains had returned to baseline except physical functioning, which remained below baseline in group 2. Emotional functioning improved postoperatively for both groups. Overall survival at 5 years was not different between groups. CONCLUSION: By using a validated quality of life assessment tool with measurements at baseline and serially after resection in a large patient population, this analysis quantifies the degree of impairment of quality of life after lobectomy and documents time to full recovery for both age groups.

Authors
Burfeind, WR; Tong, BC; O'Branski, E; Herndon, JE; Toloza, EM; D'Amico, TA; Harpole, LH; Harpole, DH
MLA Citation
Burfeind, WR, Tong, BC, O'Branski, E, Herndon, JE, Toloza, EM, D'Amico, TA, Harpole, LH, and Harpole, DH. "Quality of life outcomes are equivalent after lobectomy in the elderly." J Thorac Cardiovasc Surg 136.3 (September 2008): 597-604.
PMID
18805257
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
136
Issue
3
Publish Date
2008
Start Page
597
End Page
604
DOI
10.1016/j.jtcvs.2008.02.093

Basal cells in lung cancer

Authors
Erhunmwunsee, L; Lu, Y; Luo, X; Jr, HDH; Hogan, BLM; Onaitis, MW
MLA Citation
Erhunmwunsee, L, Lu, Y, Luo, X, Jr, HDH, Hogan, BLM, and Onaitis, MW. "Basal cells in lung cancer." September 2008.
Source
wos-lite
Published In
Journal of The American College of Surgeons
Volume
207
Issue
3
Publish Date
2008
Start Page
S30
End Page
S30
DOI
10.1016/j.jamcollsurg.2008.06.053

Local/regional recurrence following surgery for early-stage lung cancer: A 10-year experience with 975 patients.

7542 Background: Surgery, with or without chemotherapy, is the preferred treatment for early-stage NSCLC. The risk of local/regional recurrence (LRR) after resection is not well defined, but generally considered to be small in comparison to the risk of distant recurrence. We herein evaluate the actuarial risk of LRR after surgery for stage I-II disease and assess surgical and pathologic factors affecting this risk. METHODS: The medical records and pertinent radiographs of all patients who underwent surgery for pathological T1- 2N0-1 NSCLC at Duke between 1995-2005 were reviewed. Patients receiving preoperative therapy, or with synchronous/prior lung cancers were excluded. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a LRR. Nodal failures were defined as a new or enlarging LN≥1 cm on short axis on CT or hypermetabolic on PET. The actuarial rates of LRR and distant recurrence (assessed independently) were estimated using the Kaplan-Meier method. A univariate and multivariate regression analysis assessed factors associated with LRR. RESULTS: Of 975 patients, 45% were stage IA, 40% IB, and 15% stage II; 79% underwent ≥ lobectomy; 85% had sampling/dissection of mediastinal LNs; 4% had positive margins; 7% received adjuvant chemotherapy; 3% received adjuvant radiation therapy. The 5-year actuarial rate of LRR was 22% and distant recurrence was 31%. LRR was higher for stage IB, IIA, and IIB compared with IA (hazard ratio- 2, 2.6, and 1.9). Sublobar resections were associated with a higher risk of LRR on univariate, but not multivariate, analysis. On multivariate analysis, increasing size, squamous or large cell histology, visceral pleural invasion, stage IIA disease, and lack of nodal sampling were independently associated with a higher rate of LRR. CONCLUSIONS: The risk of LRR after surgery for stage I-II NSCLC is ≈22%, and is similar to the risk of distant recurrence. Thus, local control remains an important issue justifying continued clinical research in this area. Postoperative RT, utilizing modest doses and small conformal fields directed to sites most at risk, should be reevaluated. As systemic therapy improves, the relative importance of achieving local control will also increase. No significant financial relationships to disclose.

Authors
Kelsey, CR; Boyd, JA; Hubbs, JL; Hollis, DR; Crawford, J; Ready, NE; D'Amcio, TA; Harpole, DH; Garst, J; Marks, LB
MLA Citation
Kelsey, CR, Boyd, JA, Hubbs, JL, Hollis, DR, Crawford, J, Ready, NE, D'Amcio, TA, Harpole, DH, Garst, J, and Marks, LB. "Local/regional recurrence following surgery for early-stage lung cancer: A 10-year experience with 975 patients." J Clin Oncol 26.15_suppl (May 20, 2008): 7542-.
PMID
27947218
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
7542

Local/regional recurrence following surgery for early-stage lung cancer: A 10-year experience with 975 patients

Authors
Kelsey, CR; Boyd, JA; Hubbs, JL; Hollis, DR; Crawford, J; Ready, NE; D'Amcio, TA; Harpole, DH; Garst, J; Marks, LB
MLA Citation
Kelsey, CR, Boyd, JA, Hubbs, JL, Hollis, DR, Crawford, J, Ready, NE, D'Amcio, TA, Harpole, DH, Garst, J, and Marks, LB. "Local/regional recurrence following surgery for early-stage lung cancer: A 10-year experience with 975 patients." May 20, 2008.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Data from The Society of Thoracic Surgeons General Thoracic Surgery database: the surgical management of primary lung tumors.

OBJECTIVE: Our objective was to investigate the surgical management of primary lung cancer by board-certified thoracic surgeons participating in the general thoracic surgery portion of The Society of Thoracic Surgeons database. METHODS: We identified all pulmonary resections recorded in the general thoracic surgery prospective database from 1999 to 2006. Among the 49,029 recorded operations, 9033 pulmonary resections for primary lung cancer were analyzed. RESULTS: There were 4539 men and 4494 women with a median age of 67 years (range 20-94 years). Comorbidity affected 79% of patients and included hypertension in 66%, coronary artery disease in 26%, body mass index of 30 kg/m2 or more in 25.7%, and diabetes mellitus in 13%. The type of resection was a wedge resection in 1649 (18.1%), segmentectomy in 394 (4.4%), lobectomy in 6042 (67%), bilobectomy in 357 (4.0%), and pneumonectomy in 591 (6.5%). Mediastinal lymph nodes were evaluated in 5879 (65%) patients; via mediastinoscopy in 1928 (21%), nodal dissection 3722 (41%), nodal sampling in 1124 (12.4%), and nodal biopsy in 729 (8%). Median length of stay was 5 days (range 0-277 days). Operative mortality was 2.5% (179 patients). One or more postoperative events occurred in 2911 (32%) patients. CONCLUSION: The patients in the general thoracic surgery database are elderly, gender balanced, and afflicted by multiple comorbid conditions. Mediastinal lymph node evaluation is common and the pneumonectomy rate is low. The length of stay is short and operative mortality is low, despite frequent postoperative events.

Authors
Boffa, DJ; Allen, MS; Grab, JD; Gaissert, HA; Harpole, DH; Wright, CD
MLA Citation
Boffa, DJ, Allen, MS, Grab, JD, Gaissert, HA, Harpole, DH, and Wright, CD. "Data from The Society of Thoracic Surgeons General Thoracic Surgery database: the surgical management of primary lung tumors." J Thorac Cardiovasc Surg 135.2 (February 2008): 247-254.
PMID
18242243
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
135
Issue
2
Publish Date
2008
Start Page
247
End Page
254
DOI
10.1016/j.jtcvs.2007.07.060

Corrigendum: Genomic signatures to guide the use of chemotherapeutics (Nature Medicine (2006) 12, (1294-1300))

Authors
Potti, A; Dressman, HK; Bild, A; Riedel, RF; Chan, G; Sayer, R; Cragun, J; Cottrill, H; Kelley, MJ; Petersen, R; Harpole, D; Marks, J; Berchuck, A; Ginsburg, GS; Febbo, P; Lancaster, J; Nevins, JR
MLA Citation
Potti, A, Dressman, HK, Bild, A, Riedel, RF, Chan, G, Sayer, R, Cragun, J, Cottrill, H, Kelley, MJ, Petersen, R, Harpole, D, Marks, J, Berchuck, A, Ginsburg, GS, Febbo, P, Lancaster, J, and Nevins, JR. "Corrigendum: Genomic signatures to guide the use of chemotherapeutics (Nature Medicine (2006) 12, (1294-1300))." Nature Medicine 14.8 (2008): 889--.
Source
scival
Published In
Nature Medicine
Volume
14
Issue
8
Publish Date
2008
Start Page
889-
DOI
10.1038/nm0808-889

Induction therapy for stage IIIA (N2) lung cancer

One of the major goals of the International Staging System for Lung Cancer, first introduced in 1986 and subsequently revised in 1997, was the separation of patients into potentially resectable and unresectable categories. This dividing line was set between stage IIIA and stage IIIB disease with contralateral lymph node metastases or local involvement of unresectable or marginally resectable structures defining the limits of surgical treatment. treatment. The advent of modern cancer therapy with multimodality approaches including surgery, chemotherapy, and radiation therapy has raised significant questions that are still not completely resolved as to the best approach for patients with potentially resectable stage IIIA (N2) disease at presentation. © 2007 Springer-Verlag London Limited.

Authors
Meyerson, SL; Harpole, DH
MLA Citation
Meyerson, SL, and Harpole, DH. "Induction therapy for stage IIIA (N2) lung cancer." Difficult Decisions in Thoracic Surgery: An Evidence-Based Approach. December 1, 2007. 88-93.
Source
scopus
Publish Date
2007
Start Page
88
End Page
93
DOI
10.1007/978-1-84628-474-8_10

Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer.

PURPOSE: Standard treatment for advanced non-small-cell lung cancer (NSCLC) includes the use of a platinum-based chemotherapy regimen. However, response rates are highly variable. Newer agents, such as pemetrexed, have shown significant activity as second-line therapy and are currently being evaluated in the front-line setting. We utilized a genomic strategy to develop signatures predictive of chemotherapeutic response to both cisplatin and pemetrexed to provide a rational approach to effective individualized medicine. METHODS: Using in vitro drug sensitivity data, coupled with microarray data, we developed gene expression signatures predicting sensitivity to cisplatin and pemetrexed. Signatures were validated with response data from 32 independent ovarian and lung cancer cell lines as well as 59 samples from patients previously treated with cisplatin. RESULTS: Genomic-derived signatures of cisplatin and pemetrexed sensitivity were shown to accurately predict sensitivity in vitro and, in the case of cisplatin, to predict treatment response in patients treated with cisplatin. The accuracy of the cisplatin predictor, based on available clinical data, was 83.1% (sensitivity, 100%; specificity 57%; positive predictive value, 78%; negative predictive value, 100%). Interestingly, an inverse correlation was seen between in vitro cisplatin and pemetrexed sensitivity, and importantly, between the likelihood of cisplatin and pemetrexed response in patients. CONCLUSION: The use of genomic predictors of response to cisplatin and pemetrexed can be incorporated into strategies to optimize therapy for advanced solid tumors.

Authors
Hsu, DS; Balakumaran, BS; Acharya, CR; Vlahovic, V; Walters, KS; Garman, K; Anders, C; Riedel, RF; Lancaster, J; Harpole, D; Dressman, HK; Nevins, JR; Febbo, PG; Potti, A
MLA Citation
Hsu, DS, Balakumaran, BS, Acharya, CR, Vlahovic, V, Walters, KS, Garman, K, Anders, C, Riedel, RF, Lancaster, J, Harpole, D, Dressman, HK, Nevins, JR, Febbo, PG, and Potti, A. "Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer." J Clin Oncol 25.28 (October 1, 2007): 4350-4357.
PMID
17906199
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
28
Publish Date
2007
Start Page
4350
End Page
4357
DOI
10.1200/JCO.2007.11.0593

Pulmonary segmentectomy by thoracotomy or thoracoscopy: reduced hospital length of stay with a minimally-invasive approach.

BACKGROUND: Previous studies have discouraged limited pulmonary resection for primary lung cancer, but pulmonary segmentectomy has advantages for some patients. Furthermore, while thoracoscopic lobectomy has been increasingly applied with well-demonstrated advantages compared with thoracotomy, few data exist regarding thoracoscopic approaches to pulmonary segmentectomy. This study compares thoracoscopic segmentectomy (TS) with open segmentectomy (OS). METHODS: This is a retrospective review of prospectively collected data for 77 consecutive segmentectomy patients treated between 2000 and 2006 at a single center. Preoperative, intraoperative, and postoperative variables for patients undergoing TS (n = 48) were compared with those undergoing OS (n = 29). Student's t tests were used for continuous data and Fisher's exact tests for dichotomous data. RESULTS: Baseline demographics were similar between groups. Indications for pulmonary resection included non-small cell lung cancer (n = 39), metastatic disease (n = 30), and other diagnoses (n = 8). All common segmentectomies were represented. No thoracoscopic cases required conversion to open procedures. Operative times, estimated blood loss, and chest tube duration were similar between groups. Outcomes were similar except that hospital length of stay was significantly less among TS patients (length of stay 6.8 +/- 6 days OS versus 4.3 +/- 3 days TS; p = 0.03). Thirty-day mortality was 6.9% (2 of 29) for the OS group compared with 0% for the TS group. Long-term survival rates were significantly better in the TS group (p = 0.0007). CONCLUSIONS: Thoracoscopic segmentectomy is a safe and feasible procedure, comparing favorably with OS by reducing hospital length of stay. For experienced thoracoscopic surgeons, TS appears to be a sound option for lung-sparing, anatomic pulmonary resections.

Authors
Atkins, BZ; Harpole, DH; Mangum, JH; Toloza, EM; D'Amico, TA; Burfeind, WR
MLA Citation
Atkins, BZ, Harpole, DH, Mangum, JH, Toloza, EM, D'Amico, TA, and Burfeind, WR. "Pulmonary segmentectomy by thoracotomy or thoracoscopy: reduced hospital length of stay with a minimally-invasive approach." Ann Thorac Surg 84.4 (October 2007): 1107-1112.
PMID
17888955
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
84
Issue
4
Publish Date
2007
Start Page
1107
End Page
1112
DOI
10.1016/j.athoracsur.2007.05.013

Audit, quality control, and performance in thoracic surgery: a North American perspective.

Although difficult to precisely define, health care quality is often measured by components of structure, outcomes, and process. One way for thoracic surgeons to evaluate their practices is to compare themselves with evidence-based national guidelines. Outcomes data are often generated from entries into large patient databases. The largest examples of these databases include the STS National Databases and the VA/ACS NSQIP programs. Each of these has unique features, but there is the common goal of enabling participants to examine their surgical outcomes and results relative to others. The data integrity of these databases is high. The new STS composite quality score for CABG combines providers' outcome and practice data into a calculated index for comparison with national averages. In addition to providing meaningful information regarding surgical outcomes and quality, these databases are used as the basis for risk-adjusted models to accurately predict surgical morbidity and mortality. These models can be used as auditing tools against which surgeon- and site-specific morbidity and mortality can be compared with predicted values. As practices and methods continue to evolve, measures of quality--and therefore quality itself--will continue to improve, resulting in better patient care.

Authors
Tong, BC; Harpole, DH
MLA Citation
Tong, BC, and Harpole, DH. "Audit, quality control, and performance in thoracic surgery: a North American perspective." Thorac Surg Clin 17.3 (August 2007): 379-386. (Review)
PMID
18072358
Source
pubmed
Published In
Thoracic Surgery Clinics
Volume
17
Issue
3
Publish Date
2007
Start Page
379
End Page
386
DOI
10.1016/j.thorsurg.2007.08.003

Preoperative exercise Vo2 measurement for lung resection candidates: results of Cancer and Leukemia Group B Protocol 9238.

INTRODUCTION: A stepwise approach to the functional assessment of lung resection candidates is widely accepted, and this approach incorporates the measurement of exercise peak Vo2 when spirometry and radionuclear studies suggest medical inoperability. A new functional operability (FO) algorithm incorporates peak exercise Vo2 earlier in the preoperative assessment to determine which patients require preoperative radionuclear studies. This algorithm has not been studied in a multicenter study. METHODS: The CALGB (Cancer and Leukemia Group B) performed a prospective multi-institutional study to investigate the use of primary exercise Vo2 measurement for the prediction of surgical risk. Patients with known or suspected resectable non-small cell lung cancer (NSCLC) were eligible. Exercise testing including measurement of peak oxygen uptake (Vo2), spirometry, and single breath diffusion capacity (DLCO) was performed on each patient. Nuclear perfusion scans were obtained on selected high-risk patients. After surgery, morbidity and mortality data were collected and correlated with preoperative data. Mortality and morbidity were retrospectively compared by algorithm-based risk groups. RESULTS: Three hundred forty-six patients with suspected lung cancer from nine institutions underwent thoracotomy with or without resection; 57 study patients did not undergo thoracotomy. Patients who underwent surgery had a median survival time of 30.9 months, whereas patients who did not undergo surgery had a median survival time of 15.6 months. Among the 346 patients who underwent thoracotomy, 15 patients died postoperatively (4%), and 138 patients (39%) exhibited at least one cardiorespiratory complication postoperatively. We found that patients who had a peak exercise Vo2 of <65% of predicted (or a peak Vo2/kg <16 ml/min/kg) were more likely to suffer complications (p = 0.0001) and were also more likely to have a poor outcome (respiratory failure or death) if the peak Vo2 was <15 ml/min/kg (p = 0.0356). We also found a subset of 58 patients who did not meet FO algorithm criteria for operability, but who still tolerated lung resection with a 2% mortality rate. CONCLUSIONS: Our data provide multicenter validation for the use of exercise Vo2 for preoperative assessment of lung cancer patients, and we encourage an aggressive approach when evaluating these patients for surgery.

Authors
Loewen, GM; Watson, D; Kohman, L; Herndon, JE; Shennib, H; Kernstine, K; Olak, J; Mador, MJ; Harpole, D; Sugarbaker, D; Green, M; Cancer and Leukemia Group B,
MLA Citation
Loewen, GM, Watson, D, Kohman, L, Herndon, JE, Shennib, H, Kernstine, K, Olak, J, Mador, MJ, Harpole, D, Sugarbaker, D, Green, M, and Cancer and Leukemia Group B, . "Preoperative exercise Vo2 measurement for lung resection candidates: results of Cancer and Leukemia Group B Protocol 9238." J Thorac Oncol 2.7 (July 2007): 619-625.
PMID
17607117
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
2
Issue
7
Publish Date
2007
Start Page
619
End Page
625
DOI
10.1097/JTO.0b013e318074bba7

Prognostic modeling in early stage lung cancer: an evolving process from histopathology to genomics.

The goal is to validate a molecular-based tumor model that identifies patients at low-risk for cancer recurrence and who will not benefit from adjuvant chemotherapy. The remaining patients will be randomized to observation (present standard of care) or adjuvant chemotherapy to determine efficacy of adjuvant in this population. Investigators have focused on the identification of markers that may predict poor prognosis as a way to "enrich" the population by separating those likely to have early recurrence and cancer death from those not needing additional treatment after resection. The initial projects refined predictive models of cancer recurrence after resection for patients with early stage non-small cell lung cancer.

Authors
Harpole, DH
MLA Citation
Harpole, DH. "Prognostic modeling in early stage lung cancer: an evolving process from histopathology to genomics." Thorac Surg Clin 17.2 (May 2007): 167-viii. (Review)
PMID
17626395
Source
pubmed
Published In
Thoracic Surgery Clinics
Volume
17
Issue
2
Publish Date
2007
Start Page
167
End Page
viii
DOI
10.1016/j.thorsurg.2007.03.014

Thoracoscopic lobectomy facilitates the delivery of chemotherapy after resection for lung cancer.

BACKGROUND: We conducted a study of patients who underwent anatomic resection with adjuvant chemotherapy to determine if thoracoscopic lobectomy enables more effective administration of adjuvant chemotherapy than lobectomy by thoracotomy. METHODS: We reviewed the outcomes of 100 consecutive patients with non-small cell lung cancer (NSCLC) who underwent lobectomy and received adjuvant chemotherapy (1999 to 2004). The variables analyzed were time to initiation of chemotherapy, percentage of planned regimen received, number of delayed or reduced chemotherapy doses, toxicity grade, length of hospitalization, chest tube duration, 30-day mortality, and major complications (pneumonia, respiratory failure, atrial fibrillation). The chi2 test and Student t test were used to compare dichotomous and continuous variables, respectively. RESULTS: Complete resection was performed by thoracotomy in 43 patients and by thoracoscopy in 57 (no conversions). All patients received adjuvant chemotherapy, and 20 (20%) received adjuvant radiation therapy: 13 (30%) of 43 in the thoracotomy group and 7 (12%) of 57 in the thoracoscopy group (p = 0.04). Patients undergoing thoracoscopic lobectomy had significantly fewer delayed (18% versus 58%, p < 0.001) and reduced (26% versus 49%, p = 0.02) chemotherapy doses. A higher percentage of patients undergoing thoracoscopic resection received 75% or more of their planned adjuvant regimen without delayed or reduced doses (61% versus 40%, p = 0.03). There were no significant differences in time to initiation of chemotherapy or toxicity. Patients undergoing a thoracoscopic lobectomy had a shorter median length of hospitalization (4 days versus 5 days, p = 0.02). CONCLUSIONS: Thoracoscopy was associated with an overall higher compliance rate and fewer delayed or reduced doses of chemotherapy in patients receiving adjuvant chemotherapy.

Authors
Petersen, RP; Pham, D; Burfeind, WR; Hanish, SI; Toloza, EM; Harpole, DH; D'Amico, TA
MLA Citation
Petersen, RP, Pham, D, Burfeind, WR, Hanish, SI, Toloza, EM, Harpole, DH, and D'Amico, TA. "Thoracoscopic lobectomy facilitates the delivery of chemotherapy after resection for lung cancer." Ann Thorac Surg 83.4 (April 2007): 1245-1249.
PMID
17383320
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
83
Issue
4
Publish Date
2007
Start Page
1245
End Page
1249
DOI
10.1016/j.athoracsur.2006.12.029

Results of ACOSOG Z0050 trial: The utility of FDG-PET in staging potentially operable non-small cell lung cancer (vol 126, pg 1943, 2003)

Authors
Reed, CE; Harpole, DH; Posther, KE; Woolson, SL; Downey, RJ; Meyers, BR
MLA Citation
Reed, CE, Harpole, DH, Posther, KE, Woolson, SL, Downey, RJ, and Meyers, BR. "Results of ACOSOG Z0050 trial: The utility of FDG-PET in staging potentially operable non-small cell lung cancer (vol 126, pg 1943, 2003)." JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 133.4 (April 2007): 864-864.
Source
wos-lite
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
133
Issue
4
Publish Date
2007
Start Page
864
End Page
864

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma.

PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study. METHODS AND MATERIALS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy daily to 50.4 Gy). After completion, patients were restaged and evaluated for surgery. Primary endpoints included determination of dose-limiting toxicities (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and pathologic response rates. RESULTS: Thirteen patients were enrolled (10 men, 3 women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose level 1 (capecitabine 825 mg/m(2) twice daily on RT days, carboplatin area under the curve (AUC) 2 weekly, paclitaxel 60 mg/m(2) weekly) had DLT (both Grade 4 esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m(2)). Overall, 3 of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3 hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had pathologic downstaging and 2 of 6 had pCR. CONCLUSIONS: The maximally tolerated/recommended phase II doses were capecitabine 600 mg/m(2) twice daily, carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m(2) weekly with RT to 50.4 Gy. In our small study, this regimen appears active but is accompanied by significant toxicities, primarily esophagitis.

Authors
Czito, BG; Kelsey, CR; Hurwitz, HI; Willett, CG; Morse, MA; Blobe, GC; Fernando, NH; D'Amico, TA; Harpole, DH; Honeycutt, W; Yu, D; Bendell, JC
MLA Citation
Czito, BG, Kelsey, CR, Hurwitz, HI, Willett, CG, Morse, MA, Blobe, GC, Fernando, NH, D'Amico, TA, Harpole, DH, Honeycutt, W, Yu, D, and Bendell, JC. "A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma." Int J Radiat Oncol Biol Phys 67.4 (March 15, 2007): 1002-1007.
PMID
17197129
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
67
Issue
4
Publish Date
2007
Start Page
1002
End Page
1007
DOI
10.1016/j.ijrobp.2006.10.027

Refining prognosis in non-small-cell lung cancer - Reply

Authors
Potti, A; Jr, HDH; Nevins, JR
MLA Citation
Potti, A, Jr, HDH, and Nevins, JR. "Refining prognosis in non-small-cell lung cancer - Reply." NEW ENGLAND JOURNAL OF MEDICINE 356.2 (January 11, 2007): 190-191.
Source
wos-lite
Published In
The New England journal of medicine
Volume
356
Issue
2
Publish Date
2007
Start Page
190
End Page
191

Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma.

OBJECTIVES: The outcomes of patients with metastatic melanoma are poor. Although prognostic models have been developed to predict the occurrence of pulmonary metastasis from cutaneous melanoma, few data exist to define the outcomes of these patients once metastasis has occurred. The objective of this study was to discriminate predictors of survival for patients with pulmonary metastatic melanoma. METHODS: We found 1720 patients with pulmonary metastasis listed in a prospective comprehensive cancer center database of 14,057 consecutive patients with melanoma (Jan 1, 1970-June 1, 2004). Demographic and histopathologic data, time and location of recurrences, number of pulmonary nodules, and subsequent therapies were collected. Univariate and multivariate Cox proportional hazards models were used to identify predictors of survival for patients with pulmonary metastatic melanoma. RESULTS: The median survival was 7.3 months after development of pulmonary metastasis. Significant predictors of survival from the multivariate model included nodular histologic type (P = .033), disease-free interval (P < .001), number of pulmonary metastases (P = .012), presence of extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy (P < .001). Interactions were identified between metastasectomy and disease-free interval and presence of extrathoracic metastasis. Surgery was associated with a survival advantage of 12 months for patients with a disease-free interval longer than 5 years (19 vs 7 months, P < .01) and of 10 months for patients without extrathoracic metastasis (18 vs 8 months, P < .01). CONCLUSIONS: When all other identified risk factors were controlled for mathematically, metastasectomy maintained a significant survival advantage for patients with pulmonary metastatic melanoma. These data support the role of surgery for a select subset of patients with pulmonary metastasis.

Authors
Petersen, RP; Hanish, SI; Haney, JC; Miller, CC; Burfeind, WR; Tyler, DS; Seigler, HF; Wolfe, W; D'Amico, TA; Harpole, DH
MLA Citation
Petersen, RP, Hanish, SI, Haney, JC, Miller, CC, Burfeind, WR, Tyler, DS, Seigler, HF, Wolfe, W, D'Amico, TA, and Harpole, DH. "Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma." J Thorac Cardiovasc Surg 133.1 (January 2007): 104-110.
PMID
17198792
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
133
Issue
1
Publish Date
2007
Start Page
104
End Page
110
DOI
10.1016/j.jtcvs.2006.08.065

Erratum: Genomic signatures to guide the use of chemotherapeutics (Nature (2006) 12, (1294-1300))

Authors
Potti, A; Dressman, HK; Bild, A; Riedel, RF; Chan, G; Sayer, R; Cragun, J; Cottrill, H; Kelley, MJ; Petersen, R; Harpole, D; Marks, J; Berchuck, A; Ginsburg, GS; Febbo, P; Lancaster, J; Nevins, JR
MLA Citation
Potti, A, Dressman, HK, Bild, A, Riedel, RF, Chan, G, Sayer, R, Cragun, J, Cottrill, H, Kelley, MJ, Petersen, R, Harpole, D, Marks, J, Berchuck, A, Ginsburg, GS, Febbo, P, Lancaster, J, and Nevins, JR. "Erratum: Genomic signatures to guide the use of chemotherapeutics (Nature (2006) 12, (1294-1300))." Nature Medicine 13.11 (2007): 1388--.
Source
scival
Published In
Nature Medicine
Volume
13
Issue
11
Publish Date
2007
Start Page
1388-
DOI
10.1038/nm1107-1388

Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients.

BACKGROUND: Early stage lung cancer has a variable prognosis, and there are currently no markers that predict which patients will recur. This study examined the relation between tumor-regulatory T (Treg) cells and total tumor-infiltrating T-cell lymphocytes (TIL) to determine whether they correlated with recurrence. METHODS: The authors reviewed all patients in our tissue databank from 1996 to 2001 and identified 64 consecutive pathologic stage I non-small cell lung cancer (NSCLC) patients who had surgical resection and at least a 2.5 years disease-free follow-up or documented recurrence within 2 years. Immunohistochemical analyses were performed on paraffin-embedded lung cancer tissue and the relation between Treg cells, TIL, and disease-specific survival was determined. A risk index was devised deductively for various possible combinations of Treg cells and TIL. RESULTS: Treg cells and TIL were detected in 33 of 64 (51%) and 53 of 64 (83%) patients, respectively. When data were analyzed by using a Treg/TIL Combination Risk Index, patients with high-risk and intermediate-risk indices had hazard ratios of 8.2 (P = .007) and 3.3 (P = .109), respectively. CONCLUSIONS: Patients with stage I NSCLC who have a higher proportion of tumor Treg cells relative to TIL had a significantly higher risk of recurrence. These data may be useful, particularly if combined with a panel of tumor markers, to suggest at the time of diagnosis which patients with seemingly early-stage NSCLC will relapse.

Authors
Petersen, RP; Campa, MJ; Sperlazza, J; Conlon, D; Joshi, M-B; Harpole, DH; Patz, EF
MLA Citation
Petersen, RP, Campa, MJ, Sperlazza, J, Conlon, D, Joshi, M-B, Harpole, DH, and Patz, EF. "Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients." Cancer 107.12 (December 15, 2006): 2866-2872.
PMID
17099880
Source
pubmed
Published In
Cancer
Volume
107
Issue
12
Publish Date
2006
Start Page
2866
End Page
2872
DOI
10.1002/cncr.22282

Genomic signatures to guide the use of chemotherapeutics.

Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signatures can accurately predict clinical response in individuals treated with these drugs. Notably, signatures developed to predict response to individual agents, when combined, could also predict response to multidrug regimens. Finally, we integrated the chemotherapy response signatures with signatures of oncogenic pathway deregulation to identify new therapeutic strategies that make use of all available drugs. The development of gene expression profiles that can predict response to commonly used cytotoxic agents provides opportunities to better use these drugs, including using them in combination with existing targeted therapies.

Authors
Potti, A; Dressman, HK; Bild, A; Riedel, RF; Chan, G; Sayer, R; Cragun, J; Cottrill, H; Kelley, MJ; Petersen, R; Harpole, D; Marks, J; Berchuck, A; Ginsburg, GS; Febbo, P; Lancaster, J; Nevins, JR
MLA Citation
Potti, A, Dressman, HK, Bild, A, Riedel, RF, Chan, G, Sayer, R, Cragun, J, Cottrill, H, Kelley, MJ, Petersen, R, Harpole, D, Marks, J, Berchuck, A, Ginsburg, GS, Febbo, P, Lancaster, J, and Nevins, JR. "Genomic signatures to guide the use of chemotherapeutics." Nat Med 12.11 (November 2006): 1294-1300.
PMID
17057710
Source
pubmed
Published In
Nature Medicine
Volume
12
Issue
11
Publish Date
2006
Start Page
1294
End Page
1300
DOI
10.1038/nm1491

Lung cancer staging: proteomics.

The results of ACOSOG Z4031 may provide landmark information for the use of proteomic profiling to diagnose lung cancer noninvasively and to provide more accurate predictions of survival. Although the technological developments allowing generalized use of proteomic and genomic analyses are relatively recent, major progress in understanding the molecular basis of lung cancer has been made. Predicting survival is only the first step in the use of proteomics. If a reliable protein profile can be identified that is associated with poor prognosis, these proteins can then be identified and become therapeutic targets. It is not difficult to envision a day when a simple blood test will diagnose a lung cancer, perhaps even before it is clinically apparent, and, at the same time, identify the chemotherapeutic agents to which the tumor is sensitive, allowing individually directed treatment.

Authors
Harpole, DH; Meyerson, SL
MLA Citation
Harpole, DH, and Meyerson, SL. "Lung cancer staging: proteomics." Thorac Surg Clin 16.4 (November 2006): 339-343. (Review)
PMID
17240821
Source
pubmed
Published In
Thoracic Surgery Clinics
Volume
16
Issue
4
Publish Date
2006
Start Page
339
End Page
343
DOI
10.1016/j.thorsurg.2006.10.001

A first step towards validating microarray gene expression profiling for clinical testing: Characterizing biological variance.

Authors
Huening, MA; Sevilla, DW; Potti, A; Harpole, DH; Nevins, JR; Datto, MB
MLA Citation
Huening, MA, Sevilla, DW, Potti, A, Harpole, DH, Nevins, JR, and Datto, MB. "A first step towards validating microarray gene expression profiling for clinical testing: Characterizing biological variance." November 2006.
Source
wos-lite
Published In
The Journal of molecular diagnostics : JMD
Volume
8
Issue
5
Publish Date
2006
Start Page
660
End Page
660

Nine-year single center experience with cervical mediastinoscopy: complications and false negative rate.

BACKGROUND: Mediastinoscopy is a valuable tool for evaluating mediastinal pathology and is essential for establishing treatment strategies in most patients with lung cancer. We sought to determine the complication and false negative rate for mediastinoscopy in an institution that routinely performs this procedure. METHODS: We performed a retrospective review of 2,145 consecutive mediastinoscopies at a single institution between April 1996 and April 2005. Demographics and complications were analyzed. In patients with lung cancer who underwent subsequent resection, the false negative rate was calculated. RESULTS: Mean patient age was 61 +/- 0.4 years, and 58% (n = 1,253) were male. Pathology included lung cancer (n = 1,459), metastatic disease (n = 78), lymphoma (n = 51), and other benign disease (n = 557). Twenty-three patients (1.07%) experienced complications including hemorrhage (n = 7, 0.33%), vocal cord dysfunction (n = 12, 0.55%), tracheal injury (n = 2, 0.09%), and pneumothorax (n = 2, 0.09%). There was 1 death (0.05%) after pulmonary artery injury. Five of the 7 vascular injuries occurred during biopsy of level 4R. Three hundred and forty-three patients (23.5%) with lung cancer had positive mediastinoscopies. The false negative rate was 56 of 1,019 (5.5%) among lung cancer patients undergoing resection. Thirty-two (57%) of the false negatives were due to metastatic disease in lymph nodes not normally biopsied during cervical mediastinoscopy (levels 5, 6, 8, or 9). CONCLUSIONS: Although invasive, mediastinoscopy identified locally advanced disease in a significant percentage of this lung cancer population and was associated with a low false negative rate. Complications after mediastinoscopy were uncommon. These results support the continued routine use of mediastinoscopy.

Authors
Lemaire, A; Nikolic, I; Petersen, T; Haney, JC; Toloza, EM; Harpole, DH; D'Amico, TA; Burfeind, WR
MLA Citation
Lemaire, A, Nikolic, I, Petersen, T, Haney, JC, Toloza, EM, Harpole, DH, D'Amico, TA, and Burfeind, WR. "Nine-year single center experience with cervical mediastinoscopy: complications and false negative rate." Ann Thorac Surg 82.4 (October 2006): 1185-1189.
PMID
16996905
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
82
Issue
4
Publish Date
2006
Start Page
1185
End Page
1189
DOI
10.1016/j.athoracsur.2006.05.023

Yield of brain 18F-FDG PET in evaluating patients with potentially operable non-small cell lung cancer.

UNLABELLED: The American College of Surgeons Oncology Group recently completed a trial evaluating the role of PET with 18F-FDG in patients with documented or suspected non-small cell lung cancer. Subjects underwent standard imaging to exclude metastatic disease before PET. Here, we report the yield of brain PET in evaluating, for potential intracranial metastases, patients who have undergone previous brain CT or MRI with negative findings. METHODS: A total of 287 evaluable patients who had been registered from 22 institutions underwent whole-body 18F-FDG PET, including dedicated PET of the brain, after routine staging procedures had found no suggestion of metastatic disease. Patients were followed postoperatively for disease-free and overall survival, with a minimum follow-up of 6 mo. Patients with specific brain abnormalities identified by PET were further examined, and the findings were evaluated along with the results of CT and MRI, clinical management, and follow-up. RESULTS: In 4 patients, PET found focal 18F-FDG uptake in the brain suggestive of metastatic disease; however, metastatic disease was excluded clinically in all 4 by negative findings on further brain imaging. All 4 patients remained alive at follow-up (mean duration, 10.5 mo; range, 6-16 mo). CONCLUSION: In patients with suspected or proven non-small cell lung cancer considered resectable by standard imaging, including routine preoperative contrast-enhanced CT or MRI of the brain, PET of the brain provides no additional information regarding metastatic disease.

Authors
Posther, KE; McCall, LM; Harpole, DH; Reed, CE; Putnam, JB; Rusch, VW; Siegel, BA
MLA Citation
Posther, KE, McCall, LM, Harpole, DH, Reed, CE, Putnam, JB, Rusch, VW, and Siegel, BA. "Yield of brain 18F-FDG PET in evaluating patients with potentially operable non-small cell lung cancer." J Nucl Med 47.10 (October 2006): 1607-1611.
PMID
17015895
Source
pubmed
Published In
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
47
Issue
10
Publish Date
2006
Start Page
1607
End Page
1611

Thoracoscopic lobectomy is a safe and versatile procedure: experience with 500 consecutive patients.

OBJECTIVE: Advantages of thoracoscopic lobectomy for early stage non-small cell lung cancer (NSCLC), as compared with lobectomy by conventional thoracotomy, include less postoperative pain and shorter length of hospitalization. The outcomes after thoracoscopic lobectomy in patients with more complex pulmonary conditions are analyzed to determine safety, efficacy, and versatility. METHODS: A prospective database of 500 consecutive patients who underwent thoracoscopic lobectomy between June 1999 and January 2006 was queried. Demographic, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics and Kaplan-Meier survival analyses. RESULTS: Thoracoscopic lobectomy was successfully performed in 492 patients (conversion rate, 1.6%). Pathologic analysis included primary NSCLC in 416 patients (83.2%), centrally located secondary pulmonary malignancy in 37 patients (7.4%), and a variety of benign conditions in 45 patients (9%). Among the 416 patients with NSCLC, pathologic analysis demonstrated stage I in 330 patients (55.3%), stage II in 40 patients (9.6%), and stage III or greater NSCLC in 44 patients (10.6%). The operative and perioperative (30-day) mortality was 0% and 1%, respectively. The overall 2-year survival rate for the entire cohort was 80%, and the 2-year overall survival rates for stage I NSCLC, stage II or greater NSCLC, secondary pulmonary malignancy, and granulomatous disease patients were 85%, 77%, 73%, and 89%, respectively. CONCLUSIONS: Thoracoscopic lobectomy is applicable to a spectrum of malignant and benign pulmonary disease and is associated with a low perioperative morbidity and mortality rate. Survival rates are comparable to those for lobectomy with thoracotomy.

Authors
Onaitis, MW; Petersen, RP; Balderson, SS; Toloza, E; Burfeind, WR; Harpole, DH; D'Amico, TA
MLA Citation
Onaitis, MW, Petersen, RP, Balderson, SS, Toloza, E, Burfeind, WR, Harpole, DH, and D'Amico, TA. "Thoracoscopic lobectomy is a safe and versatile procedure: experience with 500 consecutive patients." Ann Surg 244.3 (September 2006): 420-425.
PMID
16926568
Source
pubmed
Published In
Annals of Surgery
Volume
244
Issue
3
Publish Date
2006
Start Page
420
End Page
425
DOI
10.1097/01.sla.0000234892.79056.63

A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer.

BACKGROUND: Clinical trials have indicated a benefit of adjuvant chemotherapy for patients with stage IB, II, or IIIA--but not stage IA--non-small-cell lung cancer (NSCLC). This classification scheme is probably an imprecise predictor of the prognosis of an individual patient. Indeed, approximately 25 percent of patients with stage IA disease have a recurrence after surgery, suggesting the need to identify patients in this subgroup for more effective therapy. METHODS: We identified gene-expression profiles that predicted the risk of recurrence in a cohort of 89 patients with early-stage NSCLC (the lung metagene model). We evaluated the predictor in two independent groups of 25 patients from the American College of Surgeons Oncology Group (ACOSOG) Z0030 study and 84 patients from the Cancer and Leukemia Group B (CALGB) 9761 study. RESULTS: The lung metagene model predicted recurrence for individual patients significantly better than did clinical prognostic factors and was consistent across all early stages of NSCLC. Applied to the cohorts from the ACOSOG Z0030 trial and the CALGB 9761 trial, the lung metagene model had an overall predictive accuracy of 72 percent and 79 percent, respectively. The predictor also identified a subgroup of patients with stage IA disease who were at high risk for recurrence and who might be best treated by adjuvant chemotherapy. CONCLUSIONS: The lung metagene model provides a potential mechanism to refine the estimation of a patient's risk of disease recurrence and, in principle, to alter decisions regarding the use of adjuvant chemotherapy in early-stage NSCLC.

Authors
Potti, A; Mukherjee, S; Petersen, R; Dressman, HK; Bild, A; Koontz, J; Kratzke, R; Watson, MA; Kelley, M; Ginsburg, GS; West, M; Harpole, DH; Nevins, JR
MLA Citation
Potti, A, Mukherjee, S, Petersen, R, Dressman, HK, Bild, A, Koontz, J, Kratzke, R, Watson, MA, Kelley, M, Ginsburg, GS, West, M, Harpole, DH, and Nevins, JR. "A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer." N Engl J Med 355.6 (August 10, 2006): 570-580.
PMID
16899777
Source
pubmed
Published In
The New England journal of medicine
Volume
355
Issue
6
Publish Date
2006
Start Page
570
End Page
580
DOI
10.1056/NEJMoa060467

Thoracoscopic lobectomy: a safe and effective strategy for patients receiving induction therapy for non-small cell lung cancer.

BACKGROUND: Thoracoscopic lobectomy is an accepted oncologic approach for early stage non-small cell lung cancer (NSCLC). We conducted a retrospective study of patients who underwent lobectomy after induction therapy to determine the feasibility of thoracoscopic lobectomy compared with conventional thoracotomy lobectomy. METHODS: The outcomes of 97 consecutive patients with NSCLC who received induction therapy followed by lobectomy from 1996 to 2005 were reviewed. Outcome variables analyzed included complete resection, chest tube duration, length of hospitalization, 30-day mortality, hemorrhage, pneumonia, respiratory failure, and other major complications. The Student t test and chi2 or RxC contingency tables were used to compare continuous and categoric variables, respectively. RESULTS: Lobectomy was performed by thoracotomy in 85 patients and thoracoscopically in 12 patients (1 conversion), with complete resection in all patients. All patients received induction chemotherapy, and 74 (76%) received induction radiotherapy as well: 66 of 85 (78%) in the thoracotomy group and 8 of 12 (67%) in the thoracoscopy group. The overall median survival was 2.3 years, with no difference between the groups. Patients undergoing a thoracoscopic lobectomy had a shorter median hospital stay (3.5 vs 5 days, p = 0.0024) and chest tube duration (2 vs 4 days, p < 0.001). There were no significant differences in 30-day mortality, hemorrhage, pneumonia, or respiratory failure. CONCLUSIONS: Thoracoscopic lobectomy is a feasible approach for selected patients undergoing resection after induction therapy, and is associated with shorter hospital stay and chest tube duration. Long-term follow-up of survival will determine the role of thoracoscopic lobectomy in the management of patients after induction therapy.

Authors
Petersen, RP; Pham, D; Toloza, EM; Burfeind, WR; Harpole, DH; Hanish, SI; D'Amico, TA
MLA Citation
Petersen, RP, Pham, D, Toloza, EM, Burfeind, WR, Harpole, DH, Hanish, SI, and D'Amico, TA. "Thoracoscopic lobectomy: a safe and effective strategy for patients receiving induction therapy for non-small cell lung cancer." Ann Thorac Surg 82.1 (July 2006): 214-218.
PMID
16798217
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
82
Issue
1
Publish Date
2006
Start Page
214
End Page
218
DOI
10.1016/j.athoracsur.2006.02.051

Genomic signatures in non-small-cell lung cancer: targeting the targeted therapies.

Despite major developments in targeted biologic agents, patients with advanced non-small-cell lung cancer have a poor prognosis. Recent development of targeted biologic agents have given us insight into possibilities of matching therapy with disease; however, the success of these agents has been marginal. In this article, we discuss the use of genomic signatures that have been developed to identify unique aspects of individual lung tumors and provide insight on how novel strategies can be used to identify populations susceptible to specific targeted agents.

Authors
Dressman, HK; Bild, A; Garst, J; Harpole, D; Potti, A
MLA Citation
Dressman, HK, Bild, A, Garst, J, Harpole, D, and Potti, A. "Genomic signatures in non-small-cell lung cancer: targeting the targeted therapies." Curr Oncol Rep 8.4 (July 2006): 252-257. (Review)
PMID
17254524
Source
pubmed
Published In
Current Oncology Reports
Volume
8
Issue
4
Publish Date
2006
Start Page
252
End Page
257

Computed tomography screening for the early detection of lung cancer.

Although lung cancer is the leading cause of cancer-related death in the world and has an increased chance of cure if detected at an earlier stage, routine lung cancer screening is currently not recommended in the United States. Unfortunately, most patients with lung cancer present only after the onset of symptoms and have advanced disease that cannot be surgically resected. The overall 5-year survival rate for all patients with lung cancer is only 15%. When the cancer is detected at its earliest stage (pathologic stage IA), however, the 5-year survival rate is more than 70%. Although past randomized screening trials evaluating the use of standard chest radiography or sputum cytology have not resulted in lower mortality, recent studies suggest that computed tomography (CT) may have promise as a screening tool. This article summarizes experience over the past decade of using low-dose spiral CT imaging as a screening tool to detect early lung cancers in asymptomatic, high-risk individuals.

Authors
Petersen, RP; Harpole, DH
MLA Citation
Petersen, RP, and Harpole, DH. "Computed tomography screening for the early detection of lung cancer." J Natl Compr Canc Netw 4.6 (July 2006): 591-594. (Review)
PMID
16813726
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
4
Issue
6
Publish Date
2006
Start Page
591
End Page
594

Differential canonical pathways derived from microarrays using RNA from paraffin-embedded non-small cell lung cancer tissue.

7226 Background: Several molecular targets have been approved for use in patients with non-small cell lung cancer (NSCLC) and several hundred are in various phases of investigation. However, the efficacy of these targets range from 5-15% of the overall population of NSCLC patients. Therefore, the challenge remains to appropriately match the most active target with the individual patient. Our goal was to investigate a novel strategy for identifying active pathways from formalin-fixed, paraffin-embedded (FFPE) NSCLC samples. METHODS: Ten 5 um sections of FFPE tumor were collected from 66 NSCLC patients consisting of equal numbers of long- (+5-year) and short-term (<2 year cancer death) survivors. Sixty samples were microdissected (6 samples contained no tumor tissue) and RNA was extracted using a proprietary procedure of Response Genetics, Inc. Amplification and labeling of RNA were done using the Affymetrix two cycle amplification kit. Resulting cRNA was hybridized to the U133 plus 2.0 GeneChip. A differentially expressed gene list between long and short survivors was determined. These data were also analyzed for differential canonical pathways using Ingenuity Pathway Analysis. RESULTS: We identified the differential pathways indicated by the unique gene signatures between early stage patients surviving <2 yrs and >2 yrs for both adenocarcinomas and squamous cell carcinomas. Adenocarcinoma pathways that differed between short- and long-term survivors were: G2M DNA damage checkpoint, EGF, estrogen receptor, hypoxia, VEGF, PDGF, IL-6 JAK/Stat and neurotrophin/Trk signaling. In contrast, for squamous cell carcinomas the main differing pathways were: Wnt/b-catenin signaling and retinol metabolism. CONCLUSIONS: We have demonstrated the feasibility of generating differential canonical pathways from FFPE NSCLC specimens which may serve as a tool to guide selection of molecular targets for the individual patient. In addition, these pathways may be a rational method for selecting the correct subset of patients most likely to respond to agents being investigated in early phase clinical trials. These data require validation in a larger prospective study. [Table: see text].

Authors
Joshi, MM; Petersen, RP; Conlon, DH; Tanaka, K; Shimizu, D; Kuramochi, H; Williams, M; Danenberg, PV; Danenberg, KD; Harpole, DH
MLA Citation
Joshi, MM, Petersen, RP, Conlon, DH, Tanaka, K, Shimizu, D, Kuramochi, H, Williams, M, Danenberg, PV, Danenberg, KD, and Harpole, DH. "Differential canonical pathways derived from microarrays using RNA from paraffin-embedded non-small cell lung cancer tissue." J Clin Oncol 24.18_suppl (June 20, 2006): 7226-.
PMID
27954001
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
18_suppl
Publish Date
2006
Start Page
7226

A lung cancer genomic risk prediction model derived from paraffin-embedded tissue.

10059 Background: We previously developed a validated fresh tissue-based genomic risk model in patients with early stage non-small cell lung cancer (NSCLC) using the Affymetrix U133 plus 2.0 Genechip. Limitations of this fresh tissue-based model include the need for immediate processing and limited availability; however, formalin-fixed, paraffin-embedded (FFPE) tissue is readily available and archived on every patient resected in North America. We investigated the ability of gene expression profiles generated on DNA microarrays using RNA isolated from FFPE NSCLC specimens to distinguish short-term and long-term survivors. METHODS: Five to ten 5 um sections of FFPE tumor were collected from 61 NSCLC patients consisting of equal numbers of long- (+5-year) and short-term (<2 year cancer death) survivors. Fifty-five samples were microdissected (6 samples contained no tumor tissue) and RNA was extracted using a proprietary procedure of Response Genetics, Inc. For this feasibility study, Actin 300 < 30 cTs was chosen as a threshold for adequate RNA quantity for amplification to the GeneChip. Amplification and labeling of RNA were done using the Affymetrix two cycle amplification kit. The resulting cRNA was successfully hybridized to the U133 plus 2.0 GeneChip in 54/55 samples (98%). Data were analyzed using the SAM statistical software with Kaplan Meier survival analyses. RESULTS: All analyses were performed using unsupervised hierarchical clustering and blinded duplicate samples had nearly identical gene expression profiles, indicating reproducibility. Adenocarcinoma segregated from squamous cell carcinoma with 98% accuracy (p=0.00004). A differentially expressed gene list between long and short survivors was determined. Distinct gene clusters were observed within each histological type segregating the tumors according to outcome. Kaplan Meier survival analysis stratifying on these clusters revealed significant differences in survival (cluster 1 and cluster 2 median survival>75 mos. vs. 30 mos., respectively; p<0.001). CONCLUSIONS: We have demonstrated the feasibility of creating a preliminary genomic risk prediction model using FFPE NSCLC tissue. Data will be presented on a larger training set (100+ patients) and a separate validation cohort of 100 patients. [Table: see text].

Authors
Harpole, DH; Joshi, MM; Petersen, RP; Conlon, DH; Tanaka, K; Shimizu, D; Kuramochi, H; Williams, M; Danenberg, PV; Danenberg, K
MLA Citation
Harpole, DH, Joshi, MM, Petersen, RP, Conlon, DH, Tanaka, K, Shimizu, D, Kuramochi, H, Williams, M, Danenberg, PV, and Danenberg, K. "A lung cancer genomic risk prediction model derived from paraffin-embedded tissue." J Clin Oncol 24.18_suppl (June 20, 2006): 10059-.
PMID
27954160
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
18_suppl
Publish Date
2006
Start Page
10059

A genomic strategy to refine prognosis in early stage non-small cell lung carcinoma (NSCLC).

Authors
Harpole, DH; Petersen, R; Mukherjee, S; Bild, A; Dressman, H; Kratzke, R; Kelley, MJ; Garst, J; Crawford, J; Nevins, JR; Potti, A
MLA Citation
Harpole, DH, Petersen, R, Mukherjee, S, Bild, A, Dressman, H, Kratzke, R, Kelley, MJ, Garst, J, Crawford, J, Nevins, JR, and Potti, A. "A genomic strategy to refine prognosis in early stage non-small cell lung carcinoma (NSCLC)." June 20, 2006.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
24
Issue
18
Publish Date
2006
Start Page
370S
End Page
370S

Differential canonical pathways derived from microarrays using RNA from paraffin-embedded non-small cell lung cancer tissue.

Authors
Joshi, MM; Petersen, RP; Conlon, DH; Tanaka, K; Shimizu, D; Kuramochi, H; Williams, M; Danenberg, PV; Danenberg, KD; Jr, HDH
MLA Citation
Joshi, MM, Petersen, RP, Conlon, DH, Tanaka, K, Shimizu, D, Kuramochi, H, Williams, M, Danenberg, PV, Danenberg, KD, and Jr, HDH. "Differential canonical pathways derived from microarrays using RNA from paraffin-embedded non-small cell lung cancer tissue." June 20, 2006.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
24
Issue
18
Publish Date
2006
Start Page
420S
End Page
420S

A lung cancer genomic risk prediction model derived from paraffin-embedded tissue.

Authors
Jr, HDH; Joshi, MM; Petersen, RP; Conlon, DH; Tanaka, K; Shimizu, D; Kuramochi, H; Williams, M; Danenberg, PV; Danenberg, K
MLA Citation
Jr, HDH, Joshi, MM, Petersen, RP, Conlon, DH, Tanaka, K, Shimizu, D, Kuramochi, H, Williams, M, Danenberg, PV, and Danenberg, K. "A lung cancer genomic risk prediction model derived from paraffin-embedded tissue." June 20, 2006.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
24
Issue
18
Publish Date
2006
Start Page
555S
End Page
555S

A genomic strategy to refine prognosis in early stage non-small cell lung carcinoma (NSCLC).

7026 Background. Although stage-specific classification identifies appropriate populations for adjuvant chemotherapy, this is likely an imprecise predictor for the individual patient with early stage NSCLC.Using previously-described methodologies that employ DNA microarray data, multiple gene expression profiles ('metagenes') that predict risk of recurrence in patients with stage I disease were identified. This analysis used an initial 'test' cohort of patients with NSCLC (n = 89) that represented an equal mix of squamous cell and adenocarcinoma. Also, each histologic subset had equal number of patients who survived more than 5 years and those who died within 2.5 years of initial diagnosis. The performance of the metagene-based model generated on the training cohort was then evaluated in independent 'validation' sets, including two multi-center cooperative group studies (ACOSOG Z0030 and CALGB 9761). Importantly, the CALGB validation was performed in a blinded fashion.Classification tree analyses that sample multiple gene expression profiles were used to develop a model of recurrence, termed the Lung Metagene Model, that accurately assesses prognosis (risk of recurrence and survival), performing significantly (p<0.001, odds ratio: 16.1, multivariate analysis) better than pathologic stage, T-size, nodal status, age, gender, histologic subtype and smoking history. The accuracy of prognosis using the Lung Metagene Model exceeded 90% (leave-one-out cross validation) in the initial training set (n = 89), 72% in the ACOSOG (n = 25), and 81% in the CALGB (n = 84) datasets. The prognostic accuracy was consistent across histologic subtypes and stages of NSCLC. Importantly, this provides an opportunity to re-classify stage IA patients to identify a subset of 'high risk' patients that may benefit from adjuvant chemotherapy. Further, stage IB and II patients identified as 'low risk' for recurrence, and who present co-morbidities, could potentially be candidates for observation, and those patients predicted to be at 'high risk' may benefit from novel therapeutic trials.The Lung Metagene Model provides a mechanism to refine the estimation of an individual patient's risk for disease recurrence and thus guide the use of adjuvant chemotherapy in NSCLC. No significant financial relationships to disclose.

Authors
Harpole, DH; Petersen, R; Mukherjee, S; Bild, A; Dressman, H; Kratzke, R; Kelley, MJ; Garst, J; Crawford, J; Nevins, JR; Potti, A
MLA Citation
Harpole, DH, Petersen, R, Mukherjee, S, Bild, A, Dressman, H, Kratzke, R, Kelley, MJ, Garst, J, Crawford, J, Nevins, JR, and Potti, A. "A genomic strategy to refine prognosis in early stage non-small cell lung carcinoma (NSCLC)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 24.18_suppl (June 2006): 7026-.
PMID
27953212
Source
epmc
Published In
Journal of Clinical Oncology
Volume
24
Issue
18_suppl
Publish Date
2006
Start Page
7026

Serum protein expression predicts recurrence in patients with early-stage lung cancer after resection.

BACKGROUND: Patients with early stage nonsmall-cell lung cancer who have undergone complete resection have a recurrence rate of approximately 50%, predominately due to the development of systemic metastases. This study is a prospective analysis of the expression of seven serum protein markers of invasion and metastasis, collected preoperatively (baseline) and serially after resection, to determine the relationship between marker expression and recurrence. METHODS: Serum was collected from 196 patients with clinical stage I nonsmall-cell lung cancer who underwent resection over a 5-year period (1996 to 2000). Samples were drawn before resection and 1, 4, 6, 12, 18, and 24 months postoperatively. All patients were followed for at least 24 months or until death. Serum protein levels of vascular endothelial growth factor, hepatocyte growth factor), E-selectin, CD44, basic fibroblast growth factor, urokinase plasminogen activator, and urokinase plasminogen activator receptor were determined using enzyme-linked immunosorbent assay. RESULTS: To date, 73 patients (37%) have demonstrated recurrence. Baseline levels of only 1 marker (CD44) correlated with pathologic stage (p = 0.02). Analysis of the serial samples demonstrated that recurrence was predicted (before clinical or radiographic determination) by decreasing levels of E-selectin (p = 0.002), increasing levels of CD44 (p = 0.001), and increasing levels of urokinase plasminogen activator receptor (p = 0.03). CONCLUSIONS: This study demonstrates the potential to predict recurrence after resection in patients with early-stage nonsmall-cell lung cancer using a panel of serum protein markers. Early identification of patients with recurrence may improve the efficacy of systemic therapy.

Authors
D'Amico, TA; Brooks, KR; Joshi, M-BM; Conlon, D; Herndon, J; Petersen, RP; Harpole, DH
MLA Citation
D'Amico, TA, Brooks, KR, Joshi, M-BM, Conlon, D, Herndon, J, Petersen, RP, and Harpole, DH. "Serum protein expression predicts recurrence in patients with early-stage lung cancer after resection." Ann Thorac Surg 81.6 (June 2006): 1982-1987.
PMID
16731117
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
81
Issue
6
Publish Date
2006
Start Page
1982
End Page
1987
DOI
10.1016/j.athoracsur.2006.01.042

Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial.

BACKGROUND: Little prospective, multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality. METHODS: Prospectively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a randomized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. RESULTS: Of the 1,111 patients randomized, 1,023 were included in the analysis. Median age was 68 years (range, 23 to 89 years); 52% were men. Lobectomy was performed in 766 (75%) and pneumonectomy in 42 (4%). Pathologic stage was IA in 424 (42%), IB in 418 (41%), IIA in 37 (4%), IIB in 97 (9%), and III in 45 (5%). Lymph node sampling was performed in 498 patients and lymph node dissection in 525. Operative mortality was 2.0% (10 of 498) for lymph node sampling and 0.76% (4 of 525) for lymph node dissection. Complications occurred in 38% of patients in each group. Lymph node dissection had a longer median operative time and greater total chest tube drainage (15 minutes, 121 mL, respectively). There was no difference in the median hospitalization, which was 6 days in each group (p = 0.404). CONCLUSIONS: Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer. These data from a current, multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future.

Authors
Allen, MS; Darling, GE; Pechet, TTV; Mitchell, JD; Herndon, JE; Landreneau, RJ; Inculet, RI; Jones, DR; Meyers, BF; Harpole, DH; Putnam, JB; Rusch, VW; ACOSOG Z0030 Study Group,
MLA Citation
Allen, MS, Darling, GE, Pechet, TTV, Mitchell, JD, Herndon, JE, Landreneau, RJ, Inculet, RI, Jones, DR, Meyers, BF, Harpole, DH, Putnam, JB, Rusch, VW, and ACOSOG Z0030 Study Group, . "Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial." Ann Thorac Surg 81.3 (March 2006): 1013-1019.
PMID
16488712
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
81
Issue
3
Publish Date
2006
Start Page
1013
End Page
1019
DOI
10.1016/j.athoracsur.2005.06.066

Pathologic nodal status predicts disease-free survival after neoadjuvant chemoradiation for gastroesophageal junction carcinoma.

BACKGROUND: The incidence of carcinoma of the gastroesophageal junction (GEJ) is rapidly increasing, and the prognosis remains poor. We examined outcomes in patients who received neoadjuvant chemoradiation for GEJ tumors to identify factors that predict disease-free (DFS) and overall (OS) survival. METHODS: A retrospective analysis was performed of 101 consecutive patients who received chemoradiation and surgery for GEJ carcinoma between 1992 and 2001. RESULTS: The median DFS and OS of all patients were 16 and 25 months, respectively. Twenty-eight patients with a complete histological response (T0N0) experienced greater DFS compared with all others (P = .02). Node-negative patients, regardless of T stage, experienced improved median DFS (24 months) compared with N1 patients (9 months; P = .01). Preoperative stage, age, tumor location, or Barrett's esophagus did not independently predict OS by univariate analysis. Multivariate analysis demonstrated that only posttreatment nodal status (P = .03)-not the degree of primary tumor response-predicted DFS. CONCLUSIONS: The nodal status of patients with GEJ tumors after neoadjuvant therapy is predictive of DFS after resection. The poor outcome in node-positive patients supports postneoadjuvant therapy nodal staging, because surgical aggressiveness should be tempered by the realization that cure is unlikely and median survival is short.

Authors
Gaca, JG; Petersen, RP; Peterson, BL; Harpole, DH; D'Amico, TA; Pappas, TN; Seigler, HF; Wolfe, WG; Tyler, DS
MLA Citation
Gaca, JG, Petersen, RP, Peterson, BL, Harpole, DH, D'Amico, TA, Pappas, TN, Seigler, HF, Wolfe, WG, and Tyler, DS. "Pathologic nodal status predicts disease-free survival after neoadjuvant chemoradiation for gastroesophageal junction carcinoma." Ann Surg Oncol 13.3 (March 2006): 340-346.
PMID
16485154
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
13
Issue
3
Publish Date
2006
Start Page
340
End Page
346
DOI
10.1245/ASO.2006.02.023

The surgical management of lung cancer.

Since the introduction of the pneumonectomy as a technically feasible strategy for the treatment of lung cancer, surgical resection has played a pivotal role in the management of early stage non-small cell lung carcinoma (NSCLC). In the last two decades, surgical, medical, and radiation oncologists have produced a growing body of evidence to support the combination of neoadjuvant or adjuvant treatments with standard surgical resection, to improve disease-free and overall survival for specific patient subgroups. Furthermore, alternatives to aggressive surgical management have evolved for patients who are medically inoperable due to compromised pulmonary function or other comorbidities. In this review, surgical options and multimodal treatment strategies are discussed, as well as completed and ongoing clinical trials addressing the surgical management of NSCLC.

Authors
Posther, KE; Harpole, DH
MLA Citation
Posther, KE, and Harpole, DH. "The surgical management of lung cancer." Cancer Invest 24.1 (February 2006): 56-67. (Review)
PMID
16466994
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
24
Issue
1
Publish Date
2006
Start Page
56
End Page
67
DOI
10.1080/07357900500449611

Oncogenic pathway signatures in human cancers as a guide to targeted therapies.

The development of an oncogenic state is a complex process involving the accumulation of multiple independent mutations that lead to deregulation of cell signalling pathways central to the control of cell growth and cell fate. The ability to define cancer subtypes, recurrence of disease and response to specific therapies using DNA microarray-based gene expression signatures has been demonstrated in multiple studies. Various studies have also demonstrated the potential for using gene expression profiles for the analysis of oncogenic pathways. Here we show that gene expression signatures can be identified that reflect the activation status of several oncogenic pathways. When evaluated in several large collections of human cancers, these gene expression signatures identify patterns of pathway deregulation in tumours and clinically relevant associations with disease outcomes. Combining signature-based predictions across several pathways identifies coordinated patterns of pathway deregulation that distinguish between specific cancers and tumour subtypes. Clustering tumours based on pathway signatures further defines prognosis in respective patient subsets, demonstrating that patterns of oncogenic pathway deregulation underlie the development of the oncogenic phenotype and reflect the biology and outcome of specific cancers. Predictions of pathway deregulation in cancer cell lines are also shown to predict the sensitivity to therapeutic agents that target components of the pathway. Linking pathway deregulation with sensitivity to therapeutics that target components of the pathway provides an opportunity to make use of these oncogenic pathway signatures to guide the use of targeted therapeutics.

Authors
Bild, AH; Yao, G; Chang, JT; Wang, Q; Potti, A; Chasse, D; Joshi, M-B; Harpole, D; Lancaster, JM; Berchuck, A; Olson, JA; Marks, JR; Dressman, HK; West, M; Nevins, JR
MLA Citation
Bild, AH, Yao, G, Chang, JT, Wang, Q, Potti, A, Chasse, D, Joshi, M-B, Harpole, D, Lancaster, JM, Berchuck, A, Olson, JA, Marks, JR, Dressman, HK, West, M, and Nevins, JR. "Oncogenic pathway signatures in human cancers as a guide to targeted therapies." Nature 439.7074 (January 19, 2006): 353-357.
PMID
16273092
Source
pubmed
Published In
Nature
Volume
439
Issue
7074
Publish Date
2006
Start Page
353
End Page
357
DOI
10.1038/nature04296

Outcomes of tracheobronchial stents in patients with malignant airway disease.

BACKGROUND: Malignant central airway obstruction is difficult to manage and is associated with poor outcome. We sought to identify the short (< 30 days) and intermediate (> 30 days) benefits and risks of tracheobronchial stents in patients with malignant airway disease. METHODS: Two hundred and twenty-five tracheobronchial stents were placed in 172 patients for benign (n = 32) and malignant (n = 140) disease from January 1, 1997, to May 31, 2003. The records of the patients with malignant disease were retrospectively analyzed to determine complication rate, reintervention rate, and survival. The malignant diagnoses included nonsmall cell cancer, small cell cancer, esophageal cancer, and metastatic disease. RESULTS: There were 172 stents placed in 140 patients with malignant disease, with no intraoperative mortality. The mean follow-up period was 142 +/- 12 days. There were 23 complications, including tumor ingrowth (n = 9), excessive granulation tissue (n = 7), stent migration (n = 5), and restenosis (n = 2). Five of the complications occurred during the short-term period (< 30 days) with the remaining complications (n = 18) occurring after 30 days. The complications required interventions including laser debridement (n = 14), dilation (n = 4), and stent removal (n = 5). CONCLUSIONS: Tracheobronchial stents offer minimally invasive palliative therapy for patients with unresectable malignant central airway obstruction. The benefit of airway stents is particularly seen in the short-term period where they provide symptomatic improvement and have low complication risk. The major impediment is excessive granulation tissue and tumor ingrowth, which occur primarily after 30 days.

Authors
Lemaire, A; Burfeind, WR; Toloza, E; Balderson, S; Petersen, RP; Harpole, DH; D'Amico, TA
MLA Citation
Lemaire, A, Burfeind, WR, Toloza, E, Balderson, S, Petersen, RP, Harpole, DH, and D'Amico, TA. "Outcomes of tracheobronchial stents in patients with malignant airway disease." Ann Thorac Surg 80.2 (August 2005): 434-437.
PMID
16039180
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
80
Issue
2
Publish Date
2005
Start Page
434
End Page
437
DOI
10.1016/j.athoracsur.2005.02.071

Low morbidity and mortality for bronchoplastic procedures with and without induction therapy.

BACKGROUND: The safety of bronchoplastic procedures after induction chemoradiotherapy is uncertain. This study examines short- and long-term outcomes after bronchoplastic procedures with and without induction therapy. METHODS: Between January 1997 and September 2004, more than 1,300 anatomic pulmonary resections for cancer were performed at a single institution. Of these, 73 patients required either sleeve lobectomy (57) or bronchoplasty (16), and were retrospectively analyzed. Nineteen patients (26%) received induction therapy; 15 received chemotherapy and radiation therapy and 4 received chemotherapy alone. Fifty-four patients underwent the bronchoplastic procedure without induction therapy. Mortality and early and late morbidity were analyzed. RESULTS: Mean follow-up was 25 months. Histology was nonsmall cell cancer in 62 (85%), carcinoid in 8 (11%), and renal cell cancer, schwannoma, and mucoepidermoid cancer in 1 patient each. There were 2 (2.7%) 30-day deaths, both in the group not receiving induction therapy. Of the surviving 71 patients, 70 had functional reconstructions at last follow-up. The overall 30-day complication rate was 30% (19 of 54) in patients not receiving induction therapy (no bronchopleural fistulas) and 42% (8 of 19) occurring in those receiving induction therapy (1 bronchopleural fistula). The long-term complication rate was 20% (11 of 54) among patients not receiving induction therapy and 5% (1 of 19) among those receiving induction therapy (completion pneumonectomy). There were no bronchovascular complications. Interventional bronchoscopy was required in 7 patients not receiving induction therapy, and was required in none of the patients receiving induction therapy. CONCLUSIONS: Anatomic pulmonary resections utilizing bronchoplastic techniques can be performed with low morbidity and mortality rates even after induction therapy.

Authors
Burfeind, WR; D'Amico, TA; Toloza, EM; Wolfe, WG; Harpole, DH
MLA Citation
Burfeind, WR, D'Amico, TA, Toloza, EM, Wolfe, WG, and Harpole, DH. "Low morbidity and mortality for bronchoplastic procedures with and without induction therapy." Ann Thorac Surg 80.2 (August 2005): 418-421.
PMID
16039176
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
80
Issue
2
Publish Date
2005
Start Page
418
End Page
421
DOI
10.1016/j.athoracsur.2005.02.058

Prospective phase II trial of pre-resection thoracoscopic (VATS) restaging following neoadjuvant therapy for IIIA(N2) non-small cell lung cancer (NSCLC): Results of CALGB 39803.

Authors
Jaklitsch, MT; Gu, L; Harpole, DH; D'Amico, TA; McKenna, RJ; Krasna, MJ; Kohman, LJ; Swanson, SJ; Decamp, MM; Sugarbaker, DJ; Surg, CALGBT
MLA Citation
Jaklitsch, MT, Gu, L, Harpole, DH, D'Amico, TA, McKenna, RJ, Krasna, MJ, Kohman, LJ, Swanson, SJ, Decamp, MM, Sugarbaker, DJ, and Surg, CALGBT. "Prospective phase II trial of pre-resection thoracoscopic (VATS) restaging following neoadjuvant therapy for IIIA(N2) non-small cell lung cancer (NSCLC): Results of CALGB 39803." June 1, 2005.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
23
Issue
16
Publish Date
2005
Start Page
636S
End Page
636S

Gene expression signatures for prognosis in NSCLC, coupled with signatures of oncogenic pathway deregulation, provide a novel approach for selection of molecular targets.

Authors
Petersen, RP; Bild, A; Dressman, H; Joshi, MBM; Conlon, DH; West, M; Nevins, JR; Harpole, DH
MLA Citation
Petersen, RP, Bild, A, Dressman, H, Joshi, MBM, Conlon, DH, West, M, Nevins, JR, and Harpole, DH. "Gene expression signatures for prognosis in NSCLC, coupled with signatures of oncogenic pathway deregulation, provide a novel approach for selection of molecular targets." June 1, 2005.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
23
Issue
16
Publish Date
2005
Start Page
626S
End Page
626S

Gene expression signatures for prognosis in NSCLC, coupled with signatures of oncogenic pathway deregulation, provide a novel approach for selection of molecular targets.

7020 Background: Gene microarray analysis can identify signatures that reflect unique aspects of individual tumors and provide precise prognostic information. Previously, we identified gene expression signatures reflecting the deregulation of oncogenic signaling pathways. In this study, we coupled gene expression data with the ability to identify the state of critical regulatory pathways within an individual tumor to determine prognosis.We prepared RNA from 101 stage I non-small cell lung cancer (NSCLC) tumor samples (51 squamous, 50 adenocarcinomas) for gene expression analysis with the Affymetrix U133 GeneChip. Each group consisted of 25 patients who died within 2 years of resection and 25 patients with a >5year survival. We developed predictive models that accurately distinguished patients with good vs. poor prognosis. We validated the model with a leave-one-out cross validation, with distinct training and validation sample sets. These data were used to predict the status of Ras, Src, β-cat, E2F & Myc pathways and then analyzed by hierarchical clustering to identify patterns of pathway deregulation. Results were expressed as a probability of pathway activation and Kaplan-Meier survival analysis was performed stratifying for pathway status.The predictive model had 80% accuracy in distinguishing patients with respect to survival. Kaplan-Meier analysis revealed that patient subgroups defined by distinct patterns of pathway deregulation exhibited statistically significant differences in disease-free survival. Tumors with deregulated Ras and Myc pathways had much worse prognosis than those with only deregulated Ras (69% vs 20% 2-yr survival, p<0.05).The capacity to stratify NSCLC patients according to individual risks using genomic-based prognostic tools provides opportunity for personalized treatment decisions. The use of gene expression data to predict the status of oncogenic signaling pathways provides an opportunity to better characterize the oncogenic process, and may provide a path to selecting targeted therapeutics. Investigations are underway for EGFR, HER2-neu and VEGF pathways. No significant financial relationships to disclose.

Authors
Petersen, RP; Bild, A; Dressman, H; Joshi, MM; Conlon, DH; West, M; Nevins, JR; Harpole, DH
MLA Citation
Petersen, RP, Bild, A, Dressman, H, Joshi, MM, Conlon, DH, West, M, Nevins, JR, and Harpole, DH. "Gene expression signatures for prognosis in NSCLC, coupled with signatures of oncogenic pathway deregulation, provide a novel approach for selection of molecular targets." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 23.16_suppl (June 2005): 7020-.
PMID
27944461
Source
epmc
Published In
Journal of Clinical Oncology
Volume
23
Issue
16_suppl
Publish Date
2005
Start Page
7020

Poor correspondence between clinical and pathologic staging in stage 1 non-small cell lung cancer: results from CALGB 9761, a prospective trial.

PURPOSE: A major problem with the staging system for non-small cell lung cancer (NSCLC) is clinical underestimation of the extent of disease. Many patients with clinical stage 1 disease do not retain that designation following surgical resection. Herein, we present data from Cancer and Leukemia Group B (CALGB) protocol 9761 evaluating the correspondence between clinical and pathologic analysis in early stage NSCLC. METHODS: Five hundred and two patients with suspected or biopsy-proven NSCLC classified as clinical stage 1 (T1-2, N0) by computed tomography (CT) scan or cervical mediastinoscopy were prospectively enrolled in CALGB 9761. The purpose of CALGB 9761 was to prospectively evaluate molecular markers of micrometastatic disease in stage 1 NSCLC. Enrollment occurred at 11 selected institutions within the CALGB. Patients with clinically suspected resectable early stage lung cancer were eligible for enrollment if they had no evidence of mediastinal or hilar adenopathy on CT scan or if they had CT evidence of potential N2 or N3 disease (lymph node > or =1.0 cm) but with negative mediastinoscopy. No prior chemotherapy or radiotherapy was permitted. RESULTS: Of the 502 patients felt to have clinical stage 1 NSCLC enrolled in CALGB 9761, 489 underwent resection with complete surgical staging and routine histopathologic analysis. From these 489 patients, only 422 (86.3%) turned out to have pathologically documented NSCLC. Of these 422 patients, 302 (71.6%) had pathologic stage 1 disease (173 stage 1A and 129 stage 1B). Despite clinical assessment of stage 1 disease, 59 (14%) patients had pathologic stage 2 disease, 57 (13.5%) had stage 3 disease, and four (0.9%) patients had stage 4 disease. Of the patients undergoing resection for clinical stage 1 NSCLC, 65 patients did not have NSCLC (44 had benign disease and 21 had malignancies other than NSCLC) and two additional patients had dual synchronous primary NSCLC tumors and were not eligible for the study. Overall, only 61.7% (302 of 489) of patients with suspected stage 1 NSCLC disease retained that stage and diagnosis after complete surgical staging, while 38.3% had an inaccurate pre-operative clinical stage or diagnosis. CONCLUSIONS: The results from this prospective trial demonstrate the poor predictive value of current clinical staging techniques in early stage NSCLC. These findings will serve as a benchmark for comparison of future clinical imaging modalities and other tests evaluating early stage NSCLC.

Authors
D'Cunha, J; Herndon, JE; Herzan, DL; Patterson, GA; Kohman, LJ; Harpole, DH; Kernstine, KH; Kern, JA; Green, MR; Maddaus, MA; Kratzke, RA; Cancer and Leukemia Group B,
MLA Citation
D'Cunha, J, Herndon, JE, Herzan, DL, Patterson, GA, Kohman, LJ, Harpole, DH, Kernstine, KH, Kern, JA, Green, MR, Maddaus, MA, Kratzke, RA, and Cancer and Leukemia Group B, . "Poor correspondence between clinical and pathologic staging in stage 1 non-small cell lung cancer: results from CALGB 9761, a prospective trial." Lung Cancer 48.2 (May 2005): 241-246.
PMID
15829324
Source
pubmed
Published In
Lung Cancer
Volume
48
Issue
2
Publish Date
2005
Start Page
241
End Page
246
DOI
10.1016/j.lungcan.2004.11.006

High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer.

PURPOSE: To assess the relationship between molecular markers associated with chemotherapy resistance and survival in esophageal cancer patients treated with trimodality therapy. EXPERIMENTAL DESIGN: The original pretreatment formalin-fixed, paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 99 patients treated with concurrent cisplatin plus 5-fluorouracil plus 45 Gy radiation followed by resection at Duke University Medical Center (Durham, NC) from 1986 to 1997. cDNA was derived from the biopsy and analyzed to determine mRNA expression relative to an internal reference gene (beta-actin) using fluorescence-based, real-time reverse transcription-PCR. Possible markers of platinum chemotherapy association [glutathione S-transferase pi (GSTP1) and excision cross-complementing gene 1 (ERCC1)] and 5-fluorouracil association [thymidylate synthase 1 (TS1)] were measured. RESULTS: Cox proportional hazards model revealed a significant inverse, linear effect for TS1 with respect to survival (P = 0.007). An inverse relationship between TS1 expression and treatment response was also detected (P < or = 0.001). Univariate analysis identified an association with decreased survival for GSTP1 > or = 3.0 (P = 0.05). In multivariate analyses, TS1 >6.0, ERCC1 >3, and GSTP1 >3 were statistically significant predictors of decreased survival (P = 0.007). Additionally, the presence of ERCC1 >3.0 or TS1 >6.0 was associated with an approximately 2-fold increase in the risk of cancer recurrence (P = 0.086 and 0.003, respectively). CONCLUSION: The measurement of relative gene expression of molecular markers associated with chemoresistance in endoscopic esophageal tumor biopsies may be a useful tool in assessing outcome in patients with trimodality-treated esophageal cancer. These data should be validated further in larger prospective studies.

Authors
Joshi, M-BM; Shirota, Y; Danenberg, KD; Conlon, DH; Salonga, DS; Herndon, JE; Danenberg, PV; Harpole, DH
MLA Citation
Joshi, M-BM, Shirota, Y, Danenberg, KD, Conlon, DH, Salonga, DS, Herndon, JE, Danenberg, PV, and Harpole, DH. "High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer." Clin Cancer Res 11.6 (March 15, 2005): 2215-2221.
PMID
15788669
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
6
Publish Date
2005
Start Page
2215
End Page
2221
DOI
10.1158/1078-0432.CCR-04-1387

Surgical strategies and outcomes after induction therapy for non-small cell lung cancer.

Surgery as the sole therapy for locally advanced non-small cell lung cancer (NSCLC) is usually not curative. Adjuvant chemotherapy has been evaluated by several randomized Phase III trials and found to confer a survival benefit over surgery alone for stage IB-IIIA NSCLC. Induction therapy applies a cytoreductive and systemic therapy before definitive locoregional therapy. Theoretical advantages include improved diffusion of chemotherapy agents into the tumor, improved compliance, and a higher complete resection rate. Results from multiple Phase II and III studies have been encouraging, but the role of surgery after induction therapy remains inconclusively defined. Randomized trials are underway to better define the role of induction therapy, and enrollment of patients into such trials should be encouraged.

Authors
Burfeind, WR; Harpole, DH
MLA Citation
Burfeind, WR, and Harpole, DH. "Surgical strategies and outcomes after induction therapy for non-small cell lung cancer." Semin Thorac Cardiovasc Surg 17.3 (2005): 186-190. (Review)
PMID
16253820
Source
pubmed
Published In
Seminars in Thoracic and Cardiovascular Surgery
Volume
17
Issue
3
Publish Date
2005
Start Page
186
End Page
190
DOI
10.1053/j.semtcvs.2005.06.015

Extended surgical staging for potentially resectable malignant pleural mesothelioma

Background. Extrapleural pneumonectomy for malignant pleural mesothelioma (MPM) is a high-risk procedure, and patients require careful preoperative staging to exclude advanced disease. Computed tomography, magnetic resonance imaging, and positron emission tomography are useful staging modalities, but do not reliably identify contralateral mediastinal involvement or transdiaphragmatic invasion. We evaluated the role of extended surgical staging procedures, which generally includes a combination of laparoscopy, peritoneal lavage, and mediastinoscopy, to more precisely stage patients with MPM. Methods. One hundred eighteen patients with MPM, deemed clinically and radiologically resectable, underwent extended surgical staging. Mediastinoscopy was performed in 111 patients, laparoscopy in 109 patients, and peritoneal lavage in 78 patients. Results. Ten (9.2%) patients had gross evidence of transdiaphragmatic or peritoneal involvement. Peritoneal lavage was positive for metastatic MPM in 2 (2.6%) patients, neither of whom had obvious transdiaphragmatic invasion. Ipsilateral mediastinal nodes contained metastatic tumor in 10 of 62 (16.1%) patients. Contralateral nodes were positive in 4 of 111 (3.6%) patients. Of the patients who underwent biopsy of both ipsilateral and contralateral mediastinal nodes, and who had complete pathologic staging after extrapleural pneumonectomy (n = 46), 14 (30.4%) had N2-positive nodes. Only 5 of these patients were correctly identified by mediastinoscopy (sensitivity 36%, accuracy 80%). Extended surgical staging identified 16 (13.6%) patients who had contralateral nodal involvement, transdiaphragmatic invasion, or positive peritoneal cytology. Conclusions. Extended surgical staging defines an important subset of patients with unresectable MPM not identified by imaging. Because of the potential morbidity associated with extrapleural pneumonectomy, we advocate that extended surgical staging be performed in all patients with MPM before resection. © 2005 by The Society of Thoracic Surgeons.

Authors
Rice, DC; Erasmus, JJ; Stevens, CW; Vaporciyan, AA; Wu, JS; Tsao, AS; Walsh, GL; Swisher, SG; Hofstetter, WL; Ordonez, NG; Smythe, WR; D'Amico, TA; Krasna, MJ; Nichols, FC; Jr, DHH
MLA Citation
Rice, DC, Erasmus, JJ, Stevens, CW, Vaporciyan, AA, Wu, JS, Tsao, AS, Walsh, GL, Swisher, SG, Hofstetter, WL, Ordonez, NG, Smythe, WR, D'Amico, TA, Krasna, MJ, Nichols, FC, and Jr, DHH. "Extended surgical staging for potentially resectable malignant pleural mesothelioma." Annals of Thoracic Surgery 80.6 (2005): 1988-1993.
PMID
16305830
Source
scival
Published In
The Annals of Thoracic Surgery
Volume
80
Issue
6
Publish Date
2005
Start Page
1988
End Page
1993
DOI
10.1016/j.athoracsur.2005.06.014

Reducing hospital morbidity and mortality following esophagectomy.

BACKGROUND: Esophagogastrectomy (EG) is a formidable operation with significant morbidity and mortality rates. Risk factor analyses have been performed, but few studies have produced strategies that have improved operative results. This study was performed in order to identify prognostic variables that might be used to develop a strategy for optimizing outcomes after EG. METHODS: The records of all patients (n = 379) who underwent EG patients at a tertiary medical center between 1996 and 2002 were retrospectively reviewed. Thirty-day morbidity and mortality were determined, and multivariable logistical regression analysis assessed the effect of preoperative and postoperative variables on early mortality. RESULTS: Operations included Ivor Lewis (n = 179), transhiatal (n = 130), and other approaches (n = 70). Operative mortality was 5.8%; 64% experienced complications, including respiratory complications (28.5%), anastamotic strictures (25%), and leak (14%). Increasing age, anastomotic leak, Charlson comorbidity index 3, worse swallowing scores, and pneumonia were associated with increased risk of mortality by univariate analysis. However, only age (p = 0.002) and pneumonia (p = 0.0008) were independently associated with mortality by multivariable analysis. Pneumonia was associated with a 20% incidence of death. Patients with pneumonia had significantly worse deglutition and anastomotic integrity on barium esophagogram compared with patients without pneumonia (p < 0.001, Mann-Whitney rank sum test). CONCLUSIONS: Morbidity and mortality of EG are significant, but most complications, including anastomotic leak, are not independent predictors of mortality. The most important complication after EG is pneumonia. Strategies to decrease postoperative mortality should include careful assessment of swallowing abnormalities and predisposition to aspiration by cineradiography or fiberoptic endoscopy. After EG, acceptable pharyngeal function and airway protection should be verified before resuming oral intake.

Authors
Atkins, BZ; Shah, AS; Hutcheson, KA; Mangum, JH; Pappas, TN; Harpole, DH; D'Amico, TA
MLA Citation
Atkins, BZ, Shah, AS, Hutcheson, KA, Mangum, JH, Pappas, TN, Harpole, DH, and D'Amico, TA. "Reducing hospital morbidity and mortality following esophagectomy." Ann Thorac Surg 78.4 (October 2004): 1170-1176. (Review)
PMID
15464465
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
78
Issue
4
Publish Date
2004
Start Page
1170
End Page
1176
DOI
10.1016/j.athoracsur.2004.02.034

Tracheobronchial stents in selected patients with benign airway disease

Authors
Lemaire, A; Burfeind, WR; Balderson, SS; Harpole, DH; D'Amico, TA
MLA Citation
Lemaire, A, Burfeind, WR, Balderson, SS, Harpole, DH, and D'Amico, TA. "Tracheobronchial stents in selected patients with benign airway disease." October 2004.
Source
wos-lite
Published In
Chest
Volume
126
Issue
4
Publish Date
2004
Start Page
801S
End Page
801S

A randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell hung cancer (NSCLC): report of cancer and leukemia group b (CALGB) protocol 9633

Authors
Strauss, GM; Herndon, JE; Maddaus, MA; Johnstone, DW; Johnson, EA; Harpole, DH; Gillenwater, HH; Watson, DM; Sugarbaker, DJ; Schilsky, RL; Vokes, EE; CALGB, MRG
MLA Citation
Strauss, GM, Herndon, JE, Maddaus, MA, Johnstone, DW, Johnson, EA, Harpole, DH, Gillenwater, HH, Watson, DM, Sugarbaker, DJ, Schilsky, RL, Vokes, EE, and CALGB, MRG. "A randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell hung cancer (NSCLC): report of cancer and leukemia group b (CALGB) protocol 9633." September 2004.
Source
wos-lite
Published In
Lung Cancer
Volume
45
Publish Date
2004
Start Page
S75
End Page
S76

Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection.

BACKGROUND: To evaluate the safety and effectiveness of a new biodegradable polymeric sealant to close intraoperative air leaks after pulmonary resection. METHODS: In a multicenter prospective randomized trial, 161 patients with a median age of 67 years old (range 18-85 years old), were randomized in a 2:1 ratio to receive sealant or control for at least one significant air leak (> or = 2.0 mm in size) after pulmonary resection. In the sealant group, all significant air leaks underwent attempted repair by standard methods (sutures, staples, or cautery) prior to the application of sealant. The control group underwent only standard methods. Blood was analyzed for immunologic response. Patients were followed up 1 month after surgery. RESULTS: Intraoperative air leaks were sealed in 77% of the sealant group compared with 16% in the control group (p < 0.001). The sealant group had significantly fewer patients with postoperative air leaks compared with the control group (65% vs 86%, p = 0.005). Median length of hospitalization was 6 days (range, 3-23 days) for the sealant group compared with 7 days (range 4-38 days) for controls (p = 0.028). There was no difference in mortality, morbidity, duration of chest tubes, or immune responses between the two groups. CONCLUSIONS: This study demonstrates the effectiveness of a biodegradable polymer when used as an adjunct to standard closure methods for sealing significant intraoperative air leaks that develop from pulmonary surgery. Use of the sealant led to a reduction in postoperative air leaks, which may have decreased the length of hospitalization.

Authors
Allen, MS; Wood, DE; Hawkinson, RW; Harpole, DH; McKenna, RJ; Walsh, GL; Vallieres, E; Miller, DL; Nichols, FC; Smythe, WR; Davis, RD; 3M Surgical Sealant Study Group,
MLA Citation
Allen, MS, Wood, DE, Hawkinson, RW, Harpole, DH, McKenna, RJ, Walsh, GL, Vallieres, E, Miller, DL, Nichols, FC, Smythe, WR, Davis, RD, and 3M Surgical Sealant Study Group, . "Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection." Ann Thorac Surg 77.5 (May 2004): 1792-1801.
PMID
15111188
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
77
Issue
5
Publish Date
2004
Start Page
1792
End Page
1801
DOI
10.1016/j.athoracsur.2003.10.049

Thoracoscopic sympathectomy in the management of vasomotor disturbances and complex regional pain syndrome of the hand.

Complex regional pain syndrome, vasospastic disorders, and hyperhidrosis are chronic and debilitating upper extremity problems. Twenty-nine consecutive patients treated with thoracoscopic sympathectomy are presented. Diagnoses included complex regional pain syndrome, hyperhidrosis, Buerger's disease, Raynaud's disease, and peripheral vascular disease. All patients with hyperhidrosis had complete symptom resolution. Patients with Buerger's and Raynaud's disease had excellent/good results. Six patients with complex regional pain syndrome had excellent or good relief; the remaining six patients had varying degrees of recurrence. A statistically significant association was noted between duration of complex regional pain syndrome prior to sympathectomy and outcome. Thoracoscopic sympathectomy is an effective treatment for hyperhidrosis and vasospastic disorders. Although the results for complex regional pain syndrome are not uniformly excellent, this technique offers promise in the treatment of this difficult problem.

Authors
Rizzo, M; Balderson, SS; Harpole, DH; Levin, LS
MLA Citation
Rizzo, M, Balderson, SS, Harpole, DH, and Levin, LS. "Thoracoscopic sympathectomy in the management of vasomotor disturbances and complex regional pain syndrome of the hand." Orthopedics 27.1 (January 2004): 49-52.
PMID
14763530
Source
pubmed
Published In
Orthopedics
Volume
27
Issue
1
Publish Date
2004
Start Page
49
End Page
52

Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: Analysis of 2588 patients

Objective: The purpose of this study was to identify risk factors associated with the onset of atrial fibrillation after thoracic surgery to allow more targeted interventions in patients with the highest risk. Methods: A comprehensive prospective database was used to identify patients undergoing major thoracic surgery from January 1, 1998, through December 31, 2002. Data collection was performed at point of contact: at preoperative evaluation, the time of the operation, discharge, and postoperative visits. All patients undergoing resection of a lung, the esophagus, the chest wall, or a mediastinal mass were included in this study. Univariate and multivariate analyses of factors associated with the development of atrial fibrillation were analyzed. Results: There were 2588 patients who met the inclusion criteria. The overall incidence of atrial fibrillation was 12.3% (n = 319). Categories of disease were primary lung cancer, pulmonary metastasis, esophageal cancer, intrathoracic metastasis, benign lung disease, other mediastinal tumors, mesothelioma, chest wall tumors, benign esophagus, and "other." Patients with atrial fibrillation had increased mean lengths of hospital stay, mortality rates, and mean hospital charges. Univariate analysis evaluated age, sex, disease category, comorbidities, preoperative therapy, and procedure, and significant variables were entered into the multivariate analysis. Significant variables (relative risk; 95% confidence interval) in the multivariate analysis were male sex (1.72; 1.29-2.28), age 50 to 59 years (1.70; 1.01-2.88), age 60 to 69 years (4.49; 2.79-7.22), age 70 years or greater (5.30; 3.28-8.59), history of congestive heart failure (2.51; 1.06-6.24), history of arrhythmias (1.92; 1.22-3.02), history of peripheral vascular disease (1.65; 0.93-2.92), resection of mediastinal tumor or thymectomy (2.36; 0.95-5.88), lobectomy (3. 89; 2.19-6.91), bilobectomy (7.16; 3.02-16.96), pneumonectomy (8.91; 4.59-17.28), esophagectomy (2.95; 1.55-5.62), and intraoperative transfusions (1.39; 0.98-1.98). Conclusions: The significant variables identified by means of multivariate analysis were associated with the occurrence of atrial fibrillation. Preventive therapies in selected populations might reduce the incidence of atrial fibrillation.

Authors
Vaporciyan, AA; Correa, AM; Rice, DC; Roth, JA; Smythe, WR; Swisher, SG; Walsh, GL; Jr, JBP; Downey, RJ; Miller, DL; Jr, DHH
MLA Citation
Vaporciyan, AA, Correa, AM, Rice, DC, Roth, JA, Smythe, WR, Swisher, SG, Walsh, GL, Jr, JBP, Downey, RJ, Miller, DL, and Jr, DHH. "Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: Analysis of 2588 patients." Journal of Thoracic and Cardiovascular Surgery 127.3 (2004): 779-786.
PMID
15001907
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
127
Issue
3
Publish Date
2004
Start Page
779
End Page
786
DOI
10.1016/j.jtcvs.2003.07.011

Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)-mediated signaling pathway

Background: Constitutive activation of the phosphoinositide 3-kinase/protein kinase B survival signal transduction pathway influences the intrinsic chemoresistance of cancer cells. This study evaluates the effect of LY294002, a pharmacologic inhibitor of phosphoinositide 3-kinase, on the sensitivity of lung and esophageal cancer cells to paclitaxel (Taxol) in vitro. Materials and Methods: Cell viability and apoptosis of cancer cells treated with paclitaxel + LY294002 combinations were quantitated by methyl-thiazol-diphenyl-tetrazolium and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-based ApoBrdU assays, respectively. The effect of LY294002-mediated phosphoinositide 3-kinase inhibition on protein kinase B (Akt) activation and nuclear factor-κB signaling was determined by Western blot analysis. Nuclear factor-κB transcription activity in cultured cancer cells either at baseline or after treatments with LY294002 or BAY11-0782 (a pharmacologic inhibitor of nuclear factor-κB) was determined by the nuclear factor κB-Luciferase reporter system. Results: A 4- to more than 20-fold reduction of paclitaxel IC50 values was observed in cancer cells treated with paclitaxel + LY294002 combinations. This was paralleled with synergistic induction of apoptosis. LY294002 treatment caused a significant dose-dependent inhibition of protein kinase B (Akt) activation and suppression of nuclear factor-κB transcriptional activity that was accompanied by elevation of IκB, the intrinsic inhibitor of nuclear factor-κB, and concomitant reduction of nuclear factor-κB-regulated antiapoptotic proteins cIAP1, cIAP2, and BclXL. Direct inhibition of nuclear factor-κB activity by BAY11-0782 also resulted in profound enhancement of paclitaxel sensitivity and paclitaxel-mediated induction of apoptosis in lung and esophageal cancer cells. Conclusion: LY294002-mediated inhibition of the phosphoinositide 3-kinase/protein kinase B-dependent survival pathway with secondary suppression of nuclear factor-κB transcriptional activity was associated with enhancement of paclitaxel cytotoxicity in lung and esophageal cancer cells. Direct inhibition of nuclear factor-κB by BAY11-0782 also sensitized these cancer cells to paclitaxel, indicating that nuclear factor-κB may be the crucial intermediary step connecting phosphoinositide 3-kinase/protein kinase B (Akt) to the intrinsic susceptibility of cancer cells to chemotherapeutic agents.

Authors
Nguyen, DM; Chen, GA; Reddy, R; Tsai, W; Schrump, WD; Jr, GC; Schrump, DS; Jones, DA; Mentzer, SJ; Jr, DHH
MLA Citation
Nguyen, DM, Chen, GA, Reddy, R, Tsai, W, Schrump, WD, Jr, GC, Schrump, DS, Jones, DA, Mentzer, SJ, and Jr, DHH. "Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)-mediated signaling pathway." Journal of Thoracic and Cardiovascular Surgery 127.2 (2004): 365-375.
PMID
14762343
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
127
Issue
2
Publish Date
2004
Start Page
365
End Page
375
DOI
10.1016/j.jtcvs.2003.09.033

Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633

Authors
Strauss, GM; Herndon, JE; Maddaus, MA; Johnstone, DW; Johnson, EA; Harpole, DH; Gillenwater, HH; Watson, DM; Sugarbaker, DJ; Schilsky, RL; Vokes, EE; Green, MR
MLA Citation
Strauss, GM, Herndon, JE, Maddaus, MA, Johnstone, DW, Johnson, EA, Harpole, DH, Gillenwater, HH, Watson, DM, Sugarbaker, DJ, Schilsky, RL, Vokes, EE, and Green, MR. "Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633." 2004.
Source
wos-lite
Published In
Annals of Oncology
Volume
15
Publish Date
2004
Start Page
13
End Page
14

Results of the American College of Surgeons Oncology Group Z0050 trial: the utility of positron emission tomography in staging potentially operable non-small cell lung cancer.

OBJECTIVES: The American College of Surgeons Oncology Group undertook a trial to ascertain whether positron emission tomography with 18F-fluorodeoxyglucose could detect lesions that would preclude pulmonary resection in a group of patients with documented or suspected non-small cell lung cancer found to be surgical candidates by routine staging procedures. METHODS: A total of 303 eligible patients registered from 22 institutions underwent positron emission tomography after routine staging (computed tomography of chest and upper abdomen, bone scintigraphy, and brain imaging) had deemed their tumors resectable. Positive findings required confirmatory procedures. RESULTS: Positron emission tomography was significantly better than computed tomography for the detection of N1 and N2/N3 disease (42% vs 13%, P =.0177, and 58% vs 32%, P =.0041, respectively). The negative predictive value of positron emission tomography for mediastinal node disease was 87%. Unsuspected metastatic disease or second primary malignancy was identified in 18 of 287 patients (6.3%). Distant metastatic disease indicated in 19 of 287 patients (6.6%) was subsequently shown to be benign. By correctly identifying advanced disease (stages IIIA, IIIB, and IV) or benign lesions, positron emission tomography potentially avoided unnecessary thoracotomy in 1 of 5 patients. CONCLUSIONS: In patients with suspected or proven non-small cell lung cancer considered resectable by standard staging procedures, positron emission tomography can prevent nontherapeutic thoracotomy in a significant number of cases. Use of positron emission tomography for mediastinal staging should not be relied on as a sole staging modality, and positive findings should be confirmed by mediastinoscopy. Metastatic disease, especially a single site, identified by positron emission tomography requires further confirmatory evaluation.

Authors
Reed, CE; Harpole, DH; Posther, KE; Woolson, SL; Downey, RJ; Meyers, BF; Heelan, RT; MacApinlac, HA; Jung, S-H; Silvestri, GA; Siegel, BA; Rusch, VW; American College of Surgeons Oncology Group Z0050 trial,
MLA Citation
Reed, CE, Harpole, DH, Posther, KE, Woolson, SL, Downey, RJ, Meyers, BF, Heelan, RT, MacApinlac, HA, Jung, S-H, Silvestri, GA, Siegel, BA, Rusch, VW, and American College of Surgeons Oncology Group Z0050 trial, . "Results of the American College of Surgeons Oncology Group Z0050 trial: the utility of positron emission tomography in staging potentially operable non-small cell lung cancer." J Thorac Cardiovasc Surg 126.6 (December 2003): 1943-1951.
PMID
14688710
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
126
Issue
6
Publish Date
2003
Start Page
1943
End Page
1951
DOI
10.1016/j.jtcvs.2003.07.030

A comparative analysis of positron emission tomography and mediastinoscopy in staging non-small cell lung cancer.

OBJECTIVES: Positron emission tomography has been demonstrated to improve the detection of distant metastases in patients with lung cancer. This study compares the efficacy of PET to mediastinoscopy in mediastinal staging of patients with non-small cell lung cancer. METHODS: Between May 1995 and May 2000, positron emission tomography was performed on 1988 patients with known or suspected non-small cell lung cancer at Duke University Medical Center. Cervical mediastinoscopy was subsequently performed in patients without demonstrable evidence of distant metastases. The efficacy of mediastinal staging was analyzed by comparing the prospective results of positron emission tomography with the histopathologic results of mediastinoscopy by nodal station. RESULTS: In this study 202 patients with non-small cell lung cancer (116 of whom were male) underwent mediastinoscopy after positron emission tomography. Of the 65 patients with positive results of positron emission tomography, only 29 patients had positive results of mediastinoscopy in the corresponding nodal station. Of the 137 patients with negative results of positron emission tomography, 16 patients were demonstrated to have N2 or N3 disease. The sensitivity, specificity, positive and negative predictive values, and accuracy for positron emission tomography were 64.4%, 77.1%, 44.6%, 88.3%, and 74.3%, respectively. Histologic findings in patients with non-small cell lung cancer and false-positive results of mediastinal positron emission tomography included granulomatous inflammation, sinus histiocytosis, and silicosis. CONCLUSIONS: Positron emission tomography neither confirms nor excludes involvement of the mediastinum in patients with non-small cell lung cancer. Cervical mediastinoscopy with lymph node biopsy remains the criterion standard for mediastinal staging.

Authors
Gonzalez-Stawinski, GV; Lemaire, A; Merchant, F; O'Halloran, E; Coleman, RE; Harpole, DH; D'Amico, TA
MLA Citation
Gonzalez-Stawinski, GV, Lemaire, A, Merchant, F, O'Halloran, E, Coleman, RE, Harpole, DH, and D'Amico, TA. "A comparative analysis of positron emission tomography and mediastinoscopy in staging non-small cell lung cancer." J Thorac Cardiovasc Surg 126.6 (December 2003): 1900-1905.
PMID
14688703
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
126
Issue
6
Publish Date
2003
Start Page
1900
End Page
1905
DOI
10.1016/S0022

Cerebral embolization during cardiac surgery: impact of aortic atheroma burden.

BACKGROUND: Aortic atheromatous disease is known to be associated with an increased risk of perioperative stroke in the setting of cardiac surgery. In this study, we sought to determine the relationship between cerebral microemboli and aortic atheroma burden in patients undergoing cardiac surgery. METHODS: Transoesophageal echocardiographic images of the ascending, arch and descending aorta were evaluated in 128 patients to determine the aortic atheroma burden. Transcranial Doppler (TCD) of the right middle cerebral artery was performed in order to measure cerebral embolic load during surgery. Using multivariate linear regression, the numbers of emboli were compared with the atheroma burden. RESULTS: After controlling for age, cardiopulmonary bypass time and the number of bypass grafts, cerebral emboli were significantly associated with atheroma in the ascending aorta (R2=0.11, P=0.02) and aortic arch (P=0.013). However, there was no association between emboli and descending aortic atheroma burden (R2=0.05, P=0.20). CONCLUSIONS: We demonstrate a positive relationship between TCD-detected cerebral emboli and the atheromatous burden of the ascending aorta and aortic arch. Previously demonstrated associations between TCD-detectable cerebral emboli and adverse cerebral outcome may be related to the presence of significant aortic atheromatous disease.

Authors
Mackensen, GB; Ti, LK; Phillips-Bute, BG; Mathew, JP; Newman, MF; Grocott, HP; Neurologic Outcome Research Group (NORG),
MLA Citation
Mackensen, GB, Ti, LK, Phillips-Bute, BG, Mathew, JP, Newman, MF, Grocott, HP, and Neurologic Outcome Research Group (NORG), . "Cerebral embolization during cardiac surgery: impact of aortic atheroma burden." Br J Anaesth 91.5 (November 2003): 656-661.
PMID
14570786
Source
pubmed
Published In
BJA: British Journal of Anaesthesia
Volume
91
Issue
5
Publish Date
2003
Start Page
656
End Page
661

Measurement of chemoresistance markers in patients with stage III non-small cell lung cancer: a novel approach for patient selection.

BACKGROUND: The long-term survival of patients with stage III non-small cell lung cancer treated with a combination of chemotherapy and radiation is 10% to 20%. Survival could potentially be increased and toxicity limited if one could identify patients most likely to respond to a particular treatment regimen. This project prospectively evaluated a panel of potential immunohistochemical markers of chemoresistance in a population of patients with pathology-confirmed stage III non-small cell lung cancer in order to determine the prognostic value of each marker in relation to response to chemotherapy or survival. METHODS: Immunohistochemical staining was performed on histologically positive mediastinal nodal specimens obtained from 59 patients (mean age, 62 years; range, 41 to 79 years) without evidence of distant metastatic disease treated with navelbine-based chemotherapy and external beam radiation therapy between 1996 and 2001. Included were markers for apoptosis (p53, bcl-2), drug efflux/degradation (MDR, GST-pi), growth factors (EGFr, Her2-neu), and mismatch repair (hMLH1, hMSH2). After chemotherapy, patients underwent radiologic evaluation for response measured by standard criteria. RESULTS: After a median 41 months of follow-up (range, 17 to 55 months), 43 patients had recurrent disease and 38 of these patients were dead of cancer (median cancer-free survival of 10 months and overall survival of 18 months). Patients who demonstrated a complete or partial response (n = 38) had a significantly improved survival (p = 0.002) compared with those with stable or progressive cancer (n = 21). Multivariable Cox step-wise regression analysis of marker expression associated overexpression of p53 and low expression of hMSH2 with poor treatment response and cancer death. CONCLUSIONS: These preliminary data suggest that marker expression may allow the separation of patients into low- and high-risk groups with respect to survival after combined navelbine-based chemotherapy and XRT. This could represent a novel method of selecting patients for a particular treatment regimen if these data are reproduced in a larger prospective trial.

Authors
Brooks, KR; To, K; Joshi, M-BM; Conlon, DH; Herndon, JE; D'Amico, TA; Harpole, DH
MLA Citation
Brooks, KR, To, K, Joshi, M-BM, Conlon, DH, Herndon, JE, D'Amico, TA, and Harpole, DH. "Measurement of chemoresistance markers in patients with stage III non-small cell lung cancer: a novel approach for patient selection." Ann Thorac Surg 76.1 (July 2003): 187-193.
PMID
12842538
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
76
Issue
1
Publish Date
2003
Start Page
187
End Page
193

Predictive value of the EphA2 receptor tyrosine kinase in lung cancer recurrence and survival.

PURPOSE: Underestimation of disease severity is a major problem confronting the successful clinical management of non-small cell lung cancer. Recent advances in molecular biological substaging may provide an opportunity to identify those patients with the most aggressive forms of the disease, but there is a continuing need for accurate markers of disease relapse and survival. EXPERIMENTAL DESIGN: In our present study, immunohistochemical analyses of a retrospective database of pathologic specimens were used to demonstrate that the EphA2 receptor kinase is frequently overexpressed in NSCLC. RESULTS: Initial presentation with high levels of EphA2 predicts subsequent survival, overall relapse, and site of relapse. Specifically, high levels of EphA2 in the primary tumor predict brain metastases, whereas low levels of EphA2 relate to disease-free survival or contralateral lung metastasis. CONCLUSIONS: These data suggest that EphA2 may provide a molecular marker to identify and predict patients who have isolated brain metastases. Moreover, the high levels of EphA2 in lung cancer may provide an opportunity for therapeutic targeting.

Authors
Kinch, MS; Moore, M-B; Harpole, DH
MLA Citation
Kinch, MS, Moore, M-B, and Harpole, DH. "Predictive value of the EphA2 receptor tyrosine kinase in lung cancer recurrence and survival." Clin Cancer Res 9.2 (February 2003): 613-618.
PMID
12576426
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
9
Issue
2
Publish Date
2003
Start Page
613
End Page
618

Outcomes after esophagectomy: a ten-year prospective cohort.

BACKGROUND: The Department of Veterans Affairs National Surgical Quality Improvement Program is a unique resource to prospectively analyze surgical outcomes from a cross-section of surgical services nationally. We used this database to assess risk factors for morbidity and mortality after esophagectomy in Veterans Affairs Medical Centers from 1991 to 2001. METHODS: A total of 1,777 patients underwent an esophagectomy at 109 Veterans Affairs hospitals with complete in-hospital and 30-day outcomes recorded. Bivariate and multivariable analyses were completed. RESULTS: Thirty-day mortality was 9.8% (174/1,777) and the incidence of one or more of 20 predefined complications was 49.5% (880/1,777). The most frequent postoperative complications were pneumonia in 21% (380/1,777), respiratory failure in 16% (288/1,777), and ventilator support more than 48 hours in 22% (387/1,777). Preoperative predictors of mortality based on multivariable analysis included neoadjuvant therapy, blood urea nitrogen level of more than 40 mg/dL, alkaline phosphatase level of more than 125 U/L, diabetes mellitus, alcohol abuse, decreased functional status, ascites, and increasing age. Preoperative factors impacting morbidity were increasing age, dyspnea, diabetes mellitus, chronic obstructive pulmonary disease, alkaline phosphatase level of more than 125 U/L, lower serum albumin concentration, increased complexity score, and decreased functional status. Intraoperative risk factors for mortality included the need for transfusion; intraoperative risk factors for morbidity included the need for transfusion and longer operative time. CONCLUSIONS: These data constitute the largest prospective outcomes cohort in the literature and document a near 50% morbidity rate and 10% mortality rate after esophagectomy. Data from this study can be used to better stratify patients before esophagectomy.

Authors
Bailey, SH; Bull, DA; Harpole, DH; Rentz, JJ; Neumayer, LA; Pappas, TN; Daley, J; Henderson, WG; Krasnicka, B; Khuri, SF
MLA Citation
Bailey, SH, Bull, DA, Harpole, DH, Rentz, JJ, Neumayer, LA, Pappas, TN, Daley, J, Henderson, WG, Krasnicka, B, and Khuri, SF. "Outcomes after esophagectomy: a ten-year prospective cohort." Ann Thorac Surg 75.1 (January 2003): 217-222.
PMID
12537219
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
75
Issue
1
Publish Date
2003
Start Page
217
End Page
222

Molecular biologic substaging of stage I NSCLC through immunohistochemistry performed on formalin-fixed, paraffin-embedded tissue.

Authors
Joshi, M-BM; D'Amico, TA; Harpole, DH
MLA Citation
Joshi, M-BM, D'Amico, TA, and Harpole, DH. "Molecular biologic substaging of stage I NSCLC through immunohistochemistry performed on formalin-fixed, paraffin-embedded tissue." Methods Mol Med 75 (2003): 369-388.
PMID
12407753
Source
pubmed
Published In
Methods in Molecular Medicine
Volume
75
Publish Date
2003
Start Page
369
End Page
388

Transthoracic versus transhiatal esophagectomy: A prospective study of 945 patients

Objective: Debate continues as to whether transhiatal esophagectomy results in lower morbidity and mortality than transthoracic esophagectomy. Most data addressing this issue are derived from single-institution studies. To investigate this question from a nationwide multicenter perspective, we used the Veterans Administration National Surgical Quality Improvement Program to prospectively analyze risk factors for morbidity and mortality in patients undergoing transthoracic esophagectomy or transhiatal esophagectomy from 1991 to 2000. Methods: Univariate and multivariate analyses were performed on 945 patients (mean age, 63 ± 10 years). There were 562 transthoracic esophagectomies and 383 transhiatal esophagectomies in 105 hospitals, with complete 30-day outcomes recorded. Results: There were no differences in recorded preoperative variables between the groups that might bias any comparisons. Overall mortality was 10.0% (56/562) for transthoracic esophagectomy and 9.9% (38/383) for transhiatal esophagectomy (P = .983). Morbidity occurred in 47% (266/562) of patients after transthoracic esophagectomy and in 49% (188/383) of patients after transhiatal esophagectomy (P = .596). Risk factors for mortality common to both groups included a serum albumin value of less than 3.5 g/dL, age greater than 65 years, and blood transfusion of greater than 4 units (P < .05). When comparing transthoracic esophagectomy with transhiatal esophagectomy, there was no difference in the incidence of respiratory failure, renal failure, bleeding, infection, sepsis, anastomotic complications, or mediastinitis. Wound dehiscence occurred in 5% (18/383) of patients undergoing transhiatal esophagectomy and only 2% (12/562) of patients undergoing transthoracic esophagectomy (P = .036). Conclusions: These data demonstrate no significant differences in preoperative variables and postoperative mortality or morbidity between transthoracic esophagectomy and transhiatal esophagectomy on the basis of a 10-year, prospective, multi-institutional, nationwide study.

Authors
Rentz, J; Bull, D; Harpole, D; Bailey, S; Neumayer, L; Pappas, T; Krasnicka, B; Henderson, W; Daley, J; Khuri, S; Ehrman, W; Wood, D; Rentz, ; Rice, T
MLA Citation
Rentz, J, Bull, D, Harpole, D, Bailey, S, Neumayer, L, Pappas, T, Krasnicka, B, Henderson, W, Daley, J, Khuri, S, Ehrman, W, Wood, D, Rentz, , and Rice, T. "Transthoracic versus transhiatal esophagectomy: A prospective study of 945 patients." Journal of Thoracic and Cardiovascular Surgery 125.5 (2003): 1114-1120.
PMID
12771885
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
125
Issue
5
Publish Date
2003
Start Page
1114
End Page
1120
DOI
10.1067/mtc.2003.315

Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model

Objectives: The objectives of the study were to test the hypothesis that hyperbaric levels of oxygen enhance the sensitivity of a sarcoma cell line to doxorubicin (Adriamycin) both in vitro and in vivo in a rat model of pulmonary metastases and to test the feasibility of arterialization of mixed venous blood by direct injection of aqueous oxygen into the pulmonary artery in a rat model. Methods: Rat sarcoma (MCA-2) cells were incubated in the presence of increasing concentrations of doxorubicin (0.1-2.0 μmol/L). A dose-dependent toxicity relationship at 12 hours of treatment was examined with and without pretreatment with hyperbaric oxygen (3.7 atm absolute for 1.5-3.5 hours). In vivo, Sprague-Dawley rats (n = 24) were injected intravenously with 106 MCA-2 cells, and the lung tumors were allowed to mature for 14 days. At that time the animals were divided into four groups: control (no treatment), doxorubicin at 2 mg/kg, hyperbaric oxygen (oxygen at 2 atm absolute for 30 minutes), and hyperbaric oxygen plus doxorubicin. Seven days after treatment, the numbers of lung nodules were counted and the lung weights were determined. In additional rats (n = 7), aqueous oxygen (1 mL oxygen/g saline solution) was infused into the pulmonary artery to determine whether arterialization of mixed venous blood was comparable to pulmonary artery oxygenation with a hyperbaric chamber (n = 7). Results: Hyperbaric oxygen plus doxorubicin produced significantly greater cytolysis of MCA-2 cells (P < .01) than did doxorubicin alone. Hyperbaric oxygen plus doxorubicin also significantly decreased the number of lung metastases and the lung weight relative to doxorubicin alone (P < .01 and P < .01, respectively). The feasibility of arterialization of mixed venous blood (>100 mm Hg) with aqueous oxygen infusion was demonstrated. Conclusions: Hyperbaric oxygen enhanced the chemotherapeutic effect of doxorubicin both in cell culture and in the rat model. Aqueous oxygen infusion can be used to oxygenate mixed venous blood at levels similar to those obtained with the use of a hyperbaric chamber.

Authors
Petre, PM; Jr, FAB; Tigan, S; Spears, JR; Patterson, GA; Swisher, SG; Jr, DHH; Goldstraw, P
MLA Citation
Petre, PM, Jr, FAB, Tigan, S, Spears, JR, Patterson, GA, Swisher, SG, Jr, DHH, and Goldstraw, P. "Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model." Journal of Thoracic and Cardiovascular Surgery 125.1 (2003): 85-95.
PMID
12538989
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
125
Issue
1
Publish Date
2003
Start Page
85
End Page
95
DOI
10.1067/mtc.2003.90

Intraoperative techniques to prevent air leaks.

Persistent air leaks prolong chest tube duration and hospital stay after lung surgery. Air leaks also may lead to life-threatening empyemas. Preventing postoperative air leaks and BPFs is the best treatment for air-leak complications. Meticulous closure of parenchymal, pleural, and bronchial defects is the mainstay of air-leak control. The reinforcement of parenchymal suture and staple lines, pleural apposition, and well-vascularized tissue-flap coverage of bronchial suture and staple lines further reduce the incidence of prolonged air leaks and BPFs.

Authors
Toloza, EM; Harpole, DH
MLA Citation
Toloza, EM, and Harpole, DH. "Intraoperative techniques to prevent air leaks." Chest Surg Clin N Am 12.3 (August 2002): 489-505. (Review)
PMID
12469483
Source
pubmed
Published In
Chest surgery clinics of North America
Volume
12
Issue
3
Publish Date
2002
Start Page
489
End Page
505

Serum creatinine patterns in coronary bypass surgery patients with and without postoperative cognitive dysfunction.

UNLABELLED: Renal dysfunction is common after coronary artery bypass graft (CABG) surgery. We have previously shown that CABG procedures complicated by stroke have a threefold greater peak serum creatinine level relative to uncomplicated surgery. However, postoperative creatinine patterns for procedures complicated by cognitive dysfunction are unknown. Therefore, we tested the hypothesis that postoperative cognitive dysfunction is associated with acute perioperative renal injury after CABG surgery. Data were prospectively gathered for 282 elective CABG surgery patients. Psychometric tests were performed at baseline and 6 wk after surgery. Cognitive dysfunction was defined both as a dichotomous variable (cognitive deficit [CD]) and as a continuous variable (cognitive index). Forty percent of patients had CD at 6 wk. However, the association between peak percentage change in postoperative creatinine and CD (parameter estimate = -0.41; P = 0.91) or cognitive index (parameter estimate = -1.29; P = 0.46) was not significant. These data indicate that postcardiac surgery cognitive dysfunction, unlike stroke, is not associated with major increases in postoperative renal dysfunction. IMPLICATIONS: We previously noted that patients with postcardiac surgery stroke also have greater acute renal injury than unaffected patients. However, in the same setting, we found no difference in renal injury between patients with and without cognitive dysfunction. Factors responsible for subtle postoperative cognitive dysfunction do not appear to be associated with clinically important renal effects.

Authors
Swaminathan, M; McCreath, BJ; Phillips-Bute, BG; Newman, MF; Mathew, JP; Smith, PK; Blumenthal, JA; Stafford-Smith, M; Perioperative Outcomes Research Group,
MLA Citation
Swaminathan, M, McCreath, BJ, Phillips-Bute, BG, Newman, MF, Mathew, JP, Smith, PK, Blumenthal, JA, Stafford-Smith, M, and Perioperative Outcomes Research Group, . "Serum creatinine patterns in coronary bypass surgery patients with and without postoperative cognitive dysfunction." Anesth Analg 95.1 (July 2002): 1-8.
PMID
12088934
Source
pubmed
Published In
Anesthesia and Analgesia
Volume
95
Issue
1
Publish Date
2002
Start Page
1
End Page
8

Impact of computed tomography-positron emission tomography fusion in staging patients with thoracic malignancies.

BACKGROUND: Positron emission tomography (PET) has been demonstrated to improve staging in patients with thoracic malignancies. This study evaluates the ability of a new imaging technique to improve the spatial resolution and accuracy of PET. METHODS: Patients with known or suspected malignancy (n = 21) who were referred for a dedicated PET scan were also evaluated with a new camera-based PET system, which uniquely allows simultaneous computed tomography (CT) and fusion of the camera-based PET images with the CT images. The dedicated PET scan was obtained 1 hour after intravenous injection of fluorodeoxyglucose. The camera-based PET imaging was fused with the CT images at approximately 2 hours after injection. The camera-based PET and CT-PET fusion images were read independently and blindly by 2 experienced observers and the presence and location of abnormalities was compared with dedicated PET scans. RESULTS: Dedicated PET identified 18 sites in the chest as abnormal. The CT-PET fusion was superior to the camera-based PET alone, concordant with the dedicated PET in 16 of 21 patients compared with 13 of 21 by camera-based PET. The lesions missed by the camera-based PET were less than 1 cm in diameter. Fused CT-PET images provided superior anatomic localization and spatial resolution compared with dedicated PET and camera-based PET. CONCLUSIONS: CT-PET fusion images were more accurate than camera-based PET alone. CT-PET fusion improves the spatial resolution compared with dedicated PET and may improve the availability and efficacy of staging of patients with thoracic malignancies.

Authors
D'Amico, TA; Wong, TZ; Harpole, DH; Brown, SD; Coleman, RE
MLA Citation
D'Amico, TA, Wong, TZ, Harpole, DH, Brown, SD, and Coleman, RE. "Impact of computed tomography-positron emission tomography fusion in staging patients with thoracic malignancies." Ann Thorac Surg 74.1 (July 2002): 160-163.
PMID
12118750
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
74
Issue
1
Publish Date
2002
Start Page
160
End Page
163

Pathologic nodal status predicts disease-free survival after neoadjuvant chemoradiation for gastroesophageal junction carcinoma

Authors
Gaca, JG; Harpole, DH; D'Amico, TA; Pappas, T; Seigler, HF; Wolfe, WG; Tyler, S
MLA Citation
Gaca, JG, Harpole, DH, D'Amico, TA, Pappas, T, Seigler, HF, Wolfe, WG, and Tyler, S. "Pathologic nodal status predicts disease-free survival after neoadjuvant chemoradiation for gastroesophageal junction carcinoma." July 2002.
Source
wos-lite
Published In
Gastroenterology
Volume
123
Issue
1
Publish Date
2002
Start Page
1
End Page
2

Molecular staging of lung and esophageal cancer.

In both esophageal and NSCLC, the TNM stage at diagnosis remains the most important determinant of survival. Significant research to investigate the biology of NSCLC and esophageal carcinoma is ongoing, and the roles of proto-oncogenes, tumor suppressor genes, angiogenic factors, extracellular matrix proteases, and adhesion molecules are being elucidated. While evidence is accumulating that various markers are involved in NSCLC and esophageal tumor virulence, the current studies are compromised by small sample sizes, heterogeneous populations, and variations in techniques. Large prospective studies with homogenous groups designed to evaluate the role of these various markers should clarify their potential involvement in NSCLC and esophageal cancer. Identification of occult micrometastases in lymph nodes and bone marrow using immunohistochemical techniques and rt-PCR is intriguing. These techniques are promising as a method to more accurately stage patients, and therefore to predict outcomes and to determine therapies. Perhaps the most promising area of research is the development of novel drugs whose mechanism of action targets the pathways of various molecular markers. Molecular biologic substaging offers an opportunity to individualize a chemotherapeutic regimen based on the molecular profile of the tumor, thus providing the potential for improved outcomes with less morbidity in patients with both NSCLC and esophageal cancer.

Authors
Lau, CL; Moore, M-BH; Brooks, KR; D'Amico, TA; Harpole, DH
MLA Citation
Lau, CL, Moore, M-BH, Brooks, KR, D'Amico, TA, and Harpole, DH. "Molecular staging of lung and esophageal cancer." Surg Clin North Am 82.3 (June 2002): 497-523. (Review)
PMID
12371582
Source
pubmed
Published In
Surgical Clinics of North America
Volume
82
Issue
3
Publish Date
2002
Start Page
497
End Page
523

The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.

UNLABELLED: Neurocognitive dysfunction is a common complication after cardiac surgery. We evaluated in this prospective study the effect of rewarming rate on neurocognitive outcome after hypothermic cardiopulmonary bypass (CPB). After IRB approval and informed consent, 165 coronary artery bypass graft surgery patients were studied. Patients received similar surgical and anesthetic management until rewarming from hypothermic (28 degrees -32 degrees C) CPB. Group 1 (control; n = 100) was warmed in a conventional manner (4 degrees -6 degrees C gradient between nasopharyngeal and CPB perfusate temperature) whereas Group 2 (slow rewarm; n = 65) was warmed at a slower rate, maintaining no more than 2 degrees C difference between nasopharyngeal and CPB perfusate temperature. Neurocognitive function was assessed at baseline and 6 wk after coronary artery bypass graft surgery. Univariable analysis revealed no significant differences between the Control and Slow Rewarming groups in the stroke rate. Multivariable linear regression analysis, examining treatment group, diabetes, baseline cognitive function, and cross-clamp time revealed a significant association between change in cognitive function and rate of rewarming (P = 0.05). IMPLICATIONS: Slower rewarming during cardiopulmonary bypass (CPB) was associated with better cognitive performance at 6 wk. These results suggest that a slower rewarming rate with lower peak temperatures during CPB may be an important factor in the prevention of neurocognitive decline after hypothermic CPB.

Authors
Grigore, AM; Grocott, HP; Mathew, JP; Phillips-Bute, B; Stanley, TO; Butler, A; Landolfo, KP; Reves, JG; Blumenthal, JA; Newman, MF; Neurologic Outcome Research Group of the Duke Heart Center,
MLA Citation
Grigore, AM, Grocott, HP, Mathew, JP, Phillips-Bute, B, Stanley, TO, Butler, A, Landolfo, KP, Reves, JG, Blumenthal, JA, Newman, MF, and Neurologic Outcome Research Group of the Duke Heart Center, . "The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery." Anesth Analg 94.1 (January 2002): 4-10.
PMID
11772792
Source
pubmed
Published In
Anesthesia and Analgesia
Volume
94
Issue
1
Publish Date
2002
Start Page
4
End Page
10

Pulmonary metastasectomy for metastatic malignant melanoma.

Melanoma is the most deadly of skin cancers, and metastatic disease most commonly first appears in the lungs. Because most patients with early metastatic pulmonary disease are asymptomatic, routine screening with chest radiographs is the most cost-effective method of discovery. The therapy for pulmonary metastatic melanoma has drastically changed over the years. Even today there is no curative immunotherapy or chemotherapy available. The long-term overall survival for these patients is still very poor, but early detection and surgery offers the only hope for control in a small number of patients.

Authors
Lewis, CW; Harpole, D
MLA Citation
Lewis, CW, and Harpole, D. "Pulmonary metastasectomy for metastatic malignant melanoma." Semin Thorac Cardiovasc Surg 14.1 (January 2002): 45-48.
PMID
11977016
Source
pubmed
Published In
Seminars in Thoracic and Cardiovascular Surgery
Volume
14
Issue
1
Publish Date
2002
Start Page
45
End Page
48

Genetic analysis of the beta-tubulin gene, TUBB, in non-small-cell lung cancer.

Authors
Kelley, MJ; Li, S; Harpole, DH
MLA Citation
Kelley, MJ, Li, S, and Harpole, DH. "Genetic analysis of the beta-tubulin gene, TUBB, in non-small-cell lung cancer." J Natl Cancer Inst 93.24 (December 19, 2001): 1886-1888.
PMID
11752014
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
93
Issue
24
Publish Date
2001
Start Page
1886
End Page
1888

Predicting the sites of metastases from lung cancer using molecular biologic markers.

BACKGROUND: The use of molecular markers in staging non-small cell lung cancer (NSCLC) has been supported in retrospective prognostic models but has not been evaluated in predicting sites of metastases. METHODS: Pathologic specimens were collected from 202 patients after complete resection for stage I NSCLC, who were subsequently found to have no metastases at 5 years (n = 108), isolated brain metastases (n = 25), or other distant metastases (n = 69). A panel of eight molecular markers of metastatic potential was chosen for immunohistochemical analysis of the tumor: p53, erbB2, angiogenesis factor viii, EphA2, E-cadherin, urokinase plasminogen activator (UPA), UPA receptor, and plasminogen activator inhibitor. RESULTS: Patients with isolated brain relapse had significantly higher expression of p53 (p = 0.02) and UPA (p = 0.002). The quantitative expression of E-cadherin was used to predict the site of metastases using recursive partitioning: 0 of 92 patients with E-cadherin expression of 0, 1, or 2 developed isolated cerebral metastases; 0 of 33 patients with E-cadherin expression of 3 with UPA of 1 or 2 and ErbB2 of 0 developed brain metastases. Of the remaining patients at risk (UPA = 3), the risk of isolated cerebral metastases was 21 of 57 patients (37%). CONCLUSIONS: This study demonstrates that molecular markers may predict the site of relapse in early stage NSCLC. If validated in an ongoing prospective study, these results could be used to select patients with isolated brain metastases for adjuvant therapy, such as prophylactic cranial irradiation.

Authors
D'Amico, TA; Aloia, TA; Moore, MB; Conlon, DH; Herndon, JE; Kinch, MS; Harpole, DH
MLA Citation
D'Amico, TA, Aloia, TA, Moore, MB, Conlon, DH, Herndon, JE, Kinch, MS, and Harpole, DH. "Predicting the sites of metastases from lung cancer using molecular biologic markers." Ann Thorac Surg 72.4 (October 2001): 1144-1148.
PMID
11603427
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
72
Issue
4
Publish Date
2001
Start Page
1144
End Page
1148

Tumor marker expression is predictive of survival in patients with esophageal cancer.

BACKGROUND: This study was designed to determine the prognostic value of immunohistochemical tumor marker expression in a population of patients with node-negative esophageal cancer treated with complete resection alone. METHODS: Resection specimens were collected from 61 patients with node-negative T1 (n = 31), T2 (n = 14), and T3 (n = 16) esophageal cancer. A panel of 10 tumor markers was chosen for immunohistochemical analysis, based on associations with differing oncologic mechanisms: apoptosis (p53), growth regulation (transforming growth factor-alpha, epidermal growth factor receptor, and Her2-neu), angiogenesis (factor VIII), metastatic potential (CD44), platinum resistance (p-glycoprotein and metallothionein), 5-fluorouracil resistance (thymidylate synthetase), and carcinogenic detoxification (glutathione S-transferase-pi). RESULTS: Complete resection was performed in all patients (44 adenocarcinoma, 17 squamous cell carcinoma), with no operative deaths. Multivariable analysis demonstrated a significant relationship between cancer-specific death and the following variables: low-level P-gp expression (p = 0.004), high-level expression of p53 (p = 0.04), and low-level expression of transforming growth factor-alpha (p = 0.03). In addition, the number of involved tumor markers present was strongly predictive of negative outcome (p = 0.0001). CONCLUSIONS: This study supports the prognostic value of immunohistochemical tumor markers, specifically the expression pattern of P-gp, p53, and transforming growth factor-alpha, in patients with esophageal carcinoma treated with complete resection alone.

Authors
Aloia, TA; Harpole, DH; Reed, CE; Allegra, C; Moore, MB; Herndon, JE; D'Amico, TA
MLA Citation
Aloia, TA, Harpole, DH, Reed, CE, Allegra, C, Moore, MB, Herndon, JE, and D'Amico, TA. "Tumor marker expression is predictive of survival in patients with esophageal cancer." Ann Thorac Surg 72.3 (September 2001): 859-866.
PMID
11565671
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
72
Issue
3
Publish Date
2001
Start Page
859
End Page
866

Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer.

PURPOSE: To correlate FDG activity on PET with the expression of glucose transporter proteins Glut-1 and Glut-3 in patients with early stage non-small cell lung cancer (NSCLC). METHODS: Over a 5 year period, all patients with a PET scan and clinical stage I NSCLC underwent an immunohistochemical analysis of their tumor for Glut-1 and Glut-3 expression. The amount of FDG uptake in the primary lesion was measured by a standardized uptake ratio (SUR) and correlated with immunohistochemical results. RESULTS: Seventy-three patients with a mean age of 66 years had clinical stage I disease. The final pathologic stage showed 64 patients with stage IA/B disease, eight with stage IIA disease, and one patient with pathologic stage IIIA (T1N2) disease. Glut-1 transporter expression was significantly higher than Glut-3 (P<0.0001), and although there was some association between the SUR and Glut-1 (P=0.085) and SUR and Glut-3 (P=0.074) expression, this did not reach statistical significance. CONCLUSIONS: Glut-1 and Glut-3 transporter expression did not demonstrate a statistically significant correlation with FDG uptake in potentially resectable lung cancer. It appears that these transporters alone do not affect the variation in FDG activity in early stage NSCLC.

Authors
Marom, EM; Aloia, TA; Moore, MB; Hara, M; Herndon, JE; Harpole, DH; Goodman, PC; Patz, EF
MLA Citation
Marom, EM, Aloia, TA, Moore, MB, Hara, M, Herndon, JE, Harpole, DH, Goodman, PC, and Patz, EF. "Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer." Lung Cancer 33.2-3 (August 2001): 99-107.
PMID
11551404
Source
pubmed
Published In
Lung Cancer
Volume
33
Issue
2-3
Publish Date
2001
Start Page
99
End Page
107

Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy.

PURPOSE: HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer. PATIENTS AND METHODS: From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). RESULTS: HER-2 ECD was positive in 29% (19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC-only 22% of patients with HER-2 in the primary tumor shed ECD into the serum. CONCLUSION: These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting.

Authors
Harris, LN; Liotcheva, V; Broadwater, G; Ramirez, MJ; Maimonis, P; Anderson, S; Everett, T; Harpole, D; Moore, MB; Berry, DA; Rizzeri, D; Vredenburgh, JJ; Bentley, RC
MLA Citation
Harris, LN, Liotcheva, V, Broadwater, G, Ramirez, MJ, Maimonis, P, Anderson, S, Everett, T, Harpole, D, Moore, MB, Berry, DA, Rizzeri, D, Vredenburgh, JJ, and Bentley, RC. "Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy." J Clin Oncol 19.6 (March 15, 2001): 1698-1706.
PMID
11250999
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
19
Issue
6
Publish Date
2001
Start Page
1698
End Page
1706
DOI
10.1200/JCO.2001.19.6.1698

The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer.

The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response (P < 0.001). High-level expression of GST-pi, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation.

Authors
Harpole, DH; Moore, MB; Herndon, JE; Aloia, T; D'Amico, TA; Sporn, T; Parr, A; Linoila, I; Allegra, C
MLA Citation
Harpole, DH, Moore, MB, Herndon, JE, Aloia, T, D'Amico, TA, Sporn, T, Parr, A, Linoila, I, and Allegra, C. "The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer." Clin Cancer Res 7.3 (March 2001): 562-569.
PMID
11297249
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
7
Issue
3
Publish Date
2001
Start Page
562
End Page
569

Integration of peripheral blood biomarkers with computed tomography to differentiate benign from malignant pulmonary opacities.

Our purpose was to determine whether peripheral blood biomarkers MUC1 and CK19 could be used to complement imaging studies in differentiating benign from malignant indeterminate pulmonary nodules or masses detected on computed tomography CT. One hundred and eighteen patients had a thoracic CT and blood drawn for tumor marker reverse transcriptase-polymerase chain reaction analysis. Thirty-five of the 118 patients had an indeterminate pulmonary nodular opacity on CT, and the findings then were correlated with the reverse transcriptase-polymerase chain reaction results. The sensitivity and specificity for the markers in determining malignancy was calculated. Thirteen of the 35 opacities on CT proved to be benign, and 22 proved to be lung cancer. Among the patients with indeterminate pulmonary abnormalities, polymorphic epithelial mucin protein 1 had a sensitivity and specificity for lung cancer of 100% and 46%, respectively. Cytokeratin 19 had a sensitivity and specificity for lung cancer of 95% and 8%, respectively. These preliminary data showed that serum biomarkers polymorphic epithelial mucin protein 1 and cytokeratin 19 were not specific for lung cancer, although patients with an indeterminate pulmonary abnormality and negative markers were unlikely to have lung cancer. Integration of imaging studies with the appropriate biomarkers may prove useful in evaluating indeterminate pulmonary nodules or masses.

Authors
Aloia, T; Bepler, G; Harpole, D; Goodman, PC; McAdams, HP; Erasmus, JJ; Herndon, JE; Patz, EF
MLA Citation
Aloia, T, Bepler, G, Harpole, D, Goodman, PC, McAdams, HP, Erasmus, JJ, Herndon, JE, and Patz, EF. "Integration of peripheral blood biomarkers with computed tomography to differentiate benign from malignant pulmonary opacities." Cancer Detect Prev 25.4 (2001): 336-343.
PMID
11531010
Source
pubmed
Published In
Cancer Detection and Prevention
Volume
25
Issue
4
Publish Date
2001
Start Page
336
End Page
343

Role of serum tumor markers CA 125 and CEA in non-small cell lung cancer

Background: CA 125 and CEA are valuable serum tumor markers that can be used to monitor response to therapy in patients with various solid tumors. Systemic studies of CA 125 and CEA have not been evaluated in lung cancer. In this study, we report the serum levels of CA 125 and compared it to CEA in newly diagnosed lung cancer and analyzed the serum levels of these markers pre- and post-therapy. Materials and Methods: Two hundred and sixteen patients with newly diagnosed non-small lung cancer were evaluated. CA 125 and CEA levels were correlated with stage and histopathology. Results: CA 125 levels and CEA levels were shown to be lower in patients with early stage disease as compared to patients with unresectable or metastatic disease. CEA levels were significantly higher among patients with adenocarcinoma, while there was no statistically significant relationship between histology and CA 125. There Was a statistically significant difference in the CEA and CA 125 levels dependent on tumor size. Thirty-seven patients were analyzed for responses to chemotherapy and responders are more likely to have decreases in CA 125 or CEA. Conclusion: When abnormally elevated inpatients witlrlung cancer, CA 125 and CEA are useful indicators of disease extent, a useful clinical therapeutic marker, and may potentially have important prognostic value.

Authors
Salgia, R; Harpole, D; II, JEH; Pisick, E; Elias, A; Skarin, AT
MLA Citation
Salgia, R, Harpole, D, II, JEH, Pisick, E, Elias, A, and Skarin, AT. "Role of serum tumor markers CA 125 and CEA in non-small cell lung cancer." Anticancer Research 21.2 B (2001): 1241-1246.
Source
scival
Published In
Anticancer Research
Volume
21
Issue
2 B
Publish Date
2001
Start Page
1241
End Page
1246

Staging techniques for lung cancer.

In summary, noninvasive clinical staging techniques aid in stratifying patients into similar prognostic and therapeutic categories. Every patient with presumed non-small cell lung cancer should undergo a thorough history and physical examination, basic routine laboratory testing, PA and lateral chest radiographs, and chest CT scan with upper abdominal cuts to allow evaluation of the liver and adrenals. Recently, FDG-PET scanning has shown tremendous promise in the noninvasive evaluation of the primary tumor, nodal involvement, and metastatic [table: see text] disease. Although valuable, clinical staging has limitations, and when pathologic confirmation of lung cancer is required, minimally invasive techniques, such as bronchoscopy, TTNA, thoracoscopy, anterior mediastinotomy, and cervical and extended mediastinoscopy, may be valuable and simple ways of obtaining tissue.

Authors
Lau, CL; Harpole, DH; Patz, E
MLA Citation
Lau, CL, Harpole, DH, and Patz, E. "Staging techniques for lung cancer." Chest Surg Clin N Am 10.4 (November 2000): 781-801. (Review)
PMID
11091926
Source
pubmed
Published In
Chest surgery clinics of North America
Volume
10
Issue
4
Publish Date
2000
Start Page
781
End Page
801

Integration of peripheral blood biomarkers with CT to differentiate benign from malignant pulmonary opacities

Authors
Aloia, T; McAdams, HP; Bepler, G; Harpole, DH; Goodman, PC; Patz, EF
MLA Citation
Aloia, T, McAdams, HP, Bepler, G, Harpole, DH, Goodman, PC, and Patz, EF. "Integration of peripheral blood biomarkers with CT to differentiate benign from malignant pulmonary opacities." November 2000.
Source
wos-lite
Published In
Radiology
Volume
217
Publish Date
2000
Start Page
469
End Page
469

Molecular biology of esophageal cancer.

Several mechanisms of resistance to chemotherapy have been identified among the agents that are commonly used in the systemic treatment of patients with esophageal cancer: paclitaxel, platinum, and 5-FU. A recent study from our laboratory evaluated the initial endoscopic biopsy material from patients who subsequently underwent trimodality therapy, including chemotherapy with cisplatin and 5-FU, radiation therapy, and surgery. IHC analysis was performed on seven markers of chemotherapy or radiation therapy resistance: P-gp, GST-pi, MT (platinum inhibitors); EGF-R, TGF-alpha, erb-B2 (activation of cell growth cascade); and p53 (interferes with chemotherapy-induced apoptosis). In this study, elevated expression of GST-pi and P-gp were associated with decreased survival and may be markers of treatment resistance. Expression of erb-B2 was associated with enhanced survival and may be a marker of treatment sensitivity. Assessment of the probability of chemoresistance of a particular tumor using the expression of molecular biologic markers may allow for the selection of a more favorable chemotherapeutic agent. Furthermore, understanding the mechanisms of resistance, including the mechanisms of DNA repair, may provide insight into mechanisms to reverse or to inhibit resistance to chemotherapy. DNA repair mechanisms are used by cells to protect themselves against mutagens and carcinogens. DNA repair inhibitors may increase the mutagenicity associated with DNA damage and may prove to be an ineffective oncologic treatment strategy; however, the possibility exists that DNA repair inhibition may improve the efficacy of anticancer agents, and this should be tested. The value of this strategy may be in allowing treatment doses to be decreased and lessening side effects while maintaining therapeutic efficacy.

Authors
D'Amico, TA; Harpole, DH
MLA Citation
D'Amico, TA, and Harpole, DH. "Molecular biology of esophageal cancer." Chest Surg Clin N Am 10.3 (August 2000): 451-469. (Review)
PMID
10967750
Source
pubmed
Published In
Chest surgery clinics of North America
Volume
10
Issue
3
Publish Date
2000
Start Page
451
End Page
469

Expression of human telomerase subunit genes in primary lung cancer and its clinical significance - Invited commentary

Authors
Harpole, DH
MLA Citation
Harpole, DH. "Expression of human telomerase subunit genes in primary lung cancer and its clinical significance - Invited commentary." ANNALS OF THORACIC SURGERY 70.2 (August 2000): 405-406.
Source
wos-lite
Published In
The Annals of Thoracic Surgery
Volume
70
Issue
2
Publish Date
2000
Start Page
405
End Page
406
DOI
10.1016/S0003-4975(00)01549-6

Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to determine the relationship between tumor size and survival in patients with stage IA non-small cell lung cancer (non-small cell lung cancer; ie, lesions < 3 cm). METHOD: Five hundred ten patients with pathologic stage IA (T1N0M0) non-small cell lung cancer were identified from our tumor registry over an 18-year period (from 1981 to 1999). There were 285 men and 225 women, with a mean age of 63 years (range, 31 to 90 years). The Cox proportional model was used to examine the effect on survival. Tumor size was incorporated into the model as a linear effect and as categorical variables. The Kaplan-Meier product limit estimator was used to graphically display the relationship between the tumor size and survival. RESULTS: The Cox proportional hazards model did not show a statistically significant relationship between tumor size and survival (p = 0.701) as a linear effect. Tumor size was then categorized into quartiles, and again there was no statistically significant difference in survival between groups (p = 0.597). Tumor size was also categorized into deciles, and there was no statistical relationship between tumor size and survival (p = 0.674). CONCLUSIONS: This study confirms stratifying patients with stage IA non-small cell lung cancer in the same TNM classification, given no apparent difference in survival. Unfortunately, these data caution that improved small nodule detection with screening CT may not significantly improve lung cancer mortality. The appropriate prospective randomized trial appears warranted.

Authors
Patz, EF; Rossi, S; Harpole, DH; Herndon, JE; Goodman, PC
MLA Citation
Patz, EF, Rossi, S, Harpole, DH, Herndon, JE, and Goodman, PC. "Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer." Chest 117.6 (June 2000): 1568-1571.
PMID
10858384
Source
pubmed
Published In
Chest
Volume
117
Issue
6
Publish Date
2000
Start Page
1568
End Page
1571

Noninvasive clinical staging modalities for lung cancer

Clinical staging of lung cancer helps to determine the extent of disease and stratify patients into similar therapeutic and prognostic categories. A primary goal of clinical staging is to separate patients with potentially resectable disease from those that are unresectable. Initial assessment of the patient by history and physical examination combined with laboratory values can suggest metastatic spread of the disease. When abnormal, these clinical factors may have value in terms of predicting prognosis, but their use in early stage lung cancer is limited because of the low prevalence of symptoms, physical exam findings, and laboratory abnormalities in this group. For clinical staging, patients almost always undergo a posteroanterior and lateral chest radiograph and a computed tomography (CT) scan of the chest and upper abdomen to include the liver and adrenal glands. Although CT scanning provides exquisite anatomic information, it is less than optimal for determining lymph node status. Over the last several years, CT scanning combined with positron-emission tomography (PET) using fluorodeoxyglucose (FDG) has significantly improved the accuracy of clinical staging. The use of FDG-PET continues to be defined in the non-invasive evaluation of the primary tumor, nodal involvement, and metastatic disease. Despite the recent advancements in radiologic assessment of lung cancer, invasive sampling is still often performed for pathologic confirmation. (C) 2000 Wiley-Liss, Inc.

Authors
Lau, CL; Harpole, DH
MLA Citation
Lau, CL, and Harpole, DH. "Noninvasive clinical staging modalities for lung cancer." Seminars in Surgical Oncology 18.2 (March 1, 2000): 116-123. (Review)
Source
scopus
Published In
Seminars in Surgical Oncology
Volume
18
Issue
2
Publish Date
2000
Start Page
116
End Page
123
DOI
10.1002/(SICI)1098-2388(200003)18:2<116::AID-SSU5>3.0.CO;2-L

Noninvasive clinical staging modalities for lung cancer.

Clinical staging of lung cancer helps to determine the extent of disease and stratify patients into similar therapeutic and prognostic categories. A primary goal of clinical staging is to separate patients with potentially resectable disease from those that are unresectable. Initial assessment of the patient by history and physical examination combined with laboratory values can suggest metastatic spread of the disease. When abnormal, these clinical factors may have value in terms of predicting prognosis, but their use in early stage lung cancer is limited because of the low prevalence of symptoms, physical exam findings, and laboratory abnormalities in this group. For clinical staging, patients almost always undergo a postero-anterior and lateral chest radiograph and a computed tomography (CT) scan of the chest and upper abdomen to include the liver and adrenal glands. Although CT scanning provides exquisite anatomic information, it is less than optimal for determining lymph node status. Over the last several years, CT scanning combined with positron-emission tomography (PET) using fluorodeoxyglucose (FDG) has significantly improved the accuracy of clinical staging. The use of FDG-PET continues to be defined in the non-invasive evaluation of the primary tumor, nodal involvement, and metastatic disease. Despite the recent advancements in radiologic assessment of lung cancer, invasive sampling is still often performed for pathologic confirmation.

Authors
Lau, CL; Harpole, DH
MLA Citation
Lau, CL, and Harpole, DH. "Noninvasive clinical staging modalities for lung cancer." Semin Surg Oncol 18.2 (March 2000): 116-123. (Review)
PMID
10657913
Source
pubmed
Published In
Seminars in Surgical Oncology
Volume
18
Issue
2
Publish Date
2000
Start Page
116
End Page
123

Molecular biologic substaging of stage I lung cancer according to gender and histology.

BACKGROUND: This study is designed to assess molecular biologic substaging according to gender and histology in patients with stage I non-small cell lung cancer (NSCLC). METHODS: Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I NSCLC, with follow-up of at least 5 years. A panel of nine molecular markers was chosen for immunohistochemical analysis of the tumor: recessive oncogenes p53 and bcl-2, the protooncogene erbB-2, KI-67 proliferation index, retinoblastoma oncogene (Rb), epidermal growth factor receptor (EGFr), angiogenesis factor viii, sialyl-Tn antigen (STN), and CD-44. Cox proportional hazards regression analysis was used to construct a risk model for cancer-specific survival according to marker status, gender, and histologic subtype. RESULTS: Among men, the only molecular marker associated with decreased cancer-specific survival is erbB-2; among women, there are four markers: p53, Rb, CD-44, and factor viii. Among patients with squamous cell carcinoma, the only molecular marker associated with decreased cancer-specific survival is erbB-2; among patients with adenocarcinoma (AC), there are three markers: p53, CD-44, and factor viii. Multivariable analysis of interactions among molecular markers, gender, and histology demonstrates two important relationships (hazard ratio): p53+/women (2.269) and CD-44+/AC (2.266). CONCLUSIONS: Molecular biologic substaging of patients with stage I NSCLC demonstrates differential cancer-specific survival according to marker expression, gender, and histologic subtype.

Authors
D'Amico, TA; Aloia, TA; Moore, MB; Herndon, JE; Brooks, KR; Lau, CL; Harpole, DH
MLA Citation
D'Amico, TA, Aloia, TA, Moore, MB, Herndon, JE, Brooks, KR, Lau, CL, and Harpole, DH. "Molecular biologic substaging of stage I lung cancer according to gender and histology." Ann Thorac Surg 69.3 (March 2000): 882-886.
PMID
10750777
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
69
Issue
3
Publish Date
2000
Start Page
882
End Page
886

Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma

Background: The adenomatous polyposis coli (APC) locus on chromosome 5q21-22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. Methods: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P value to test for the strength of this association. This cutoff value was used to generate Kaplan-Meier survival curves. All P values were based on two-sided tests. Results: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P = .016). Conclusion: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.

Authors
Kawakami, K; Brabender, J; Lord, RV; Groshen, S; Greenwald, BD; Krasna, MJ; Yin, J; Fleisher, AS; Abraham, JM; Beer, DG; Sidransky, D; Huss, HT; Demeester, TR; Eads, C; Laird, PW; Ilson, DH; Kelsen, DP; Harpole, D; Moore, M-B; Danenberg, KD; Danenberg, PV; Meltzer, SJ
MLA Citation
Kawakami, K, Brabender, J, Lord, RV, Groshen, S, Greenwald, BD, Krasna, MJ, Yin, J, Fleisher, AS, Abraham, JM, Beer, DG, Sidransky, D, Huss, HT, Demeester, TR, Eads, C, Laird, PW, Ilson, DH, Kelsen, DP, Harpole, D, Moore, M-B, Danenberg, KD, Danenberg, PV, and Meltzer, SJ. "Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma." Journal of the National Cancer Institute 92.22 (2000): 1805-1811.
PMID
11078757
Source
scival
Published In
Journal of the National Cancer Institute
Volume
92
Issue
22
Publish Date
2000
Start Page
1805
End Page
1811

Rationale and design of the National Emphysema Treatment Trial - A prospective randomized trial of lung volume reduction surgery

Authors
Espada, R; Rodarte, J; Miller, C; Barnard, C; Carter, J; Harpole, D; et, A
MLA Citation
Espada, R, Rodarte, J, Miller, C, Barnard, C, Carter, J, Harpole, D, and et, A. "Rationale and design of the National Emphysema Treatment Trial - A prospective randomized trial of lung volume reduction surgery." Chest 116.6 (December 1, 1999): 1750-1761.
Source
manual
Published In
Chest
Volume
116
Issue
6
Publish Date
1999
Start Page
1750
End Page
1761
DOI
10.1378/chest.116.6.1750

Cognitive decline after major noncardiac operations: a preliminary prospective study.

BACKGROUND: Cardiac operations frequently are complicated by postoperative cognitive decline. Less common and less studied is postoperative cognitive decline after noncardiac surgery, so we determined its incidence, severity, and possible predictors. METHODS: Twenty-nine patients who had thoracic and vascular procedures were studied. A neurocognitive test battery was administered preoperatively and 6 to 12 weeks postoperatively. A change score (preoperative minus postoperative) was calculated for each measure in each individual. Cognitive deficit (a measure of incidence) was defined as a 20% decrement in 20% or more of the completed tests. The average scores of all tests and the average decline (a measure of severity) were determined. RESULTS: The incidence of cognitive deficit was 44.8%. Overall the severity of the decline was an average of 15% decline. In the 44.8% of patients who had cognitive deficit, the severity was 24.7%. Multivariable predictors of cognitive decline were age (for incidence and severity) and years of education (for severity). CONCLUSIONS: Cognitive decline after noncardiac operations is a frequent complication of surgical procedures. The severity could preclude successful return to a preoperative lifestyle.

Authors
Grichnik, KP; Ijsselmuiden, AJ; D'Amico, TA; Harpole, DH; White, WD; Blumenthal, JA; Newman, MF
MLA Citation
Grichnik, KP, Ijsselmuiden, AJ, D'Amico, TA, Harpole, DH, White, WD, Blumenthal, JA, and Newman, MF. "Cognitive decline after major noncardiac operations: a preliminary prospective study." Ann Thorac Surg 68.5 (November 1999): 1786-1791.
PMID
10585059
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
68
Issue
5
Publish Date
1999
Start Page
1786
End Page
1791

Rationale and design of the national emphysema treatment trial (NETT): A prospective randomized trial of lung volume reduction surgery

Authors
Rodarte, J; Miller, C; Barnard, P; Carter, J; DuBose, K; Harpole, D; et, A
MLA Citation
Rodarte, J, Miller, C, Barnard, P, Carter, J, DuBose, K, Harpole, D, and et, A. "Rationale and design of the national emphysema treatment trial (NETT): A prospective randomized trial of lung volume reduction surgery." Ed. J Rodarte, C Miller, P Barnard, J Carter, K DuBose, and D Harpole. The Journal of Thoracic and Cardiovascular Surgery 118.3 (September 1999): 518-528.
Source
manual
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
118
Issue
3
Publish Date
1999
Start Page
518
End Page
528
DOI
10.1016/S0022-5223(99)70191-1

Rationale and design of the national emphysema treatment trial (NETT): A prospective randomized trial of lung volume reduction surgery

Authors
Rodarte, J; Miller, C; Barnard, P; Carter, J; DuBose, K; Harpole, D; et, A
MLA Citation
Rodarte, J, Miller, C, Barnard, P, Carter, J, DuBose, K, Harpole, D, and et, A. "Rationale and design of the national emphysema treatment trial (NETT): A prospective randomized trial of lung volume reduction surgery." Ed. J Rodarte, C Miller, P Barnard, J Carter, K DuBose, and D Harpole. The Journal of Thoracic and Cardiovascular Surgery 118.3 (September 1999): 518-528.
Source
manual
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
118
Issue
3
Publish Date
1999
Start Page
518
End Page
528
DOI
10.1016/S0022-5223(99)70191-1

Prognostic models of thirty-day mortality and morbidity after major pulmonary resection.

BACKGROUND: A part of the prospective, multi-institutional National Veterans Affairs Surgical Quality Improvement Program was developed to predict 30-day mortality and morbidity for patients undergoing a major pulmonary resection. METHODS: Perioperative data were acquired from 194,319 noncardiac surgical operations at 123 Veterans Affairs Medical Centers between October 1, 1991, and August 31, 1995. Current Procedural Terminology code-based analysis was undertaken for major pulmonary resections (lobectomy and pneumonectomy). Preoperative, intraoperative, and outcome variables were collected. The 30-day mortality and morbidity models were developed by means of multivariable stepwise logistic regression with the preoperative and intraoperative variables used as independent predictors of outcome. RESULTS: A total of 3516 patients (mean age 64 9 years) underwent either lobectomy (n = 2949) or pneumonectomy (n = 567). Thirty-day mortality was 4.0% for lobectomy (119/2949) and 11.5% for pneumonectomy (65/567). The preoperative predictors of 30-day mortality were albumin, do not resuscitate status, transfusion of more than 4 units, age, disseminated cancer, impaired sensorium, prothrombin time more than 12 seconds, type of operation, and dyspnea. When the intraoperative variables were considered, intraoperative blood loss was added to the preoperative model. In the presence of these intraoperative variables in the model, do not resuscitate status and prothrombin time more than 12 seconds were only marginally significant. Thirty-day morbidity, defined as the presence of 1 or more of the 21 predefined complications, was 23.8% for lobectomy (703/2949) and 25.7% for pneumonectomy (146/567). In multivariable models, independent preoperative predictors (P <.05) of 30-day morbidity were age, weight loss greater than 10% in the 6 months before surgery, history of chronic obstructive pulmonary disease, transfusion of more than 4 units, albumin, hemiplegia, smoking, and dyspnea. When intraoperative variables were added to the preoperative model, the duration of operation time and intraoperative transfusions were included in the model and albumin became marginally significant. CONCLUSIONS: This analysis identifies independent patient risk factors that are associated with 30-day mortality and morbidity for patients undergoing a major pulmonary resection. This series provides an initial risk-adjustment model for major pulmonary resections. Future refinements will allow comparative assessment of surgical outcomes and quality of care at many institutions.

Authors
Harpole, DH; DeCamp, MM; Daley, J; Hur, K; Oprian, CA; Henderson, WG; Khuri, SF
MLA Citation
Harpole, DH, DeCamp, MM, Daley, J, Hur, K, Oprian, CA, Henderson, WG, and Khuri, SF. "Prognostic models of thirty-day mortality and morbidity after major pulmonary resection." J Thorac Cardiovasc Surg 117.5 (May 1999): 969-979.
PMID
10220692
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
117
Issue
5
Publish Date
1999
Start Page
969
End Page
979
DOI
10.1016/S0022-5223(99)70378-8

A biologic risk model for stage I lung cancer: immunohistochemical analysis of 408 patients with the use of ten molecular markers.

OBJECTIVE: The standard treatment of patients with stage I non-small cell lung cancer is resection of the primary tumor; however, the recurrence rate is 28% to 45%. This study evaluates a panel of molecular markers in a large population of patients with stage I non-small cell lung cancer to determine the prognostic value of each marker and to create a biologic risk model. METHODS: Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I non-small cell lung cancer at a single institution, with follow-up of at least 5 years. A panel of 10 molecular markers was chosen for immunohistochemical analysis of the primary tumor on the basis of differing oncogenic mechanisms. Local tumor expansion requires growth regulating proteins (epidermal growth factor receptor, the protooncogene erb-b2); apoptosis proteins (p53, bcl-2); and cell cycle regulating proteins (retinoblastoma recessive oncogene, KI-67). Local tumor invasion requires angiogenesis (factor viii). The development of distant metastases involves the expression of adhesion proteins (CD-44, sialyl-Tn, blood group A). Cox proportional hazards regression analysis was used to construct an independent risk model for cancer recurrence and death. RESULTS: Multivariable analysis demonstrated significantly elevated risk for the following molecular markers: p53 (hazard ratio, 1.68; P =.004); factor viii (hazard ratio, 1.47 P =. 033); erb-b2 (hazard ratio, 1.43; P =.044); CD-44 (hazard ratio, 1. 40; P =.050); and retinoblastoma recessive oncogene (hazard ratio, 0. 747; P =.084). CONCLUSIONS: Five molecular markers were associated with the risk of recurrence and death, representing independent metastatic pathways: apoptosis (p53), angiogenesis (factor viii), growth regulation (erb-b2), adhesion (CD-44), and cell cycle regulation (retinoblastoma recessive oncogene). This study demonstrates the validity of this molecular biologic risk model in patients with stage I non- small cell lung cancer.

Authors
D'Amico, TA; Massey, M; Herndon, JE; Moore, MB; Harpole, DH
MLA Citation
D'Amico, TA, Massey, M, Herndon, JE, Moore, MB, and Harpole, DH. "A biologic risk model for stage I lung cancer: immunohistochemical analysis of 408 patients with the use of ten molecular markers." J Thorac Cardiovasc Surg 117.4 (April 1999): 736-743.
PMID
10096969
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
117
Issue
4
Publish Date
1999
Start Page
736
End Page
743

Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: Clinical implications

Authors
Kwiatkowski, DJ; Jr, DHH; Godlewski, J; II, JEH; Shieh, D-B; Richards, W; Blanco, R; Xu, H-J; Strauss, GM; Sugarbaker, DJ
MLA Citation
Kwiatkowski, DJ, Jr, DHH, Godlewski, J, II, JEH, Shieh, D-B, Richards, W, Blanco, R, Xu, H-J, Strauss, GM, and Sugarbaker, DJ. "Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: Clinical implications." Pneumologie 53.2 (1999): 105--.
Source
scival
Published In
Pneumologie
Volume
53
Issue
2
Publish Date
1999
Start Page
105-

Prognostic significance of HER-2/neu overexpression in stage I adenocarcinoma of lung

Authors
Harpole, DH
MLA Citation
Harpole, DH. "Prognostic significance of HER-2/neu overexpression in stage I adenocarcinoma of lung." ANNALS OF THORACIC SURGERY 66.4 (October 1998): 1163-1164.
Source
wos-lite
Published In
The Annals of Thoracic Surgery
Volume
66
Issue
4
Publish Date
1998
Start Page
1163
End Page
1164

Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications.

PURPOSE: To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). METHODS: All patients with stage I NSCLC resected at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. RESULTS: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge resection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. CONCLUSION: Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors for recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87%; those with three factors are graded Ib, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%.

Authors
Kwiatkowski, DJ; Harpole, DH; Godleski, J; Herndon, JE; Shieh, DB; Richards, W; Blanco, R; Xu, HJ; Strauss, GM; Sugarbaker, DJ
MLA Citation
Kwiatkowski, DJ, Harpole, DH, Godleski, J, Herndon, JE, Shieh, DB, Richards, W, Blanco, R, Xu, HJ, Strauss, GM, and Sugarbaker, DJ. "Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications." J Clin Oncol 16.7 (July 1998): 2468-2477.
PMID
9667266
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
16
Issue
7
Publish Date
1998
Start Page
2468
End Page
2477
DOI
10.1200/JCO.1998.16.7.2468

The evolution of therapy for patients with stage IIIA (N2) lung cancer.

This is a demonstrable case report and discussion of recent trends in neoadjuvant therapy for patients with locally advanced stage IIIA (N2) non-small cell lung cancer.

Authors
Harpole, DH
MLA Citation
Harpole, DH. "The evolution of therapy for patients with stage IIIA (N2) lung cancer." Chest 112.4 Suppl (October 1997): 201S-202S.
PMID
9337288
Source
pubmed
Published In
Chest
Volume
112
Issue
4 Suppl
Publish Date
1997
Start Page
201S
End Page
202S

Methemoglobinemia complicating topical anesthesia during bronchoscopic procedures

Authors
Clary, B; Skaryak, L; Tedder, M; Hilton, A; Botz, G; Harpole, D
MLA Citation
Clary, B, Skaryak, L, Tedder, M, Hilton, A, Botz, G, and Harpole, D. "Methemoglobinemia complicating topical anesthesia during bronchoscopic procedures." Journal of Thoracic and Cardiovascular Surgery 114.2 (1997): 293-295.
PMID
9270654
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
114
Issue
2
Publish Date
1997
Start Page
293
End Page
295
DOI
10.1016/S0022-5223(97)70163-6

Video-assisted thoracic surgery in the elderly. A review of 307 cases

Authors
Jaklitsch, MT; Decamp, MM; Liptay, MJ; Harpole, DH; Swanson, SJ; Mentzer, SJ; Sugarbaker, DJ
MLA Citation
Jaklitsch, MT, Decamp, MM, Liptay, MJ, Harpole, DH, Swanson, SJ, Mentzer, SJ, and Sugarbaker, DJ. "Video-assisted thoracic surgery in the elderly. A review of 307 cases." 1997.
Source
wos-lite
Published In
INTERNATIONAL CONGRESS OF THORAX SURGERY
Publish Date
1997
Start Page
599
End Page
601

Video-assisted thoracic surgery in the elderly. A review of 307 cases.

STUDY OBJECTIVE: The objective of the study was to investigate the impact of video-assisted thoracic surgery (VATS) on age-related morbidity and mortality for thoracic surgical procedures. DESIGN: Prospective data were collected on 896 consecutive VATS procedures from July 1991 to June 1994. Daily in-hospital, postoperative data collection by a full-time thoracic surgical nurse and postdischarge follow-up in a thoracic surgery clinic at 1 and 6 weeks were done. PATIENTS: On 296 patients aged 65 or older, 307 procedures were performed. One hundred nine procedures were performed on patients between 65 and 69 years, 110 on patients between 70 and 74 years, 55 on patients between 75 and 79 years, and 33 on those between 80 and 90 years. MEASUREMENTS AND RESULTS: The population was divided into four cohorts of 5-year age spans for analysis. Comparison was made with Fisher's Exact Test. Overall, 61% of the 307 procedures were for pulmonary disease. There were 32 anatomic lung resections (VATS lobectomies or segmentectomies), 156 extra-anatomic lung resections (thoracoscopic wedge or bullectomy), 78 procedures for pleural disease (25%), 27 mediastinal dissections (9%), and 14 pericardial windows (5%). There was a trend toward a lower mean FEV1 with increasing age. There were 3 deaths; overall mortality was less than 1%. There were 4 conversions to open thoracotomy (1%). Complications occurred with 45 procedures (15% morbidity). Twenty-two operations (7%) were associated with major complications adding to the length of stay and 27 procedures (9%) had minor complications. Median length of stay after VATS was 4 days for patients aged 65 to 79 years and 5 days for those aged 80 to 90 years. Morbidity and mortality were unrelated to age. CONCLUSIONS: The 30-day operative mortality is superior to previous reports of standard thoracotomy. Morbidity is low and length of hospital stay appears improved. VATS techniques may be safer than open thoracotomy in the aged. Age alone should not be a contraindication to operative intervention.

Authors
Jaklitsch, MT; DeCamp, MM; Liptay, MJ; Harpole, DH; Swanson, SJ; Mentzer, SJ; Sugarbaker, DJ
MLA Citation
Jaklitsch, MT, DeCamp, MM, Liptay, MJ, Harpole, DH, Swanson, SJ, Mentzer, SJ, and Sugarbaker, DJ. "Video-assisted thoracic surgery in the elderly. A review of 307 cases." Chest 110.3 (September 1996): 751-758.
PMID
8797422
Source
pubmed
Published In
Chest
Volume
110
Issue
3
Publish Date
1996
Start Page
751
End Page
758

Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients.

OBJECTIVE: The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors. BACKGROUND: Mesothelioma is a rare, uniformly fatal disease that has increased in incidence in recent decades. Single and bimodality therapies do not improve survival. METHODS: From 1980 to 1995, 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women's Hospital and Dana-Farber Cancer Institute (Boston, MA). Initial patient evaluation was performed by a multimodality team. Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy. RESULTS: The cohort included 27 women and 93 men with a mean age of 56 years. Operative mortality rate was 5.0%, with a major morbidity rate of 22%. Overall survival rates were 45% at 2 years and 22% at 5 years. Two and 5-year survival rates were 65% and 27%, respectively, for patients with epithelial cell type, and 20% and 0%, respectively, for patients with sarcomatous or mixed histology tumors. Nodal involvement was a significant negative prognostic factor. Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74% and 39%, respectively. Involvement of margins at time of resection did not affect survival, except in the case of full-thickness, transdiaphragmatic invasion. Classification on the basis of a revised staging system stratified median survivals, which were 22, 17, and 11 months for stages I, II, and III, respectively (p = 0.04). CONCLUSIONS: Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system.

Authors
Sugarbaker, DJ; Garcia, JP; Richards, WG; Harpole, DH; Healy-Baldini, E; DeCamp, MM; Mentzer, SJ; Liptay, MJ; Strauss, GM; Swanson, SJ
MLA Citation
Sugarbaker, DJ, Garcia, JP, Richards, WG, Harpole, DH, Healy-Baldini, E, DeCamp, MM, Mentzer, SJ, Liptay, MJ, Strauss, GM, and Swanson, SJ. "Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients." Ann Surg 224.3 (September 1996): 288-294.
PMID
8813257
Source
pubmed
Published In
Annals of Surgery
Volume
224
Issue
3
Publish Date
1996
Start Page
288
End Page
294

Effects of valve replacement on ventricular mechanics in mitral regurgitation and aortic stenosis.

BACKGROUND: This study in humans assessed changes in left ventricular function early and late after correction of mitral regurgitation (MR) (n = 9) or aortic stenosis (AS) (n = 10). METHODS: Ventricular function was measured with radionuclide and micromanometer-derived pressure-volume loops during preload manipulation, thermodilution cardiac outputs, and echocardiograms. Late radionuclide and echocardiographic data were acquired at 24 hours and 20 months. RESULTS: Perioperative left ventricular performance (stroke work-end-diastolic volume relationship) did not change for patients with MR or AS. Significant changes in afterload occurred: ejection fraction (MR, 0.49 to 0.37; AS, 0.54 to 0.60; both, p = 0.013), mean left ventricular ejection pressure (MR, 73 to 91 mm Hg; AS, 138 to 93 mm Hg; both, p < 0.01), and end-systolic wall stress (MR, 26 to 42 x 10(3) dynes/cm2; AS, 37 to 22 x 10(3) dynes/cm2; both, p < 0.01). Ejection efficiency improved for MR patients (0.69 +/- 0.26 to 1.0 +/- 0.15; p < 0.05). The 20-month data showed improved New York Heart Association functional class, normal resting ejection fraction, and normal exercise response for both groups. CONCLUSIONS: Early after operation, a significant change in left ventricular load was seen with correction of MR and AS. Data obtained late after operation showed improvement consistent with ventricular remodeling.

Authors
Harpole, DH; Gall, SA; Wolfe, WG; Rankin, JS; Jones, RH
MLA Citation
Harpole, DH, Gall, SA, Wolfe, WG, Rankin, JS, and Jones, RH. "Effects of valve replacement on ventricular mechanics in mitral regurgitation and aortic stenosis." Ann Thorac Surg 62.3 (September 1996): 756-761.
PMID
8784004
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
62
Issue
3
Publish Date
1996
Start Page
756
End Page
761

Chest wall invasive non-small cell lung cancer: patterns of failure and implications for a revised staging system.

BACKGROUND: To assess outcomes and patterns of failure for chest wall invasive non-small cell lung cancer (T3 or IIIA NSCLC), data were acquired prospectively on 47 consecutive patients at a single institution over 6 years. METHODS: Preresectional stagings included bone scan, head and chest/abdominal computed tomography, and mediastinoscopy. There were 25 superior sulcus tumors (radiation and/or chemotherapy followed by resection) and 22 other chest wall invasive NSCLCs (resection alone). RESULTS: There were no perioperative deaths. Seventeen patients (36%) had an operative complication (median length of stay increased from 7 to 12 days; p < 0.05). A complete pathologic resection was achieved for 44 of 47 patients (94%). The median survival was 38 months (actuarial 2- and 5-year survival rates of 62% and 50%, respectively). Median lengths of survival for superior sulcus and other chest wall tumors were 36 and > 60 months, respectively. Significant univariate predictors of decreased overall and cancer-free survival were poor performance status, positive margins, and positive lymph nodes. Recurrence was observed in 22 of 47 patients (46%) at a median of 8 months (range 2-24); patterns of failure were in the ipsilateral chest (n = 2; 4%) and at a distant site (n = 15; 32%) or both (n = 5; 11%). CONCLUSIONS: The operative risk for chest wall invasive NSCLC is acceptable, even after neoadjuvant therapy, allowing for a 94% complete resection rate. The survival of this subset of stage IIIA patients may warrant a reappraisal of the international staging system.

Authors
Harpole, DH; Healey, EA; DeCamp, MM; Mentzer, SJ; Strauss, GM; Sugarbaker, DJ
MLA Citation
Harpole, DH, Healey, EA, DeCamp, MM, Mentzer, SJ, Strauss, GM, and Sugarbaker, DJ. "Chest wall invasive non-small cell lung cancer: patterns of failure and implications for a revised staging system." Ann Surg Oncol 3.3 (May 1996): 261-269.
PMID
8726181
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
3
Issue
3
Publish Date
1996
Start Page
261
End Page
269

Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer.

BACKGROUND: Although complete surgical resection remains the primary treatment for localized stage I non-small cell lung cancer, the cancer recurrence rate is 25% to 40%. If one could identify, a subset of patients using molecular factors that contribute to tumour aggressiveness, one might improve prognosis in this group with additional treatment. High expression of angiogenesis factor viii has been associated with the presence of nodal metastases in breast cancer; here we examined its relation to survival with non-small lung cancer. METHODS: We examined angiogenesis using immunohistochemistry on paraffin blocks of tumour from 275 consecutive patients with stage I non-small cell lung cancer, more than 68 months of follow-up, and a 64% 5-year survival. Angiogenesis was calculated from the microvessel number per ten 200 x microscope fields measured at the tumor periphery, in the center, and in the area of highest concentration. RESULTS: Measurements in the central area were inconsistent due to prominent necrosis. However, microvessel number recorded at the periphery and at the "hottest" are correlated well (r2 = 0.952; p = 0.001), and a significant survival advantage was noted for low-level expression at both areas (peripheral, p = 0.046; "hottest", p = 0.006). Multivariate survival analysis using angiogenesis, protooncogene erbB-2, tumor suppressor gene p53, and the proliferation marker KI-67 defined angiogenesis as the most significant prognostic factor in stage I lung cancer. CONCLUSIONS: This molecular biologic substaging system including angiogenesis for stage I non-small cell lung cancer is independent of routine histopathologic factors and revealed an additive adverse effect with expression of several biologic markers (5-year survival: no marker [n = 51] 81%, 1 marker [n = 82] 71%, 2 markers [n = 84] 54%, and 3 to 4 markers [n = 58] 49%; p = 0.0001).

Authors
Harpole, DH; Richards, WG; Herndon, JE; Sugarbaker, DJ
MLA Citation
Harpole, DH, Richards, WG, Herndon, JE, and Sugarbaker, DJ. "Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer." Ann Thorac Surg 61.5 (May 1996): 1470-1476.
PMID
8633961
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
61
Issue
5
Publish Date
1996
Start Page
1470
End Page
1476
DOI
10.1016/0003-4975(96)00104-X

Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer - Discussion

Authors
Miller, DL; Harpole, DH; Pass, HI
MLA Citation
Miller, DL, Harpole, DH, and Pass, HI. "Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer - Discussion." ANNALS OF THORACIC SURGERY 61.5 (May 1996): 1476-1476.
Source
wos-lite
Published In
The Annals of Thoracic Surgery
Volume
61
Issue
5
Publish Date
1996
Start Page
1476
End Page
1476

Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias.

BACKGROUND: Data were acquired prospectively on 136 consecutive patients undergoing pneumonectomy for cancer from 1988 to 1993, to define factors that increase the risk of major morbidity and postoperative cardiac dysrhythmias. METHODS: There were 81 patients (60%) with non-small cell lung cancer (standard pneumonectomy) and 55 patients (40%) with malignant pleural mesothelioma (extrapleural pneumonectomy). RESULTS: Four perioperative deaths occurred (3%) with no identifiable associated risk factors. Twenty-three patients (17%) had a major complication with an increase in the median length of stay from 7 to 11 days (p < 0.01). Age greater than 65 years, right-sided procedures, and dysrhythmias were associated with an increased risk of a major complication (p < 0.05). Thirty-two patients (24%) had supraventricular dysrhythmias, which occurred on postoperative days 1 to 2 (n = 8), 3 to 4 (n = 13), 5 to 6 (n = 6), and 7 to 12 (n = 5). The median length of stay increased from 8 to 11 days with dysrhythmias (p < 0.05). Factors associated with an increased risk of dysrhythmias included age greater than 65 years, intrapericardial or extrapleural pneumonectomy, right-sided procedure, and any major complication. CONCLUSIONS: Pneumonectomy can be performed safely in selected patients with cancer. Supraventricular dysrhythmia was the most common complication noted with a peak incidence at 3 to 4 days after resection.

Authors
Harpole, DH; Liptay, MJ; DeCamp, MM; Mentzer, SJ; Swanson, SJ; Sugarbaker, DJ
MLA Citation
Harpole, DH, Liptay, MJ, DeCamp, MM, Mentzer, SJ, Swanson, SJ, and Sugarbaker, DJ. "Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias." Ann Thorac Surg 61.3 (March 1996): 977-982.
PMID
8619729
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
61
Issue
3
Publish Date
1996
Start Page
977
End Page
982
DOI
10.1016/0003-4975(95)01174-9

Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths in women and men in the United States, with more than 157,000 estimated deaths in 1995. Surgical resection remains the mainstay of therapy in Stage I and II disease. However, local and distant recurrence account for the disappointing survival rates after resection. Appropriate selection of surgical procedures and effective use of adjuvant therapies will depend upon the elucidation of prognostic factors that predict for recurrence. METHODS: A detailed analysis was undertaken to evaluate surgical therapy and to define risk factors associated with recurrence and cancer death in 289 consecutive patients with NSCLC who were diagnosed, resected and followed at the Duke University Medical Center from January 1, 1980, until December 31, 1988. These patients had no evidence of metastases on head and chest/abdominal computed tomograms and radionuclide bone scans before resection. Resected specimens from these patients pathologic verification of Stage I disease. Follow-up was complete in all cases through 8/1/94 (median, 61 months). Variables analyzed included age, sex, smoking history, presenting signs and symptoms, operative procedure, histopathology, hospital course including complications, and the time and location of any recurrence or cancer death. RESULTS: The 30-day mortality rate was 5 of 289 (1.7%), with minor and major morbidity rates of 17% and 9%, respectively. Statistical comparison of lobectomy (193) wedge resection (75) and pneumonectomy (21) revealed significantly (P < 0.04) smaller tumors (T1), more comorbidity, and fewer complications for wedge resection patients. A trend (P < 0.09) toward an increased rate of local/regional recurrence and no difference in survival was also observed for wedge resection. One hundred five patients died of cancer (13-month median time to recurrence) for an actual 5-year survival of 63%. Significant univariate predictors of early recurrence and decreased survival (P < 0.01) were: male sex, the presence of symptoms, hemoptysis, chest pain, type of cough, tumor size in cm and by T-classification, visceral pleural invasion, high mitotic index, and vascular invasion. Significant (P < 0.05) multivariate independent variables for early recurrence and cancer death were the presence of symptoms, vascular invasion, pleural invasion, high mitotic index, and tumor size greater than 3 cm. CONCLUSION: Current surgical therapy for stage I NSCLC has an acceptable morbidity and mortality rate. The current data also stratify patients with Stage I NSCLC into high and low risk populations that can be used in future randomized trials of adjuvant therapy.

Authors
Harpole, DH; Herndon, JE; Young, WG; Wolfe, WG; Sabiston, DC
MLA Citation
Harpole, DH, Herndon, JE, Young, WG, Wolfe, WG, and Sabiston, DC. "Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence." Cancer 76.5 (September 1, 1995): 787-796.
PMID
8625181
Source
pubmed
Published In
Cancer
Volume
76
Issue
5
Publish Date
1995
Start Page
787
End Page
796

The safety and versatility of video-thoracoscopy: a prospective analysis of 895 consecutive cases.

BACKGROUND: The application of video-endoscopy to general thoracic surgery is radically changing the approach to many benign and malignant diseases of the chest. Since July 1991, we have performed 794 purely thoracoscopic and 101 video-assisted thoracic surgical (VATS) procedures on 860 patients. STUDY DESIGN: Comprehensive, prospectively acquired data examining the specific indications for and outcomes of this new technique were prospectively entered into a thoracic surgical database. Preoperative, intraoperative, postoperative, and outcome variables were studied for the entire group as well as three high-risk cohorts: age over 70 years (n = 198), forced expiratory volume in one second (FEV1) of less than 1 L (n = 46), and Karnofsky performance index of less than 8 (n = 61). RESULTS: The 895 cases involved 449 men and 446 women of ages 15 to 89 years (mean 56 +/- 16 years standard deviation). The indications for surgery were diagnostic in 501 cases (56 percent), therapeutic in 244 cases (27 percent), and both diagnostic and therapeutic in an additional 150 cases (17 percent). The specific procedures performed were operations on the lung (569 cases), pleura (196 cases), esophagus (42 cases), mediastinum (51 cases), and pericardium (37 cases). Fifty-seven percent of the procedures were for a malignant process and 43 percent were for benign or infectious pathology. There were nine deaths for a series operative mortality rate of 1.0 percent. Thirteen patients (1.4 percent) required conversion to a limited thoracotomy for technical reasons. There were 127 complications in 121 patients yielding a morbidity rate in all patients of 14 percent. Mortality rates in the elderly, poor lung function, and depressed performance index cohorts were 1.5, 2.1, and 9.8 percent, respectively. Morbidity rates in these high-risk populations were 19, 30, and 18 percent, respectively. The median postoperative length of stay was three days after closed thoracoscopy and five days after VATS resection. CONCLUSIONS: These data underscore the flexibility, safety, efficacy, and potential for cost savings of videoscopic surgery in patients with thoracic diseases. The ability to perform excisional biopsy improves diagnostic specificity and sensitivity to nearly 100 percent. Video-assisted thoracic surgical techniques also offer a minimally invasive procedure with acceptable risk to patients heretofore inoperable by standard thoracotomy.

Authors
DeCamp, MM; Jaklitsch, MT; Mentzer, SJ; Harpole, DH; Sugarbaker, DJ
MLA Citation
DeCamp, MM, Jaklitsch, MT, Mentzer, SJ, Harpole, DH, and Sugarbaker, DJ. "The safety and versatility of video-thoracoscopy: a prospective analysis of 895 consecutive cases." J Am Coll Surg 181.2 (August 1995): 113-120.
PMID
7627382
Source
pubmed
Published In
Journal of The American College of Surgeons
Volume
181
Issue
2
Publish Date
1995
Start Page
113
End Page
120

Thoracoscopy and video-assisted thoracic surgery in the treatment of lung cancer.

The contemporary surgical repertoire for the evaluation and treatment of patients with lung cancer includes the bronchoscope, mediastinoscope, thoracoscope, and standard surgical instrumentation. The recent advances in video optics and the development of endoscopic instruments have significantly expanded the surgical options for patients with lung cancer. Thoracoscopy, or the more inclusive term of video-assisted thoracic surgery (VATS), has been characterized as "minimally invasive" surgery. Thoracoscopy and VATS have decreased operative trauma and facilitated surgical staging prior to neoadjuvant therapy. An ancillary benefit to diminished surgical morbidity is shorter hospital stays with a concomitant reduction in costs to the patient and health-care system. These advantages make VATS ideal for elderly patients or patients with significant comorbidity.

Authors
Mentzer, SJ; DeCamp, MM; Harpole, DH; Sugarbaker, DJ
MLA Citation
Mentzer, SJ, DeCamp, MM, Harpole, DH, and Sugarbaker, DJ. "Thoracoscopy and video-assisted thoracic surgery in the treatment of lung cancer." Chest 107.6 Suppl (June 1995): 298S-301S.
PMID
7781410
Source
pubmed
Published In
Chest
Volume
107
Issue
6 Suppl
Publish Date
1995
Start Page
298S
End Page
301S

Prognostic issues in non-small cell lung cancer.

Authors
Harpole, DH
MLA Citation
Harpole, DH. "Prognostic issues in non-small cell lung cancer." Chest 107.6 Suppl (June 1995): 267S-269S.
PMID
7781404
Source
pubmed
Published In
Chest
Volume
107
Issue
6 Suppl
Publish Date
1995
Start Page
267S
End Page
269S

Localized adenocarcinoma of the lung: oncogene expression of erbB-2 and p53 in 150 patients.

Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53, and erbB-2 gene amplification. Pathological material after resection was reviewed to verify histological staging, and patient follow-up was complete in all cases for at least 68 months. Immunohistochemistry of erbB-2 (HER-2/neu) and p53 oncogene expression was performed on two separate paraffin tumor blocks for each patient with normal lung as control. Gene amplification of erbB-2 was measured after DNA extraction from 20-micrometer sections of erbB-2-positive and -negative tumors. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Two adequate blocks of tumor and normal lung were available for 138 (92%) patients. Immunohistochemical identification of expression of p53 was observed in 49 (37%) patients and erbB-2 in 17 (13%) patients. DNA dot blot analyses were performed on 17 erbB-2-positive and 13 randomly selected erbB-2-negative tumors. There was 1 (6%) of 17 erbB-2-positve tumors with 4-fold erbB-2 gene amplification. Actual 5-year survival was 63% and actuarial 10-year survival was 59% for the entire population of 150 patients. Significant univariate predictors (P < 0.05) of cancer death were the presence of symptoms, tumor size >3 cm, poor differentiation, visceral pleural invasion, and p53 expression. Multivariate analysis associated symptoms and p53 expression as independent factors with decreased survival. Thus, this project examined p53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival. Multicenter collection of data should allow the development of a model of cancer recurrence in this most common lung cancer.

Authors
Harpole, DH; Marks, JR; Richards, WG; Herndon, JE; Sugarbaker, DJ
MLA Citation
Harpole, DH, Marks, JR, Richards, WG, Herndon, JE, and Sugarbaker, DJ. "Localized adenocarcinoma of the lung: oncogene expression of erbB-2 and p53 in 150 patients." Clin Cancer Res 1.6 (June 1995): 659-664.
PMID
9816029
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
1
Issue
6
Publish Date
1995
Start Page
659
End Page
664

Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.

PURPOSE: Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively. METHODS: Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed. RESULTS: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome. CONCLUSION: At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies.

Authors
Strauss, GM; Kwiatkowski, DJ; Harpole, DH; Lynch, TJ; Skarin, AT; Sugarbaker, DJ
MLA Citation
Strauss, GM, Kwiatkowski, DJ, Harpole, DH, Lynch, TJ, Skarin, AT, and Sugarbaker, DJ. "Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung." J Clin Oncol 13.5 (May 1995): 1265-1279. (Review)
PMID
7738631
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
13
Issue
5
Publish Date
1995
Start Page
1265
End Page
1279
DOI
10.1200/JCO.1995.13.5.1265

Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence

Background. Nonsmall cell lung cancer (NSCLC) has become the leading cause of cancer‐related deaths in women and men in the United States, with more than 157,000 estimated deaths in 1995. Surgical resection remains the mainstay of therapy in Stage I and II disease. However, local and distant recurrence account for the disappointing survival rates after resection. Appropriate selection of surgical procedures and effective use of adjuvant therapies will depend upon the elucidation of prognostic factors that predict for recurrence. Methods. A detailed analysis was undertaken to evaluate surgical therapy and to define risk factors associated with recurrence and cancer death in 289 consecutive patients with NSCLC who were diagnosed, resected and followed at the Duke University Medical Center from January 1, 1980, until December 31, 1988. These patients had no evidence of metastases on head and chest/abdominal computed tomograms and radionuclide bone scans before resection. Resected specimens from these patients pathologic verification of Stage I disease. Follow‐up was complete in all cases through 8/1/94 (median, 61 months). Variables analyzed included age, sex, smoking history, presenting signs and symptoms, operative procedure, histopathology, hospital course including complications, and the time and location of any recurrence or cancer death. Results. The 30‐day mortality rate was 5 of 289 (1.7%), with minor and major morbidity rates of 17% and 9%, respectively. Statistical comparison of lobectomy (193) wedge resection (75) and pneumonectomy (21) revealed significantly (P < 0.04) smaller tumors (T1), more comorbidity, and fewer complications for wedge resection patients. A trend (P < 0.09) toward an increased rate of local/regional recurrence and no difference in survival was also observed for wedge resection. One hundred five patients died of cancer (13‐month median time to recurrence) for an actual 5‐year survival of 63%. Significant univariate predictors of early recurrence and decreased survival (P < 0.01) were: male sex, the presence of symptoms, hemoptysis, chest pain, type of cough, tumor size in cm and by T‐classification, visceral pleural invasion, high mitotic index, and vascular invasion. Significant (P < 0.05) multivariate independent variables for early recurrence and cancer death were the presence of symptoms, vascular invasion, pleural invasion, high mitotic index, and tumor size greater than 3 cm. Conclusion. Current surgical therapy for stage I NSCLC has an acceptable morbidity and mortality rate. The current data also stratify patients with Stage I NSCLC into high and low risk populations that can be used in future randomized trials of adjuvant therapy. Copyright © 1995 American Cancer Society

Authors
Harpole, DH; Herndon, JE; Young, WG; Wolfe, WG; Sabiston, DC
MLA Citation
Harpole, DH, Herndon, JE, Young, WG, Wolfe, WG, and Sabiston, DC. "Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence." Cancer 76.5 (January 1, 1995): 787-796.
Source
scopus
Published In
Cancer
Volume
76
Issue
5
Publish Date
1995
Start Page
787
End Page
796
DOI
10.1002/1097-0142(19950901)76:5<787::AID-CNCR2820760512>3.0.CO;2-Q

A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression.

In order to construct a multivariate model for predicting early recurrence and cancer death for patients with stage I non-small cell lung cancer, 271 consecutive patients (mean age, 63 +/- 8 years) who were diagnosed, treated, and followed at one institution were studied. All patients were clinical stage I with head and chest/abdominal computed tomograms and radionuclide bone scans without evidence of metastatic disease. Pathological material after resection was reviewed to verify histological staging. Follow-up documented the time and location of any recurrence, was a median 56 months in duration, and was complete in all cases. Data recorded included age, sex, smoking history, presenting symptoms, pathological description, and oncoprotein staining for erbB-2 (HER-2/neu), p53, and KI-67 proliferation protein. Immunohistochemistry of oncogene expression was performed on two separate archived paraffin tumor blocks for each patient, with normal lung as control. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Data, including immunohistochemistry, were complete for all 271 patients. Actual 5-year survival was 63% and actuarial 10-year survival was 58%. Significant univariate predictors (P < 0.05) of early recurrence and cancer-death were: male sex; the presence of symptoms; chest pain; type of cough; hemoptysis; tumor size > 3 cm diameter (T2); poor differentiation; vascular invasion; erbB-2 expression; p53 expression; and a higher KI-67 proliferation index (> 5%). An additive oncogene expression curve demonstrated a 5-year survival of 72% for 136 patients without p53 or erbB-2, 58% for 108 patients who expressed either oncogene, and 38% for 27 who expressed both (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Harpole, DH; Herndon, JE; Wolfe, WG; Iglehart, JD; Marks, JR
MLA Citation
Harpole, DH, Herndon, JE, Wolfe, WG, Iglehart, JD, and Marks, JR. "A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression." Cancer Res 55.1 (January 1, 1995): 51-56.
PMID
7805040
Source
pubmed
Published In
Cancer Research
Volume
55
Issue
1
Publish Date
1995
Start Page
51
End Page
56

Current Issues in the Staging of Esophageal Cancer.

Staging technology and the 1983 international staging system for esophageal cancer have changed. The 1988 system is based on depth of wall penetration and regional lymph node involvement; it abandons the previous criteria of tumor length and degree of obstruction. The clinical reasoning behind this change is reviewed. New staging technology includes chest computed tomography (CT), magnetic resonance imaging (MRI), tranesophageal ultrasound (EUS), and invasive surgical staging. Overall accuracy of CT to predict depth of penetration is 80% to 85%. CT accuracy of regional lymph node status is less than 69%, but it is 90% accurate in the detection of distant metastases. MRI is comparable. EUS is 71% to 98% accurate in predicting depth of tumor invasion. Although highly sensitive (85% to 95%), the accuracy of EUS in predicting the status of lymph nodes is adversely affected by low specificity (50% to 60%), reducing its overall accuracy of node prediction to 70% to 88%. EUS may fail to assess intra-abdominal disease in 21% to 36% of patients secondary to esophageal obstruction. Regional nodes on both sides of the diaphragm can be assessed by laparoscopy combined with thoracoscopy. Thoracoscopy and laparoscopy have a greater than 92% accuracy in staging regional nodes. Such information is indispensable for the design of treatment fields. Combinations of these new technologies may provide improved preresectional staging.

Authors
Jaklitsch, MT; Harpole, DH; Healey, EA; Sugarbaker, DJ
MLA Citation
Jaklitsch, MT, Harpole, DH, Healey, EA, and Sugarbaker, DJ. "Current Issues in the Staging of Esophageal Cancer." Semin Radiat Oncol 4.3 (July 1994): 135-145.
PMID
10717101
Source
pubmed
Published In
Seminars in Radiation Oncology
Volume
4
Issue
3
Publish Date
1994
Start Page
135
End Page
145
DOI
10.1053/SRAO00400135

Left ventricular function under stress before and after myocardial revascularization.

To compare left ventricular responses to stress during exercise-induced myocardial ischemia and after myocardial revascularization, 35 patients (mean age 55 +/- 7 years, class III angina) with three-vessel coronary artery disease underwent a rest and exercise initial-transit radionuclide angiocardiography before aortocoronary bypass grafting. Left ventricular ejection fraction decreased during exercise (p less than 0.01), but cardiac output was augmented with an increased heart rate (p less than 0.0001) and left ventricular end-diastolic volume (p less than 0.001). Group A (n = 15) underwent six serial resting studies at different volume loads during the first 24 hours after operation while heart rate and blood pressure were held constant. These data revealed no significant change in left ventricular ejection fraction, but preload varied in all patients because of bleeding and fluid administration, with a mean end-diastolic volume change of 115 to 176 ml. This range of end-diastolic volume was similar to that defined with rest and exercise testing before operation. Group B (n = 20) underwent a repeat rest and exercise test 3 months after operation that demonstrated no change in resting function. However, exercise ejection fraction and peak systolic pressure/end-systolic volume ratio increased (p less than 0.001 and p less than 0.05, respectively) while end-diastolic volume decreased (p less than 0.05) compared with the values before operation. These data indicate that patients with coronary artery disease have chronically adapted cardiac function that makes use of both rapid heart rate and a wide range in preload to augment cardiac function under stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Harpole, DH; Jones, RH
MLA Citation
Harpole, DH, and Jones, RH. "Left ventricular function under stress before and after myocardial revascularization." Am Heart J 124.2 (August 1992): 273-279.
PMID
1636571
Source
pubmed
Published In
American Heart Journal
Volume
124
Issue
2
Publish Date
1992
Start Page
273
End Page
279

Bronchial carcinoid tumors: a retrospective analysis of 126 patients.

From 1970 until 1990, 8,958 cases of primary carcinoma of the lung were diagnosed at the Duke University Medical Center. During the same period, 126 patients (mean age, 53 +/- 13 years) were diagnosed with bronchial carcinoid. The overall survival was 78% for 5 years and 71% for 10 years. Surgical treatment in 106 patients included pneumonectomy (15), lobectomy (63 with 9 bronchoplastic procedures), stapled wedge resection (22), and bronchoscopic laser resection (6). The method of diagnosis was chest roentgenography (121), chest computed tomography (77), mediastinal tomography (31), bronchoscopy (81), bronchoscopic brushing and washing (50), bronchoscopic biopsy (40), transthoracic needle biopsy (27), thoracotomy (100), and autopsy (5). Univariate analysis of the medical history, presenting signs and symptoms, diagnostic test results, and pathologic data predicted improved survival (p less than 0.001) for: female sex (n = 58), asymptomatic presentation (n = 47), normal serum serotonin or urinary hydroxyindoleacetic acid levels (n = 76), peripheral location of the primary tumor (n = 50), pathologic stage I or II (n = 91), negative lymph nodes (n = 80), primary tumor 2 cm or less in diameter (n = 67), and typical histology (n = 80). No significance (p greater than 0.1) was observed for age, smoking history, race, family history of carcinoid, environmental exposure, or hemoptysis. The most important factors affecting survival defined by multivariate analysis were (p less than 0.01) pathologic stage, atypical histology, and asymptomatic presentation. Bronchial carcinoid tumors are unique, making up 1% to 2% of primary lung neoplasms and having an excellent prognosis after resection with a 95% 5-year and 93% 10-year survival for pathologic stage I disease.

Authors
Harpole, DH; Feldman, JM; Buchanan, S; Young, WG; Wolfe, WG
MLA Citation
Harpole, DH, Feldman, JM, Buchanan, S, Young, WG, and Wolfe, WG. "Bronchial carcinoid tumors: a retrospective analysis of 126 patients." Ann Thorac Surg 54.1 (July 1992): 50-54.
PMID
1610254
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
54
Issue
1
Publish Date
1992
Start Page
50
End Page
54

Analysis of 945 cases of pulmonary metastatic melanoma.

From 1970 to 1990, 7564 patients with melanoma were seen at Duke University Cancer Center. Complete follow-up data were available in all patients. The estimated probability of a pulmonary metastasis developing 5, 10, or 20 years after initial diagnosis was 0.13, 0.19, and 0.30, respectively. Pulmonary metastases were documented in 945 patients (12%), these having 1-, 3-, and 5-year survival rates of 30%, 9%, and 4%, respectively. The methods of diagnosis were chest radiograph (n = 544), computed tomography (n = 157), transthoracic needle biopsy (n = 121), bronchoscopy (n = 14), thoracotomy (n = 112), and autopsy (n = 7). Evidence of advanced pulmonic spread included bilateral disease in 543 and more than two nodules in 595. Univariate predictors for early formation of pulmonary metastases (p less than 0.001) were male sex, black race, increased primary thickness (millimeters), higher Clark's level, nodular or acral lentiginous histology, location on trunk or head and neck, and regional lymph nodes positive for metastasis. Multivariate predictors of improved survival (p less than 0.001) in order of importance were complete resection of pulmonary disease, longer time for formation of metastases, treatment with chemotherapy, one or two pulmonary nodules, lymph nodes negative for metastasis lymph nodes (p less than 0.005), and histologic type (p less than 0.04). Additionally, survival in patients with one nodule and resection (n = 84) was better than in those with similar disease and no resection (n = 142 months, p less than 0.001). These data comprise the largest series to date and emphasize the importance of long-term follow-up, as well as supporting the selective use of resection for isolated pulmonary metastases, increasing the 5-year survival rate from 4% to 20%.

Authors
Harpole, DH; Johnson, CM; Wolfe, WG; George, SL; Seigler, HF
MLA Citation
Harpole, DH, Johnson, CM, Wolfe, WG, George, SL, and Seigler, HF. "Analysis of 945 cases of pulmonary metastatic melanoma." J Thorac Cardiovasc Surg 103.4 (April 1992): 743-748.
PMID
1548916
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
103
Issue
4
Publish Date
1992
Start Page
743
End Page
748

Early and late changes in left ventricular systolic performance after percutaneous aortic balloon valvuloplasty.

To evaluate early and late hemodynamics after aortic valvuloplasty, 17 patients underwent first-pass radionuclide angiocardiography with simultaneous high-fidelity micromanometer pressure before, 10 minutes after and 6 months after aortic valvuloplasty. Pressure-volume and stress data were assessed. Immediately after the procedure, no significant change was observed in heart rate, systemic blood pressure, cardiac output or aortic insufficiency (as measured by visual or quantitative aortography). The mean and peak transvalvular gradient decreased from 64 to 36 mm Hg (p less than 0.001) and 76 to 38 mm Hg (p less than 0.001), respectively. The mean aortic valve area increased from 0.5 to 0.8 cm2 (p less than 0.001). Using echocardiography, meridional end-systolic wall stress decreased from 81 to 63 x 10(3) dynes/cm2 (p less than 0.001). Left ventricular ejection fraction increased from 0.48 to 0.54 (p less than 0.01), end-diastolic volume decreased from 161 to 143 ml (p less than 0.001) and end-diastolic pressure decreased from 18 to 13 mm Hg (p less than 0.01). Left ventricular stroke work (the area of the pressure-volume loop) also decreased from 17.5 to 14.7 x 10(6) ergs (p less than 0.001). The loop shifted to the left and downward. At the 6-month study, the mean and peak aortic valve gradient increased from 36 to 56 mm Hg (p less than 0.001) and 38 to 61 mm Hg (p less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Harpole, DH; Davidson, CJ; Skelton, TN; Kisslo, KB; Jones, RH; Bashore, TM
MLA Citation
Harpole, DH, Davidson, CJ, Skelton, TN, Kisslo, KB, Jones, RH, and Bashore, TM. "Early and late changes in left ventricular systolic performance after percutaneous aortic balloon valvuloplasty." Am J Cardiol 66.3 (August 1, 1990): 327-332.
PMID
2368678
Source
pubmed
Published In
The American Journal of Cardiology
Volume
66
Issue
3
Publish Date
1990
Start Page
327
End Page
332

Effects of standard mitral valve replacement on left ventricular function.

Recent studies have suggested that excision of the mitral valve apparatus during mitral valve replacement impairs left ventricular performance. However, functional measurements in humans have been difficult to obtain in a load-independent fashion. To investigate this concept, 12 patients (mean age, 65 +/- 8 years; mean New York Heart Association functional class, 3.3 +/- 0.7) with 4+ mitral regurgitation (n = 8) or mitral stenosis (valve area, 1.2 +/- 0.2 cm2) (n = 4) underwent prosthetic valve replacement using crystalloid cardioplegia. No patient required therapeutic inotropic support, every patient had at least the anterior mitral leaflet excised, and paced heart rate was maintained constant throughout. Left ventricular volume was measured with radionuclide angiocardiography, left ventricular pressure with a 3F micromanometer, and left ventricular wall volume with two-dimensional transesophageal echocardiography. Left ventricular preload was varied over a mean end-diastolic pressure range of 9 to 20 mm Hg and an end-diastolic volume range of 134 to 170 mL to generate four to five steady-state pressure-volume loops before and ten minutes after cardiopulmonary bypass. Left ventricular performance was estimated with the stroke work/end-diastolic volume relationship, which is insensitive to load. After bypass, no significant change (p greater than 0.1) was noted in wall volume for patients with mitral regurgitation or mitral stenosis (175 +/- 68 to 189 +/- 63 mL/m2 and 130 +/- 22 to 127 +/- 19 mL/m2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Harpole, DH; Rankin, JS; Wolfe, WG; Clements, FM; Van Trigt, P; Young, WG; Jones, RH
MLA Citation
Harpole, DH, Rankin, JS, Wolfe, WG, Clements, FM, Van Trigt, P, Young, WG, and Jones, RH. "Effects of standard mitral valve replacement on left ventricular function." Ann Thorac Surg 49.6 (June 1990): 866-873.
PMID
2369184
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
49
Issue
6
Publish Date
1990
Start Page
866
End Page
873

Changes in left ventricular systolic performance immediately after percutaneous aortic balloon valvuloplasty.

To evaluate the acute changes in left ventricular (LV) performance before and immediately after percutaneous aortic valvuloplasty, 25 patients underwent first-pass radionuclide angiocardiography for construction of pressure-volume loops. Simultaneously, high-fidelity micromanometric aortic and LV pressures were recorded. Echocardiographic wall thickness was used to define wall stress. After valvuloplasty, no acute changes were observed in the heart rate, aortic systolic pressure, cardiac output or degree of aortic insufficiency. Valvuloplasty decreased the peak aortic valve gradient from 73 to 40 mm Hg (p less than 0.001) and the mean gradient from 61 to 30 mm Hg (p less than 0.001); aortic valve area increased from 0.55 to 0.80 cm2 (p less than 0.001). Meridional end-systolic wall stress decreased from 83 to 55 X 10(3) dynes/cm2 (p less than 0.01). LV ejection fraction increased from 0.41 to 0.48 (p less than 0.01). LV end-diastolic volume decreased from 186 to 160 ml (p less than 0.001), end-systolic volume decreased from 115 to 87 ml (p less than 0.001) and end-diastolic pressure decreased from 22 to 17 mm Hg (p less than 0.01). LV stroke work decreased from 16.0 to 14.0 X 10(6) erg (p less than 0.001). No change was observed in peak positive LV dP/dt or the end-systolic pressure-volume ratio. This study documents variable and complex changes in the measures of cardiac function after aortic valvuloplasty. A decrease in the amount of LV outflow obstruction with maintenance of the cardiac output at a decreased level of LV filling occurs.

Authors
Harpole, DH; Davidson, CJ; Skelton, TN; Kisslo, KB; Jones, RH; Bashore, TM
MLA Citation
Harpole, DH, Davidson, CJ, Skelton, TN, Kisslo, KB, Jones, RH, and Bashore, TM. "Changes in left ventricular systolic performance immediately after percutaneous aortic balloon valvuloplasty." Am J Cardiol 65.18 (May 15, 1990): 1213-1218.
PMID
2337030
Source
pubmed
Published In
The American Journal of Cardiology
Volume
65
Issue
18
Publish Date
1990
Start Page
1213
End Page
1218

Serial assessment of ventricular performance after valve replacement for aortic stenosis.

The purpose of this investigation was to examine changes in cardiac function after aortic valve replacement in patients with chronic aortic stenosis. Eleven consecutive patients with severe aortic stenosis were studied by radionuclide angiocardiography before; after 1, 2, 4, 6, 8, and 18 to 24 hours; and late after operation. Measurements of cardiac output, mean systemic blood pressure, heart rate, and left ventricular ejection fraction were similar before and immediately after operation. Significant early changes were observed in pulmonary capillary wedge pressure (27 to 13 mm Hg; p less than 0.001), left ventricular end-diastolic volume (214 to 166 ml; p less than 0.01), pulmonary blood volume (700 to 462 ml/m2; p less than 0.01), and right ventricular ejection fraction (0.54 to 0.68; p less than 0.001). A radionuclide angiocardiogram acquired a mean of 3.5 months after operation revealed increased resting left ventricular ejection fraction (0.49 to 0.58; p = 0.05), decreased end-systolic volume (91 to 59 ml; p less than 0.05), and decreased end-diastolic volume (166 to 135 ml; p less than 0.02) compared with measurements before operation. Improved exercise tolerance occurred in nine patients. The significant change in function during the early period after valve replacement was a maintenance of baseline cardiac output at a reduced level of left ventricular filling. Several months after operation, left ventricular volumes decreased further, resting ventricular performance was improved, and improved maximal exercise function was demonstrated. These changes probably reflected morphologic normalization after aortic valve replacement.

Authors
Harpole, DH; Jones, RH
MLA Citation
Harpole, DH, and Jones, RH. "Serial assessment of ventricular performance after valve replacement for aortic stenosis." J Thorac Cardiovasc Surg 99.4 (April 1990): 645-650.
PMID
2319785
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
99
Issue
4
Publish Date
1990
Start Page
645
End Page
650

Estimation of left ventricular volume and ejection fraction by two-dimensional transoesophageal echocardiography: comparison of short axis imaging and simultaneous radionuclide angiography.

We have compared short axis images of the left ventricle (LV) obtained with transoesophageal echocardiography (TOE) to assess LV size and function with those obtained by radionuclide angiography (RNA). Simultaneous TOE and RNA images were attempted in 14 patients and results obtained in 12 patients undergoing repair of abdominal aortic aneurysms. The area of the LV cavity seen in the short axis images at a mid-papillary muscle level at end-systole (ESA) and end-diastole (EDA) were compared with volumes measured by RNA at end-systole (ESV) and end-diastole (EDV). An area ejection fraction (AEF) calculated from the TOE images (AEF = EDA-ESA/EDA) was compared with the RNA ejection fraction (EF) where EF = EDV-ESV/EDV. Good correlations were found between TOE log EDA and RNA log EDV (r = 0.86), TOE log ESA and RNA log ESV (r = 0.92) and TOE AEF and RNA EF (r = 0.96). This suggests that TOE short axis imaging at a mid-papillary muscle level is generally adequate for monitoring LV function during operation.

Authors
Clements, FM; Harpole, DH; Quill, T; Jones, RH; McCann, RL
MLA Citation
Clements, FM, Harpole, DH, Quill, T, Jones, RH, and McCann, RL. "Estimation of left ventricular volume and ejection fraction by two-dimensional transoesophageal echocardiography: comparison of short axis imaging and simultaneous radionuclide angiography." Br J Anaesth 64.3 (March 1990): 331-336.
PMID
2328181
Source
pubmed
Published In
BJA: British Journal of Anaesthesia
Volume
64
Issue
3
Publish Date
1990
Start Page
331
End Page
336

Serial evaluation of ventricular function after percutaneous aortic balloon valvuloplasty.

To evaluate the serial changes in right and left ventricular performance after percutaneous aortic balloon valvuloplasty, 15 patients, mean age 75 +/- 18 years, and in New York Heart Association (NYHA) class III, were studied with first-pass radionuclide angiocardiography (RNA) immediately before, then 5 minutes, 2 hours, 4 hours, 6 hours, and 3 days after valvuloplasty. No change was observed in heart rate, aortic root systolic pressure, Fick, or RNA cardiac output, amount of aortic insufficiency measured either angiographically or with the regurgitant fraction determination immediately after valvuloplasty. However, significant changes were observed in the peak-to-peak aortic valve gradient (63 to 35 mm Hg; p less than 0.001), mean aortic valve gradient (54 to 33 mm Hg; p less than 0.001), aortic valve area (0.60 to 0.90 cm2; p less than 0.001), and meridional wall stress (79 to 50 10(3) dynes/cm2; p less than 0.01) immediately following valvuloplasty. In addition, left ventricular end-diastolic volume decreased from 186 to 153 ml (p less than 0.001), end-systolic volume decreased from 114 to 86 ml (p less than 0.001), micromanometric left ventricular end-diastolic pressure decreased from 20 to 14 mm Hg (p less than 0.02), and left ventricular ejection fraction increased from 0.39 to 0.45 (p less than 0.001). Peak positive left ventricular dP/dt and end-systolic pressure-volume ratio did not change after valvuloplasty (1700 to 1550 mm Hg/sec, 2.1 to 2.5 mm Hg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Harpole, DH; Davidson, C; Skelton, T; Jones, RH; Bashore, TM
MLA Citation
Harpole, DH, Davidson, C, Skelton, T, Jones, RH, and Bashore, TM. "Serial evaluation of ventricular function after percutaneous aortic balloon valvuloplasty." Am Heart J 119.1 (January 1990): 130-135.
PMID
2296854
Source
pubmed
Published In
American Heart Journal
Volume
119
Issue
1
Publish Date
1990
Start Page
130
End Page
135

Assessment of left ventricular functional preservation during isolated cardiac valve operations.

To evaluate intraoperative changes in myocardial performance during valvular operations, ventricular functional measurements were obtained in 16 patients before and after elective cardiac valvular replacement. Six patients had mitral regurgitation, four had mitral stenosis, and six had calcific aortic stenosis; all patients underwent isolated mitral or aortic valve replacement. Cold potassium crystalloid cardioplegia, topical hypothermia, and low-flow systemic hypothermia were employed uniformly. Just before and 10 minutes after cardiopulmonary bypass was discontinued, left ventricular pressure and volume data were recorded at four to five different steady-state levels of filling produced by blood infusion or withdrawal from the aortic cannula (mean end-diastolic pressure range, 10-22 mm Hg; mean end-diastolic volume range, 120-168 ml). Portable first-pass radionuclide ventriculography and simultaneous micromanometry were used for construction of left ventricular pressure-volume loops from which stroke work and end-diastolic volume were calculated. Two-dimensional transesophageal echocardiograms also were recorded, and epicardial pacing maintained heart rate as constant as possible. As compared with prebypass measurements, echocardiographic left ventricular wall volume changed insignificantly after the valvular procedures (178-181 ml/m2, p greater than 0.5). The stroke work-end-diastolic volume relationship before and after operation was highly linear in all studies (mean = 0.97). The slope and x intercept of this relationship did not change significantly after operation, indicating a stable level of left ventricular function (from 12.7 x 10(4) to 10.0 x 10(4) ergs/ml and from 67 to 57 ml, respectively; p greater than 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Harpole, DH; Rankin, JS; Wolfe, WG; Smith, LR; Young, WG; Clements, FM; Jones, RH
MLA Citation
Harpole, DH, Rankin, JS, Wolfe, WG, Smith, LR, Young, WG, Clements, FM, and Jones, RH. "Assessment of left ventricular functional preservation during isolated cardiac valve operations." Circulation 80.5 Pt 2 (November 1989): III1-III9.
PMID
2805286
Source
pubmed
Published In
Circulation
Volume
80
Issue
5 Pt 2
Publish Date
1989
Start Page
III1
End Page
III9

Validation of pressure-volume data obtained in patients by initial transit radionuclide angiocardiography.

In order to validate the measurement of pressure-volume loops and stroke work in humans, simultaneous digital subtraction ventriculography (DSA) and first-pass radionuclide angiocardiography (RNA) coupled with high-fidelity micromanometer left ventricular pressure measurements were undertaken in 34 patients, mean age 75 +/- 9 years, with aortic stenosis. Twenty-nine patients had a repeat study after balloon valvuloplasty, for a total of 63 DSA and RNA pressure-volume loops. All data were analyzed in a systemic fashion in order to minimize intra- and interobserver error. Linear regression analysis was used to calculate the degree of agreement between the two technologies. Left ventricular ejection fraction (RNA: 0.47 +/- 0.17, DSA: 0.49 +/- 0.18) had a correlation coefficient of 0.96; left ventricular end-diastolic volume (RNA: 171 +/- 42 ml, DAS: 168 +/- 52 ml) and end-systolic volume (RNA: 95 +/- 50 ml, DSA: 89 +/- 50 ml) had correlation coefficients of 0.89 and 0.95, respectively. Left ventricular stroke volume (RNA: 75 +/- 26 ml, DSA: 75 +/- 27 ml) had a correlation coefficient of 0.92, while integrated pressure-volume loop or stroke work (RNA: 15.6 +/- 6.6 ergs 10(6), DSA: 15.9 +/- 6.3 ergs 10(6] had a correlation coefficient of 0.89. These data demonstrate that RNA measurements of left ventricular chamber dynamics concur with that obtained with DSA. With semiautomated data analysis, the portable first-pass RNA pressure-volume data are also less labor-intensive. Moreover, multiple measurements of ventricular performance during hemodynamic manipulations in the catheterization laboratory or operating room would allow for a more precise estimation of left ventricular performance.

Authors
Harpole, DH; Skelton, TN; Davidson, CJ; Jones, RH; Bashore, TM
MLA Citation
Harpole, DH, Skelton, TN, Davidson, CJ, Jones, RH, and Bashore, TM. "Validation of pressure-volume data obtained in patients by initial transit radionuclide angiocardiography." Am Heart J 118.5 Pt 1 (November 1989): 983-989.
PMID
2816710
Source
pubmed
Published In
American Heart Journal
Volume
118
Issue
5 Pt 1
Publish Date
1989
Start Page
983
End Page
989

Right and left ventricular performance during and after abdominal aortic aneurysm repair.

To evaluate the effect of aortic occlusion and limb reperfusion on global and regional function of the right and left ventricle during infrarenal abdominal aortic aneurysm repair, 23 patients underwent five intraoperative first-pass radionuclide angiocardiograms: 1) before the skin incision, 2) at aortic cross-clamp, 3) 20 minutes after aortic occlusion, 4) at unclamping, and 5) after skin closure. A subset of twelve patients had simultaneous transesophageal echocardiography to evaluate left ventricular wall stress. Parameters measured included the electrocardiogram (ECG), heart rate, blood pressure, pulmonary artery pressure, the cardiac output, the left and right ventricular ejection fractions, left ventricular volumes, and left ventricular wall stress. Significant changes (p less than 0.01) were observed at aortic clamping in the left ventricular ejection fraction (from 0.56 to 0.48), end-diastolic volume (from 171 to 225 ml), end-systolic volume (from 85 to 127 ml), mean blood pressure (from 82 to 91 mmHg), and meridional end-systolic wall stress (from 53 to 67 10(3) dyne/cm2). Once the clamp was removed, significant variations were seen in the left ventricular ejection fraction (from 0.51 to 0.58), end-diastolic volume (from 205 to 187 ml), end-systolic volume (from 105 to 94 ml), mean blood pressure (from 84 to 69 mmHg), and meridional end-systolic wall stress (from 67 to 46 10(3) dyne/cm2). No differences were observed between the two aortic occlusion studies, and the baseline level of function was recovered in all parameters during the last study. These data quantify the changes in heart function that occur during abdominal aortic aneurysm operation and demonstrate that the majority of the adaptations that occurred were due to a variation in afterload.

Authors
Harpole, DH; Clements, FM; Quill, T; Wolfe, WG; Jones, RH; McCann, RL
MLA Citation
Harpole, DH, Clements, FM, Quill, T, Wolfe, WG, Jones, RH, and McCann, RL. "Right and left ventricular performance during and after abdominal aortic aneurysm repair." Ann Surg 209.3 (March 1989): 356-362.
PMID
2923517
Source
pubmed
Published In
Annals of Surgery
Volume
209
Issue
3
Publish Date
1989
Start Page
356
End Page
362

Analysis of the early rise in aortic transvalvular gradient after aortic valvuloplasty.

The relationship between dynamic changes in aortic valve gradient and left ventricular ejection performance in the early period after successful percutaneous aortic valvuloplasty has not been described in detail. Accordingly 20 adult patients with severe symptomatic calcific aortic stenosis underwent first-pass radionuclide angiography and Doppler echocardiography before, immediately after, and 2 to 4 days after the valvuloplasty procedure. A significant (p less than 0.001) reduction in peak-to-peak (72 +/- 24 mm Hg to 36 +/- 11 mmHg) and mean (60 +/- 20 mm Hg to 34 +/- 9 mm Hg) transaortic gradient and an increase in aortic valve area (0.5 +/- 0.2 cm2 to 0.8 +/- 0.2 cm2) were measured by high-fidelity micromanometer catheters immediately after aortic valvuloplasty. Results of Doppler echocardiography showed a significant (p less than 0.001) immediate decrease in peak instantaneous (81 +/- 22 mm Hg to 53 +/- 15 mm Hg) and mean (48 +/- 14 mm Hg to 31 +/- 9 mm Hg) aortic gradients. However, 2 to 4 days later a significant (p less than 0.001) return of peak (56 +/- 15 mm Hg to 65 +/- 20 mm Hg) and mean (31 +/- 9 mm Hg to 39 +/- 12 mm Hg) transvalvular gradient occurred. Aortic valve area as determined by the continuity equation also increased from 0.4 +/- 0.2 cm2 to 0.6 +/- 0.2 cm2 immediately after the procedure (p less than 0.001), then partially returned to baseline (0.5 +/- 0.2 cm2; p less than 0.005) at 2 to 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Davidson, CJ; Harpole, DA; Kisslo, K; Skelton, TN; Kisslo, J; Jones, RH; Bashore, TM
MLA Citation
Davidson, CJ, Harpole, DA, Kisslo, K, Skelton, TN, Kisslo, J, Jones, RH, and Bashore, TM. "Analysis of the early rise in aortic transvalvular gradient after aortic valvuloplasty." Am Heart J 117.2 (February 1989): 411-417.
PMID
2916414
Source
pubmed
Published In
American Heart Journal
Volume
117
Issue
2
Publish Date
1989
Start Page
411
End Page
417

Alveolar cell carcinoma of the lung: a retrospective analysis of 205 patients.

From 1970 to 1986, survival of 205 patients with alveolar cell carcinoma was retrospectively studied. Analysis examined the predictive value of presenting symptoms and diagnostic screening results for pathological Stage III or IV disease (advanced) and survival. The lesion presented as a peripheral mass in 121 patients (59%) and as an infiltrate in 84 (41%). Follow-up data were available on 199 patients (97%). Variables analyzed included indices of background or risk factors, presenting symptoms, diagnostic test results, and clinical management. Seventy-nine patients (39%) had a histological diagnosis of advanced disease by TMN staging criteria. Of the 152 deaths (74%), 117 (77%) were related to the pulmonary carcinoma. Univariate analysis associated short-term and long-term anorexia, weight loss, generalized weakness, and profound dyspnea with advanced disease and ultimately with death due to cancer. Multivariate logistic regression analyses suggested that weight loss and dyspnea disclosed independent information about the likelihood of advanced disease for this population (p less than 0.0003). Cox proportional hazard regression analyses of survival revealed a significant association between weight loss and death due to alveolar cell carcinoma after pathological stage was taken into account (p = 0.001). In this series, the 80 patients with Stage I disease had the best prognosis (5-year survival of 55%). There was no significant difference in disease-free survival between patients having wedge resection (N = 17) and those having lobectomy (N = 63) for Stage I disease.

Authors
Harpole, DH; Bigelow, C; Young, WG; Wolfe, WG; Sabiston, DC
MLA Citation
Harpole, DH, Bigelow, C, Young, WG, Wolfe, WG, and Sabiston, DC. "Alveolar cell carcinoma of the lung: a retrospective analysis of 205 patients." Ann Thorac Surg 46.5 (November 1988): 502-507.
PMID
2847663
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
46
Issue
5
Publish Date
1988
Start Page
502
End Page
507

Prognostic factors in head and neck melanoma. Effect of lesion location.

Cutaneous malignant melanomas of the head and neck are prognostically engimatic. In addition to known prognostic determinants of stage and lesion microstage, lesion location also appears to have prognostic importance. The authors have reviewed a series of 83 microstaged head and neck melanoma patients in order to analyze the relative importance of these factors. There were 36 males and 47 females with a median age of 56 years. Eighty-one percent had pathologic Stage I disease, 7% were Stage II, and 12% were Stage III. The primary location was face in 32 patients, neck in 18, ear in 12, and scalp in 21 patients. The actuarial 5-year survival according to lesion thickness was 86% for melanoma less than 1.0 mm, 56% for 1 to 2 mm thick lesions, 47% for 2.1 to 4 mm thick lesions, and 25% for melanomas greater than 4.0 mm. The 5-year survival according to lesion location was 78% for facial and 58% for neck melanomas; for ear and scalp, the respective survivals were 33% and 37%. Median thickness was 2.0 mm for facial and 1.85 mm for neck lesions. It was 2.7 mm for ear and 2.0 mm for scalp lesions (differences not significant). There were no microstage factors that correlated with the adverse prognosis seen with scalp and ear melanomas. Multivariate analysis in the entire series (all clinical stages) showed the following to be significant: stage, thickness, and location of the primary melanoma (all less than 0.0002). In clinical Stage I melanoma, the significant prognostic factors were location (P = 0.035), thickness (P = 0.008), level (P = 0.024), and ulceration (P = 0.035). The prognosis of head and neck melanoma is uniquely influenced by location of the primary lesions in addition to stage, thickness, level, and ulceration, as observed with other cutaneous melanomas at other sites. Ear and scalp melanomas are high-risk lesions whose poor prognosis is not readily explained by any of the microstage factors reviewed.

Authors
Wanebo, HJ; Cooper, PH; Young, DV; Harpole, DH; Kaiser, DL
MLA Citation
Wanebo, HJ, Cooper, PH, Young, DV, Harpole, DH, and Kaiser, DL. "Prognostic factors in head and neck melanoma. Effect of lesion location." Cancer 62.4 (August 15, 1988): 831-837.
PMID
3395962
Source
pubmed
Published In
Cancer
Volume
62
Issue
4
Publish Date
1988
Start Page
831
End Page
837

RESECTION OF PULMONARY BULLOUS CYSTS WITH YAG LASER

Authors
HARPOLE, DH
MLA Citation
HARPOLE, DH. "RESECTION OF PULMONARY BULLOUS CYSTS WITH YAG LASER." 1988.
Source
wos-lite
Published In
Lasers in Surgery and Medicine
Volume
8
Issue
2
Publish Date
1988
Start Page
195
End Page
195

Radionuclide lymphoscintigraphy with technetium 99m antimony sulfide colloid to identify lymphatic drainage of cutaneous melanoma at ambiguous sites in the head and neck and trunk

Frequently the primary lesion in a cutaneous melanoma is in an ambiguous lymphatic drainage site on the trunk, pelvic and shoulder girdles, and head and neck area. Lymphoscintigrams were performed by a circumferential intradermal injection of the biopsy site using technetium 99m (99mTc) antimony sulfide colloid in a total dose of 0.2 to 0.6 mCi in a volume of 0.1 to 0.5 ml. Imaging was done with a large-field gamma camera with high-resolution parallel hole collimator. Technetium 99m antimony sulfide colloid is an ideal agent for lymphoscintigrams because of small particle size (3-30 μm), which permits early migration into the interstitial space and lymphatics and rapid pickup by lymph nodes. Although it is a gamma emmitter with high activity, it has a short half-life and does not induce tissue necrosis. It does not localize the site of lymph node metastases, but indicates only the drainage pattern. Images were obtained at 1, 5, 10, 15, 30, and 60 minutes, respectively, and then three times every hour. Surgery was usually performed 24 hours later. The majority of patients had lesions with ambiguous drainage sites: head and neck (4 of 5 patients) and trunk (9 of 13 patients). The drainage by scan was to unpredictive sites in 72%, and resulted in a change of treatment planning by location and extent of ablation with node dissection in 9 of 18 patients. Ambiguous dissection sites included: (1) question of preauricular dissection with parotidectomy versus posterior auricular and cervical dissection for selected scalp lesions; (2) low-neck with or without axillary dissection for upper chest and shoulder lesions; and (3) axillary versus groin dissections for midflank lesions at zone of ambiguity between axilla and groin. It was concluded that preoperative 99mTc antimony sulfide lymphoscintigraphy is a highly useful planning technique in determining the appropriate lymphatic drainage basin for dissection in selected melanoma patients.

Authors
Wanebo, HJ; Harpole, D; Teates, CD
MLA Citation
Wanebo, HJ, Harpole, D, and Teates, CD. "Radionuclide lymphoscintigraphy with technetium 99m antimony sulfide colloid to identify lymphatic drainage of cutaneous melanoma at ambiguous sites in the head and neck and trunk." Cancer 55.6 (1985): 1403-1413.
PMID
3971311
Source
scival
Published In
Cancer
Volume
55
Issue
6
Publish Date
1985
Start Page
1403
End Page
1413
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