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Onaitis, Mark William

Overview:

Mouse Models of Foregut Malignancies
Normal Tissue and Cancer Stem Cells
Risk Prediction in Thoracic Malignancies

Positions:

Adjunct Associate Professor in the Department of Surgery

Surgery, Cardiovascular and Thoracic Surgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1997

M.D. — Duke University

M.H.S. 2010

M.H.S. — Duke University School of Medicine

Grants:

Translational Research in Surgical Oncology

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

Novel target for therapy refractory lung tumors

Administered By
Pharmacology & Cancer Biology
AwardedBy
National Institutes of Health
Role
Collaborating Investigator
Start Date
May 08, 2015
End Date
April 30, 2020

National Longitudinal Outcomes Following Surgical Therapy for Lung Cancer

Administered By
Duke Clinical Research Institute
AwardedBy
Society of Thoracic Surgeons
Role
Co Investigator
Start Date
August 01, 2014
End Date
July 31, 2018

Targeting Integrator Kinases in Lung Cancer Metastasis

Administered By
Pharmacology & Cancer Biology
AwardedBy
Free to Breathe
Role
Co-Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2018

Anti-CTGF Therapy for Squamous Cell Lung Cancer

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 12, 2016
End Date
December 31, 2017

K-RAS mutant lung adenocarcinoma treatment

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
AATS Graham Foundation
Role
Principal Investigator
Start Date
July 01, 2014
End Date
August 01, 2016

Novel druggable pathway required for lung cancer progression and metastasis

Administered By
Pharmacology & Cancer Biology
AwardedBy
Uniting Against Lung Cancer
Role
Collaborator
Start Date
March 01, 2014
End Date
February 28, 2016
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Publications:

Inactivation of ABL kinases suppresses non-small cell lung cancer metastasis.

Current therapies to treat non-small cell lung carcinoma (NSCLC) have proven ineffective owing to transient, variable, and incomplete responses. Here we show that ABL kinases, ABL1 and ABL2, promote metastasis of lung cancer cells harboring EGFR or KRAS mutations. Inactivation of ABL kinases suppresses NSCLC metastasis to brain and bone, and other organs. ABL kinases are required for expression of prometastasis genes. Notably, ABL1 and ABL2 depletion impairs extravasation of lung adenocarcinoma cells into the lung parenchyma. We found that ABL-mediated activation of the TAZ and β-catenin transcriptional coactivators is required for NSCLC metastasis. ABL kinases activate TAZ and β-catenin by decreasing their interaction with the β-TrCP ubiquitin ligase, leading to increased protein stability. High-level expression of ABL1, ABL2, and a subset of ABL-dependent TAZ- and β-catenin-target genes correlates with shortened survival of lung adenocarcinoma patients. Thus, ABL-specific allosteric inhibitors might be effective to treat metastatic lung cancer with an activated ABL pathway signature.

Authors
Gu, JJ; Rouse, C; Xu, X; Wang, J; Onaitis, MW; Pendergast, AM
MLA Citation
Gu, JJ, Rouse, C, Xu, X, Wang, J, Onaitis, MW, and Pendergast, AM. "Inactivation of ABL kinases suppresses non-small cell lung cancer metastasis." JCI insight 1.21 (December 22, 2016): e89647-.
PMID
28018973
Source
epmc
Published In
JCI insight
Volume
1
Issue
21
Publish Date
2016
Start Page
e89647
DOI
10.1172/jci.insight.89647

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; Yang, C-FJ; Speicher, PJ; Yerokun, BA; Tong, BC; Onaitis, MW; D'Amico, TA; Harpole, DH; Hartwig, MG; Berry, MF
MLA Citation
Gulack, BC, Yang, C-FJ, 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

The Society of Thoracic Surgeons General Thoracic Surgery Database: 2016 Update on Research.

The Society of Thoracic Surgeons General Thoracic Surgery Database has grown to more than 500,000 case records. Clinical research supported by the database is increasingly used to advance patient outcomes. This research review from the General Thoracic Surgery Database in 2014 and 2015 discusses 6 recent publications and an ongoing study on longitudinal outcomes in lung cancer surgery from The Society of Thoracic Surgeons Task Force for Linked Registries and Longitudinal Follow-up. A lack of database variables specific for certain uncommon procedures limits the ability to study these operations; inclusion of clinical descriptors for selected infrequent but clinically important thoracic disorders is suggested.

Authors
Gaissert, HA; Fernandez, FG; Allen, MS; Burfeind, WR; Block, MI; Donahue, JM; Mitchell, JD; Schipper, PH; Onaitis, MW; Kosinski, AS; Jacobs, JP; Shahian, DM; Kozower, BD; Edwards, FH; Conrad, EA; Patterson, GA
MLA Citation
Gaissert, HA, Fernandez, FG, Allen, MS, Burfeind, WR, Block, MI, Donahue, JM, Mitchell, JD, Schipper, PH, Onaitis, MW, Kosinski, AS, Jacobs, JP, Shahian, DM, Kozower, BD, Edwards, FH, Conrad, EA, and Patterson, GA. "The Society of Thoracic Surgeons General Thoracic Surgery Database: 2016 Update on Research." The Annals of thoracic surgery 102.5 (November 2016): 1444-1451.
PMID
27772572
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
102
Issue
5
Publish Date
2016
Start Page
1444
End Page
1451
DOI
10.1016/j.athoracsur.2016.09.014

Teaching robotic surgery: Making progress

Authors
Onaitis, M; Park, B
MLA Citation
Onaitis, M, and Park, B. "Teaching robotic surgery: Making progress." The Journal of Thoracic and Cardiovascular Surgery 152.4 (October 2016): 950-951.
Source
crossref
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
152
Issue
4
Publish Date
2016
Start Page
950
End Page
951
DOI
10.1016/j.jtcvs.2016.07.039

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; Yang, C-FJ; Gulack, BC; Speicher, PJ; Adam, MA; D'Amico, TA; Onaitis, MW; Harpole, DH; Berry, MF; Hartwig, MG
MLA Citation
Yerokun, BA, Sun, Z, Yang, C-FJ, 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

Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer.

To determine the feasibility and toxicity of radiation therapy, delivered either as definitive treatment or following surgery, following neo-adjuvant immune checkpoint inhibition for locally advanced NSCLC sixteen patients who received neo-adjuvant chemotherapy including ipilimumab as part of a phase II study were identified. Patients were analyzed by intent of radiation and toxicity graded based on CTCAE 4.0. There were seven patients identified who received definitive radiation and nine who received post-operative radiation. There was no grade 3 or greater toxicity in the definitive treatment group although one patient stopped treatment early due to back pain secondary to progression outside of the treatment field. In the post-operative treatment group, one patient required a one week break due to grade 2 odynophagia and no grade 3 or greater toxicity was observed. In this study of radiation as definitive or post-operative treatment following neo-adjuvant chemotherapy including ipilimumab for locally advanced NSCLC was feasible and well tolerated with limited toxicity.

Authors
Boyer, MJ; Gu, L; Wang, X; Kelsey, CR; Yoo, DS; Onaitis, MW; Dunphy, FR; Crawford, J; Ready, NE; Salama, JK
MLA Citation
Boyer, MJ, Gu, L, Wang, X, Kelsey, CR, Yoo, DS, Onaitis, MW, Dunphy, FR, Crawford, J, Ready, NE, and Salama, JK. "Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer." Lung cancer (Amsterdam, Netherlands) 98 (August 2016): 76-78.
PMID
27393510
Source
epmc
Published In
Lung Cancer
Volume
98
Publish Date
2016
Start Page
76
End Page
78
DOI
10.1016/j.lungcan.2016.05.014

Surgery versus stereotactic body radiation therapy for operable stage I non-small cell lung cancer: Can we achieve equipoise?

Authors
Onaitis, MW; Salama, J
MLA Citation
Onaitis, MW, and Salama, J. "Surgery versus stereotactic body radiation therapy for operable stage I non-small cell lung cancer: Can we achieve equipoise?." The Journal of thoracic and cardiovascular surgery 152.1 (July 2016): 1-2.
PMID
27343902
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
152
Issue
1
Publish Date
2016
Start Page
1
End Page
2
DOI
10.1016/j.jtcvs.2016.04.016

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

Longitudinal Follow-up of Lung Cancer Resection From the Society of Thoracic Surgeons General Thoracic Surgery Database in Patients 65 Years and Older.

The Society of Thoracic Surgeons (STS) General Thoracic Surgery Database (GTSD) does not capture long-term survival after lung cancer surgery. Our objective was to provide longitudinal follow-up to the STS GTSD through linkage to Centers for Medicare and Medicaid Services (CMS) data for patients 65 years of age or older.Lung cancer operations reported in the STS GTSD from 2002 through 2012 were linked to CMS data for patients 65 years of age or older using variables common to both databases with a deterministic matching algorithm. Mortality data were abstracted for each linked patient from the CMS data. The Kaplan-Meier method was used to estimate long-term survival for lung cancer surgery patients based on tumor stage.From 2002 through 2012, 60,089 lung cancer resections were identified in the GTSD, and 37,009 (61.7%) were in patients 65 years or older. Of these, 26,055 of 37,099 lung cancer resections (70%) in patients 65 years or older were successfully linked to CMS data. Failure to link was most commonly related to having a health maintenance organization or commercial insurance as the primary payer: 40.5% (5,290 of 13,065) of such patients were not linked from 2009 to 2012 (years payer data available). Median survival after lung cancer resection was 6.7 years for pathologic stage I, 3.5 years for stage II, 2.4 years for stage III, and 2.2 years for stage IV.The CMS data complement the STS GTSD data by enabling examination of long-term survival and resource utilization in patients 65 years or older. Linked data from the STS GTSD and the CMS will allow for longitudinal analyses of comparative effectiveness among different surgical approaches for the treatment of lung cancer.

Authors
Fernandez, FG; Furnary, AP; Kosinski, AS; Onaitis, MW; Kim, S; Boffa, D; Cowper, P; Jacobs, JP; Wright, CD; Putnam, JB
MLA Citation
Fernandez, FG, Furnary, AP, Kosinski, AS, Onaitis, MW, Kim, S, Boffa, D, Cowper, P, Jacobs, JP, Wright, CD, and Putnam, JB. "Longitudinal Follow-up of Lung Cancer Resection From the Society of Thoracic Surgeons General Thoracic Surgery Database in Patients 65 Years and Older." The Annals of thoracic surgery 101.6 (June 2016): 2067-2076.
PMID
27157052
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
101
Issue
6
Publish Date
2016
Start Page
2067
End Page
2076
DOI
10.1016/j.athoracsur.2016.03.034

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

Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls.

Centrosome abnormalities are often observed in premalignant lesions and in situ tumors and have been associated with aneuploidy and tumor development. We investigated the associations of 9354 single-nucleotide polymorphisms (SNPs) in 106 centrosomal genes with lung cancer risk by first using the summary data from six published genome-wide association studies (GWASs) of the Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16 838 controls) and then conducted in silico replication in two additional independent lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1319 cases and 26,380 controls). A total of 44 significant SNPs with false discovery rate (FDR) ≤ 0.05 were mapped to one novel gene FGFR1OP and two previously reported genes (TUBB and BRCA2). After combined the results from TRICL with those from Harvard and deCODE, the most significant association (P combined = 8.032 × 10(-6)) was with rs151606 within FGFR1OP. The rs151606 T>G was associated with an increased risk of lung cancer [odds ratio (OR) = 1.10, 95% confidence interval (95% CI) = 1.05-1.14]. Another significant tagSNP rs12212247 T>C (P combined = 9.589 × 10(-6)) was associated with a decreased risk of lung cancer (OR = 0.93, 95% CI = 0.90-0.96). Further in silico functional analyzes revealed that rs151606 might affect transcriptional regulation and result in decreased FGFR1OP expression (P trend = 0.022). The findings shed some new light on the role of centrosome abnormalities in the susceptibility to lung carcinogenesis.

Authors
Kang, X; Liu, H; Onaitis, MW; Liu, Z; Owzar, K; Han, Y; Su, L; Wei, Y; Hung, RJ; Brhane, Y; McLaughlin, J; Brennan, P; Bickeböller, H; Rosenberger, A; Houlston, RS; Caporaso, N; Landi, MT; Heinrich, J; Risch, A; Wu, X; Ye, Y; Christiani, DC; Amos, CI; Wei, Q
MLA Citation
Kang, X, Liu, H, Onaitis, MW, Liu, Z, Owzar, K, Han, Y, Su, L, Wei, Y, Hung, RJ, Brhane, Y, McLaughlin, J, Brennan, P, Bickeböller, H, Rosenberger, A, Houlston, RS, Caporaso, N, Landi, MT, Heinrich, J, Risch, A, Wu, X, Ye, Y, Christiani, DC, Amos, CI, and Wei, Q. "Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls." Carcinogenesis 37.3 (March 2016): 280-289.
PMID
26905588
Source
epmc
Published In
Carcinogenesis
Volume
37
Issue
3
Publish Date
2016
Start Page
280
End Page
289
DOI
10.1093/carcin/bgw014

Modern Management of Pulmonary Metastases.

Authors
Onaitis, MW; D'Amico, TA
MLA Citation
Onaitis, MW, and D'Amico, TA. "Modern Management of Pulmonary Metastases." Thoracic surgery clinics 26.1 (February 2016): xi-.
PMID
26611517
Source
epmc
Published In
Thoracic Surgery Clinics
Volume
26
Issue
1
Publish Date
2016
Start Page
xi
DOI
10.1016/j.thorsurg.2015.10.001

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

Comparison Between the 2007 and 2014 American College of Cardiology/American Heart Association Guidelines on Perioperative Evaluation for Noncardiac Surgery.

Authors
Oprea, AD; Fontes, ML; Onaitis, MW; Kertai, MD
MLA Citation
Oprea, AD, Fontes, ML, Onaitis, MW, and Kertai, MD. "Comparison Between the 2007 and 2014 American College of Cardiology/American Heart Association Guidelines on Perioperative Evaluation for Noncardiac Surgery." Journal of cardiothoracic and vascular anesthesia 29.6 (December 2015): 1639-1650.
PMID
26341877
Source
epmc
Published In
Journal of Cardiothoracic and Vascular Anesthesia
Volume
29
Issue
6
Publish Date
2015
Start Page
1639
End Page
1650
DOI
10.1053/j.jvca.2015.04.021

Benign emptying of the postpneumonectomy space.

A drop in the air-fluid level in the postpneumonectomy space on a chest radiogram is an early sign of bronchopleural fistula (BPF). Any suspicion of BPF points to the need for urgent evaluation and appropriate management. Very rarely may this drop occur without the existence of a fistula, but such a condition is defined as benign emptying of the postpneumonectomy space. We share our successful conservative management in a case of postpneumonectomy space emptying with a suspicion of BPF.

Authors
Kara, HV; Mallipeddi, MK; Javidfar, J; Onaitis, MW
MLA Citation
Kara, HV, Mallipeddi, MK, Javidfar, J, and Onaitis, MW. "Benign emptying of the postpneumonectomy space." Lung India : official organ of Indian Chest Society 32.6 (November 2015): 614-615.
PMID
26664171
Source
epmc
Published In
Lung India
Volume
32
Issue
6
Publish Date
2015
Start Page
614
End Page
615
DOI
10.4103/0970-2113.168136

Invited Commentary.

Authors
Onaitis, M
MLA Citation
Onaitis, M. "Invited Commentary." The Annals of thoracic surgery 100.3 (September 2015): 917-.
PMID
26354625
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
100
Issue
3
Publish Date
2015
Start Page
917
DOI
10.1016/j.athoracsur.2015.05.005

Right-Sided vs. Left-Sided Pneumonectomy after Induction Therapy for Non-Small Cell Lung Cancer

Authors
Yang, C-FJ; Chan, DY; Gulack, BC; Ranney, DN; Tong, BC; Onaitis, MW; Harpole, D; D'Amico, TA; Hartwig, MG; Berry, MF
MLA Citation
Yang, C-FJ, Chan, DY, Gulack, BC, Ranney, DN, Tong, BC, Onaitis, MW, Harpole, D, D'Amico, TA, Hartwig, MG, and Berry, MF. "Right-Sided vs. Left-Sided Pneumonectomy after Induction Therapy for Non-Small Cell Lung Cancer." JOURNAL OF THORACIC ONCOLOGY 10.9 (September 2015): S335-S336.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S335
End Page
S336

Survival after Surgery for pN1 and pN2 Small Cell Lung Cancer: A Comparison with Surgical Treatment of Non-Small Cell Lung Cancer

Authors
Yang, C-FJ; Chan, DY; Gulack, BC; Speicher, PJ; Hartwig, MG; Berry, MF; Tong, BC; Onaitis, MW; D'Amico, TA; Harpole, D
MLA Citation
Yang, C-FJ, Chan, DY, Gulack, BC, Speicher, PJ, Hartwig, MG, Berry, MF, Tong, BC, Onaitis, MW, D'Amico, TA, and Harpole, D. "Survival after Surgery for pN1 and pN2 Small Cell Lung Cancer: A Comparison with Surgical Treatment of Non-Small Cell Lung Cancer." JOURNAL OF THORACIC ONCOLOGY 10.9 (September 2015): S399-S400.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S399
End Page
S400

Long-Term Survival after Surgery for Pathologic N1 and N2 Small Cell Lung Cancer: A Comparison with Nonoperative Management

Authors
Yang, C-FJ; Chan, DY; Speicher, PJ; Gulack, BC; Onaitis, MW; Hartwig, MG; Tong, BC; Berry, MF; D'Amico, TA; Harpole, D
MLA Citation
Yang, C-FJ, Chan, DY, Speicher, PJ, Gulack, BC, Onaitis, MW, Hartwig, MG, Tong, BC, Berry, MF, D'Amico, TA, and Harpole, D. "Long-Term Survival after Surgery for Pathologic N1 and N2 Small Cell Lung Cancer: A Comparison with Nonoperative Management." JOURNAL OF THORACIC ONCOLOGY 10.9 (September 2015): S193-S194.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S193
End Page
S194

Wedge Resection vs Segmentectomy for Patients with T1A N0 Non-Small Cell Lung Cancer

Authors
Yang, C-FJ; Chan, DY; Gulack, BC; Speicher, PJ; Onaitis, MW; Tong, BC; D'Amico, TA; Harpole, D; Berry, MF; Hartwig, MG
MLA Citation
Yang, C-FJ, Chan, DY, Gulack, BC, Speicher, PJ, Onaitis, MW, Tong, BC, D'Amico, TA, Harpole, D, Berry, MF, and Hartwig, MG. "Wedge Resection vs Segmentectomy for Patients with T1A N0 Non-Small Cell Lung Cancer." JOURNAL OF THORACIC ONCOLOGY 10.9 (September 2015): S242-S242.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S242
End Page
S242

Impact of Radiation on Recurrence Patterns and Survival for Patients Undergoing Lobectomy for Stage IIIA-pN2 Non-Small Cell Lung Cancer

Authors
Yang, C-FJ; Adil, SM; Meyerhoff, RR; Anderson, KL; Hirji, SA; Harpole, D; Tong, BC; Onaitis, MW; Hartwig, MG; D'Amico, TA; Berry, MF
MLA Citation
Yang, C-FJ, Adil, SM, Meyerhoff, RR, Anderson, KL, Hirji, SA, Harpole, D, Tong, BC, Onaitis, MW, Hartwig, MG, D'Amico, TA, and Berry, MF. "Impact of Radiation on Recurrence Patterns and Survival for Patients Undergoing Lobectomy for Stage IIIA-pN2 Non-Small Cell Lung Cancer." JOURNAL OF THORACIC ONCOLOGY 10.9 (September 2015): S573-S573.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S573
End Page
S573

Right Minithoracotomy Versus Median Sternotomy for Mitral Valve Surgery: A Propensity Matched Study.

The efficacy of conventional median sternotomy versus a right minithoracotomy (RT) approach to mitral valve surgery was evaluated in a single high-volume institution.A retrospective analysis of a single institution's experience was performed using propensity matching of 1,694 patients who underwent mitral valve surgery during a 15-year period. Patients who had procedures that were not usually performed through an RT approach were excluded. Using 1:1 propensity score matching, we obtained 215 matched patients in each group for outcomes analysis.There was no difference in the median year of operation between the two groups (2002 versus 2001; p = 0.142). The RT approach was not a predictor of postoperative mortality. Predictors of mortality included increasing age, diabetes, smoking, preoperative dialysis, lung disease, advanced congestive heart failure class, and peripheral vascular disease. The RT approach was associated with less new-onset atrial fibrillation (8% versus 16%; p = 0.018), pneumonia (1% versus 5%; p = 0.049), respiratory failure (3% versus 8%; p = 0.036), and acute renal failure (2% versus 7%; p = 0.006), lower chest tube output (350 versus 840 mL; p < 0.001), and fewer red blood transfusions (2 versus 3 units; p = 0.001).Right minithoracotomy compared with median sternotomy for mitral valve surgery was associated with less postoperative atrial fibrillation, respiratory complications, acute renal failure, chest tube output, and use of packed red blood cells. Given study limitations, the RT approach for mitral valve surgery may have advantages over median sternotomy in selected patients.

Authors
Tang, P; Onaitis, M; Gaca, JG; Milano, CA; Stafford-Smith, M; Glower, D
MLA Citation
Tang, P, Onaitis, M, Gaca, JG, Milano, CA, Stafford-Smith, M, and Glower, D. "Right Minithoracotomy Versus Median Sternotomy for Mitral Valve Surgery: A Propensity Matched Study." The Annals of thoracic surgery 100.2 (August 2015): 575-581.
PMID
26141780
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
100
Issue
2
Publish Date
2015
Start Page
575
End Page
581
DOI
10.1016/j.athoracsur.2015.04.027

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; Yang, C-FJ; Hartwig, MG; Tong, BC; Harpole, DH; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, Yang, C-FJ, 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

Tumor Endothelial Cells with Distinct Patterns of TGF -Driven Endothelial-to-Mesenchymal Transition

Authors
Xiao, L; Kim, DJ; Davis, CL; McCann, JV; Dunleavey, JM; Vanderlinden, AK; Xu, N; Pattenden, SG; Frye, SV; Xu, X; Onaitis, M; Monaghan-Benson, E; Burridge, K; Dudley, AC
MLA Citation
Xiao, L, Kim, DJ, Davis, CL, McCann, JV, Dunleavey, JM, Vanderlinden, AK, Xu, N, Pattenden, SG, Frye, SV, Xu, X, Onaitis, M, Monaghan-Benson, E, Burridge, K, and Dudley, AC. "Tumor Endothelial Cells with Distinct Patterns of TGF -Driven Endothelial-to-Mesenchymal Transition." Cancer Research 75.7 (April 1, 2015): 1244-1254.
Source
crossref
Published In
Cancer Research
Volume
75
Issue
7
Publish Date
2015
Start Page
1244
End Page
1254
DOI
10.1158/0008-5472.CAN-14-1616

Outcomes after treatment of 17,378 patients with locally advanced (T3N0-2) non-small-cell lung cancer.

Treatment patterns and outcomes in a population-based database were examined to identify patients likely to benefit from surgical resection of locally advanced (T3N0-2) non-small-cell lung cancer (NSCLC).Factors predicting the use of surgery for patients with T3N0-2M0 NSCLC in the Surveillance, Epidemiology and End Results (SEER) database from 1988 to 2010 were assessed using a multivariable logistic regression model. Survival was analysed using the Kaplan-Meier approach and Cox proportional hazard models. Propensity matching was used to compare outcomes after surgery and outcomes in patients who refused surgery and underwent radiation therapy (RT).Of 17 378 patients identified for study inclusion [8597 (50%) T3N0, 2304 (13%) T3N1 and 6477 (37%) T3N2], surgery was used in 7120 (41%). Only female sex and being married predicted the use of surgery, while older age, black race and N2 nodal disease predicted non-surgical management. Surgical patients overall had better long-term survival than non-surgical patients [odds ratio (OR) 0.42, 95% confidence interval (CI): 0.41-0.45, P < 0.001]. After propensity adjustment, patients who refused surgery and instead were treated with RT had significantly worse long-term survival than matched surgery patients (OR 0.65, 95% CI: 0.48-0.89, P = 0.0074). Sublobar resection and pneumonectomy predicted worse survival in patients who had surgery. Nodal disease also predicted worse survival after surgery, but surgery maintained an association with better overall survival compared with non-operative therapy among patients with both N1 (OR 0.53, P < 0.001) and N2 disease (OR 0.50, P < 0.001) in separate analyses stratified by nodal status. Older age also predicted worse survival after surgery, but patients older than 75 who were treated with surgery had significantly better long-term survival than non-operative patients (OR 0.49, 95% CI: 0.45-0.53, P < 0.001).Surgery is used in a minority of patients with locally advanced NSCLC, but is associated with better survival than non-surgical treatment, even for patients older than 75 and patients with nodal disease. Given the very poor outcomes observed with non-operative management, surgical resection should be carefully considered in all patients with locally advanced NSCLC and should not necessarily be denied because of patient age or nodal disease.

Authors
Speicher, PJ; Englum, BR; Ganapathi, AM; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Englum, BR, Ganapathi, AM, Onaitis, MW, D'Amico, TA, and Berry, MF. "Outcomes after treatment of 17,378 patients with locally advanced (T3N0-2) non-small-cell lung cancer." European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 47.4 (April 2015): 636-641.
PMID
25005840
Source
epmc
Published In
European Journal of Cardio-Thoracic Surgery
Volume
47
Issue
4
Publish Date
2015
Start Page
636
End Page
641
DOI
10.1093/ejcts/ezu270

Impact of pretreatment imaging on survival of esophagectomy after induction therapy for esophageal cancer: who should be given the benefit of the doubt?: esophagectomy outcomes of patients with suspicious metastatic lesions.

We examined survival of patients who underwent esophagectomy for locally advanced esophageal cancer with foci that were suspicious for metastatic disease on initial imaging but whose disease did not progress after induction chemoradiation treatment (CRT).The impact of pre- and posttherapy staging characteristics on survival of patients who underwent esophagectomy after CRT between 2003 and 2009 was evaluated using multivariable logistic regression. Survival of patients with and without possible metastatic disease on initial imaging was compared with the log-rank test.During the study period, 71 (32%) of 220 patients who underwent CRT followed by esophagectomy had possible distant metastatic disease on initial imaging. Patients with initial suspicion of metastases had a 5-year survival of 24.8%. Overall survival of patients with and without possible metastatic disease on initial imaging was not significantly different (p = 0.4), but pretreatment positron emission tomography (PET) suggesting a liver lesion (hazard ratio [HR] 3.2, p = 0.003) predicted worse survival. Additional predictors of worse survival were clinical T4 status (HR 3.1, p = 0.001), post-CRT pathologic nodal status (HR 1.6, p = 0.04), and pathologically confirmed metastatic disease at or before resection (HR 3.1, p = 0.01). None of 10 patients with pathologic metastatic disease at resection lived longer than 2.5 years.Patients with possible liver metastases on pretreatment PET and patients with confirmed metastatic disease at the time of surgery do not benefit from resection. However, patients with pretreatment imaging that shows possible metastatic disease in sites other than the liver still have reasonable long-term survival after resection.

Authors
Erhunmwunsee, L; Englum, BR; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Erhunmwunsee, L, Englum, BR, Onaitis, MW, D'Amico, TA, and Berry, MF. "Impact of pretreatment imaging on survival of esophagectomy after induction therapy for esophageal cancer: who should be given the benefit of the doubt?: esophagectomy outcomes of patients with suspicious metastatic lesions." Annals of surgical oncology 22.3 (March 2015): 1020-1025.
PMID
25234017
Source
epmc
Published In
Annals of Surgical Oncology
Volume
22
Issue
3
Publish Date
2015
Start Page
1020
End Page
1025
DOI
10.1245/s10434-014-4079-6

Adjuvant chemotherapy after resection of N1 non-small cell lung cancer: differential impact of new evidence on physician and patient decisions.

Adjuvant cisplatin-based chemotherapy (ACT) after resection of stages II-IIIA non-small cell lung cancer (NSCLC) modestly increased survival in several clinical trials. This study evaluated the subsequent impact of those trials on ACT use in clinical practice.Patients who underwent lobectomy or more extensive lung resection without induction chemotherapy for pathologically confirmed N1 positive NSCLC between 2000 and 2012 were reviewed. Referrals to medical oncology, oncologist recommendations for ACT, and initiation of ACT were evaluated. Because major trials supporting ACT were published in 2004 and 2005, analysis was stratified into two eras: 2000-2005 and 2006-2012.During the study period, 272 patients met inclusion criteria (110 in the 2000-2005 cohort, 162 in the 2006-2012 cohort). Referrals to medical oncology increased from 74.5% (n=82) in the 2000-2005 cohort to 90.1% (n=146) in the 2006-2012 cohort (P=0.002). Due to lack of referral or missed appointments, 35.5% (n=39) of the 2000-2005 patients and 17.9% (n=32) of the 2006-2012 patients did not have a documented conversation with an oncologist regarding ACT. The proportion of patients recommended for ACT increased from 61% (n=50) to 81.5% (n=119) between the eras (P<0.001). Of patients recommended for chemotherapy, 14% (7/50) in 2000-2005 and 13.4% (16/119) in 2006-2012 declined ACT (P=0.666).Publication of supporting evidence increased recommendations for ACT but did not change the percentage of patients who ultimately agreed to receive ACT. Additional research is needed to better understand patient decision-making in this situation.

Authors
Coleman, BK; Curtis, LH; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Coleman, BK, Curtis, LH, Onaitis, MW, D'Amico, TA, and Berry, MF. "Adjuvant chemotherapy after resection of N1 non-small cell lung cancer: differential impact of new evidence on physician and patient decisions." Journal of thoracic disease 7.3 (March 2015): 243-251.
PMID
25922700
Source
epmc
Published In
Journal of Thoracic Disease
Volume
7
Issue
3
Publish Date
2015
Start Page
243
End Page
251
DOI
10.3978/j.issn.2072-1439.2015.01.42

Defining the role of adjuvant chemotherapy after lobectomy for typical bronchopulmonary carcinoid tumors.

BACKGROUND: Treatment guidelines for typical bronchopulmonary carcinoid tumors recommend observation alone after resection of stage I-IIIA disease, but there are limited data related to the use of adjuvant chemotherapy in the setting of nodal metastases found at operation. METHODS: Patients in the National Cancer Data Base (NDCB) who underwent lobectomy for typical carcinoid and had metastatic nodal disease were stratified by the use of adjuvant chemotherapy. Baseline characteristics and outcomes were compared between groups. Next, patients were propensity matched using a 3:1 nearest-neighbor algorithm, and adjusted outcomes were compared. Finally, long-term survival was evaluated using the Kaplan-Meier method with comparisons based on the log-rank test. RESULTS: Overall, 4,612 patients were identified, among whom 629 (13.6%) had positive lymph nodes at the time of operation. Of them, adjuvant chemotherapy was used in 37 patients (5.9%). There were no baseline differences between patients who did and those who did not receive adjuvant chemotherapy. Patients treated with chemotherapy demonstrated a survival disadvantage at 5 years (69.7% versus 81.9%; p = 0.042). After propensity matching, all baseline characteristics between groups were highly similar. There remained a trend toward inferior 5-year survival for patients who received adjuvant chemotherapy, although the difference no longer met statistical significance (69.7% versus 80.9%; p = 0.096). CONCLUSIONS: Adjuvant chemotherapy is not associated with improved survival among patients who undergo lobectomy for typical carcinoids and nodal metastases. These data support current treatment guidelines.

Authors
Nussbaum, DP; Speicher, PJ; Gulack, BC; Hartwig, MG; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Nussbaum, DP, Speicher, PJ, Gulack, BC, Hartwig, MG, Onaitis, MW, D'Amico, TA, and Berry, MF. "Defining the role of adjuvant chemotherapy after lobectomy for typical bronchopulmonary carcinoid tumors." The Annals of thoracic surgery 99.2 (February 2015): 428-434.
PMID
25499480
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
99
Issue
2
Publish Date
2015
Start Page
428
End Page
434
DOI
10.1016/j.athoracsur.2014.08.030

Adjuvant chemotherapy is associated with improved survival after esophagectomy without induction therapy for node-positive adenocarcinoma.

This study investigated adjuvant chemotherapy (AC) use after esophagectomy without induction therapy for node-positive (pN+) adenocarcinoma using the National Cancer Database, including the impact of complications related to surgery (CRS) on outcomes.Predictors of AC use in 1694 patients in the National Cancer Data Base who underwent R0 esophagectomy from 2003-2011 without induction therapy for pN+ adenocarcinoma of the middle or lower esophagus and survived more than 30 days were identified with multivariable logistic regression. The impact of AC on survival was estimated using Kaplan-Meier and Cox-proportional hazards methods.AC was given to 874 of 1694 (51.6%) patients; 618 (70.7%) AC patients received radiation. Older age (adjusted odds ratio [AOR] 0.58/decade, p < 0.001), longer travel distance (AOR 0.78 per 100 miles, p = 0.03) and CRS (AOR 0.45, p < 0.001) predicted that AC was not used. Patients given AC had better 5-year survival than patients not given AC (24.2% versus 14.9%, p < 0.001), and AC use predicted improved survival in multivariate analysis (hazard ratio 0.67, p = 0.008). Receiving radiation in addition to AC did not improve survival (p = 0.35). Although CRS was associated with worse survival, patients who had CRS but received AC had superior survival compared to patients who did not have CRS or get AC (p = 0.016).AC after esophagectomy is associated with improved survival but was only used in half of patients with pN+ esophageal adenocarcinoma. We also found that the addition of radiation to AC was not associated with a survival benefit. CRS predict worse long-term survival and lower the chance of getting AC, but even patients with CRS had improved survival when given AC.

Authors
Speicher, PJ; Englum, BR; Ganapathi, AM; Mulvihill, MS; Hartwig, MG; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Englum, BR, Ganapathi, AM, Mulvihill, MS, Hartwig, MG, Onaitis, MW, D'Amico, TA, and Berry, MF. "Adjuvant chemotherapy is associated with improved survival after esophagectomy without induction therapy for node-positive adenocarcinoma." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 10.1 (January 2015): 181-188.
PMID
25490005
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
10
Issue
1
Publish Date
2015
Start Page
181
End Page
188
DOI
10.1097/jto.0000000000000384

The prognostic importance of the number of dissected lymph nodes after induction chemoradiotherapy for esophageal cancer.

BACKGROUND: Analyses of adequacy of lymph node dissection during resection of esophageal cancer are based on patients who have not undergone induction chemoradiotherapy. We sought to determine the minimum number of dissected lymph nodes necessary to ensure adequate staging after induction chemoradiotherapy. METHODS: A prospectively maintained thoracic surgery database was queried to identify consecutive patients undergoing postinduction esophagectomy from 1996 to 2010. Cox proportional hazard and recursive partitioning survival analyses were performed. RESULTS: Complete lymph node data were available for 395 patients. Mean age was 59.5 years, and 64 patients (16%) were female. The median number of dissected lymph nodes was 8 (range, 0 to 63). When pathologic (p)T stage, pN stage, and the number of dissected lymph nodes were used as predictors, only pN stage (odds ratio, 1.3; 95% confidence interval, 1.2 to 1.7) and age (odds ratio, 1.03; 95% confidence interval, 1.01 to 1.04) independently predicted survival. Recursive partitioning was performed on 262 pN0 patients using T stage and the number of dissected lymph nodes as predictors. No pN0 patient with 28 lymph nodes dissected died during follow-up. For patients with fewer than 28 lymph nodes dissected, the next prognostic factor was T stage. For pT1-2 N0 patients, the number of lymph nodes dissected did not affect survival. For pT3-4 N0 patients, a significant survival decrement was noted for patients with fewer than 7 lymph nodes dissected compared with those with more than 7 lymph nodes dissected. CONCLUSIONS: T stage determines prognosis in postinduction pN0 patients with fewer than 28 lymph nodes evaluated. Postinduction pT3N0 patients with fewer than 7 lymph nodes evaluated are understaged.

Authors
Hanna, JM; Erhunmwunsee, L; Berry, M; D'Amico, T; Onaitis, M
MLA Citation
Hanna, JM, Erhunmwunsee, L, Berry, M, D'Amico, T, and Onaitis, M. "The prognostic importance of the number of dissected lymph nodes after induction chemoradiotherapy for esophageal cancer." The Annals of thoracic surgery 99.1 (January 2015): 265-269.
PMID
25440285
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
99
Issue
1
Publish Date
2015
Start Page
265
End Page
269
DOI
10.1016/j.athoracsur.2014.08.073

Quantifying the safety benefits of wedge resection: a society of thoracic surgery database propensity-matched analysis.

BACKGROUND: Wedge resection is often used instead of anatomic resection in an attempt to mitigate perioperative risk. In propensity-matched populations, we sought to compare the perioperative outcomes of patients undergoing wedge resection with those undergoing anatomic resection. METHODS: The Society of Thoracic Surgery database was reviewed for stage I and II non-small cell lung cancer patients undergoing wedge resection and anatomic resection to analyze postoperative morbidity and mortality. Propensity scores were estimated using a logistic model adjusted for a variety of risk factors. Patients were then matched by propensity score using a greedy 5- to 1-digit matching algorithm, and compared using McNemar's test. RESULTS: Between 2009 and 2011, 3,733 wedge resection and 3,733 anatomic resection patients were matched. The operative mortality was 1.21% for wedge resection versus 1.93% for anatomic resection (p=0.0118). Major morbidity occurred in 4.53% of wedge resection patients versus 8.97% of anatomic resection patients (p<0.0001). A reduction was noted in the incidence of pulmonary complications, but not cardiovascular or neurologic complications. There was a consistent reduction in major morbidity regardless of age, lung function, or type of incision. Mortality was reduced in patients with preoperative forced expiratory volume in 1 second less than 85% predicted. CONCLUSIONS: Wedge resection has a 37% lower mortality and 50% lower major morbidity rate than anatomic resection in these propensity-matched populations. The mortality benefit is most apparent in patients with forced expiratory volume in 1 second less than 85% predicted. These perioperative benefits must be carefully weighed against the increase in locoregional recurrence and possible decrease in long-term survival associated with the use of wedge resection for primary lung cancers.

Authors
Linden, PA; D'Amico, TA; Perry, Y; Saha-Chaudhuri, P; Sheng, S; Kim, S; Onaitis, M
MLA Citation
Linden, PA, D'Amico, TA, Perry, Y, Saha-Chaudhuri, P, Sheng, S, Kim, S, and Onaitis, M. "Quantifying the safety benefits of wedge resection: a society of thoracic surgery database propensity-matched analysis." The Annals of thoracic surgery 98.5 (November 2014): 1705-1711.
PMID
25201723
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
98
Issue
5
Publish Date
2014
Start Page
1705
End Page
1711
DOI
10.1016/j.athoracsur.2014.06.017

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

Use of amiodarone after major lung resection.

We evaluated the association of respiratory complications and amiodarone use in patients with atrial fibrillation (AF) after major lung resection.Outcomes of patients who had postoperative AF treated with or without amiodarone after lobectomy, bilobectomy, or pneumonectomy at a single institution between 2003 and 2010 were evaluated using multivariable logistic modeling.Of 1,412 patients who underwent lobectomy, bilobectomy, or pneumonectomy, AF occurred in 232 (16%). Atrial fibrillation developed after a respiratory complication in 31 patients, who were excluded from subsequent analysis. The remaining 201 patients who had AF without an antecedent respiratory complication had similar mortality (3.0% [6 of 201] vs 2.5% [30 of 1,180], p = 0.6) and respiratory morbidity (10% [20 of 201] vs 9% [101 of 1,180], p = 0.5) but longer hospital stays (5 [4 to 7] vs 4 days [3 to 6], p < 0.0001) compared with the 1,180 patients who did not have AF. Amiodarone was used in 101 (50%) of these 201 patients, including 5 patients who had a pneumonectomy. Age, pulmonary function, and operative resection were similar between the patients treated with and without amiodarone. Amiodarone use was not associated with a significant difference in the incidence of subsequent respiratory complications (12% [12 of 101 amiodarone patients] vs 8% [8 of 100 non-amiodarone patients], p = 0.5).Atrial fibrillation that occurs without an antecedent respiratory complication in patients after major lung resection results in longer hospital stay but not increased mortality or respiratory morbidity. Using amiodarone to treat atrial fibrillation after major lung resection is not associated with an increased incidence of respiratory complications.

Authors
Berry, MF; D'Amico, TA; Onaitis, MW
MLA Citation
Berry, MF, D'Amico, TA, and Onaitis, MW. "Use of amiodarone after major lung resection." The Annals of thoracic surgery 98.4 (October 2014): 1199-1206.
PMID
25106684
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
98
Issue
4
Publish Date
2014
Start Page
1199
End Page
1206
DOI
10.1016/j.athoracsur.2014.05.038

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

The cell of origin and subtype of K-Ras-induced lung tumors are modified by Notch and Sox2.

Cell type-specific conditional activation of oncogenic K-Ras is a powerful tool for investigating the cell of origin of adenocarcinomas in the mouse lung. Our previous studies showed that K-Ras activation with a CC10(Scgb1a1)-CreER driver leads to adenocarcinoma in a subset of alveolar type II cells and hyperplasia in the bronchioalveolar duct region. However, no tumors develop in the bronchioles, although recombination occurs throughout this region. To explore underlying mechanisms, we simultaneously modulated either Notch signaling or Sox2 levels in the CC10+ cells along with activation of K-Ras. Inhibition of Notch strongly inhibits adenocarcinoma formation but promotes squamous hyperplasia in the alveoli. In contrast, activation of Notch leads to widespread Sox2+, Sox9+, and CC10+ papillary adenocarcinomas throughout the bronchioles. Chromatin immunoprecipitation demonstrates Sox2 binding to NOTCH1 and NOTCH2 regulatory regions. In transgenic mouse models, overexpression of Sox2 leads to a significant reduction of Notch1 and Notch2 transcripts, while a 50% reduction in Sox2 leads to widespread papillary adenocarcinoma in the bronchioles. Taken together, our data demonstrate that the cell of origin of K-Ras-induced tumors in the lung depends on levels of Sox2 expression affecting Notch signaling. In addition, the subtype of tumors arising from type II cells is determined in part by Notch activation or suppression.

Authors
Xu, X; Huang, L; Futtner, C; Schwab, B; Rampersad, RR; Lu, Y; Sporn, TA; Hogan, BLM; Onaitis, MW
MLA Citation
Xu, X, Huang, L, Futtner, C, Schwab, B, Rampersad, RR, Lu, Y, Sporn, TA, Hogan, BLM, and Onaitis, MW. "The cell of origin and subtype of K-Ras-induced lung tumors are modified by Notch and Sox2." Genes & development 28.17 (September 2014): 1929-1939.
PMID
25184679
Source
epmc
Published In
Genes & development
Volume
28
Issue
17
Publish Date
2014
Start Page
1929
End Page
1939
DOI
10.1101/gad.243717.114

Fewer complications result from a video-assisted approach to anatomic resection of clinical stage I lung cancer.

Anatomic resection is currently the standard of care for clinical stage I lung cancer, yet clinicians increasingly pursue nonsurgical, ablative therapies to avoid the morbidity of thoracotomy. The video-assisted thoracic surgery (VATS) approach is a minimally invasive alternative to thoracotomy yet the effect of VATS on the morbidity of patients undergoing lung cancer resection is not fully characterized. We evaluated complications following anatomic resection of clinical stage I lung cancer by VATS and thoracotomy to clarify the effect of the minimally invasive approach.The Society of Thoracic Surgeons database was queried for lobectomies and segmentectomies performed between 2001 and 2010 for clinical stage I primary cancer.A total of 11,531 (7137 open and 4394 VATS) patients with clinical stage I primary lung cancers underwent resection. Propensity scoring was used to match cases into 2745 well-balanced pairs. Overall complications were significantly more likely in the thoracotomy group (36%) than in the VATS cohort (30%; P < .001). Patients undergoing thoracotomy experienced significantly more pulmonary complications (21% vs 18%), atrial arrhythmias (13% vs 10%), and were more likely to undergo transfusion (6% vs 4%). Operative mortality was similar (thoracotomy 1.8%, VATS 1.3%; P = .13).Anatomic resection of early stage lung cancer is performed with a low mortality rate, according to data from the Society of Thoracic Surgeons database. Perioperative complications are significantly less likely to occur when patients with stage I lung cancers undergo resection using the VATS approach. Further study is warranted to determine long-term effects of these differences in perioperative outcomes.

Authors
Boffa, DJ; Dhamija, A; Kosinski, AS; Kim, AW; Detterbeck, FC; Mitchell, JD; Onaitis, MW; Paul, S
MLA Citation
Boffa, DJ, Dhamija, A, Kosinski, AS, Kim, AW, Detterbeck, FC, Mitchell, JD, Onaitis, MW, and Paul, S. "Fewer complications result from a video-assisted approach to anatomic resection of clinical stage I lung cancer." The Journal of thoracic and cardiovascular surgery 148.2 (August 2014): 637-643.
PMID
24529729
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
148
Issue
2
Publish Date
2014
Start Page
637
End Page
643
DOI
10.1016/j.jtcvs.2013.12.045

Induction therapy does not improve survival for clinical stage T2N0 esophageal cancer.

This study compared survival after initial treatment with esophagectomy as primary therapy to induction therapy followed by esophagectomy for patients with clinical T2N0 (cT2N0) esophageal cancer in the National Cancer Database (NCDB).Predictors of therapy selection for patients with cT2N0 esophageal cancer in the NCDB from 1998 to 2011 were identified with multivariable logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional hazards methods.Surgery was used in 42.9% (2057 of 4799) of cT2N0 patients. Of 1599 esophagectomy patients for whom treatment timing was recorded, induction therapy was used in 44.1% (688). Pretreatment staging was proven accurate in only 26.7% of patients (210 of 786) who underwent initial surgery without induction treatment and had complete pathologic data available: 41.6% (n = 327) were upstaged and 31.7% (n = 249) were downstaged. Adjuvant therapy (chemotherapy or radiation therapy) was given to 50.2% of patients treated initially with surgery who were found after resection to have nodal disease. There was no significant difference in long-term survival between strategies of primary surgery and induction therapy followed by surgery (median 41.1 versus 41.9 months, p = 0.51). In multivariable analysis, induction therapy was not independently associated with risk of death (hazard ratio [HR], 1.16, p = 0.32).Current clinical staging for early-stage esophageal cancer is highly inaccurate, with only a quarter of surgically resected cT2N0 patients found to have had accurate pretreatment staging. Induction therapy for patients with cT2N0 esophageal cancer in the NCDB is not associated with improved survival.

Authors
Speicher, PJ; Ganapathi, AM; Englum, BR; Hartwig, MG; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Ganapathi, AM, Englum, BR, Hartwig, MG, Onaitis, MW, D'Amico, TA, and Berry, MF. "Induction therapy does not improve survival for clinical stage T2N0 esophageal cancer." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 9.8 (August 2014): 1195-1201.
PMID
25157773
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
9
Issue
8
Publish Date
2014
Start Page
1195
End Page
1201
DOI
10.1097/jto.0000000000000228

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

Thoracoscopic lobectomy is associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40% of normal.

OBJECTIVE: A predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1%) or diffusing capacity of the lung for carbon monoxide (DLCO%) of <40% has traditionally been considered to convey a high risk of lobectomy owing to elevated postoperative morbidity and mortality. These recommendations, however, were largely derived from the pre-video-assisted thoracoscopic surgical (VATS) era. We hypothesized that VATS lobectomy would be associated with acceptable morbidity and mortality at ppoFEV1% and ppoDLCO% values < 40%. METHODS: PpoFEV1% and ppoDLCO% were calculated for patients undergoing open or VATS lobectomy for lung cancer in the Society of Thoracic Surgeons General Thoracic database from 2009 to 2011. Univariate comparisons, multivariate analyses, and 1:1 propensity matching were performed. RESULTS: A total of 13,376 patients underwent lobectomy (50.9% open, 49.1% VATS). A decreased ppoFEV1% and ppoDLCO% were each independent predictors for both cardiopulmonary complications and mortality in the open group (all P ≤ .008). In the VATS group, ppoFEV1% was an independent predictor of complications (P = .001) but not mortality (P = .77), and ppoDLCO% was an independent predictor of complications (P = .046) and mortality (P = .008). With decreasing ppoFEV1% or ppoDLCO%, complications and mortality increased at a greater rate in the open lobectomy than in a propensity-matched VATS group (n = 4215 each). For patients with ppoFEV1% < 40%, mortality was greater in the open (4.8%) than in the matched VATS group (0.7%, P = .003). Similar results were seen for ppoDLCO% < 40% (5.2% open, 2.0% VATS, P = .003). The rate of complications was significantly greater at ppoFEV1% < 40% in the open (21.9%) than in the matched VATS (12.8%, P = .005) group and similar results were seen with ppoDLCO% < 40% (14.9% open, 10.4% VATS, P = .016). CONCLUSIONS: VATS lobectomy can be performed with acceptable rates of morbidity and mortality in patients with reduced ppoFEV1% or ppoDLCO%.

Authors
Burt, BM; Kosinski, AS; Shrager, JB; Onaitis, MW; Weigel, T
MLA Citation
Burt, BM, Kosinski, AS, Shrager, JB, Onaitis, MW, and Weigel, T. "Thoracoscopic lobectomy is associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40% of normal." The Journal of thoracic and cardiovascular surgery 148.1 (July 2014): 19-28.
PMID
24766848
Source
epmc
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
148
Issue
1
Publish Date
2014
Start Page
19
End Page
28
DOI
10.1016/j.jtcvs.2014.03.007

Thoracoscopic approach to lobectomy for lung cancer does not compromise oncologic efficacy.

We compared survival between video-assisted thoracoscopic surgery (VATS) and thoracotomy approaches to lobectomy for non-small cell lung cancer.Overall survival of patients who had lobectomy for any stage non-small cell lung cancer without previous chemotherapy or radiation from 1996 to 2008 was evaluated using the Kaplan-Meier method and multivariate Cox analysis. Propensity scoring was used to assess the impact of selection bias.Overall, 1,087 patients met inclusion criteria (610 VATS, 477 thoracotomy). Median follow-up was not significantly different between VATS and thoracotomy patients overall (53.4 versus 45.4 months, respectively; p=0.06) but was longer for thoracotomy for surviving patients (102.4 versus 67.9 months, p<0.0001). Thoracotomy patients had larger tumors (3.9±2.3 versus 2.8±1.5 cm, p<0.0001), and more often had higher stage cancers (50% [n=237] versus 71% [n=435] stage I, p<0.0001) compared with VATS patients. In multivariate analysis of all patients, thoracotomy approach (hazard ratio [HR] 1.22, p=0.01), increasing age (HR 1.02 per year, p<0.0001), pathologic stage (HR 1.45 per stage, p<0.0001), and male sex (HR 1.35, p=0.0001) predicted worse survival. In a cohort of 560 patients (311 VATS, 249 thoracotomy) who were assembled using propensity scoring and were similar in age, stage, tumor size, and sex, the operative approach did not impact survival (p=0.5), whereas increasing age (HR 1.02 per year, p=0.01), pathologic stage (HR 1.44 per stage, p<0.0001), and male sex (HR 1.29, p=0.01) predicted worse survival.The thoracoscopic approach to lobectomy for non-small cell lung cancer does not result in worse long-term survival compared with thoracotomy.

Authors
Berry, MF; D'Amico, TA; Onaitis, MW; Kelsey, CR
MLA Citation
Berry, MF, D'Amico, TA, Onaitis, MW, and Kelsey, CR. "Thoracoscopic approach to lobectomy for lung cancer does not compromise oncologic efficacy." The Annals of thoracic surgery 98.1 (July 2014): 197-202.
PMID
24820392
Source
epmc
Published In
The Annals of Thoracic Surgery
Volume
98
Issue
1
Publish Date
2014
Start Page
197
End Page
202
DOI
10.1016/j.athoracsur.2014.03.018

When should surgeons begin surveillance with CT scans after lobectomy for stage 1A non-small cell lung cancer?

Authors
Mallipeddi, MK; Eltaraboulsi, WR; Shoffner, AR; Naqvi, IA; D'Amico, TA; Onaitis, MW; Berry, MF
MLA Citation
Mallipeddi, MK, Eltaraboulsi, WR, Shoffner, AR, Naqvi, IA, D'Amico, TA, Onaitis, MW, and Berry, MF. "When should surgeons begin surveillance with CT scans after lobectomy for stage 1A non-small cell lung cancer?." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Association of adjuvant chemotherapy with improved survival after esophagectomy without induction therapy for node-positive adenocarinoma.

Authors
Speicher, PJ; Englum, BR; Ganapathi, AM; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Englum, BR, Ganapathi, AM, Onaitis, MW, D'Amico, TA, and Berry, MF. "Association of adjuvant chemotherapy with improved survival after esophagectomy without induction therapy for node-positive adenocarinoma." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Robotic benign esophageal procedures.

Robotic master-slave devices can assist surgeons to perform minimally invasive esophageal operations with approaches that have already been demonstrated using laparoscopy and thoracoscopy. Robotic-assisted surgery for benign esophageal disease is described for the treatment of achalasia, epiphrenic diverticula, refractory reflux, paraesophageal hernias, duplication cysts, and benign esophageal masses, such as leiomyomas. Indications and contraindications for robotic surgery in benign esophageal disease should closely approximate the indications for laparoscopic and thoracoscopic procedures. Given the early application of the technology and paucity of clinical evidence, there are currently no procedures for which robotic esophageal surgery is the clinically proven preferred approach.

Authors
Hanna, JM; Onaitis, MW
MLA Citation
Hanna, JM, and Onaitis, MW. "Robotic benign esophageal procedures." Thoracic surgery clinics 24.2 (May 2014): 223-vii.
PMID
24780427
Source
epmc
Published In
Thoracic Surgery Clinics
Volume
24
Issue
2
Publish Date
2014
Start Page
223
End Page
vii
DOI
10.1016/j.thorsurg.2014.02.004

Minimally invasive and robotic Ivor Lewis esophagectomy.

Esophageal cancer is the eighth most common malignancy and the sixth most common cause of cancer-related death worldwide. Esophagectomy provides a curative treatment but carries significant morbidity and mortality. Ivor Lewis esophagectomy (ILE) is one of the most commonly employed open techniques of esophagectomy. Minimally invasive approaches have been explored in ILE in an effort to reduce operative morbidity. This article reviews recent literature of minimally invasive Ivor Lewis esophagectomy (MI-ILE), discusses its clinical outcomes, and introduces the robotic approach in MI-ILE. MI-ILE has demonstrated comparable postoperative outcomes to open ILE, and it has shown potential to reduce blood loss and length of hospitalization. Due to limited studies, no significant improvement of long-term survival has been reported in MI-ILE. Robotic ILE is safe and feasible, but more studies are needed to prove identifiable benefits. Randomized controlled trials comparing MI-ILE or robotic ILE with conventional open ILE are warranted to determine the optimal surgical procedure for the treatment of esophageal cancer.

Authors
Huang, L; Onaitis, M
MLA Citation
Huang, L, and Onaitis, M. "Minimally invasive and robotic Ivor Lewis esophagectomy." Journal of thoracic disease 6 Suppl 3 (May 2014): S314-S321. (Review)
PMID
24876936
Source
epmc
Published In
Journal of Thoracic Disease
Volume
6 Suppl 3
Publish Date
2014
Start Page
S314
End Page
S321
DOI
10.3978/j.issn.2072-1439.2014.04.32

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

Hedgehog-GLI signaling inhibition suppresses tumor growth in squamous lung cancer.

Lung squamous cell carcinoma (LSCC) currently lacks effective targeted therapies. Previous studies reported overexpression of Hedgehog (HH)-GLI signaling components in LSCC. However, they addressed neither the tumor heterogeneity nor the requirement for HH-GLI signaling. Here, we investigated the role of HH-GLI signaling in LSCC, and studied the therapeutic potential of HH-GLI suppression.Gene expression datasets of two independent LSCC patient cohorts were analyzed to study the activation of HH-GLI signaling. Four human LSCC cell lines were examined for HH-GLI signaling components. Cell proliferation and apoptosis were assayed in these cells after blocking the HH-GLI pathway by lentiviral-shRNA knockdown or small-molecule inhibitors. Xenografts in immunodeficient mice were used to determine the in vivo efficacy of GLI inhibitor GANT61.In both cohorts, activation of HH-GLI signaling was significantly associated with the classical subtype of LSCC. In cell lines, genetic knockdown of Smoothened (SMO) produced minor effects on cell survival, whereas GLI2 knockdown significantly reduced proliferation and induced extensive apoptosis. Consistently, the SMO inhibitor GDC-0449 resulted in limited cytotoxicity in LSCC cells, whereas the GLI inhibitor GANT61 was very effective. Importantly, GANT61 demonstrated specific in vivo antitumor activity in xenograft models of GLI(+) cell lines.Our studies demonstrate an important role for GLI2 in LSCC, and suggest GLI inhibition as a novel and potent strategy to treat a subset of patients with LSCC.

Authors
Huang, L; Walter, V; Hayes, DN; Onaitis, M
MLA Citation
Huang, L, Walter, V, Hayes, DN, and Onaitis, M. "Hedgehog-GLI signaling inhibition suppresses tumor growth in squamous lung cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 20.6 (March 2014): 1566-1575.
PMID
24423612
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
20
Issue
6
Publish Date
2014
Start Page
1566
End Page
1575
DOI
10.1158/1078-0432.ccr-13-2195

The contemporary role of minimally invasive esophagectomy in esophageal cancer.

Open surgical resection via transhiatal or transthoracic, including McKeown, access is the most viable option for curing esophageal cancer; however, the extensive nature of open surgery in both the chest and abdomen results in significant rates of morbidity and mortality. A natural response was the introduction of minimally invasive esophagectomy (MIE) and, later, endoscopic resection. In the hands of experienced surgeons, MIE can achieve equivalent or better perioperative mortality, morbidity, and oncologic outcomes as compared to open surgery. This review starts with an overview of open esophagectomy before delving into the evolving body of evidence on MIE outcomes and practices.

Authors
Mallipeddi, MK; Onaitis, MW
MLA Citation
Mallipeddi, MK, and Onaitis, MW. "The contemporary role of minimally invasive esophagectomy in esophageal cancer." Current oncology reports 16.3 (March 2014): 374-.
PMID
24488547
Source
epmc
Published In
Current Oncology Reports
Volume
16
Issue
3
Publish Date
2014
Start Page
374
DOI
10.1007/s11912-013-0374-9

Survival in the elderly after pneumonectomy for early-stage non-small cell lung cancer: a comparison with nonoperative management.

Short-term outcomes of morbidity, mortality, and quality of life after pneumonectomy worsen with increasing age. The impact of age on long-term outcomes has not been well described. The purpose of this study was to quantify the impact of patient age on long-term survival after pneumonectomy for early-stage non-small cell lung cancer.Overall survival (OS) of patients who had a pneumonectomy for stage I to II non-small cell lung cancer in the Surveillance Epidemiology and End Results program registry from 1988 through 2010 was evaluated using multivariable and propensity score adjusted Cox proportional hazard models. Age was stratified as younger than 50 years, 50 to 69 years, 70 to 79 years, and 80 years and older. Pneumonectomy patients' OS was compared with matched patients who refused surgery and underwent radiation therapy (RT).Pneumonectomies comprised 10.8% of non-small cell lung cancer resections in 1988, but only 2.9% in 2010. Overall, 5-year OS of 5,701 pneumonectomy patients was 49.8% (95% CI, 45.3-54.8%) for patients younger than 50 years, 40.5% (95% CI, 38.8-42.2%) for patients 50 to 69 years, 28.9% (95% CI, 26.6-31.5%) for patients 70 to 79 years, and 18.8% (95% CI, 14.2-24.8%) for patients 80 and older (p < 0.001). Increasing patient age was the most important predictor of worse OS (hazard ratio = 1.34 per decade; p < 0.001). For patients younger than 70 years, 5-year OS was 46.3% (95% CI, 36.2-59.2%) after pneumonectomy vs 18.4% (95% CI, 11.9-28.3%) for matched RT patients (p < 0.001). In matched groups of patients 70 years and older, 5-year OS for pneumonectomy was 25.8% (95% CI, 20.8-32.0%) vs 12.2% for RT (95% CI, 8.6-17.4%; p = 0.02).Survival after pneumonectomy for stage I to II non-small cell lung cancer decreases steadily with patient age. The incremental benefit of pneumonectomy vs RT in matched patients is less in patients older than 70 years than in younger patients, although outcomes with pneumonectomy are superior to RT in all age groups. Patients should not be denied pneumonectomy based on age alone, but careful patient selection in elderly patients is essential to optimize survival.

Authors
Speicher, PJ; Ganapathi, AM; Englum, BR; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Speicher, PJ, Ganapathi, AM, Englum, BR, Onaitis, MW, D'Amico, TA, and Berry, MF. "Survival in the elderly after pneumonectomy for early-stage non-small cell lung cancer: a comparison with nonoperative management." Journal of the American College of Surgeons 218.3 (March 2014): 439-449.
PMID
24559956
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
218
Issue
3
Publish Date
2014
Start Page
439
End Page
449
DOI
10.1016/j.jamcollsurg.2013.12.005

Impact of Pre-treatment Imaging on Survival of Esophagectomy after Induction Therapy for Esophageal Cancer: Who Should be Given the Benefit of Doubt?

Authors
Erhunmwunsee, L; Englum, BR; D'Amico, TA; Onaitis, MW; Berry, MF
MLA Citation
Erhunmwunsee, L, Englum, BR, D'Amico, TA, Onaitis, MW, and Berry, MF. "Impact of Pre-treatment Imaging on Survival of Esophagectomy after Induction Therapy for Esophageal Cancer: Who Should be Given the Benefit of Doubt?." February 2014.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
21
Publish Date
2014
Start Page
S151
End Page
S151

The Impact of Surveillance after Lobectomy for Stage IA Non-small Cell Lung Cancer

Authors
Mallipeddi, MK; Eltaraboulsi, WR; Shoffner, AR; Naqvi, IA; D'Amico, TA; Onaitis, MW; Berry, MF
MLA Citation
Mallipeddi, MK, Eltaraboulsi, WR, Shoffner, AR, Naqvi, IA, D'Amico, TA, Onaitis, MW, and Berry, MF. "The Impact of Surveillance after Lobectomy for Stage IA Non-small Cell Lung Cancer." February 2014.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
21
Publish Date
2014
Start Page
S153
End Page
S154

Minimally invasive and robotic Ivor Lewis esophagectomy

Esophageal cancer is the eighth most common malignancy and the sixth most common cause of cancer-related death worldwide. Esophagectomy provides a curative treatment but carries significant morbidity and mortality. Ivor Lewis esophagectomy (ILE) is one of the most commonly employed open techniques of esophagectomy. Minimally invasive approaches have been explored in ILE in an effort to reduce operative morbidity. This article reviews recent literature of minimally invasive Ivor Lewis esophagectomy (MI-ILE), discusses its clinical outcomes, and introduces the robotic approach in MI-ILE. MI-ILE has demonstrated comparable postoperative outcomes to open ILE, and it has shown potential to reduce blood loss and length of hospitalization. Due to limited studies, no significant improvement of long-term survival has been reported in MI-ILE. Robotic ILE is safe and feasible, but more studies are needed to prove identifiable benefits. Randomized controlled trials comparing MI-ILE or robotic ILE with conventional open ILE are warranted to determine the optimal surgical procedure for the treatment of esophageal cancer. © Pioneer Bioscience Publishing Company.

Authors
Huang, L; Onaitis, M
MLA Citation
Huang, L, and Onaitis, M. "Minimally invasive and robotic Ivor Lewis esophagectomy." Journal of Thoracic Disease 6.SUPPL.3 (January 1, 2014). (Review)
Source
scopus
Published In
Journal of Thoracic Disease
Volume
6
Issue
SUPPL.3
Publish Date
2014
DOI
10.3978/j.issn.2072-1439.2014.04.32

Quantifying the safety benefits of wedge resection: A society of thoracic surgery database propensity-matched analysis

© 2014 by The Society of Thoracic Surgeons.Background. Wedge resection is often used instead of anatomic resection in an attempt to mitigate perioperative risk. In propensity-matched populations, we sought to compare the perioperative outcomes of patients undergoing wedge resection with those undergoing anatomic resection. Methods. The Society of Thoracic Surgery database was reviewed for stage I and II non-small cell lung cancer patients undergoing wedge resection and anatomic resection to analyze postoperative morbidity and mortality. Propensity scores were estimated using a logistic model adjusted for a variety of risk factors. Patients were then matched by propensity score using a greedy 5- to 1-digit matching algorithm, and compared using McNemar's test. Results. Between 2009 and 2011, 3,733 wedge resection and 3,733 anatomic resection patients were matched. The operative mortality was 1.21% for wedge resection versus 1.93% for anatomic resection (p = 0.0118). Major morbidity occurred in 4.53% of wedge resection patients versus 8.97% of anatomic resection patients (p < 0.0001). A reduction was noted in the incidence of pulmonary complications, but not cardiovascular or neurologic complications. There was a consistent reduction in major morbidity regardless of age, lung function, or type of incision. Mortality was reduced in patients with preoperative forced expiratory volume in 1 second less than 85% predicted. Conclusions. Wedge resection has a 37% lower mortality and 50% lower major morbidity rate than anatomic resection in these propensity-matched populations. The mortality benefit is most apparent in patients with forced expiratory volume in 1 second less than 85% predicted. These perioperative benefits must be carefully weighed against the increase in locoregional recurrence and possible decrease in long-term survival associated with the use of wedge resection for primary lung cancers.

Authors
Linden, PA; D'Amico, TA; Perry, Y; Saha-Chaudhuri, P; Sheng, S; Kim, S; Onaitis, M
MLA Citation
Linden, PA, D'Amico, TA, Perry, Y, Saha-Chaudhuri, P, Sheng, S, Kim, S, and Onaitis, M. "Quantifying the safety benefits of wedge resection: A society of thoracic surgery database propensity-matched analysis." Annals of Thoracic Surgery 98.5 (January 1, 2014): 1705-1711.
Source
scopus
Published In
The Annals of Thoracic Surgery
Volume
98
Issue
5
Publish Date
2014
Start Page
1705
End Page
1711
DOI
10.1016/j.athoracsur.2014.06.017

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

A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.

OBJECTIVE: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC). BACKGROUND: Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens. METHODS: Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study. RESULTS: Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group. CONCLUSIONS: Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).

Authors
Morse, MA; Niedzwiecki, D; Marshall, JL; Garrett, C; Chang, DZ; Aklilu, M; Crocenzi, TS; Cole, DJ; Dessureault, S; Hobeika, AC; Osada, T; Onaitis, M; Clary, BM; Hsu, D; Devi, GR; Bulusu, A; Annechiarico, RP; Chadaram, V; Clay, TM; Lyerly, HK
MLA Citation
Morse, MA, Niedzwiecki, D, Marshall, JL, Garrett, C, Chang, DZ, Aklilu, M, Crocenzi, TS, Cole, DJ, Dessureault, S, Hobeika, AC, Osada, T, Onaitis, M, Clary, BM, Hsu, D, Devi, GR, Bulusu, A, Annechiarico, RP, Chadaram, V, Clay, TM, and Lyerly, HK. "A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer." Ann Surg 258.6 (December 2013): 879-886.
PMID
23657083
Source
pubmed
Published In
Annals of Surgery
Volume
258
Issue
6
Publish Date
2013
Start Page
879
End Page
886
DOI
10.1097/SLA.0b013e318292919e

Minithoracotomy versus sternotomy for mitral surgery in patients with chronic renal impairment: a propensity-matched study.

OBJECTIVE: Compared with median sternotomy, a right thoracotomy (RT) approach to mitral surgery is associated with decreased postoperative acute renal failure. Therefore, we examined propensity-matched patients with chronic renal impairment to compare outcomes. METHODS: A retrospective review at a single institution identified patients who underwent mitral valve surgery from 1986 to 2010. After excluding patients who had procedures that were not usually performed through an RT approach, 2306 patients were identified. Of this group, we found 446 patients with preoperative creatinines of 1.3 mg/dL or greater. Using propensity score matching based on comorbidities, operative year, and surgeon, 90 matched patients in each group were included. RESULTS: There was no difference in the median year of operation. Postoperative mortality is 20% lower for the RT group (P = 0.037) using Mantel-Cox statistics. This greater survival in the RT group occurred early within the first year and was maintained on long-term follow-up. The RT approach was also associated with a Cox proportional hazard for mortality of 0.528 (P = 0.006). Incidence of postoperative complications with an RT approach was lower in terms of acute renal failure (10% vs 21%, P = 0.05), stroke (1% vs 9%, P = 0.017), and permanent pacemaker insertion (3% vs 11%, P = 0.044). Right thoracotomy was associated with lower chest tube outputs (503 vs 1333 mL, P < 0.001). CONCLUSIONS: The RT approach was associated with lower postoperative mortality and morbidity in patients with impaired renal function. The RT approach to the mitral valve may be preferred in this high-risk population.

Authors
Tang, P; Onaitis, M; Desai, B; Gaca, JG; Milano, CA; Stafford-Smith, M; Glower, DD
MLA Citation
Tang, P, Onaitis, M, Desai, B, Gaca, JG, Milano, CA, Stafford-Smith, M, and Glower, DD. "Minithoracotomy versus sternotomy for mitral surgery in patients with chronic renal impairment: a propensity-matched study." Innovations (Phila) 8.5 (September 2013): 325-331.
PMID
24346579
Source
pubmed
Published In
Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery
Volume
8
Issue
5
Publish Date
2013
Start Page
325
End Page
331
DOI
10.1097/IMI.0000000000000020

Does pneumonectomy have a role in the treatment of stage IIIA non-small cell lung cancer?

BACKGROUND: The role of surgical resection for stage IIIA non-small cell lung cancer (NSCLC) is unclear. We sought to examine outcomes after pneumonectomy for patients with stage IIIA disease. METHODS: All patients with stage IIIA NSCLC who had pneumonectomy at a single institution between 1999 and 2010 were reviewed. The Kaplan-Meier method was used to estimate long-term survival and multivariable Cox proportional hazards regression was used to identify clinical characteristics associated with survival. RESULTS: During the study period, 324 patients had surgical resection of stage IIIA NSCLC. Pneumonectomy was performed in 55 patients, 23 (42%) of whom had N2 disease. Induction treatment was used in 17 patients (31%) overall and in 11 of the patients (48%) with N2 disease. Perioperative mortality was 9% (n = 5) overall and 18% (n = 3) in patients that had received induction therapy (p = 0.17). Complications occurred in 32 patients (58%). Three-year survival was 36% and 5-year survival was 29% for all patients. Three-year survival was 40% for N0-1 patients and 29% for N2 patients (p = 0.59). In multivariable analysis, age over 60 years (hazard ratio [HR] 3.65, p = 0.001), renal insufficiency (HR 5.80, p = 0.007), and induction therapy (HR 2.17, p = 0.05) predicted worse survival, and adjuvant therapy (HR 0.35, p = 0.007) predicted improved survival. CONCLUSIONS: Long-term survival after pneumonectomy for stage IIIA NSCLC is within an acceptable range, but pneumonectomy may not be appropriate after induction therapy or in patients with renal insufficiency. Patient selection and operative technique that limit perioperative morbidity and facilitate the use of adjuvant chemotherapy are critical to optimizing outcomes.

Authors
Shah, AA; Worni, M; Kelsey, CR; Onaitis, MW; D'Amico, TA; Berry, MF
MLA Citation
Shah, AA, Worni, M, Kelsey, CR, Onaitis, MW, D'Amico, TA, and Berry, MF. "Does pneumonectomy have a role in the treatment of stage IIIA non-small cell lung cancer?." Ann Thorac Surg 95.5 (May 2013): 1700-1707.
PMID
23545195
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
95
Issue
5
Publish Date
2013
Start Page
1700
End Page
1707
DOI
10.1016/j.athoracsur.2013.02.044

Sox2 cooperates with inflammation-mediated Stat3 activation in the malignant transformation of foregut basal progenitor cells.

Sox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment-activated Stat3 is required for Sox2-driven tumorigenesis.

Authors
Liu, K; Jiang, M; Lu, Y; Chen, H; Sun, J; Wu, S; Ku, W-Y; Nakagawa, H; Kita, Y; Natsugoe, S; Peters, JH; Rustgi, A; Onaitis, MW; Kiernan, A; Chen, X; Que, J
MLA Citation
Liu, K, Jiang, M, Lu, Y, Chen, H, Sun, J, Wu, S, Ku, W-Y, Nakagawa, H, Kita, Y, Natsugoe, S, Peters, JH, Rustgi, A, Onaitis, MW, Kiernan, A, Chen, X, and Que, J. "Sox2 cooperates with inflammation-mediated Stat3 activation in the malignant transformation of foregut basal progenitor cells." Cell Stem Cell 12.3 (March 7, 2013): 304-315.
PMID
23472872
Source
pubmed
Published In
Cell Stem Cell
Volume
12
Issue
3
Publish Date
2013
Start Page
304
End Page
315
DOI
10.1016/j.stem.2013.01.007

Impact of T status and N status on perioperative outcomes after thoracoscopic lobectomy for lung cancer.

OBJECTIVE: We sought to evaluate the effect of tumor size, location, and clinical nodal status on outcomes after thoracoscopic lobectomy for lung cancer. METHODS: All patients who underwent attempted thoracoscopic lobectomy for lung cancer between June 1999 and October 2010 at a single institution were reviewed. A model for morbidity including published risk factors as well as tumor size, location, and clinical N status was developed by multivariable logistic regression. RESULTS: During the study period, 916 thoracoscopic lobectomies met study criteria: 329 for peripheral, clinical N0 tumors ≤ 3 cm and 504 for tumors that were central, clinical node positive, or >3 cm. Tumor location could not be documented for 83 patients. Conversions to thoracotomy occurred in 36 patients (4%); patients with clinically node-positive disease had higher conversion rates (11 conversions in 153 clinical N1 to N3 patients [7.2%] vs 25 in 763 clinical N0 patients [3.3%, P = .03]. Overall operative mortality was 1.6% (14 patients) and morbidity was 32% (296 patients). Although patients with larger tumors (P = .006) and central tumors (P = .01) had increased complications by univariate analysis, tumor size >3 cm (P = .17) and central location (P = .5) did not predict significantly overall morbidity in multivariate analysis. Clinical node status did not predict increased complications by univariate or multivariate analysis. Significant predictors of morbidity in multivariable analysis were increasing age, decreasing forced expiratory volume in 1 second, prior chemotherapy, and congestive heart failure. CONCLUSIONS: Thoracoscopic lobectomy for lung cancers that are central, clinically node positive, or >3 cm does not confer increased morbidity compared with peripheral, clinical N0 cancers that are <3 cm.

Authors
Villamizar, NR; Darrabie, M; Hanna, J; Onaitis, MW; Tong, BC; D'Amico, TA; Berry, MF
MLA Citation
Villamizar, NR, Darrabie, M, Hanna, J, Onaitis, MW, Tong, BC, D'Amico, TA, and Berry, MF. "Impact of T status and N status on perioperative outcomes after thoracoscopic lobectomy for lung cancer." J Thorac Cardiovasc Surg 145.2 (February 2013): 514-520.
PMID
23177123
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
145
Issue
2
Publish Date
2013
Start Page
514
End Page
520
DOI
10.1016/j.jtcvs.2012.10.039

Invited commentary

Authors
Onaitis, M
MLA Citation
Onaitis, M. "Invited commentary." Annals of Thoracic Surgery 96.5 (2013): 1775--.
PMID
24182463
Source
scival
Published In
The Annals of Thoracic Surgery
Volume
96
Issue
5
Publish Date
2013
Start Page
1775-
DOI
10.1016/j.athoracsur.2013.06.001

Cell of origin of lung cancer.

Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s) of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell of origin, and cancer stem cells has been hampered by the heterogeneity of the disease, the lack of good in vivo transplantation models to assess stem cell behavior, and an overall incomplete understanding of the epithelial stem cell hierarchy. As such, a systematic computerized literature search of the MEDLINE database was used to identify articles discussing current knowledge about normal lung and lung cancer stem cells or progenitor cells. In this review, we discuss what is currently known about the role of cancer-initiating cells and normal stem cells in the development of lung tumors.

Authors
Hanna, JM; Onaitis, MW
MLA Citation
Hanna, JM, and Onaitis, MW. "Cell of origin of lung cancer. (Published online)" J Carcinog 12 (2013): 6-.
PMID
23599688
Source
pubmed
Published In
J Carcinog
Volume
12
Publish Date
2013
Start Page
6
DOI
10.4103/1477-3163.109033

Impact of T status and N status on perioperative outcomes after thoracoscopic lobectomy for lung cancer

Objective: We sought to evaluate the effect of tumor size, location, and clinical nodal status on outcomes after thoracoscopic lobectomy for lung cancer. Methods: All patients who underwent attempted thoracoscopic lobectomy for lung cancer between June 1999 and October 2010 at a single institution were reviewed. A model for morbidity including published risk factors as well as tumor size, location, and clinical N status was developed by multivariable logistic regression. Results: During the study period, 916 thoracoscopic lobectomies met study criteria: 329 for peripheral, clinical N0 tumors ≤3 cm and 504 for tumors that were central, clinical node positive, or >3 cm. Tumor location could not be documented for 83 patients. Conversions to thoracotomy occurred in 36 patients (4%); patients with clinically node-positive disease had higher conversion rates (11 conversions in 153 clinical N1 to N3 patients [7.2%] vs 25 in 763 clinical N0 patients [3.3%, P = .03]. Overall operative mortality was 1.6% (14 patients) and morbidity was 32% (296 patients). Although patients with larger tumors (P = .006) and central tumors (P = .01) had increased complications by univariate analysis, tumor size >3 cm (P = .17) and central location (P = .5) did not predict significantly overall morbidity in multivariate analysis. Clinical node status did not predict increased complications by univariate or multivariate analysis. Significant predictors of morbidity in multivariable analysis were increasing age, decreasing forced expiratory volume in 1 second, prior chemotherapy, and congestive heart failure. Conclusions: Thoracoscopic lobectomy for lung cancers that are central, clinically node positive, or >3 cm does not confer increased morbidity compared with peripheral, clinical N0 cancers that are <3 cm. Copyright © 2013 by The American Association for Thoracic Surgery.

Authors
Villamizar, NR; Darrabie, M; Hanna, J; Onaitis, MW; Tong, BC; D'Amico, TA; Berry, MF
MLA Citation
Villamizar, NR, Darrabie, M, Hanna, J, Onaitis, MW, Tong, BC, D'Amico, TA, and Berry, MF. "Impact of T status and N status on perioperative outcomes after thoracoscopic lobectomy for lung cancer." Journal of Thoracic and Cardiovascular Surgery 145.2 (2013): 514-521.
Source
scival
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
145
Issue
2
Publish Date
2013
Start Page
514
End Page
521
DOI
10.1016/j.jtcvs.2012.10.039

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

Lymph node evaluation by open or video-assisted approaches in 11,500 anatomic lung cancer resections.

BACKGROUND: Unsuspected lymph node metastases are found in the surgical specimens of 10% to 25% clinical stage I lung cancers. Video-assisted thoracic surgery (VATS) is a minimally invasive alternative to thoracotomy. Because detection of clinically occult metastases is dependent on the completeness of surgical lymph node dissection, the influence of surgical approach on nodal evaluation is of interest. We determined the frequency of nodal metastases identified in clinically node-negative tumors by thoracotomy ("open") and VATS approaches to approximate the completeness of surgical nodal dissections. METHODS: The Society of Thoracic Surgery database was queried for lobectomies and segmentectomies from 2001 to 2010. RESULTS: A total of 11,531 (7,137 open and 4,394 VATS) clinical stage I primary lung cancers were resected. Nodal upstaging was seen in 14.3% (1,024) in the open group and 11.6% (508) in the VATS group (p<0.001). Upstaging from N0 to N1 was more common in the open group (9.3% versus 6.7%; p<0.001); however, upstaging from N0 to N2 was similar (5.0% open and 4.9% VATS; p=0.52). Among 2,745 propensity-matched pairs, N0 to N1 upstaging remained less common with VATS (6.8% versus 9%; p=0.002). CONCLUSIONS: During lobectomy or segmentectomy for clinical N0 lung cancer, mediastinal nodal evaluation by VATS and thoracotomy results in equivalent upstaging. In contrast, lower rates of N1 upstaging in the VATS group may indicate variability in the completeness of the peribronchial and hilar lymph node evaluation. Systematic hilar dissection is encouraged, particularly as more surgeons adopt the VATS approach.

Authors
Boffa, DJ; Kosinski, AS; Paul, S; Mitchell, JD; Onaitis, M
MLA Citation
Boffa, DJ, Kosinski, AS, Paul, S, Mitchell, JD, and Onaitis, M. "Lymph node evaluation by open or video-assisted approaches in 11,500 anatomic lung cancer resections." Ann Thorac Surg 94.2 (August 2012): 347-353.
PMID
22742843
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
94
Issue
2
Publish Date
2012
Start Page
347
End Page
353
DOI
10.1016/j.athoracsur.2012.04.059

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

Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma.

Identifying the cells of origin of lung cancer may lead to new therapeutic strategies. Previous work has focused upon the putative bronchoalveolar stem cell at the bronchioalveolar duct junction as a cancer cell of origin when a codon 12 K-Ras mutant is induced via adenoviral Cre inhalation. In the present study, we use two "knock-in" Cre-estrogen receptor alleles to inducibly express K-RasG12D in CC10(+) epithelial cells and Sftpc(+) type II alveolar cells of the adult mouse lung. Analysis of these mice identifies type II cells, Clara cells in the terminal bronchioles, and putative bronchoalveolar stem cells as cells of origin for K-Ras-induced lung hyperplasia. However, only type II cells appear to progress to adenocarcinoma.

Authors
Xu, X; Rock, JR; Lu, Y; Futtner, C; Schwab, B; Guinney, J; Hogan, BLM; Onaitis, MW
MLA Citation
Xu, X, Rock, JR, Lu, Y, Futtner, C, Schwab, B, Guinney, J, Hogan, BLM, and Onaitis, MW. "Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma." Proc Natl Acad Sci U S A 109.13 (March 27, 2012): 4910-4915.
PMID
22411819
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
109
Issue
13
Publish Date
2012
Start Page
4910
End Page
4915
DOI
10.1073/pnas.1112499109

Retraction: characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.

Authors
Stevenson, M; Mostertz, W; Acharya, CR; Kim, W; Walters, K; Barry, W; Higgins, K; Tuchman, SA; Crawford, J; Vlahovic, G; Ready, N; Onaitis, M; Potti, A
MLA Citation
Stevenson, M, Mostertz, W, Acharya, CR, Kim, W, Walters, K, Barry, W, Higgins, K, Tuchman, SA, Crawford, J, Vlahovic, G, Ready, N, Onaitis, M, and Potti, A. "Retraction: characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma." Clin Cancer Res 18.6 (March 15, 2012): 1818-.
PMID
22355011
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
6
Publish Date
2012
Start Page
1818
DOI
10.1158/1078-0432.CCR-12-0337

Molecular biology of lung cancer

Authors
Onaitis, MW; D'amico, TA
MLA Citation
Onaitis, MW, and D'amico, TA. "Molecular biology of lung cancer." Cardiothoracic Surgery Review. January 5, 2012. 984-986.
Source
scopus
Publish Date
2012
Start Page
984
End Page
986

Self-perceived video-assisted thoracic surgery lobectomy proficiency by recent graduates of North American thoracic residencies

Minimally invasive surgical techniques offer several advantages over traditional open procedures, yet the pathway to minimally invasive proficiency can be difficult to navigate. As a part of an effort of the Joint Council of Thoracic Surgical Education to increase access to this skill set in the general thoracic community, recent graduates of thoracic residencies were surveyed to determine the self-reported achievement of video-assisted thoracic surgery (VATS) lobectomy proficiency and the merits of various educational opportunities. The objective of this study was to estimate the comfort level of recent graduates with the minimally invasive approach, as this demographic not only reflects the current status of training, but represents the future of the specialty. Surgeons graduating North American thoracic residencies between 2006 and 2008 identifying themselves as practitioners of general thoracic surgery were surveyed. A total of 271 surgeons completed training between 2006 and 2008 and indicated general thoracic to be a part of their practice (84 dedicated thoracic and 187 mixed). One hundred and forty-six surgeons completed the survey (54%) including 74 of 84 (88%) dedicated thoracic surgeons. Overall, 58% of recent graduates who perform general thoracic procedures consider themselves proficient in VATS lobectomies (86% of dedicated thoracic surgeons and 28% of surgeons with a mixed practice, P < 0.0001). Of surgeons considering themselves to be proficient at VATS lobectomies, 66% felt thoracic residency was critical or very important to achieving proficiency. Fellowships after completing board residency, animal labs, and follow-up VATS courses put on by experts were much less consistently beneficial. The vast majority of the 25 dedicated general thoracic surgeons who graduate each year consider themselves proficient in VATS lobectomies, largely due to training in their thoracic residencies. On the other hand, the minority of surgeons performing general thoracic procedures as a part of a mixed practice consider themselves proficient in VATS lobectomies. Further study is warranted to enhance the VATS lobectomy experience of mixed practice surgeons particularly during their thoracic residencies. © 2012 The Author.

Authors
Boffa, DJ; Gangadharan, S; Kent, M; Kerendi, F; Onaitis, M; Verrier, E; Roselli, E
MLA Citation
Boffa, DJ, Gangadharan, S, Kent, M, Kerendi, F, Onaitis, M, Verrier, E, and Roselli, E. "Self-perceived video-assisted thoracic surgery lobectomy proficiency by recent graduates of North American thoracic residencies." Interactive Cardiovascular and Thoracic Surgery 14.6 (2012): 797-800.
PMID
22381653
Source
scival
Published In
Interactive Cardiovascular and Thoracic Surgery
Volume
14
Issue
6
Publish Date
2012
Start Page
797
End Page
800
DOI
10.1093/icvts/ivr098

Technique of Video-Assisted Thoracoscopic Chest Wall Resection

Authors
Hanna, JM; Onaitis, MW
MLA Citation
Hanna, JM, and Onaitis, MW. "Technique of Video-Assisted Thoracoscopic Chest Wall Resection." Operative Techniques in Thoracic and Cardiovascular Surgery 17.4 (2012): 280-291.
Source
scival
Published In
Operative Techniques in Thoracic and Cardiovascular Surgery
Volume
17
Issue
4
Publish Date
2012
Start Page
280
End Page
291
DOI
10.1053/j.optechstcvs.2012.11.002

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

Persistent N2 disease after neoadjuvant chemotherapy for non-small-cell lung cancer.

OBJECTIVES: Patients achieving a mediastinal pathologic complete response with neoadjuvant chemotherapy have improved outcomes compared with patients with persistent N2 disease. How to best manage this latter group of patients is unknown, prompting a review of our institutional experience. METHODS: All patients who initiated neoadjuvant therapy for non-small-cell lung cancer from 1995 to 2008 were evaluated. The patients were excluded if they had received preoperative radiotherapy, had had a mediastinal pathologic complete response, or had evidence of disease progression after neoadjuvant chemotherapy. The clinical endpoints were calculated using the Kaplan-Meier product-limit method and compared using a log-rank test. RESULTS: A total of 28 patients were identified. The median follow-up period was 24 months. Several neoadjuvant chemotherapy regimens were used, most commonly carboplatin with vinorelbine (36%) or paclitaxel (32%). A partial response to chemotherapy was noted in 23 (82%) and stable disease was noted in 5 (18%) on postchemotherapy imaging. Resection was performed in 22 of 28 patients, consisting of lobectomy in 14, pneumonectomy in 2, and wedge/segmentectomy in 6 (21/22 R0, 1/22 R1). There were no postoperative deaths. Postoperative therapy (radiotherapy and/or additional chemotherapy) was administered to 12 patients (55%). The remaining 6 patients generally received definitive radiotherapy with or without additional chemotherapy. The overall and disease-free survival rate at 1, 3, and 5 years was 75%, 37%, and 37% and 50%, 23%, and 19%, respectively. The survival rate at 5 years was similar between patients undergoing resection (34%) and those receiving definitive radiotherapy with or without chemotherapy (40%; P = .73). CONCLUSIONS: Disease-free and overall survival was sufficiently high to warrant aggressive local therapy (surgery or radiotherapy) in patients with persistent N2 disease after neoadjuvant chemotherapy.

Authors
Higgins, KA; Chino, JP; Ready, N; Onaitis, MW; Berry, MF; D'Amico, TA; Kelsey, CR
MLA Citation
Higgins, KA, Chino, JP, Ready, N, Onaitis, MW, Berry, MF, D'Amico, TA, and Kelsey, CR. "Persistent N2 disease after neoadjuvant chemotherapy for non-small-cell lung cancer." J Thorac Cardiovasc Surg 142.5 (November 2011): 1175-1179.
PMID
22014344
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
142
Issue
5
Publish Date
2011
Start Page
1175
End Page
1179
DOI
10.1016/j.jtcvs.2011.07.059

Does method of sternal repair influence long-term outcome of postoperative mediastinitis?

BACKGROUND: Post-sternotomy mediastinitis reduces survival after cardiac surgery, potentially further affected by details of mediastinal vascularized flap reconstruction. The aim of this study was to evaluate survival after different methods for sternal reconstruction in mediastinitis. METHODS: Two hundred twenty-two adult cardiac surgery patients with post-sternotomy mediastinitis were reviewed. After controlling infection, often augmented by negative pressure therapy, muscle flap, omental flap, or secondary closure was performed. Outcomes were reviewed and survival analysis was performed. RESULTS: Baseline characteristics were similar. In-hospital mortality (15.7%) did not differ between groups. Secondary closure was correlated with negative pressure therapy and reduced length hospital of stay. Recurrent wound complications were more common with muscle flap repair. Survival was unaffected by sternal repair technique. By multivariate analysis, heart failure, sepsis, age, and vascular disease independently predicted mortality, while negative pressure therapy was associated with survival. CONCLUSIONS: Choice of sternal repair was unrelated to survival, but mediastinal treatment with negative pressure therapy promotes favorable early and late outcomes.

Authors
Atkins, BZ; Onaitis, MW; Hutcheson, KA; Kaye, K; Petersen, RP; Wolfe, WG
MLA Citation
Atkins, BZ, Onaitis, MW, Hutcheson, KA, Kaye, K, Petersen, RP, and Wolfe, WG. "Does method of sternal repair influence long-term outcome of postoperative mediastinitis?." Am J Surg 202.5 (November 2011): 565-567.
PMID
21924401
Source
pubmed
Published In
American Journal of Surgery
Volume
202
Issue
5
Publish Date
2011
Start Page
565
End Page
567
DOI
10.1016/j.amjsurg.2011.06.013

Bayesian probit regression model for the diagnosis of pulmonary fibrosis: proof-of-principle.

BACKGROUND: The accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is a major clinical challenge. We developed a model to diagnose IPF by applying Bayesian probit regression (BPR) modelling to gene expression profiles of whole lung tissue. METHODS: Whole lung tissue was obtained from patients with idiopathic pulmonary fibrosis (IPF) undergoing surgical lung biopsy or lung transplantation. Controls were obtained from normal organ donors. We performed cluster analyses to explore differences in our dataset. No significant difference was found between samples obtained from different lobes of the same patient. A significant difference was found between samples obtained at biopsy versus explant. Following preliminary analysis of the complete dataset, we selected three subsets for the development of diagnostic gene signatures: the first signature was developed from all IPF samples (as compared to controls); the second signature was developed from the subset of IPF samples obtained at biopsy; the third signature was developed from IPF explants. To assess the validity of each signature, we used an independent cohort of IPF and normal samples. Each signature was used to predict phenotype (IPF versus normal) in samples from the validation cohort. We compared the models' predictions to the true phenotype of each validation sample, and then calculated sensitivity, specificity and accuracy. RESULTS: Surprisingly, we found that all three signatures were reasonably valid predictors of diagnosis, with small differences in test sensitivity, specificity and overall accuracy. CONCLUSIONS: This study represents the first use of BPR on whole lung tissue; previously, BPR was primarily used to develop predictive models for cancer. This also represents the first report of an independently validated IPF gene expression signature. In summary, BPR is a promising tool for the development of gene expression signatures from non-neoplastic lung tissue. In the future, BPR might be used to develop definitive diagnostic gene signatures for IPF, prognostic gene signatures for IPF or gene signatures for other non-neoplastic lung disorders such as bronchiolitis obliterans.

Authors
Meltzer, EB; Barry, WT; D'Amico, TA; Davis, RD; Lin, SS; Onaitis, MW; Morrison, LD; Sporn, TA; Steele, MP; Noble, PW
MLA Citation
Meltzer, EB, Barry, WT, D'Amico, TA, Davis, RD, Lin, SS, Onaitis, MW, Morrison, LD, Sporn, TA, Steele, MP, and Noble, PW. "Bayesian probit regression model for the diagnosis of pulmonary fibrosis: proof-of-principle. (Published online)" BMC Med Genomics 4 (October 5, 2011): 70-.
PMID
21974901
Source
pubmed
Published In
BMC Medical Genomics
Volume
4
Publish Date
2011
Start Page
70
DOI
10.1186/1755-8794-4-70

Fundoplication after lung transplantation prevents the allograft dysfunction associated with reflux.

BACKGROUND: Gastroesophageal reflux disease (GERD) in lung recipients is associated with decreased survival and attenuated allograft function. This study evaluates fundoplication in preventing GERD-related allograft dysfunction. METHODS: Prospectively collected data on patients who underwent transplantation between January 2001 and August 2009 were included. Lung transplant candidates underwent esophageal pH probe testing before transplantation and surveillance spirometry evaluation after transplantation. Bilateral lung transplant recipients who had pretransplant pH probe testing and posttransplant 1-year forced expiratory volume in the first second of expiration (FEV1) data were included for analysis. RESULTS: Of 297 patients who met study criteria, 222 (75%) had an abnormal pH probe study before or early after transplantation and 157 (53%) had a fundoplication performed within the first year after transplantation. Patients with total proximal acid contact times greater than 1.2% or total distal acid contact times greater than 7.0% demonstrated an absolute decrease of 9.4% (±4.6) or 12.0% (±5.4) in their respective mean 1-year FEV1 values. Patients with abnormal acid contact times who did not undergo fundoplication had considerably worse predicted peak and 1-year FEV1 results compared with recipients receiving fundoplication (peak percent predicted=75% vs. 84%; p=0.004 and 1-year percent predicted=68% vs. 77%; p=0.003, respectively). CONCLUSIONS: Lung transplant recipients with abnormal esophageal pH studies attain a lower peak allograft function as well as a diminished 1-year FEV1 after transplantation. However a strategy of early fundoplication in these recipients appears to preserve lung allograft function.

Authors
Hartwig, MG; Anderson, DJ; Onaitis, MW; Reddy, S; Snyder, LD; Lin, SS; Davis, RD
MLA Citation
Hartwig, MG, Anderson, DJ, Onaitis, MW, Reddy, S, Snyder, LD, Lin, SS, and Davis, RD. "Fundoplication after lung transplantation prevents the allograft dysfunction associated with reflux." Ann Thorac Surg 92.2 (August 2011): 462-468.
PMID
21801907
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
92
Issue
2
Publish Date
2011
Start Page
462
End Page
468
DOI
10.1016/j.athoracsur.2011.04.035

Incorporating research into thoracic surgery practice.

The incorporation of research into a career in thoracic surgery is a complex process. Ideally, the preparation for a career in academic thoracic surgery begins with a research fellowship during training. In the academic setting, a research portfolio might include clinical research, translational research, or basic research. Using strategies for developing collaboration, thoracic surgeons in community-based programs may also be successful clinical investigators. In addition to the rigors of conducting research, strategies for reserving protected time and obtaining grant support must be considered to be successful in academic surgery.

Authors
D'Amico, TA; Tong, BC; Berry, MF; Burfeind, WR; Onaitis, MW
MLA Citation
D'Amico, TA, Tong, BC, Berry, MF, Burfeind, WR, and Onaitis, MW. "Incorporating research into thoracic surgery practice." Thorac Surg Clin 21.3 (August 2011): 369-377.
PMID
21762860
Source
pubmed
Published In
Thoracic Surgery Clinics
Volume
21
Issue
3
Publish Date
2011
Start Page
369
End Page
377
DOI
10.1016/j.thorsurg.2011.04.004

Efficacy of mediastinal lymph node dissection during lobectomy for lung cancer by thoracoscopy and thoracotomy.

BACKGROUND: Mediastinal lymph node dissection (MLND) is an integral component of complete resection for non-small cell lung cancer (NSCLC). This study analyzed the National Comprehensive Cancer Network's (NCCN) NSCLC Database to compare the efficacy of MLND during lobectomy by video-assisted thoracoscopy surgery (VATS) and thoracotomy (open). METHODS: The NCCN NSCLC Database was queried to identify patients who underwent lobectomy to analyze the adequacy of MLND by the number of LN stations. The percentage of patients with at least three N2 stations, the number of N2 LN stations, and the total number of LN stations (N1+N2) resected was compared by approach. RESULTS: Of 4215 patients with NSCLC (January 2007 to September 2010), 388 patients underwent lobectomy (199 VATS and 189 open) and met entry criteria. The groups were similar in age, sex, comorbidities, performance status, and histology. MLN assessment was similar in both groups as measured by number of N2 stations (median, 3 stations; p=0.12). At least three MLN stations were assessed in 130 patients (66%) in the VATS group vs 107 patients (58%) in the open group (p=0.12). The total number of N1+N2 stations resected for each group was also similar (median, 4 in both groups (p=0.06). CONCLUSIONS: The NCCN database indicates at least three MLN stations were assessed in most patients who underwent lobectomy by either approach. As evaluated by the number of LN stations, there was no difference in the efficacy of MLN dissection by approach.

Authors
D'Amico, TA; Niland, J; Mamet, R; Zornosa, C; Dexter, EU; Onaitis, MW
MLA Citation
D'Amico, TA, Niland, J, Mamet, R, Zornosa, C, Dexter, EU, and Onaitis, MW. "Efficacy of mediastinal lymph node dissection during lobectomy for lung cancer by thoracoscopy and thoracotomy." Ann Thorac Surg 92.1 (July 2011): 226-231.
PMID
21718849
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
92
Issue
1
Publish Date
2011
Start Page
226
End Page
231
DOI
10.1016/j.athoracsur.2011.03.134

CASE PRESENTATION: SMALL T1 SUBPLEURAL LUNG LESION IN THE RIGHT UPPER LOBE, INCIDENTALLY FOUND

Authors
Onaitis, MW
MLA Citation
Onaitis, MW. "CASE PRESENTATION: SMALL T1 SUBPLEURAL LUNG LESION IN THE RIGHT UPPER LOBE, INCIDENTALLY FOUND." June 2011.
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
6
Issue
6
Publish Date
2011
Start Page
S155
End Page
S155

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

How well does the new lung cancer staging system predict for local/regional recurrence after surgery?: A comparison of the TNM 6 and 7 systems.

INTRODUCTION: To evaluate how well the tumor, node, metastasis (TNM) 6 and TNM 7 staging systems predict rates of local/regional recurrence (LRR) after surgery alone for non-small cell lung cancer. METHODS: All patients who underwent surgery for non-small cell lung cancer at Duke between 1995 and 2005 were reviewed. Those undergoing sublobar resections, with positive margins or involvement of the chest wall, or those who received any chemotherapy or radiation therapy (RT) were excluded. Disease recurrence at the surgical margin, or within ipsilateral hilar and/or mediastinal lymph nodes, was considered as a LRR. Stage was assigned based on both TNM 6 and TNM 7. Rates of LRR were estimated using the Kaplan-Meier method. A Cox regression analysis evaluated the hazard ratio of LRR by stage within TNM 6 and TNM 7. RESULTS: A total of 709 patients were eligible for the analysis. Median follow-up was 32 months. For all patients, the 5-year actuarial risk of LRR was 23%. Conversion from TNM 6 to TNM 7 resulted in 21% stage migration (upstaging in 13%; downstaging in 8%). Five-year rates of LRR for stages IA, IB, IIA, IIB, and IIIA disease using TNM 6 were 16%, 26%, 43%, 35%, and 40%, respectively. Using TNM 7, corresponding rates were 16%, 23%, 37%, 39%, and 30%, respectively. The hazard ratios for LRR were statistically different for IA and IB in both TNM 6 and 7 but were also different for IB and IIA in TNM 7. CONCLUSIONS: LRR risk increases monotonically for stages IA to IIB in the new TNM 7 system. This information might be valuable when designing future studies of postoperative RT.

Authors
Pepek, JM; Chino, JP; Marks, LB; D'amico, TA; Yoo, DS; Onaitis, MW; Ready, NE; Hubbs, JL; Boyd, J; Kelsey, CR
MLA Citation
Pepek, JM, Chino, JP, Marks, LB, D'amico, TA, Yoo, DS, Onaitis, MW, Ready, NE, Hubbs, JL, Boyd, J, and Kelsey, CR. "How well does the new lung cancer staging system predict for local/regional recurrence after surgery?: A comparison of the TNM 6 and 7 systems." J Thorac Oncol 6.4 (April 2011): 757-761.
PMID
21325975
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
6
Issue
4
Publish Date
2011
Start Page
757
End Page
761
DOI
10.1097/JTO.0b013e31821038c0

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

The role of intrathoracic free flaps for chronic empyema.

BACKGROUND: The management of chronic empyema associated with a bronchopleural fistula can be a particularly challenging problem. Successful eradication may not occur without interposition of healthy vascularized tissue. Pedicled muscle flaps for coverage on the thorax have been well described. However, secondary to trauma or previous surgical procedures, a pedicle flap may not be sufficiently sized or available. Free tissue transfer is an attractive option to provide the appropriate vascularized tissue. METHODS: Six patients with chronic empyema-bronchopleural fistulae were reconstructed with 4 rectus abdominis myocutaneous and 2 gracilis muscle flaps. The choice of recipient vessels was dictated by existing local anatomy but included intercostal, thoracodorsal, thoracoacromial, azygous, and circumflex humeral vessels. One flap required interposition saphenous vein grafts for both artery and vein. RESULTS: Patient follow-up ranged from 2 to 14 years. There were no episodes of flap loss or postoperative mortality. Empyema resolution without recurrent bronchopleural fistula was achieved in all patients. CONCLUSIONS: Free tissue transfer is an excellent option for vascularized tissue interposition in patients who are not candidates for pedicled muscle transfer. Multiple potential recipient vessels provide tremendous versatility, arguing for early consideration of free tissue transfer.

Authors
Walsh, MD; Bruno, AD; Onaitis, MW; Erdmann, D; Wolfe, WG; Toloza, EM; Levin, LS
MLA Citation
Walsh, MD, Bruno, AD, Onaitis, MW, Erdmann, D, Wolfe, WG, Toloza, EM, and Levin, LS. "The role of intrathoracic free flaps for chronic empyema." Ann Thorac Surg 91.3 (March 2011): 865-868.
PMID
21353016
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
91
Issue
3
Publish Date
2011
Start Page
865
End Page
868
DOI
10.1016/j.athoracsur.2010.10.019

Human lung stem cells: has the future arrived?

An intriguing paper was recently published that describes c-kit-positive human lung stem cells that self-renew and differentiate into multiple lineages. While these findings are potentially therapeutically exciting, several questions remain to be answered. We review the paper and the issues that have arisen.

Authors
Hanna, JM; Onaitis, MW
MLA Citation
Hanna, JM, and Onaitis, MW. "Human lung stem cells: has the future arrived?." Semin Thorac Cardiovasc Surg 23.4 (2011): 259-260.
PMID
22443640
Source
pubmed
Published In
Seminars in Thoracic and Cardiovascular Surgery
Volume
23
Issue
4
Publish Date
2011
Start Page
259
End Page
260
DOI
10.1053/j.semtcvs.2011.10.009

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

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

Invited commentary.

Authors
Welsby, IJ; Phillips-Bute, B; Onaitis, MW
MLA Citation
Welsby, IJ, Phillips-Bute, B, and Onaitis, MW. "Invited commentary." Ann Thorac Surg 90.1 (July 2010): 115-116.
PMID
20609759
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
90
Issue
1
Publish Date
2010
Start Page
115
End Page
116
DOI
10.1016/j.athoracsur.2010.04.053

Evidence that SOX2 overexpression is oncogenic in the lung.

BACKGROUND: SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung. METHODOLOGY/PRINCIPAL FINDINGS: We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63). CONCLUSIONS: These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer.

Authors
Lu, Y; Futtner, C; Rock, JR; Xu, X; Whitworth, W; Hogan, BLM; Onaitis, MW
MLA Citation
Lu, Y, Futtner, C, Rock, JR, Xu, X, Whitworth, W, Hogan, BLM, and Onaitis, MW. "Evidence that SOX2 overexpression is oncogenic in the lung. (Published online)" PLoS One 5.6 (June 10, 2010): e11022-.
Website
http://hdl.handle.net/10161/4546
PMID
20548776
Source
pubmed
Published In
PloS one
Volume
5
Issue
6
Publish Date
2010
Start Page
e11022
DOI
10.1371/journal.pone.0011022

Does the revised TNM staging system for lung cancer better estimate actuarial rates of local/regional recurrence after surgery?

Authors
Pepek, JM; Chino, JP; Onaitis, MW; Marks, LB; Ready, N; Crawford, J; D'Amico, TA; Hubbs, JL; Kelsey, CR
MLA Citation
Pepek, JM, Chino, JP, Onaitis, MW, Marks, LB, Ready, N, Crawford, J, D'Amico, TA, Hubbs, JL, and Kelsey, CR. "Does the revised TNM staging system for lung cancer better estimate actuarial rates of local/regional recurrence after surgery?." May 20, 2010.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

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

Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.

PURPOSE: Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities are the result of a common biological phenotype, such as regulatory pathways. EXPERIMENTAL DESIGN: Lung cancer cell lines with corresponding gene expression data and genes associated with an embryonic stem cell identity were used to develop a signature of embryonic stemness (ES) activity specific to lung adenocarcinoma. Biological characteristics were elucidated as a function of cancer biology/oncogenic pathway dysregulation. The ES signature was applied to three independent early-stage (I-IIIa) lung adenocarcinoma data sets with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin (current standard of care) sensitivity was evaluated. RESULTS: Pathway analysis identified specific regulatory networks [Ras (P = 0.0005), Myc (P = 0.0224), wound healing (P < 0.0001), chromosomal instability (P < 0.0001), and invasiveness (P < 0.0001)] associated with the ES phenotype. The prognostic relevance of the ES signature, as related to patient survival, was characterized in three cohorts [CALGB 9761 (n = 82; P = 0.0001), National Cancer Institute Director's Challenge Consortium (n = 442; P = 0.0002), and Duke (n = 45; P = 0.06)]. The ES signature was not prognostic in prostate, breast, or ovarian adenocarcinomas. Lung tumors (n = 569) and adenocarcinoma cell lines (n = 31) expressing the ES phenotype were more likely to be resistant to cisplatin (P < 0.0001 and P = 0.006, respectively). CONCLUSIONS: Lung adenocarcinomas that share a common gene expression pattern with normal human embryonic stem cells were associated with decreased survival, increased biological complexity, and increased likelihood of resistance to cisplatin. This indicates the aggressiveness of these tumors.

Authors
Stevenson, M; Mostertz, W; Acharya, C; Kim, W; Walters, K; Barry, W; Higgins, K; Tuchman, SA; Crawford, J; Vlahovic, G; Ready, N; Onaitis, M; Potti, A
MLA Citation
Stevenson, M, Mostertz, W, Acharya, C, Kim, W, Walters, K, Barry, W, Higgins, K, Tuchman, SA, Crawford, J, Vlahovic, G, Ready, N, Onaitis, M, and Potti, A. "Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma." Clin Cancer Res 15.24 (December 15, 2009): 7553-7561.
PMID
19996213
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
24
Publish Date
2009
Start Page
7553
End Page
7561
DOI
10.1158/1078-0432.CCR-09-1939

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

Basal cells as stem cells of the mouse trachea and human airway epithelium.

The pseudostratified epithelium of the mouse trachea and human airways contains a population of basal cells expressing Trp-63 (p63) and cytokeratins 5 (Krt5) and Krt14. Using a KRT5-CreER(T2) transgenic mouse line for lineage tracing, we show that basal cells generate differentiated cells during postnatal growth and in the adult during both steady state and epithelial repair. We have fractionated mouse basal cells by FACS and identified 627 genes preferentially expressed in a basal subpopulation vs. non-BCs. Analysis reveals potential mechanisms regulating basal cells and allows comparison with other epithelial stem cells. To study basal cell behaviors, we describe a simple in vitro clonal sphere-forming assay in which mouse basal cells self-renew and generate luminal cells, including differentiated ciliated cells, in the absence of stroma. The transcriptional profile identified 2 cell-surface markers, ITGA6 and NGFR, which can be used in combination to purify human lung basal cells by FACS. Like those from the mouse trachea, human airway basal cells both self-renew and generate luminal daughters in the sphere-forming assay.

Authors
Rock, JR; Onaitis, MW; Rawlins, EL; Lu, Y; Clark, CP; Xue, Y; Randell, SH; Hogan, BLM
MLA Citation
Rock, JR, Onaitis, MW, Rawlins, EL, Lu, Y, Clark, CP, Xue, Y, Randell, SH, and Hogan, BLM. "Basal cells as stem cells of the mouse trachea and human airway epithelium." Proc Natl Acad Sci U S A 106.31 (August 4, 2009): 12771-12775.
PMID
19625615
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
106
Issue
31
Publish Date
2009
Start Page
12771
End Page
12775
DOI
10.1073/pnas.0906850106

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

Basal cells as stem cells of the mouse trachea and human conducting airways

Authors
Rock, JR; Rawlins, EL; Onaitis, MW; Hogan, BL
MLA Citation
Rock, JR, Rawlins, EL, Onaitis, MW, and Hogan, BL. "Basal cells as stem cells of the mouse trachea and human conducting airways." July 15, 2009.
Source
wos-lite
Published In
Developmental Biology
Volume
331
Issue
2
Publish Date
2009
Start Page
503
End Page
503
DOI
10.1016/j.ydbio.2009.05.438

Smoking cessation and the success of lung cancer surgery.

Lung cancer is the number one cause of cancer-related mortality in the United States. Cigarette smoke is associated with 90% of lung cancer deaths, making it the most important risk factor for the disease. The strong correlation between smoking and lung cancer is well established, but there is evidence that smoking further increases the morbidity and mortality of lung cancer patients who undergo curative resection. Thus, smoking not only leads to lung cancer but also lowers the survival of those who undergo treatment of their cancer.

Authors
Erhunmwunsee, L; Onaitis, MW
MLA Citation
Erhunmwunsee, L, and Onaitis, MW. "Smoking cessation and the success of lung cancer surgery." Curr Oncol Rep 11.4 (July 2009): 269-274. (Review)
PMID
19508831
Source
pubmed
Published In
Current Oncology Reports
Volume
11
Issue
4
Publish Date
2009
Start Page
269
End Page
274

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

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

Factors influencing outcome after pulmonary resection for colorectal cancer (CRC) metastases in the current era.

4024 Background: We examined the role for surgery and factors associated with relapse-free and overall survival after pulmonary metastasectomy for CRC. METHODS: A retrospective review of prospective databases at two tertiary-care centers was performed to identify patients who underwent complete resection of all macroscopic disease from 1998 to 2007. RESULTS: 377 study patients were identified. The primary site of disease was rectum (52%), left colon (26%), right colon (16%), and other (6%). Before thoracic recurrence, 156 patients (41%) underwent resection of extrathoracic metastases. Median disease-free interval (DFI) was 24 months from time of primary operation. Resection was a single or multiple wedge resections in 72%, lobectomy in 19%, segmentectomy in 7%, and bilobectomy in 2%. Number of metastatic deposits resected was 1 in 60%, 2 in 20%, 3 in 10%, and 4 or more in 10%. Median size of the largest nodule was 1.5 cm. Pre-resection chemotherapy was administered to 87 patients (23%). Post-resection chemotherapy was delivered to 169 patients (45%). Kaplan-Meier recurrence-free survival was 28% and overall survival was 78% at 3 years. Regarding recurrence-free survival, univariate analysis revealed age <65 years, gender, DFI <1 year, number of metastases ≥3 as significant predictors, and presence of prior extrathoracic disease trended toward signficance. Multivariable analysis revealed age <65 years, female gender, DFI <1 year, and number of metastases ≥3 as independent predictors of recurrence. Of 44 patients with 3 or more lesions and <1 year DFI, none was cured by operaton. By contrast, recurrence-free survival was 49% at 3 years for those with 1 lesion and DFI >1 year. CONCLUSIONS: Age less than 65 years, female gender, DFI <1 year, and number of metastases 3 or greater are independent predictors of recurrence. Non-surgical management should be considered standard for patients who have both 3 or more pulmonary metastases and <1 year DFI. [Table: see text] No significant financial relationships to disclose.

Authors
Onaitis, MW; Haney, J; Petersen, R; Saltz, LB; Flores, RM; Rizk, N; Bains, MS; D'Amico, T; Kemeny, NE; Rusch, VW; Downey, RJ
MLA Citation
Onaitis, MW, Haney, J, Petersen, R, Saltz, LB, Flores, RM, Rizk, N, Bains, MS, D'Amico, T, Kemeny, NE, Rusch, VW, and Downey, RJ. "Factors influencing outcome after pulmonary resection for colorectal cancer (CRC) metastases in the current era." J Clin Oncol 26.15_suppl (May 20, 2008): 4024-.
PMID
27949322
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15_suppl
Publish Date
2008
Start Page
4024

Factors influencing outcome after pulmonary resection for colorectal cancer (CRC) metastases in the current era

Authors
Onaitis, MW; Haney, J; Petersen, R; Saltz, LB; Flores, RM; Rizk, N; Bains, MS; D'Amico, T; Kemeny, NE; Rusch, VW; Downey, RJ
MLA Citation
Onaitis, MW, Haney, J, Petersen, R, Saltz, LB, Flores, RM, Rizk, N, Bains, MS, D'Amico, T, Kemeny, NE, Rusch, VW, and Downey, RJ. "Factors influencing outcome after pulmonary resection for colorectal cancer (CRC) metastases in the current era." May 20, 2008.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

The Kraske procedure: a critical analysis of a surgical approach for mid-rectal lesions.

BACKGROUND AND OBJECTIVES: To analyze the Kraske procedure as an approach to mid-rectal disease. METHODS: Twenty-two patients underwent a Kraske procedure at either Duke University Medical Center, the Durham Veterans Administration Medical Center, or the Durham Regional Hospital between 1992 and 1997. The clinical and pathologic characteristics of these patients were retrospectively analyzed and compared with previous published series. RESULTS: Of the 22 patients, 13 underwent resection of an adenocarcinoma and 9 underwent resection of a villous adenoma. Post-operative complications included four fecal fistulas (two of which required a temporary diverting colostomy), two wound infections, two cases of urinary retention, and one case of transient fecal incontinence. CONCLUSIONS: The Kraske procedure minimizes exposure of mid-rectal lesions without the morbidity of a major laparotomy. However, it does carry a moderate complication rate and thus should be utilized selectively in managing patients with mid-rectal tumors not amenable to other treatment options.

Authors
Onaitis, M; Ludwig, K; Perez-Tamayo, A; Gottfried, M; Russell, L; Shadduck, P; Pappas, T; Seigler, HF; Tyler, DS
MLA Citation
Onaitis, M, Ludwig, K, Perez-Tamayo, A, Gottfried, M, Russell, L, Shadduck, P, Pappas, T, Seigler, HF, and Tyler, DS. "The Kraske procedure: a critical analysis of a surgical approach for mid-rectal lesions." J Surg Oncol 94.3 (September 1, 2006): 194-202.
PMID
16900535
Source
pubmed
Published In
Journal of Surgical Oncology
Volume
94
Issue
3
Publish Date
2006
Start Page
194
End Page
202
DOI
10.1002/jso.20591

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

Discussions

Authors
Luketich, JD; Onaitis, MW; Lerut, A; Kohman, LJ
MLA Citation
Luketich, JD, Onaitis, MW, Lerut, A, and Kohman, LJ. "Discussions." Annals of Surgery 244.3 (2006): 424-425.
Source
scival
Published In
Annals of Surgery
Volume
244
Issue
3
Publish Date
2006
Start Page
424
End Page
425
DOI
10.1097/01.sla.0000234892.79056.63

Predictors of outcome after hyperthermic isolated limb perfusion: role of tumor response.

HYPOTHESIS: Analysis of multiple clinical and pathological factors in patients undergoing therapeutic hyperthermic isolated limb perfusion for extremity melanoma can identify variables with prognostic significance. DESIGN: Retrospective review of a prospectively collected limb perfusion database with a median follow-up interval of 32.2 months. SETTING: Single-institution tertiary care surgical oncology unit. PATIENTS: We report a series of 59 consecutive therapeutic hyperthermic isolated limb perfusion treatments (14 upper extremity and 45 lower extremity) in 54 patients with melanoma from January 1, 1995, through December 31, 2002, using a standard melphalan dosing protocol. At the time of perfusion, 31 cases had fewer than 10 lesions, with none greater than 3 cm in diameter. The remaining 28 cases had 10 or more lesions or at least 1 lesion greater than 3 cm in diameter. MAIN OUTCOME MEASURES: Response, recurrence, and survival were assessed in relation to multiple demographic, clinical, and technical variables using chi2, log-rank, and Kaplan-Meier survival analyses. RESULTS: The 3-year survival for the entire cohort was 54%. Thirty-three (56%) of the 59 perfusion treatments resulted in a persistent complete response of at least 6 months' duration. Statistical analysis showed that patients with no evidence of regional nodal involvement had a significantly lower incidence of distant recurrence (P = .02). Those patients achieving a complete response to therapy had a survival advantage (P = .03). CONCLUSION: In patients undergoing therapeutic hyperthermic isolated limb perfusion for in-transit melanoma, the ability to achieve a complete response following treatment, independent of regional nodal status, was the strongest predictor of long-term survival.

Authors
Aloia, TA; Grubbs, E; Onaitis, M; Mosca, PJ; Cheng, T-Y; Seigler, H; Tyler, DS
MLA Citation
Aloia, TA, Grubbs, E, Onaitis, M, Mosca, PJ, Cheng, T-Y, Seigler, H, and Tyler, DS. "Predictors of outcome after hyperthermic isolated limb perfusion: role of tumor response." Arch Surg 140.11 (November 2005): 1115-1120.
PMID
16301451
Source
pubmed
Published In
Archives of Surgery
Volume
140
Issue
11
Publish Date
2005
Start Page
1115
End Page
1120
DOI
10.1001/archsurg.140.11.1115

Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses.

BACKGROUND: Cotransfection of dendritic cells (DC) with MART-1 and constitutively active TLR4 (caTLR4) RNA enhances the maturation of DC. MATERIALS AND METHODS: Immature DC were cotransfected with RNA constructs encoding MART-1 and caTLR4, and CTL responses were analyzed. RESULTS: Cotransfection of DC with MART-1 + caTLR4 enhanced the expression of CD80 and CD83 surface markers and increased the secretion of cytokines IL-6, IL-12, and TNFalpha. Neither the native nor the A27L-modified MART-1 RNA could induce significant DC maturation or cytokine secretion. More importantly, DC cotransfected with caTLR4 + MART-1 RNA induced MART-1-specific CTL responses of a higher magnitude than DC transfected with either the native or A27L MART-1 RNA. When the MART-1 RNA-transfected DC were treated with DC-maturing cytokines, the induced CTL were less frequent and less lytic than those induced with MART-1 + caTLR4. A 2- to 100-fold increase in MART-1 tetramer+ cells and 2- to 10-fold increases in IFNgamma secretion and cytotoxicity were seen in CTL induced with MART-1 + caTLR4 compared to CTL induced with either MART-1 or A27L RNA. CTL induced with the mixed RNA displayed high percentages of CD8+ cells coexpressing CD45RA, CD56, and 2B4 antigens. Transfection with caTLR4 alone induced DC maturation, but did not induce lytic CTL, suggesting that CTL responses were induced solely by MART-1 epitopes. CONCLUSIONS: caTLR4 increases the CTL-inducing capacity of DC generating a lytic response specific for the accompanying antigen. These results demonstrate the possibility of enhancing the immunogenicity of the native MART-1 and other RNA derived from weakly immunogenic tumors in DC-based immunotherapy.

Authors
Abdel-Wahab, Z; Cisco, R; Dannull, J; Ueno, T; Abdel-Wahab, O; Kalady, MF; Onaitis, MW; Tyler, DS; Pruitt, SK
MLA Citation
Abdel-Wahab, Z, Cisco, R, Dannull, J, Ueno, T, Abdel-Wahab, O, Kalady, MF, Onaitis, MW, Tyler, DS, and Pruitt, SK. "Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses." J Surg Res 124.2 (April 2005): 264-273.
PMID
15820257
Source
pubmed
Published In
Journal of Surgical Research
Volume
124
Issue
2
Publish Date
2005
Start Page
264
End Page
273
DOI
10.1016/j.jss.2004.10.002

Coloanal anastomotic integrity after total mesorectal excision is not compromised by preoperative chemoradiation for rectal cancer

Authors
Kalady, MF; Onaitis, MW; Mantyh, CR; Tyler, DS; Ludwig, KA
MLA Citation
Kalady, MF, Onaitis, MW, Mantyh, CR, Tyler, DS, and Ludwig, KA. "Coloanal anastomotic integrity after total mesorectal excision is not compromised by preoperative chemoradiation for rectal cancer." March 2005.
Source
wos-lite
Published In
Diseases of the Colon and Rectum
Volume
48
Issue
3
Publish Date
2005
Start Page
601
End Page
602

Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients.

BACKGROUND: Iodine-131 metaiodobenzylguanidine (131I-MIBG) is useful for imaging carcinoid tumors and recently has been applied to the palliative treatment of metastatic carcinoid in small studies. The authors now report their results on the therapeutic utility of high-dose 131I-MIBG treatment in a large group of patients with metastatic carcinoid tumors. METHODS: The authors performed a retrospective review of 98 patients with metastatic carcinoid who were treated at their institution with 131I-MIBG over a 15-year period. Endpoints examined included the World Health Organization criteria for treatment response: symptoms, hormone (5-hydroxyindoleacetic acid [5-HIAA]) production, and clinical tumor response. RESULTS: Patients received a median dose of 401 +/- 202 millicuries (mCi) 131I-MIBG. The median survival after treatment was 2.3 years. Patients who experienced a symptomatic response had improved survival (5.76 years vs. 2.09 years; P < 0.01). For the 56 patients who had 5-HIAA levels monitored, the mean urine 5-HIAA levels decreased significantly after 131I-MIBG treatment (126 +/- 122 ng/mL vs. 91 +/- 125 ng/mL; P < 0.01); however, the patients with reduced 5-HIAA levels did not experience improved survival (4.11 years vs. 3.42 years; P = 0.2). Patients who received an initial 131I-MIBG dose > 400 mCi lived longer than patients who received < 400 mCi (4.69 years vs. 1.86 years; P = 0.05). Radiographic tumor response did not predict survival. Toxicity included pancytopenia, thrombocytopenia, nausea, and emesis. CONCLUSIONS: The current data support 131I-MIBG treatment in select patients with metastatic carcinoid who progress despite optimal medical management. Improved survival was predicted best by symptomatic response to 131I-MIBG treatment, but not by hormone or radiographic response.

Authors
Safford, SD; Coleman, RE; Gockerman, JP; Moore, J; Feldman, J; Onaitis, MW; Tyler, DS; Olson, JA
MLA Citation
Safford, SD, Coleman, RE, Gockerman, JP, Moore, J, Feldman, J, Onaitis, MW, Tyler, DS, and Olson, JA. "Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients." Cancer 101.9 (November 1, 2004): 1987-1993.
PMID
15455358
Source
pubmed
Published In
Cancer
Volume
101
Issue
9
Publish Date
2004
Start Page
1987
End Page
1993
DOI
10.1002/cncr.20592

Pancreatic duct strictures: identifying risk of malignancy.

BACKGROUND: This study aimed to define PDS characteristics that predict malignancy and would thus invoke further diagnostic evaluation or aggressive treatment. METHODS: 355 cases of PDS were diagnosed by ERCP during a 7-year period at a single institution. A retrospective review identified clinical/demographic patient data and ERCP results. RESULTS: 218 (61%) patients with a PDS were found to have an isolated PDS. Twelve percent of isolated PDS and 79% of CBD stricture-associated PDS were malignant. The sensitivity and specificity for the double duct sign for malignancy were 77% and 80% respectively, and the positive predictive value was 65%. Predictors of malignancy were statistically similar for both isolated PDS and those associated with a CBD stricture. Univariate predictors of malignancy included stricture location in the pancreatic head/neck, jaundice, and patient age. Predictors of benign disease included a history of pancreatitis, the presence of multiple strictures, pancreatic duct stones, pseudocyst, pancreas divisum anatomy, irregular side branches, and irregular pancreatic duct morphology. Less than 1% of patients with either pancreas divisum anatomy, pancreatic duct stones, or pancreatic pseudocyst had malignancy. Using malignancy as the dependent variable, multivariate factors included in the final prognostic equation were history of pancreatitis (odds ratio 0.009 with history of pancreatitis), stricture location in the head or neck (odds ratio 42) and irregular pancreatic duct side branches (odds ratio 0.05 with irregular branches). CONCLUSIONS: This study demonstrates that certain characteristics of PDS can predict the subset of patients who have an increased risk of cancer.

Authors
Kalady, MF; Peterson, B; Baillie, J; Onaitis, MW; Abdul-Wahab, OI; Howden, JK; Jowell, PS; Branch, MS; Clary, BM; Pappas, TN; Tyler, DS
MLA Citation
Kalady, MF, Peterson, B, Baillie, J, Onaitis, MW, Abdul-Wahab, OI, Howden, JK, Jowell, PS, Branch, MS, Clary, BM, Pappas, TN, and Tyler, DS. "Pancreatic duct strictures: identifying risk of malignancy." Ann Surg Oncol 11.6 (June 2004): 581-588.
PMID
15150064
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
11
Issue
6
Publish Date
2004
Start Page
581
End Page
588
DOI
10.1245/ASO.2004.03.070

Dendritic cells pulsed with pancreatic cancer total tumor RNA generate specific antipancreatic cancer T cells.

RNA-based dendritic cell immunotherapy with the use of total tumor RNA provides the potential to generate a polyclonal immune response to multiple known and unknown tumor antigens without HLA restriction. Our study evaluated this approach as potential immunotherapy for patients with pancreatic cancer. Dendritic cells were generated using adherent monocytes isolated from peripheral blood of patients with pancreatic cancer and evaluated phenotypically by flow cytometry to determine whether dendritic cells could be generated from the blood of patients with pancreatic cancer. Immature dendritic cells were transfected with mRNA encoding full-length carcinoembryonic antigen (CEA) or pancreatic cancer total tumor messenger RNA, and then matured. Matured dendritic cell phenotypes were also analyzed by flow cytometry. Transfected, matured dendritic cells were used to stimulate autologous T cells, and the resultant antigen-specific effector T cells were analyzed by interferon-gamma Elispot assay. Immature dendritic cells with characteristic phenotypic markers CD40, CD80, and CD86 were successfully isolated from the blood of patients with pancreatic cancer. Incubation with maturation agents increased expression of CD80 and CD83, demonstrating the induction of a mature antigen-presenting phenotype. Dendritic cells transfected with a pancreatic cancer-associated antigen (CEA) generated antigen-specific T cells (P<0.05). Dendritic cells transfected with autologous total tumor pancreatic cancer RNA generated T cells that specifically recognized HLA-matched pancreatic cancer cell lines (P<0.05 compared to control cell lines). Dendritic cells from patients with pancreatic cancer maintain the ability to translate and process transfected RNA and serve as mature antigen-presenting cells. These RNA-transfected dendritic cells from pancreatic cancer patients successfully generate specific T cells against the pancreatic cancer-associated antigen CEA as well as T cells that specifically recognize pancreatic cancer cells. These data suggest that total tumor RNA-pulsed dendritic cells may have potential as an adjuvant immunotherapy for patients with pancreatic cancer.

Authors
Kalady, MF; Onaitis, MW; Emani, S; Abdul-Wahab, Z; Pruitt, SK; Tyler, DS
MLA Citation
Kalady, MF, Onaitis, MW, Emani, S, Abdul-Wahab, Z, Pruitt, SK, and Tyler, DS. "Dendritic cells pulsed with pancreatic cancer total tumor RNA generate specific antipancreatic cancer T cells." J Gastrointest Surg 8.2 (February 2004): 175-181.
PMID
15036193
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
8
Issue
2
Publish Date
2004
Start Page
175
End Page
181
DOI
10.1016/j.gassur.2003.11.003

Sequential delivery of maturation stimuli increases human dendritic cell IL-12 production and enhances tumor antigen-specific immunogenicity.

BACKGROUND: Despite the increasing use of dendritic cells (DCs) in clinical trials, questions regarding the optimal means of DC preparation, in particular how to achieve optimal maturation, remain unanswered. We hypothesized that delivering two separate sequential maturation signals to DC in vitro, mimicking the process of DC maturation that occurs in vivo, would enhance the ability of DCs to generate antigen-specific effector T cells in an experimental in vitro antimelanoma model. MATERIALS AND METHODS: Human monocyte-derived DCs were transfected with mRNA encoding melanoma-associated antigen Mart-1 (MART) or influenza M1 matrix protein (M1). After mRNA transfection, DCs were left untreated or exposed to different maturation stimuli either added simultaneously or delivered sequentially 18 h after first stimulation. Phenotypic DC cell-surface marker changes and IL-12 secretion were analyzed. Specific antigen presentation by DCs was measured by IFN-gamma release Elispot assay using a CD8(+) MART peptide-specific T cell clone. RNA-transfected and treated DCs were cultured with autologous naive T cells and the induction of antigen-specific effector T cells were assessed by IFN-gamma release Elispot assay. RESULTS: DCs transfected and matured had increased cell-surface expression of CD40 and costimulatory molecules CD80, and CD86. DCs matured and further treated by soluble CD40 ligand (sCD40L) had a 10- and 2-fold increase in MART antigen presentation compared to untreated (immature) DCs and DCs treated only with a first maturation signal, respectively (Elispot P = 0.02). Delivery of sequential maturation stimuli resulted in maximal DC IL-12 secretion compared to simultaneous stimuli. Last, generation of antigen-specific effector T cells more than doubled with the sequential addition of sCD40L to mature DC stimulators (Elispot P = 0.009). CONCLUSIONS: Maturation of DCs following mRNA transfection increases expression of cell-surface costimulatory molecules. Delivery of a second sequential maturation stimulus enhances antigen presentation, increases IL-12 secretion, and augments immunogenicity as evidenced by generation of tumor antigen-specific effector T cells. This strategy should be considered in the future development of RNA-based DC vaccine strategies for the treatment of cancer.

Authors
Kalady, MF; Onaitis, MW; Emani, S; Abdel-Wahab, Z; Tyler, DS; Pruitt, SK
MLA Citation
Kalady, MF, Onaitis, MW, Emani, S, Abdel-Wahab, Z, Tyler, DS, and Pruitt, SK. "Sequential delivery of maturation stimuli increases human dendritic cell IL-12 production and enhances tumor antigen-specific immunogenicity." J Surg Res 116.1 (January 2004): 24-31.
PMID
14732346
Source
pubmed
Published In
Journal of Surgical Research
Volume
116
Issue
1
Publish Date
2004
Start Page
24
End Page
31

Immunotherapy of surgical malignancies.

Authors
Morse, MA; Lyerly, HK; Clay, TM; Abdel-Wahab, O; Chui, SY; Garst, J; Gollob, J; Grossi, PM; Kalady, M; Mosca, PJ; Onaitis, M; Sampson, JH; Seigler, HF; Toloza, EM; Tyler, D; Vieweg, J; Yang, Y
MLA Citation
Morse, MA, Lyerly, HK, Clay, TM, Abdel-Wahab, O, Chui, SY, Garst, J, Gollob, J, Grossi, PM, Kalady, M, Mosca, PJ, Onaitis, M, Sampson, JH, Seigler, HF, Toloza, EM, Tyler, D, Vieweg, J, and Yang, Y. "Immunotherapy of surgical malignancies." Curr Probl Surg 41.1 (January 2004): 15-132. (Review)
PMID
14749625
Source
pubmed
Published In
Current Problems in Surgery
Volume
41
Issue
1
Publish Date
2004
Start Page
15
End Page
132
DOI
10.1016/S0011384003001321

Ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: historical development and current status.

In summary, the history and development of the proctocolectomy and ileal pouch-anal anastomosis has involved innovative animal and clinical research by several surgical investigators. This evolution followed the classic process of academic surgical progress: a clinical problem is identified; solutions are studied in the laboratory; and these solutions are applied back to the clinical situation with success. Dr. Sabiston's disappointment with clinical results in ulcerative colitis and familial polyposis patients led to laboratory experiments in which a new technique was shown safe in dogs. The further work of his collaborator Dr. Ravitch as well as that of Sir Alan Parks and Dr. Utsunoimya proved small-scale clinical application of the new technique. Finally, large-scale outcomes work by Dr. Fazio at the Cleveland Clinic Foundation and others has allowed further refinements to occur and has highlighted other areas to study. The work of these investigators and other has allowed lack of a permanent ostomy with satisfactory functional results in more than 95% of patients. Continued experience with these procedures has and will lead to further improvements in operative times, morbidity rates, and functional results. Although research in this area will continue, the evolution of this operation has allowed it to become the gold standard for the treatment of ulcerative colitis and familial adenomatous polyposis.

Authors
Onaitis, MW; Mantyh, C
MLA Citation
Onaitis, MW, and Mantyh, C. "Ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: historical development and current status." Ann Surg 238.6 Suppl (December 2003): S42-S48. (Review)
PMID
14703744
Source
pubmed
Published In
Annals of Surgery
Volume
238
Issue
6 Suppl
Publish Date
2003
Start Page
S42
End Page
S48

Induction of anti-melanoma CTL response using DC transfected with mutated mRNA encoding full-length Melan-A/MART-1 antigen with an A27L amino acid substitution.

Modification of the parental immunodominant Melan-A/MART-1 peptide (MART-1(26-35)) by replacing the alanine with leucine (A27L) enhances its immunogenicity. Because of the reported advantages of RNA over peptides in DC vaccines, we sought to mutate the MART-1 gene to encode a full-length MART-1 antigen with an A27L amino acid substitution. Human DC were transfected with A27L-mutated MART-1 RNA (A27L RNA) or native MART-1 RNA, and then used to stimulate autologous T cells from a series of 8 HLA-A2+ volunteers. After three stimulations, all CTL induced with DC/A27L RNA exhibited more tetramer+ cells, and demonstrated stronger antigen-specific IFNgamma-secreting activity compared to CTL induced with DC/native RNA. A potent MART-1-specific, and predominantly class-I-restricted lysis was detected in most CTL induced with DC/A27L RNA, while native RNA-induced CTL showed minimal and non-specific lysis. HLA-A2+ DC and MART-1 negative/A2+ melanoma cells transfected with the A27L RNA were recognized and killed by MART-1-specific CTL, suggesting that these APC efficiently processed the A27L RNA and presented correct MART-1-specific epitope(s). In summary, introducing an A27L mutation into the MART-1 full-length mRNA sequence enhanced the immunogenicity of the encoded MART-1 Ag. The ease with which such a mutation can be made in RNA presents another potential advantage of using RNA for immunotherapy. Our results support considering this strategy for enhancing the immunogenicity of DC-based RNA vaccines.

Authors
Abdel-Wahab, Z; Kalady, MF; Emani, S; Onaitis, MW; Abdel-Wahab, OI; Cisco, R; Wheless, L; Cheng, T-Y; Tyler, DS; Pruitt, SK
MLA Citation
Abdel-Wahab, Z, Kalady, MF, Emani, S, Onaitis, MW, Abdel-Wahab, OI, Cisco, R, Wheless, L, Cheng, T-Y, Tyler, DS, and Pruitt, SK. "Induction of anti-melanoma CTL response using DC transfected with mutated mRNA encoding full-length Melan-A/MART-1 antigen with an A27L amino acid substitution." Cell Immunol 224.2 (August 2003): 86-97.
PMID
14609574
Source
pubmed
Published In
Cellular Immunology
Volume
224
Issue
2
Publish Date
2003
Start Page
86
End Page
97

CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy.

BACKGROUND: Dendritic cell (DC)-based immunotherapy is a promising form of adjuvant therapy for high-risk tumors. DCs transfected with tumor-associated antigens are capable of stimulating antigen-specific T cells, but cytolytic responses have been disappointing. Activation of DC surface CD40 influences DC cytokine production, particularly that of interleukin (IL)-12, which favors a Th1 (cytotoxic) helper T cell response. This study evaluated the effects of exogenous soluble CD40 ligand (sCD40L) on RNA-transfected DC preparations and their subsequent ability to generate antimelanoma cytolytic T cells. METHODS: Human monocyte-derived DCs were cultured and transfected with mRNA encoding full-length melanoma-associated antigen, Mart-1, and matured with and without sCD40L. DC IL-12 secretion and the ability to stimulate naïve T cells were assessed by enzyme-linked immunosorbent assay (ELISA), tetramer analysis, Elispot, and (51)Cr release assay. RESULTS: Mature DCs stimulated with sCD40L secreted higher levels of IL-12 compared with immature DCs and DCs matured without sCD40L (P <.001). DCs treated with sCD40L generated a greater number of antigen-specific T cells (P <.05) by tetramer and Elispot analyses, and yielded specific T cells with significant cytotoxicity against HLA-matched melanoma cell lines. CONCLUSIONS: CD40L augments DC IL-12 secretion and is essential to potentiate specific antimelanoma cytolytic responses stimulated by the Mart-1 antigen. sCD40L should be considered a crucial adjuvant in DC preparations for RNA-based DC vaccine therapies.

Authors
Onaitis, MW; Kalady, MF; Emani, S; Abdel-Wahab, Z; Tyler, DS; Pruitt, SK
MLA Citation
Onaitis, MW, Kalady, MF, Emani, S, Abdel-Wahab, Z, Tyler, DS, and Pruitt, SK. "CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy." Surgery 134.2 (August 2003): 300-305.
PMID
12947333
Source
pubmed
Published In
Surgery
Volume
134
Issue
2
Publish Date
2003
Start Page
300
End Page
305
DOI
10.1067/msy.2003.240

Adjuvant hepatic arterial chemotherapy following metastasectomy in patients with isolated liver metastases.

OBJECTIVE: To examine survival and toxicity by querying a single-institutional experience with adjuvant hepatic arterial infusional (HAI) chemotherapy. SUMMARY BACKGROUND DATA: Three randomized series in the literature have examined adjuvant HAI after complete resection of liver metastases. Only one of these trials showed an overall survival benefit at 2 years but not over the entire time period of the study. Previous studies in patients with unresectable disease were plagued by high rates of biliary toxicity. METHODS: A retrospective review of a prospectively maintained database was performed. Hepatic arterial pumps were placed in the standard fashion. Patients received floxuridine at doses previously demonstrated as safe in the literature. Standard statistical methods were used. RESULTS: Twenty-one of 92 patients underwent placement of hepatic arterial pumps at the time of liver resection. The HAI group was similar in all demographic measures to the non-HAI group, with the exception that the HAI patients were significantly younger. No differences were seen between the groups in either disease-free or overall survival, although a trend toward improved hepatic progression-free survival was noted. Significant biliary sclerosis developed in six patients in the HAI group, requiring chronic indwelling stents in four patients. One patient died of progressive liver failure associated with this toxicity. CONCLUSIONS: Biliary toxicity is an important potential side effect of hepatic arterial chemotherapy. Although larger randomized studies and this one suggest significant improvements in hepatic recurrences, these have not reliably translated into overall survival benefit. This fact, in light of the potential toxicity, would argue for a larger confirmatory trial of HAI in the adjuvant setting, incorporating recent advances in systemic therapy and careful attention to hepatotoxicity.

Authors
Onaitis, M; Morse, M; Hurwitz, H; Cotton, P; Tyler, D; Clavien, P; Clary, B
MLA Citation
Onaitis, M, Morse, M, Hurwitz, H, Cotton, P, Tyler, D, Clavien, P, and Clary, B. "Adjuvant hepatic arterial chemotherapy following metastasectomy in patients with isolated liver metastases." Ann Surg 237.6 (June 2003): 782-788.
PMID
12796574
Source
pubmed
Published In
Annals of Surgery
Volume
237
Issue
6
Publish Date
2003
Start Page
782
End Page
788
DOI
10.1097/01.SLA.0000071561.76384.19

Dendritic cells pulsed with pancreatic cancer total tumor RNA generate specific anti-pancreatic cancer T cells

Authors
Kalady, MF; Onaitis, MW; Abdul-Wahab, Z; Emani, S; Pruitt, SK; Tyler, DS
MLA Citation
Kalady, MF, Onaitis, MW, Abdul-Wahab, Z, Emani, S, Pruitt, SK, and Tyler, DS. "Dendritic cells pulsed with pancreatic cancer total tumor RNA generate specific anti-pancreatic cancer T cells." April 2003.
Source
wos-lite
Published In
Gastroenterology
Volume
124
Issue
4
Publish Date
2003
Start Page
A788
End Page
A788
DOI
10.1016/S0016-5085(03)83977-X

Improved survival in patients with colorectal metastases to the liver undergoing preoperative FDG-PET

Authors
Onaitis, MW; Tyler, DS; Coleman, E; Cotton, P; Clary, BM
MLA Citation
Onaitis, MW, Tyler, DS, Coleman, E, Cotton, P, and Clary, BM. "Improved survival in patients with colorectal metastases to the liver undergoing preoperative FDG-PET." April 2003.
Source
wos-lite
Published In
Gastroenterology
Volume
124
Issue
4
Publish Date
2003
Start Page
A825
End Page
A825
DOI
10.1016/S0016-5085(03)84160-4

Carcinoid tumors of the gastrointestinal tract. A review and the Duke University institutional overview.

Carcinoid tumors are relatively rare neoplasms arising from the amine precursor uptake and decarboxylation (APUD) cells of the gastrointestinal tract and bronchial tree. Presenting symptoms vary by site of origin, and various modalities may be used to diagnose them. Initial treatment is surgical, with procedure depending upon site of origin. Several experimental therapies may be used in treatment of metastatic carcinoid tumors.

Authors
Onaitis, M; White, R; Tyler, D
MLA Citation
Onaitis, M, White, R, and Tyler, D. "Carcinoid tumors of the gastrointestinal tract. A review and the Duke University institutional overview." Minerva Chir 58.1 (February 2003): 1-8. (Review)
PMID
12692491
Source
pubmed
Published In
Minerva chirurgica
Volume
58
Issue
1
Publish Date
2003
Start Page
1
End Page
8

I-131-meta-iodobenzylguanidine treatment for metastatic carcinoid tumors in 98 patients

Authors
Safford, SD; Coleman, RE; Gockerman, JP; Moore, J; Feldman, J; Onaitis, MW; Tyler, DS; Olson, JA
MLA Citation
Safford, SD, Coleman, RE, Gockerman, JP, Moore, J, Feldman, J, Onaitis, MW, Tyler, DS, and Olson, JA. "I-131-meta-iodobenzylguanidine treatment for metastatic carcinoid tumors in 98 patients." January 2003.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
10
Issue
1
Publish Date
2003
Start Page
S12
End Page
S12

Carcinoid and chylous ascites: an unusual association.

Chylous ascites caused by carcinoid tumors is extremely rare. While carcinoid tumors usually have an indolent course, their association with chylous ascites is a harbinger of a poor outcome.

Authors
Kypson, AP; Onaitis, MW; Feldman, JM; Tyler, DS
MLA Citation
Kypson, AP, Onaitis, MW, Feldman, JM, and Tyler, DS. "Carcinoid and chylous ascites: an unusual association." J Gastrointest Surg 6.5 (September 2002): 781-783.
PMID
12399070
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
6
Issue
5
Publish Date
2002
Start Page
781
End Page
783

Thoracoscopic lobectomy: a safe and effective strategy for patients with stage I lung cancer.

BACKGROUND: Thoracoscopic lobectomy is emerging as a potential alternative to thoracotomy for early stage lung cancer. The issues of safety and oncologic efficacy should be analyzed before recommending this procedure for widespread use. METHODS: Thoracoscopic lobectomy was attempted in 110 consecutive patients (age, 35 to 81 years) with tumors that were judged to be amenable to lobectomy over a 26-month period. Exclusion criteria included tumors greater than 5 cm in diameter, T3 tumors, endobronchial tumors visible at bronchoscopy, the use of induction therapy, extensive N1 disease on computed tomographic scan, and N2 disease at mediastinoscopy. The procedures were performed without rib spreading using two ports and included anatomic hilar dissection and individual vessel stapling. RESULTS: Thoracoscopic lobectomy and mediastinal lymph dissection was successfully performed in 108 patients (98.2%); 2 patients required conversion to thoracotomy to control bleeding in the setting of dense hilar adenopathy. There were no intraoperative deaths and 4 perioperative deaths (3.6%) caused by pneumonia and associated adult respiratory distress syndrome (3 patients) and stroke (1 patient). Major complications included pneumonia (5 patients), stroke (1 patient), and return to the operating room to revise the bronchial closure (1 patient). Minor complications included prolonged air leak (6 patients), atrial fibrillation (4 patients), blood transfusion (2 patients) and ileus (1 patient). Median time to chest tube removal was 3 days, and median length of stay was 3 days. CONCLUSIONS: Thoracoscopic lobectomy is a safe and effective strategy for patients with early stage lung cancer. Long-term follow-up is required to determine if recurrence rate and 5-year survival are comparable with thoracotomy for lobectomy.

Authors
Daniels, LJ; Balderson, SS; Onaitis, MW; D'Amico, TA
MLA Citation
Daniels, LJ, Balderson, SS, Onaitis, MW, and D'Amico, TA. "Thoracoscopic lobectomy: a safe and effective strategy for patients with stage I lung cancer." Ann Thorac Surg 74.3 (September 2002): 860-864.
PMID
12238851
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
74
Issue
3
Publish Date
2002
Start Page
860
End Page
864

Dendritic cell gene therapy.

All of these studies taken together highlight key areas that must be addressed in the future in order for the field to continue to move forward. These issues are many, including but not limited to method of delivery of dendritic cells to patients, maturation status of the dendritic cells, and methods of monitoring responses to these vaccines. Each of these requires some comment. Different strategies of immunization were used in these studies. DCs were injected at various times and in various locations, including intradermally/subcutaneously, intranodally, and intravenously. Investigation of the pattern of spread of subcutaneously injected fluorescently labeled DCs in the chimpanzee was studied at the University of Pittsburgh. Although rodent DCs had previously been shown to remain at the site of injection, these immature primate DCs migrated to draining lymph nodes and interact appropriately with T cells for as long as 5 days after administration. Data not shown in the same study reveal that intravenously administered DCs were undetectable in draining lymph nodes. Two groups have undertaken evaluation of route of administration of DCs in humans. The first of these examined migration of immature, indium-111-labeled dendritic cells after RNA-loading in metastatic cancer patients [44]. The DCs were injected either intravenously, subcutaneously, and intradermally. Only DCs injected intradermally were cleared from the injection site with migration to regional lymph nodes. The immunologic significance of these findings is unclear, however. Another study examined this issue by studying prostatic acid phosphatase (PAP) protein-loaded mature DCs injected intravenously, intradermally, and intralymphatically in prostate cancer patients [45]. Regardless of route of administration, T cell responses were induced as measured by proliferation when PBMCs in vitro were stimulated with the PAP protein. Cytokine analysis of the patients revealed that the majority of patients undergoing either intralymphatic or intradermal injection had increases in measurable interferon-gamma but that none of the intravenously-injected patients did. The intralymphatic and intradermal routes thus seem to lead to stronger Th1 responses. But no data was presented regarding the numbers of PAP precursors induced by vaccination nor their specificity/cytotoxicity. Another issue in DC administration that should also affect route of administration is maturation status of the dendritic cells. Many of the studies used immature dendritic cells to immunize patients whereas others used mature cells. A number of studies have demonstrated that maturation signals such as inflammatory cytokines and CD40 ligation lead to down-regulation of antigen processing and up-regulation of the chemokine receptor CCR7, which leads to homing to lymph nodes [46] as well as the MHC molecules, costimulatory molecules, and maturation markers [8,47,48]. In addition, different maturation agents and sequences of addition of these maturation agents may lead to differences in functions of dendritic cells [48-51]. Others have found that injection of immature DCs pulsed with influenza matrix peptide and KLH, and lead to greater numbers of influenza-specific T cells, but these cells had reduced interferon-gamma production and lacked killer activity [52]. Perhaps the most impressive results in a clinical trial, however, were gained by injecting similar cells loaded with melanoma peptides [21]. In addition, sequence of loading and maturation may be important in creating vaccines. One study using CEA peptides and CEA RNA found that optimal T cell presentation occurs when peptides are loaded after maturation with CD40 ligand and when RNA is transfected before maturation with CD40 ligand [53]. As all of these studies reveal, more investigation into the role of DC maturation as well as its timing and sequence is needed. Finally, a multitude of methods to detect response to vaccination have been attempted in all of the above studies. Many use DTH responses, but these may measure CD4 T cells instead of CD8 T cells. The availability of tetramers allows easier quantification of CTL precursors, but they provide no assessment of the function of these T cells. Enzyme-linked immunospot assays allow identification and quantification of numbers of cells producing cytokines such as interferon-gamma when encountering target antigens, but cytokine production may not correlate with tumor cell killing. Chromium release assays or flow cytometric assays for molecules such as perforin may be used to validate killing, but inability of many tumors to grow in vitro precludes direct assessment of tumor cell killing via this method. Other responses in human subjects may also be measured. Some of the cited studies yielded clinical responses that could be measured via physical examination or radiologic study. This is the exception rather than the rule, however. Others have monitored the decrease in serum tumor markers such as PSA or CEA. But these may not correlate directly with tumor burden. Indirect calculation of tumor burden by using quantitative PCR to estimate the number of circulating tumor cells in peripheral blood may be promising in this regard. Despite the lack of consensus as to what constitutes an effective response, most would agree that monitoring of these patients should include measures of both immunologic response and clinical tumor effect. All of this leads to the conclusion that DC-based cancer vaccines have progressed a great deal but that much work still needs to be done. Only rigorous bench top experimentation followed by careful patient selection and vaccine administration, and then by meticulous patient monitoring, will lead to advances in the field.

Authors
Onaitis, M; Kalady, MF; Pruitt, S; Tyler, DS
MLA Citation
Onaitis, M, Kalady, MF, Pruitt, S, and Tyler, DS. "Dendritic cell gene therapy." Surg Oncol Clin N Am 11.3 (July 2002): 645-660. (Review)
PMID
12487060
Source
pubmed
Published In
Surgical Oncology Clinics of North America
Volume
11
Issue
3
Publish Date
2002
Start Page
645
End Page
660

Routine contrast imaging of low pelvic anastomosis before temporary stoma closure: Lack of clinical impact on patient management

Authors
Kalady, MF; Fields, RC; Wilkins, KB; Onaitis, MW; Tyler, DS; Mantyh, CR; Ludwig, K
MLA Citation
Kalady, MF, Fields, RC, Wilkins, KB, Onaitis, MW, Tyler, DS, Mantyh, CR, and Ludwig, K. "Routine contrast imaging of low pelvic anastomosis before temporary stoma closure: Lack of clinical impact on patient management." July 2002.
Source
wos-lite
Published In
Gastroenterology
Volume
123
Issue
1
Publish Date
2002
Start Page
29
End Page
29

Enhanced dendritic cell antigen presentation in RNA-based immunotherapy.

BACKGROUND: Dendritic cells pulsed with mRNA provide a unique approach to tumor immunotherapy. We hypothesized that increased mRNA transfection efficiency and dendritic cell maturation would improve antigen processing and presentation as well as T-cell costimulation, resulting in enhanced induction of antimelanoma immune responses. METHODS: Immature monocyte-derived dendritic cells were transfected with mRNA by passive pulsing, lipofection, or electroporation. Dendritic cells were either left untreated or matured using the double-stranded RNA poly(I:C). T-Cell cultures were generated by stimulation of naïve T-cells with each set of dendritic cells. Specific antigen presentation and specific effector T-cell generation were analyzed by an IFN-gamma release Elispot assay. RESULTS: Greatest intracellular green fluorescent protein was observed by flow cytometry following dendritic cell electroporation with green fluorescent protein mRNA. DC presentation of Mart-1/Melan A peptide, as measured by Elispot assay using a specific T-cell clone, was greatest following transfection with Mart-1/Melan A mRNA by electroporation. Maturation of dendritic cells further improved antigen presentation regardless of transfection technique. Specific Mart-1/Melan A effector T cells were produced after culture of naïve T cells with dendritic cells that were electroporated with Mart-1/Melan A mRNA and then matured, but not for dendritic cells that remained immature. CONCLUSIONS: Efficient mRNA transfection by electroporation as well as dendritic cell maturation results in increased levels of Mart-1/Melan A antigen presentation and enhanced production of antigen-specific effector T cells. This combination of strategies may be used to enhance immune responses to RNA-based dendritic cell vaccines.

Authors
Kalady, MF; Onaitis, MW; Padilla, KM; Emani, S; Tyler, DS; Pruitt, SK
MLA Citation
Kalady, MF, Onaitis, MW, Padilla, KM, Emani, S, Tyler, DS, and Pruitt, SK. "Enhanced dendritic cell antigen presentation in RNA-based immunotherapy." J Surg Res 105.1 (June 1, 2002): 17-24.
PMID
12069496
Source
pubmed
Published In
Journal of Surgical Research
Volume
105
Issue
1
Publish Date
2002
Start Page
17
End Page
24
DOI
10.1006/jsre.2002.6435

Pancreatic duct strictures without an associated common bile duct stricture: Identifying risk of malignancy

Authors
Kalady, MF; Onaitis, MW; Howden, JK; Baillie, J; Jowell, PS; Branch, MS; Pappas, TN; Tyler, DS
MLA Citation
Kalady, MF, Onaitis, MW, Howden, JK, Baillie, J, Jowell, PS, Branch, MS, Pappas, TN, and Tyler, DS. "Pancreatic duct strictures without an associated common bile duct stricture: Identifying risk of malignancy." January 2002.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
9
Issue
1
Publish Date
2002
Start Page
S12
End Page
S13

Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival.

BACKGROUND: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses. RESULTS: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.

Authors
Onaitis, MW; Noone, RB; Fields, R; Hurwitz, H; Morse, M; Jowell, P; McGrath, K; Lee, C; Anscher, MS; Clary, B; Mantyh, C; Pappas, TN; Ludwig, K; Seigler, HF; Tyler, DS
MLA Citation
Onaitis, MW, Noone, RB, Fields, R, Hurwitz, H, Morse, M, Jowell, P, McGrath, K, Lee, C, Anscher, MS, Clary, B, Mantyh, C, Pappas, TN, Ludwig, K, Seigler, HF, and Tyler, DS. "Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival." Ann Surg Oncol 8.10 (December 2001): 801-806.
PMID
11776494
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
8
Issue
10
Publish Date
2001
Start Page
801
End Page
806

Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience.

OBJECTIVE: To examine clinical outcomes in patients receiving neoadjuvant chemoradiation for locally advanced rectal adenocarcinoma. SUMMARY BACKGROUND DATA: Preoperative radiation therapy, either alone or in combination with 5-fluorouracil-based chemotherapy, has proven both safe and effective in the treatment of rectal cancer. However, data are lacking regarding which subgroups of patients benefit from the therapy in terms of decreased local recurrence and increased survival rates. METHODS: A retrospective chart review was performed on 141 consecutive patients who received neoadjuvant chemoradiation (5-fluorouracil +/- cisplatin and 4,500-5,040 cGy) for biopsy-proven locally advanced adenocarcinoma of the rectum. Surgery was performed 4 to 8 weeks after completion of chemoradiation. Standard statistical methods were used to analyze recurrence and survival. RESULTS: Median follow-up was 27 months, and mean age was 59 years (range 28-81). Mean tumor distance from the anal verge was 6 cm (range 1-15). Of those staged before surgery with endorectal ultrasound or magnetic resonance imaging, 57% of stage II patients and 82% of stage III patients were downstaged. The chemotherapeutic regimens were well tolerated, and resections were performed on 140 patients. The percentage of sphincter-sparing procedures increased from 20% before 1996 to 76% after 1996. On pathologic analysis, 24% of specimens were T0. However, postoperative pathologic T stage had no effect on either recurrence or survival. Positive lymph node status predicted increased local recurrence and decreased survival. CONCLUSIONS: Neoadjuvant chemoradiation is safe, effective, and well tolerated. Postoperative lymph node status is the only independent predictor of recurrence and survival.

Authors
Onaitis, MW; Noone, RB; Hartwig, M; Hurwitz, H; Morse, M; Jowell, P; McGrath, K; Lee, C; Anscher, MS; Clary, B; Mantyh, C; Pappas, TN; Ludwig, K; Seigler, HF; Tyler, DS
MLA Citation
Onaitis, MW, Noone, RB, Hartwig, M, Hurwitz, H, Morse, M, Jowell, P, McGrath, K, Lee, C, Anscher, MS, Clary, B, Mantyh, C, Pappas, TN, Ludwig, K, Seigler, HF, and Tyler, DS. "Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience." Ann Surg 233.6 (June 2001): 778-785.
PMID
11371736
Source
pubmed
Published In
Annals of Surgery
Volume
233
Issue
6
Publish Date
2001
Start Page
778
End Page
785

Laparoscopic Heller myotomy as an effective and durable treatment for achalasia: The Duke University experience

Authors
Daniels, LJ; O'Halloran, EK; Onaitis, MW; Eubanks, S
MLA Citation
Daniels, LJ, O'Halloran, EK, Onaitis, MW, and Eubanks, S. "Laparoscopic Heller myotomy as an effective and durable treatment for achalasia: The Duke University experience." April 2001.
Source
wos-lite
Published In
Gastroenterology
Volume
120
Issue
5
Publish Date
2001
Start Page
A479
End Page
A479

Validation of delayed sentinel lymph node mapping for melanoma

Authors
Kalady, MF; White, DC; Onaitis, MW; Coleman, E; Seigler, HF; Tyler, D
MLA Citation
Kalady, MF, White, DC, Onaitis, MW, Coleman, E, Seigler, HF, and Tyler, D. "Validation of delayed sentinel lymph node mapping for melanoma." 2001.
Source
wos-lite
Published In
Cancer Journal
Volume
7
Issue
6
Publish Date
2001
Start Page
521
End Page
522

Gastrointestinal carcinoids: characterization by site of origin and hormone production.

OBJECTIVE: To describe a large series of patients with carcinoid tumors in terms of presenting symptoms, hormonal data, stage at diagnosis, pathologic features, and survival. SUMMARY BACKGROUND DATA: Published series have described significant prognostic features of carcinoid tumors as site of origin, age, sex, stage at diagnosis, presence of high hormone levels, and increased T stage. Of these, stage at diagnosis and T stage seem to emerge most often as independent predictors of survival in multivariate analyses. Of carcinoid tumors, those arising from a midgut location have higher levels of serotonin and serotonin breakdown products, as well as more frequent metastatic disease at presentation, than those arising from either foregut or hindgut locations. METHODS: A prospective database of carcinoid patients seen at Duke University Medical Center was kept from 1970 to the present. Retrospective medical record review was performed on this database to record presenting symptoms, hormonal data, pathologic features, and survival. Statistical methods included analysis of variance, Kaplan-Meier analysis, and Mantel-Cox proportional hazard survival analysis, with P <.05 considered significant for all tests. RESULTS: Carcinoids arising in different locations had different presentations: rectal carcinoids presented significantly more often with gastrointestinal bleeding, and midgut carcinoids presented significantly more often with flushing, diarrhea, and the carcinoid syndrome. Patients with midgut tumors had significantly higher levels of serotonin and serotonin breakdown products, corresponding to higher metastatic tumor burdens. Although age, stage, region of origin, and urinary level of 5-hydroxyindoleacetic acid predicted survival by univariate analysis, only the latter three were independent predictors of survival by multivariate analysis. Of the patients with metastatic disease at diagnosis, those with midgut tumors had better survival than those with foregut or hindgut tumors. CONCLUSIONS: Although region of origin is certainly an important factor in determination of prognosis, stage of disease at presentation is more predictive of survival. Pancreatic and midgut carcinoids are metastatic at diagnosis more often than those arising in other locations, leading to a worse overall prognosis. Among patients with distant metastases, patients with midgut primary tumors have improved survival despite increased hormone production compared with patients with tumors arising in other primary sites.

Authors
Onaitis, MW; Kirshbom, PM; Hayward, TZ; Quayle, FJ; Feldman, JM; Seigler, HF; Tyler, DS
MLA Citation
Onaitis, MW, Kirshbom, PM, Hayward, TZ, Quayle, FJ, Feldman, JM, Seigler, HF, and Tyler, DS. "Gastrointestinal carcinoids: characterization by site of origin and hormone production." Ann Surg 232.4 (October 2000): 549-556.
PMID
10998653
Source
pubmed
Published In
Annals of Surgery
Volume
232
Issue
4
Publish Date
2000
Start Page
549
End Page
556

Gastrointestinal carcinoids: Characterization by site of origin and hormone production - Discussion

Authors
Friesen, SR; Onaitis, MW; Frilling, A; Kelly, KA; Kaplan, EL; Mark, JBD; Debas, HT
MLA Citation
Friesen, SR, Onaitis, MW, Frilling, A, Kelly, KA, Kaplan, EL, Mark, JBD, and Debas, HT. "Gastrointestinal carcinoids: Characterization by site of origin and hormone production - Discussion." ANNALS OF SURGERY 232.4 (October 2000): 555-556.
Source
wos-lite
Published In
Annals of Surgery
Volume
232
Issue
4
Publish Date
2000
Start Page
555
End Page
556

Positron emission tomography scanning in malignant melanoma.

BACKGROUND: Several recent studies have demonstrated the low yield of anatomically based computed tomography scans in evaluating Stage III (American Joint Committee on Cancer) patients with malignant melanoma. The purpose of this study was to investigate the efficacy and clinical utility of functionally based positron emission tomography (PET) scans in the same patient population. METHODS: A prospective evaluation of 106 whole body PET scans obtained after injection of 2-fluorine-18, 2-fluoro-2-deoxy-D-glucose (FDG) was performed in 95 patients with clinically evident Stage III lymph node and/or in-transit melanoma. Areas of abnormality on FDG PET scanning were identified visually as foci of increased metabolic activity compared with background, and all positive foci were assessed pathologically. RESULTS: In this patient population, there were 234 areas that were evaluated pathologically of which 165 were confirmed histologically to be melanoma. PET scanning identified 144 of the 165 areas of melanoma for a sensitivity of 87.3%. The 21 areas of melanoma that were missed included 10 microscopic foci, 9 foci less than 1 cm, and 2 foci greater than 1 cm. There were 39 areas of increased PET activity that were not associated with malignancy for a 78.6% predictive value of a positive test. Of the 39 false-positive areas (false-positive rate of 56.5%), 13 could be attributed to recent surgery, 3 to arthritis, 3 to infection, 2 to superficial phlebitis, 1 to a benign skin nevus, and 1 to a colonic polyp. Pathologic evaluation of the remaining false-positive areas failed to reveal a definitive etiology for their increased activity on PET scan. With the application of pertinent clinical information, the predictive value of a positive PET scan could be improved to 90. 6%. The specificity of PET scanning in this study was only 43.5% because very few prophylactic lymph node dissections were performed. Thirty-six of the total 183 abnormal areas (19.7%) on PET scanning proved to be unsuspected areas of metastatic disease. These findings led to a change in the planned clinical management in patients after 16 of the 106 PET scans (15.1%). CONCLUSIONS: FDG PET scanning can be helpful in managing patients with Stage III melanoma in whom further surgery is contemplated. Although false-positive areas are not uncommon, PET scans did change the management of patients 15% of the time. PET's inability to identify microscopic disease suggests that it is of limited use in evaluating patients with Stage I-II disease.

Authors
Tyler, DS; Onaitis, M; Kherani, A; Hata, A; Nicholson, E; Keogan, M; Fisher, S; Coleman, E; Seigler, HF
MLA Citation
Tyler, DS, Onaitis, M, Kherani, A, Hata, A, Nicholson, E, Keogan, M, Fisher, S, Coleman, E, and Seigler, HF. "Positron emission tomography scanning in malignant melanoma." Cancer 89.5 (September 1, 2000): 1019-1025.
PMID
10964332
Source
pubmed
Published In
Cancer
Volume
89
Issue
5
Publish Date
2000
Start Page
1019
End Page
1025

Foregut carcinoids: a clinical and biochemical analysis.

BACKGROUND: Gastrointestinal foregut carcinoids make up a small percentage (3% to 6%) of all reported carcinoids. Because these tumors are so uncommon, comparisons between the subtypes have been difficult. The goal of this study was to compare the hormonal and clinical characteristics of gastric, duodenal, and pancreatic carcinoids. METHODS: A prospective database of approximately 750 carcinoid patients seen by one author over 25 years was reviewed, and the 104 patients with gastric (33), duodenal (17), or pancreatic (54) carcinoids were selected as the subgroup for analysis. These patients were compared with regard to hormone levels, clinical course, treatment, and survival. RESULTS: Duodenal carcinoids exhibited significantly lower serotoninergic hormone levels than did the gastric and pancreatic carcinoids (urine 5-hydroxyindoleacetic acid [mg/24 h], 5 +/- 1 vs 16 +/- 5 and 47 +/- 12, respectively, P = .03). Pancreatic carcinoids presented with more advanced stage (distant metastases 87% vs 42% and 20% for gastric and duodenal, respectively) and had worse outcomes than patients with gastric and duodenal tumors with 10-year survivals of 10%, 59%, and 58%, respectively (P = .003). CONCLUSIONS: Pancreatic carcinoids produce higher levels of serotoninergic hormones and have a significantly higher stage and worse outcome than other foregut carcinoids. This study demonstrates that the organ of origin is an important determinant of hormonal activity and clinical course for patients with foregut carcinoids.

Authors
Kirshbom, PM; Kherani, AR; Onaitis, MW; Hata, A; Kehoe, TE; Feldman, C; Feldman, JM; Tyler, DS
MLA Citation
Kirshbom, PM, Kherani, AR, Onaitis, MW, Hata, A, Kehoe, TE, Feldman, C, Feldman, JM, and Tyler, DS. "Foregut carcinoids: a clinical and biochemical analysis." Surgery 126.6 (December 1999): 1105-1110.
PMID
10598194
Source
pubmed
Published In
Surgery
Volume
126
Issue
6
Publish Date
1999
Start Page
1105
End Page
1110

Carcinoids of unknown origin: comparative analysis with foregut, midgut, and hindgut carcinoids.

BACKGROUND: Carcinoids are rare neuroendocrine tumors typically arising in the gastrointestinal tract. A significant percentage of these tumors present as metastatic disease of unknown primary site. The aim of this study was to better define the functional and clinical characteristics of carcinoids of unknown primary (CUP) site. METHODS: This study examines the hormonal activity, clinical characteristics, and survival of 434 patients with carcinoids originating in the foregut, midgut, hindgut, or unknown location. The 143 patients with CUP were compared with the other groups with regard to presenting characteristics, diagnostic tests and therapeutic modalities used, hormonal activity, and survival. RESULTS: The hormone levels (urinary 5-hydroxyindoleacetic acid and serotonin, serum and platelet serotonin) of CUP were not significantly different from midgut carcinoids with metastatic disease. Although survival with CUP was shorter than with carcinoids with identified primaries (10-year survivals of 22% vs 62%, 50%, and 48% for foregut, midgut, and hindgut, respectively), the survival curve for CUP was quite similar to that of patients with midgut carcinoids with distant disease (10-year survival of 22% vs 28%). CONCLUSIONS: CUP are similar to midgut carcinoids presenting with metastatic disease with regard to hormone production and survival. Like other carcinoids, CUP can be an indolent disease process with gradual progression over decades.

Authors
Kirshbom, PM; Kherani, AR; Onaitis, MW; Feldman, JM; Tyler, DS
MLA Citation
Kirshbom, PM, Kherani, AR, Onaitis, MW, Feldman, JM, and Tyler, DS. "Carcinoids of unknown origin: comparative analysis with foregut, midgut, and hindgut carcinoids." Surgery 124.6 (December 1998): 1063-1070.
PMID
9854584
Source
pubmed
Published In
Surgery
Volume
124
Issue
6
Publish Date
1998
Start Page
1063
End Page
1070
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