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White, Rebekah Ruth

Positions:

Adjunct Associate Professor in the Department of Surgery

Surgery, Advanced Oncologic and Gastrointestinal Surgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1997

M.D. — Duke University

News:

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

Aptamers as Proteomic Tools for Pancreatic Cancer Biomarker Identification

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 2015
End Date
December 31, 2016

RNA Therapeutics for Pancreatic Cancer

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 17, 2011
End Date
July 31, 2015

In Vivo Selection of Aptamers Targeting Pancreatic Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Sponsor
Start Date
July 01, 2011
End Date
June 30, 2012

Comprehensive Cancer Center Core Support Grant - Supplement

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Research Assistant
Start Date
April 27, 2001
End Date
December 31, 2001
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Publications:

Cell-SELEX Identifies a "Sticky" RNA Aptamer Sequence.

Cell-SELEX is performed to select for cell binding aptamers. We employed an additional selection pressure by using RNAse to remove surface-binding aptamers and select for cell-internalizing aptamers. A common RNA sequence was identified from independent cell-SELEX procedures against two different pancreatic cancer cell lines, indicating a strong selection pressure towards this sequence from the large pool of other available sequences present in the aptamer library. The aptamer is not specific for the pancreatic cancer cell lines, and a similar sequence motif is present in previously published internalizing aptamers. The identified sequence forms a structural motif that binds to a surface protein, which either is highly abundant or has strong affinity for the selected aptamer sequence. Deselecting (removing) this sequence during cell-SELEX may increase the probability of identifying aptamers against cell type-specific targets on the cell surface.

Authors
Ray, P; White, RR
MLA Citation
Ray, P, and White, RR. "Cell-SELEX Identifies a "Sticky" RNA Aptamer Sequence." Journal of nucleic acids 2017 (January 17, 2017): 4943072-.
PMID
28194280
Source
epmc
Published In
Journal of Nucleic Acids
Volume
2017
Publish Date
2017
Start Page
4943072
DOI
10.1155/2017/4943072

Aptamers as Therapeutics.

Aptamers are single-stranded nucleic acid molecules that bind to and inhibit proteins and are commonly produced by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers undergo extensive pharmacological revision, which alters affinity, specificity, and therapeutic half-life, tailoring each drug for a specific clinical need. The first therapeutic aptamer was described 25 years ago. Thus far, one aptamer has been approved for clinical use, and numerous others are in preclinical or clinical development. This review presents a short history of aptamers and SELEX, describes their pharmacological development and optimization, and reviews potential treatment of diseases including visual disorders, thrombosis, and cancer.

Authors
Nimjee, SM; White, RR; Becker, RC; Sullenger, BA
MLA Citation
Nimjee, SM, White, RR, Becker, RC, and Sullenger, BA. "Aptamers as Therapeutics." Annual review of pharmacology and toxicology 57 (January 2017): 61-79.
PMID
28061688
Source
epmc
Published In
Annual Review of Pharmacology and Toxicology
Volume
57
Publish Date
2017
Start Page
61
End Page
79
DOI
10.1146/annurev-pharmtox-010716-104558

TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer in part due to inherent resistance to chemotherapy, including the first-line drug gemcitabine. Although low expression of the nucleoside transporters hENT1 and hCNT3 that mediate cellular uptake of gemcitabine has been linked to gemcitabine resistance, the mechanisms regulating their expression in the PDAC tumor microenvironment are largely unknown. Here, we report that the matricellular protein cysteine-rich angiogenic inducer 61 (CYR61) negatively regulates the nucleoside transporters hENT1 and hCNT3. CRISPR/Cas9-mediated knockout of CYR61 increased expression of hENT1 and hCNT3, increased cellular uptake of gemcitabine and sensitized PDAC cells to gemcitabine-induced apoptosis. In PDAC patient samples, expression of hENT1 and hCNT3 negatively correlates with expression of CYR61 We demonstrate that stromal pancreatic stellate cells (PSCs) are a source of CYR61 within the PDAC tumor microenvironment. Transforming growth factor-β (TGF-β) induces the expression of CYR61 in PSCs through canonical TGF-β-ALK5-Smad2/3 signaling. Activation of TGF-β signaling or expression of CYR61 in PSCs promotes resistance to gemcitabine in PDAC cells in an in vitro co-culture assay. Our results identify CYR61 as a TGF-β-induced stromal-derived factor that regulates gemcitabine sensitivity in PDAC and suggest that targeting CYR61 may improve chemotherapy response in PDAC patients.

Authors
Hesler, RA; Huang, JJ; Starr, MD; Treboschi, VM; Bernanke, AG; Nixon, AB; McCall, SJ; White, RR; Blobe, GC
MLA Citation
Hesler, RA, Huang, JJ, Starr, MD, Treboschi, VM, Bernanke, AG, Nixon, AB, McCall, SJ, White, RR, and Blobe, GC. "TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3." Carcinogenesis (September 7, 2016).
PMID
27604902
Source
epmc
Published In
Carcinogenesis
Publish Date
2016

In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9.

The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo selection strategy to identify RNA aptamers (targeting motifs) that could localize to tumor in situ. One of the selected molecules is an aptamer that binds to the protein DHX9, an RNA helicase that is known to be upregulated in colorectal cancer. Upon systemic administration, the aptamer preferentially localized to the nucleus of cancer cells in vivo and thus has the potential to be used for targeted delivery.

Authors
Mi, J; Ray, P; Liu, J; Kuan, C-T; Xu, J; Hsu, D; Sullenger, BA; White, RR; Clary, BM
MLA Citation
Mi, J, Ray, P, Liu, J, Kuan, C-T, Xu, J, Hsu, D, Sullenger, BA, White, RR, and Clary, BM. "In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9." Molecular therapy. Nucleic acids 5 (April 26, 2016): e315-.
PMID
27115840
Source
epmc
Published In
Molecular Therapy - Nucleic Acids
Volume
5
Publish Date
2016
Start Page
e315
DOI
10.1038/mtna.2016.27

A standardized care plan is associated with shorter hospital length of stay in patients undergoing pancreaticoduodenectomy.

BACKGROUND: In this retrospective review, we evaluate a standardized care plan (SCP) for patients undergoing pancreaticoduodenectomy, which included selective placement of feeding jejunostomy tubes (FJTs) and a perioperative fast-track recovery pathway (FTRP). METHODS: A review of 242 patients undergoing pancreaticoduodenectomy was completed. Patients treated pre- and post-SCP implementation were compared. Univariate comparison followed by multivariable linear regression were performed to identify predictors of hospital length of stay (HLOS). RESULTS: SCP patients (n = 100) were slightly older but otherwise similar to pre-SCP patients (n = 142). FJT placement occurred less frequently in SCP patients (38 versus 94%, P < 0.001). All SCP patients were initiated on the FTRP. Among SCP patients, an oral diet was introduced earlier (5 versus 8.5 d, P < 0.001) and HLOS was shorter (11 versus 13 d, P = 0.015). Readmission rates were similar. Following adjustment with linear regression, we confirmed SCP status as a predictor of HLOS. To assess SCP components, HLOS was evaluated separately based on FTRP status and FJT placement. Although both were highly associated with HLOS, neither was independently predictive in multivariable analysis. CONCLUSIONS: Implementation of an SCP resulted in shorter HLOS without an increase in readmissions. Future studies are necessary to identify specific components of SCPs that most influence outcomes.

Authors
Nussbaum, DP; Penne, K; Stinnett, SS; Speicher, PJ; Cocieru, A; Blazer, DG; Zani, S; Clary, BM; Tyler, DS; White, RR
MLA Citation
Nussbaum, DP, Penne, K, Stinnett, SS, Speicher, PJ, Cocieru, A, Blazer, DG, Zani, S, Clary, BM, Tyler, DS, and White, RR. "A standardized care plan is associated with shorter hospital length of stay in patients undergoing pancreaticoduodenectomy." The Journal of surgical research 193.1 (January 2015): 237-245.
PMID
25062813
Source
epmc
Published In
Journal of Surgical Research
Volume
193
Issue
1
Publish Date
2015
Start Page
237
End Page
245
DOI
10.1016/j.jss.2014.06.036

Wound classification reporting in HPB surgery: can a single word change public perception of institutional performance?

The drive to improve outcomes and the inevitability of mandated public reporting necessitate uniform documentation and accurate databases. The reporting of wound classification in patients undergoing hepato-pancreatico-biliary (HPB) surgery and the impact of inconsistencies on quality metrics were investigated.The 2005-2011 National Surgical Quality Improvement Program (NSQIP) participant use file was interrogated to identify patients undergoing HPB resections. The effect of wound classification on post-operative surgical site infection (SSI) rates was determined through logistic regression. The impact of variations in wound classification reporting on perceived outcomes was modelled by simulating observed-to-expected (O/E) ratios for SSI.In total, 27,376 patients were identified with significant heterogeneity in wound classification. In spite of clear guidelines prompting at least 'clean-contaminated' designation for HPB resections, 8% of all cases were coded as 'clean'. Contaminated [adjusted odds ratio (AOR): 1.39, P = 0.001] and dirty (AOR: 1.42, P = 0.02] cases were associated with higher odds of SSI, whereas clean-contaminated were not (P = 0.99). O/E ratios were highly sensitive to modest changes in wound classification.Perceived performance is affected by heterogeneous reporting of wound classification. As institutions work to improve outcomes and prepare for public reporting, it is imperative that all adhere to consistent reporting practices to provide accurate and reproducible outcomes.

Authors
Speicher, PJ; Nussbaum, DP; Scarborough, JE; Zani, S; White, RR; Blazer, DG; Mantyh, CR; Tyler, DS; Clary, BM
MLA Citation
Speicher, PJ, Nussbaum, DP, Scarborough, JE, Zani, S, White, RR, Blazer, DG, Mantyh, CR, Tyler, DS, and Clary, BM. "Wound classification reporting in HPB surgery: can a single word change public perception of institutional performance?." HPB : the official journal of the International Hepato Pancreato Biliary Association 16.12 (December 2014): 1068-1073.
PMID
24852206
Source
epmc
Published In
HPB
Volume
16
Issue
12
Publish Date
2014
Start Page
1068
End Page
1073
DOI
10.1111/hpb.12275

Defining the learning curve for team-based laparoscopic pancreaticoduodenectomy.

BACKGROUND: The purpose of this study was to define the learning curves for laparoscopic pancreaticoduodenectomy (LPD) with and without laparoscopic reconstruction, using paired surgical teams consisting of advanced laparoscopic-trained surgeons and advanced oncologic-trained surgeons. METHODS: All patients undergoing PD without vein resection at a single institution were retrospectively analyzed. LPD was introduced by initially focusing on laparoscopic resection followed by open reconstruction (hybrid) for 18 months prior to attempting a totally LPD (TLPD) approach. Cases were compared with Chi square, Fisher's exact test, and Kruskal-Wallis analysis of variance (ANOVA). RESULTS: Between March 2010 and June 2013, 140 PDs were completed at our institution, of which 56 (40 %) were attempted laparoscopically. In 31/56 procedures we planned to perform only the resection laparoscopically (hybrid), of which 7 (23 %) required premature conversion before completion of resection. Following the first 23 of these hybrid cases, a total of 25 TLPDs have been performed, of which there were no conversions to open. For all LPD, a significant reduction in operative times was identified following the first 10 patients (median 478.5 vs. 430.5 min; p = 0.01), approaching open PD levels. After approximately 50 cases, operative times and estimated blood loss were consistently lower than those for open PD. CONCLUSIONS: In our experience of building an LPD program, the initial ten cases represent the biggest hurdle with respect to operative times. For an experienced teaching center using a staged and team-based approach, LPD appears to offer meaningful reductions in operative time and blood loss within the first 50 cases.

Authors
Speicher, PJ; Nussbaum, DP; White, RR; Zani, S; Mosca, PJ; Blazer, DG; Clary, BM; Pappas, TN; Tyler, DS; Perez, A
MLA Citation
Speicher, PJ, Nussbaum, DP, White, RR, Zani, S, Mosca, PJ, Blazer, DG, Clary, BM, Pappas, TN, Tyler, DS, and Perez, A. "Defining the learning curve for team-based laparoscopic pancreaticoduodenectomy." November 2014.
PMID
24923222
Source
epmc
Published In
Annals of Surgical Oncology
Volume
21
Issue
12
Publish Date
2014
Start Page
4014
End Page
4019
DOI
10.1245/s10434-014-3839-7

Abstract 4117: Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma

Authors
Naqvi, IA; White, RR; Moylan, CA; Diehl, AM; Choi, SS
MLA Citation
Naqvi, IA, White, RR, Moylan, CA, Diehl, AM, and Choi, SS. "Abstract 4117: Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma." October 1, 2014.
Source
crossref
Published In
Cancer Research
Volume
74
Issue
19 Supplement
Publish Date
2014
Start Page
4117
End Page
4117
DOI
10.1158/1538-7445.AM2014-4117

Feeding jejunostomy tube placement in patients undergoing pancreaticoduodenectomy: an ongoing dilemma.

BACKGROUND: Concomitant placement of feeding jejunostomy tubes (FJT) during pancreaticoduodenectomy is common, yet there are limited data regarding catheter-specific morbidity and associated outcomes. This information is crucial to appropriately select patients for feeding tube placement and to optimize perioperative nutrition strategies. METHODS: A review of all patients undergoing pancreaticoduodenectomy with FJT placement was completed. Patients were grouped by the occurrence of FJT-related morbidity. Multivariable logistic regression was performed to identify predictors of FJT morbidity; these complications were then further defined. Finally, associated postoperative outcomes were compared between groups. RESULTS: In total, 126 patients were included, of which 18 (14 %) had complications directly related to their FJT, including pericatheter infection (n = 6), pneumatosis intestinalis (n = 4), severe tube feed intolerance (n = 3), and primary catheter malfunction (n = 7). Following adjustment with logistic regression, preoperative hypoalbuminemia was identified as the only independent predictor of FJT complications (OR 2.23, p = 0.035). Patients with FJT complications were more likely to be initiated on total parenteral nutrition (TPN; 55.6 vs. 7.4 %, p -0.035) and to require TPN at discharge (16.7 vs. 0%, p = 0.003). Correspondingly, these patients resumed an oral diet later (14 vs. 8 days, p = 0.06). Both reoperation (50.0 vs. 6.5%, p < 0.001) and readmission (50.0 vs. 22.4%, p = 0.041) rates were higher among patients with FJT complications. CONCLUSIONS: FJT-related morbidity is common among patients undergoing pancreaticoduodenectomy and is associated with inferior outcomes and other performance metrics. Preoperative malnutrition appears to predict FJT complications, creating an ongoing dilemma regarding FJT placement. In the future, it will be important to better define criteria for FJT placement during pancreaticoduodenectomy.

Authors
Nussbaum, DP; Zani, S; Penne, K; Speicher, PJ; Stinnett, SS; Clary, BM; White, RR; Tyler, DS; Blazer, DG
MLA Citation
Nussbaum, DP, Zani, S, Penne, K, Speicher, PJ, Stinnett, SS, Clary, BM, White, RR, Tyler, DS, and Blazer, DG. "Feeding jejunostomy tube placement in patients undergoing pancreaticoduodenectomy: an ongoing dilemma." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 18.10 (October 2014): 1752-1759.
PMID
24961442
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
18
Issue
10
Publish Date
2014
Start Page
1752
End Page
1759
DOI
10.1007/s11605-014-2581-6

The role of clinical care pathways: an experience with distal pancreatectomy.

BACKGROUND: Previous studies have indicated that clinical pathways may shorten hospital length of stay (HLOS) among patients undergoing distal pancreatectomy (DP). Here, we evaluate an institutional standardized care pathway (SCP) for patients undergoing DP. MATERIALS AND METHODS: A retrospective review of patients undergoing DP from November 2006 to November 2012 was completed. Patients treated before and after implementation of the SCP were compared. Multivariable linear regression was then performed to identify independent predictors of HLOS. RESULTS: There were no differences in patient characteristics between SCP (n=50) and pre-SCP patients (n=100). Laparoscopic technique (62% versus 13%, P<0.001), splenectomy (52% versus 38%, P=0.117), and concomitant major organ resection (24% versus 13%, P=0.106) were more common among SCP patients. Overall, important complication rates were similar (24% versus 26%, P=0.842). SCP patients resumed a normal diet earlier (4 versus 5 d, P=0.025) and had shorter HLOS (6 versus 7 d, P=0.026). There was no increase in 30-d resurgery or readmission. In univariate comparison, SCP, cancer diagnoses, intraductal papillary mucinous neoplasm diagnoses, neoadjuvant therapy, operative technique, major organ resection, and feeding tube placement were associated with HLOS; however, after multivariable adjustment, only laparoscopic technique (-33%, P=0.001), concomitant major organ resection (+38%, P<0.001), and feeding tube placement (+68%, P<0.001) were independent predictors of HLOS. CONCLUSIONS: Implementation of a clinical pathway did not improve HLOS at our institution. The increasing use of laparoscopy likely accounts for shorter HLOS in the SCP cohort. In the future, it will be important to identify clinical scenarios most likely to benefit from implementation of a clinical pathway.

Authors
Nussbaum, DP; Penne, K; Speicher, PJ; Stinnett, SS; Perez, A; White, RR; Clary, BM; Tyler, DS; Blazer, DG
MLA Citation
Nussbaum, DP, Penne, K, Speicher, PJ, Stinnett, SS, Perez, A, White, RR, Clary, BM, Tyler, DS, and Blazer, DG. "The role of clinical care pathways: an experience with distal pancreatectomy." The Journal of surgical research 190.1 (July 2014): 64-71.
PMID
24666986
Source
epmc
Published In
Journal of Surgical Research
Volume
190
Issue
1
Publish Date
2014
Start Page
64
End Page
71
DOI
10.1016/j.jss.2014.02.026

Neoadjuvant chemotherapy for localized pancreatic cancer: too little or too long?

Authors
White, RR; Evans, DB
MLA Citation
White, RR, and Evans, DB. "Neoadjuvant chemotherapy for localized pancreatic cancer: too little or too long?." Annals of surgical oncology 21.5 (May 2014): 1508-1509.
PMID
24452411
Source
epmc
Published In
Annals of Surgical Oncology
Volume
21
Issue
5
Publish Date
2014
Start Page
1508
End Page
1509
DOI
10.1245/s10434-014-3490-3

Groove Pancreatitis: Four Cases from a Single Center and Brief Review of the Literature.

Groove pancreatitis is a rare form of chronic pancreatitis that affects the groove anatomical area between the head of the pancreas, duodenum, and common bile duct. We provide a summary of the clinical findings of 4 groove pancreatitis cases diagnosed at a tertiary academic medical center over a 5-year period. A detailed review of the current literature surrounding this clinical entity is also provided. Although rare, groove pancreatitis should be considered in the differential diagnosis of patients presenting with pancreatic head mass lesions, as appropriate diagnosis can help avoid unnecessary surgical procedures.

Authors
Black, TP; Guy, CD; White, RR; Obando, J; Burbridge, RA
MLA Citation
Black, TP, Guy, CD, White, RR, Obando, J, and Burbridge, RA. "Groove Pancreatitis: Four Cases from a Single Center and Brief Review of the Literature." ACG case reports journal 1.3 (April 4, 2014): 154-157.
PMID
26157859
Source
epmc
Published In
ACG Case Reports Journal
Volume
1
Issue
3
Publish Date
2014
Start Page
154
End Page
157
DOI
10.14309/crj.2014.35

Hepatic resection for hepatocellular carcinoma: do contemporary morbidity and mortality rates demand a transition to ablation as first-line treatment?

BACKGROUND: Despite the rising incidence of hepatocellular carcinoma (HCC), challenges and controversy persist in optimizing treatment. As recent randomized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC, the relative morbidity of the 2 approaches is a central issue in treatment decisions. Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units, it is not clear that they can be replicated in broader practice. Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions. STUDY DESIGN: Mortality and morbidity data were extracted from the 2005-2010 NSQIP Participant Use Data Files based on Current Procedural Terminology (hepatectomy and ablation) and ICD-9 (HCC). Perioperative outcomes were reviewed, and factors associated with morbidity and mortality were identified with multivariable logistic regression. RESULTS: Eight hundred and thirty-seven (52%) underwent minor hepatectomy, 444 (28%) underwent major hepatectomy, and 323 (20%) underwent surgical ablation. Mortality rates were 3.4% for minor hepatectomy, 3.7% for ablation, and 8.3% for major hepatectomy (p < 0.01). Major complication rates were 21.3% for minor hepatectomy, 9.3% for ablation, and 35.1% for major hepatectomy (p < 0.01). When controlling for confounders, ablation was associated with decreased mortality (adjusted odds ratio = 0.20; 95% CI, 0.04-0.97; p = 0.046) and major complications (adjusted odds ratio = 0.34; 95% CI, 0.22-0.52; p < 0.001). CONCLUSIONS: Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment. These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible.

Authors
Li, GZ; Speicher, PJ; Lidsky, ME; Darrabie, MD; Scarborough, JE; White, RR; Turley, RS; Clary, BM
MLA Citation
Li, GZ, Speicher, PJ, Lidsky, ME, Darrabie, MD, Scarborough, JE, White, RR, Turley, RS, and Clary, BM. "Hepatic resection for hepatocellular carcinoma: do contemporary morbidity and mortality rates demand a transition to ablation as first-line treatment?." Journal of the American College of Surgeons 218.4 (April 2014): 827-834.
PMID
24655879
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
218
Issue
4
Publish Date
2014
Start Page
827
End Page
834
DOI
10.1016/j.jamcollsurg.2013.12.036

Further characterization of the target of a potential aptamer biomarker for pancreatic cancer: cyclophilin B and its posttranslational modifications.

Posttranslational modifications on proteins can serve as useful biomarkers for disease. However, their discovery and detection in biological fluids is challenging. Aptamers are oligonucleotide ligands that demonstrate high affinity toward their target proteins and can discriminate closely related proteins with superb specificity. Previously, we generated a cyclophilin B aptamer (M9-5) that could discriminate sera from pancreatic cancer patients and healthy volunteers with high specificity and sensitivity. In our present work we further characterize the aptamer and the target protein, cyclophilin B, and demonstrate that the aptamer could discriminate between cyclophilin B expressed in human cells versus bacteria. Using mass-spectrometric analysis, we discovered post-translational modifications on cyclophilin B that might be responsible for the M9-5 selectivity. The ability to distinguish between forms of the same protein with differing post-translational modifications is an important advantage of aptamers as tools for identification and detection of biomarkers.

Authors
Ray, P; Sullenger, BA; White, RR
MLA Citation
Ray, P, Sullenger, BA, and White, RR. "Further characterization of the target of a potential aptamer biomarker for pancreatic cancer: cyclophilin B and its posttranslational modifications." Nucleic Acid Ther 23.6 (December 2013): 435-442.
PMID
24152208
Source
pubmed
Published In
Nucleic Acid Therapeutics
Volume
23
Issue
6
Publish Date
2013
Start Page
435
End Page
442
DOI
10.1089/nat.2013.0439

Trends in racial disparities in pancreatic cancer surgery.

OBJECTIVES: We tested three hypotheses: (1) blacks with pancreatic cancer are recommended surgical resection less often than whites; (2) when recommended surgical resection, blacks refuse surgery more often than whites; and lastly, (3) racial differences in refusal of surgical resection have decreased over time. METHODS: A retrospective cohort study was conducted on patients with potentially resectable, nonmetastatic pancreatic adenocarcinoma of the Surveillance, Epidemiology, and End Results registry from 1988 to 2009. Univariate and multivariable logistic regression analyses were performed to assess whether differences in the proportion of whites versus blacks refusing surgery among patients recommended for resection changed over time. RESULTS: A total of 35,944 patients were included; most were white (87.6 %). After adjusting for covariates including tumor stage, pancreatic cancer resection was less often recommended to and performed in blacks compared with whites (adjusted odds ratio (aOR) 0.88, 95 % confidence interval (CI) 0.82-0.95; aOR 0.83, 95 % CI 0.76-0.91, respectively). Blacks also underwent surgical resection less often when surgery was recommended (aOR 0.73, 95 % CI 0.64-0.85). Racial disparities in surgery recommendation and its performance did not decrease from 1988 to 2009. In multivariable adjusted analyses, blacks refused surgery more often when it was recommended (aOR in 1988 4.75, 95 % CI 2.51-9.01); this disparity decreased over time (aOR 0.93 per year, 95 % CI 0.89-0.97). CONCLUSIONS: Although racial disparities in pancreatic cancer surgery refusal have diminished over the past two decades, significant disparities in the recommendation and performance of surgery persist. It is likely that both provider- and patient-level factors have a substantial impact on surgery recommendation and its acceptance. The identification of such factors is critical to design a framework for eliminating disparities in cancer-directed surgery for pancreatic cancer.

Authors
Shah, A; Chao, KSC; Ostbye, T; Castleberry, AW; Pietrobon, R; Gloor, B; Clary, BM; White, RR; Worni, M
MLA Citation
Shah, A, Chao, KSC, Ostbye, T, Castleberry, AW, Pietrobon, R, Gloor, B, Clary, BM, White, RR, and Worni, M. "Trends in racial disparities in pancreatic cancer surgery." J Gastrointest Surg 17.11 (November 2013): 1897-1906.
PMID
24002757
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
17
Issue
11
Publish Date
2013
Start Page
1897
End Page
1906
DOI
10.1007/s11605-013-2304-4

Modest improvement in overall survival for patients with metastatic pancreatic cancer: a trend analysis using the surveillance, epidemiology, and end results registry from 1988 to 2008.

OBJECTIVES: Patients with pancreatic adenocarcinoma often present with distant metastatic disease. We aimed to assess whether improvements in survival of clinical trials translated to a population-based level. METHODS: The US Surveillance, Epidemiology, and End Results registry was queried. Adult patients with distant metastatic adenocarcinoma of the pancreas were included from 1988 to 2008. Overall survival was analyzed using Kaplan-Meier curves as well as multivariable-adjusted Cox proportional hazards models. RESULTS: In total, 32,452 patients were included. Mean age was 67.6 (SD: 11.7) years, and 15,341 (47.3%) were female. Median overall survival was 3 months (95% confidence interval [CI], 3-3 months), which increased from 2 (CI, 2-2) months in 1988 to 3 (CI, 3-4) months in 2008. After adjustment for multiple covariates, the hazard ratio (HR) decreased by 0.977 per year (CI, 0.975-0.980). In multivariable-adjusted survival analyses, tumor location in the pancreatic body/tail (HR, 1.10), male sex (HR, 1.09), increasing age (HR, 1.016), African American ethnicity (HR, 1.16), nonmarried civil status (HR, 1.18), and absence of radiotherapy (HR, 1.41) were associated with worse survival (P < 0.001 for all predictors). CONCLUSIONS: The improvement in overall survival over the past 2 decades among patients with metastatic pancreatic adenocarcinoma is modest and disappointing. More effective therapeutic strategies for advanced disease are desperately needed.

Authors
Worni, M; Guller, U; White, RR; Castleberry, AW; Pietrobon, R; Cerny, T; Gloor, B; Koeberle, D
MLA Citation
Worni, M, Guller, U, White, RR, Castleberry, AW, Pietrobon, R, Cerny, T, Gloor, B, and Koeberle, D. "Modest improvement in overall survival for patients with metastatic pancreatic cancer: a trend analysis using the surveillance, epidemiology, and end results registry from 1988 to 2008." Pancreas 42.7 (October 2013): 1157-1163.
PMID
23867367
Source
pubmed
Published In
Pancreas
Volume
42
Issue
7
Publish Date
2013
Start Page
1157
End Page
1163
DOI
10.1097/MPA.0b013e318291fbc5

Examining reoperation and readmission after hepatic surgery.

BACKGROUND: Although the perioperative mortality from hepatic resection has improved considerably, this procedure is still associated with substantial morbidity and resource use. The goal of this investigation was to characterize the incidence, patterns, and risk factors for early reoperation and readmission after hepatectomy. STUDY DESIGN: Perioperative outcomes of 1,281 patients undergoing hepatic resection at an academic center from 1996 to 2009 were analyzed. The indications for early reoperation and readmission (90 days) were reviewed. Multivariate logistic regression analysis was performed to determine variables associated with reoperation and readmission. A scoring system was generated to predict the need for readmission after hepatectomy. RESULTS: Eighty-seven patients (6.8%) required reoperation. The perioperative mortality in patients requiring reoperation was significantly higher than for those not requiring reoperation (23.0% vs 3.4%; p < 0.001). Variables associated with reoperation included male sex, performance of concomitant major nonhepatic procedures, and greater intraoperative blood loss. One hundred and eighty-four patients (14.4%) required readmission. Variables associated with readmission included major hepatectomy, development of major postoperative complications, and index hospitalization >7 days. A Readmission Prediction Score ranging from 0 to 4 was generated and directly correlated with need for readmission. CONCLUSIONS: In the current era of hepatic surgery, early reoperation and readmission remain relatively frequent. As we care for patients who are increasingly receiving regionalized care far from home, we must be mindful of patients at increased risk for readmission. The development of strategies to minimize the complications that necessitate reoperation and readmission is critical to improving patient care.

Authors
Barbas, AS; Turley, RS; Mallipeddi, MK; Lidsky, ME; Reddy, SK; White, RR; Clary, BM
MLA Citation
Barbas, AS, Turley, RS, Mallipeddi, MK, Lidsky, ME, Reddy, SK, White, RR, and Clary, BM. "Examining reoperation and readmission after hepatic surgery." J Am Coll Surg 216.5 (May 2013): 915-923.
PMID
23518253
Source
pubmed
Published In
Journal of the American College of Surgeons
Volume
216
Issue
5
Publish Date
2013
Start Page
915
End Page
923
DOI
10.1016/j.jamcollsurg.2013.01.008

The role of local excision in invasive adenocarcinoma of the ampulla of Vater.

BACKGROUND: Ampulla of Vater carcinomas are rare malignancies that have been traditionally treated with radical surgical resection. Given the mortality associated with pancreaticoduodenectomy, some patients may benefit from local resection. A single-institution outcomes analysis was performed to define the role of local resection. METHODS: Patients undergoing local resection (ampullectomy) for ampullary carcinomas at Duke University between 1976 and 2010 were analyzed retrospectively. Time-to-event analysis was conducted analyzing all patients undergoing surgery, with and without adjuvant chemoradiation therapy (CRT). Overall survival (OS), local control (LC), metastases-free survival (MFS), and disease-free survival (DFS) were studied using Kaplan-Meier analysis. RESULTS: A total of 17 patients with invasive carcinoma underwent ampullectomy. The 3-and 5-year LC, MFS, DFS and OS rates were 36% and 24%, 68% and 54%, 31% and 21%, and 35% and 21%, respectively. Patients receiving adjuvant CRT did not appear to have improved outcomes compared with surgery alone, although this group tended to have poorer histological grade, more advanced tumor staging and involved surgical margins. CONCLUSIONS: Ampullectomy for invasive ampullary adenocarcinomas is a safe procedure but does not offer satisfactory long-term results, mostly due to high local failure rates. Adjuvant CRT therapy does not appear to offer increased local control or survival benefit following ampullectomy, although these results may suffer from selection bias and small sample size. Local resection should be limited to benign ampullary lesions or patients with very small, early tumors with favorable histologic features where radical resection is not feasible.

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; Bulusu, A; Tyler, DS; White, RR; Uronis, HE; Pappas, TN; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, Bulusu, A, Tyler, DS, White, RR, Uronis, HE, Pappas, TN, and Czito, BG. "The role of local excision in invasive adenocarcinoma of the ampulla of Vater." J Gastrointest Oncol 4.1 (March 2013): 8-13.
PMID
23450004
Source
pubmed
Published In
Journal of Gastrointestinal Oncology
Volume
4
Issue
1
Publish Date
2013
Start Page
8
End Page
13
DOI
10.3978/j.issn.2078-6891.2012.055

Primary hepatic malignancies

Authors
Barbas, AS; White, RR
MLA Citation
Barbas, AS, and White, RR. "Primary hepatic malignancies." Contemporary Surgical Management of Liver, Biliary Tract, and Pancreatic Disease. January 1, 2013. 77-90.
Source
scopus
Publish Date
2013
Start Page
77
End Page
90
DOI
10.1142/9789814293068_0006

Surgical techniques: Whipple

Authors
White, RR; Ceppa, EP
MLA Citation
White, RR, and Ceppa, EP. "Surgical techniques: Whipple." Contemporary Surgical Management of Liver, Biliary Tract, and Pancreatic Disease. January 1, 2013. 577-590.
Source
scopus
Publish Date
2013
Start Page
577
End Page
590
DOI
10.1142/9789814293068_0045

Examining reoperation and readmission after hepatic surgery

Background: Although the perioperative mortality from hepatic resection has improved considerably, this procedure is still associated with substantial morbidity and resource use. The goal of this investigation was to characterize the incidence, patterns, and risk factors for early reoperation and readmission after hepatectomy. Study Design: Perioperative outcomes of 1,281 patients undergoing hepatic resection at an academic center from 1996 to 2009 were analyzed. The indications for early reoperation and readmission (90 days) were reviewed. Multivariate logistic regression analysis was performed to determine variables associated with reoperation and readmission. A scoring system was generated to predict the need for readmission after hepatectomy. Results: Eighty-seven patients (6.8%) required reoperation. The perioperative mortality in patients requiring reoperation was significantly higher than for those not requiring reoperation (23.0% vs 3.4%; p < 0.001). Variables associated with reoperation included male sex, performance of concomitant major nonhepatic procedures, and greater intraoperative blood loss. One hundred and eighty-four patients (14.4%) required readmission. Variables associated with readmission included major hepatectomy, development of major postoperative complications, and index hospitalization >7 days. A Readmission Prediction Score ranging from 0 to 4 was generated and directly correlated with need for readmission. Conclusions: In the current era of hepatic surgery, early reoperation and readmission remain relatively frequent. As we care for patients who are increasingly receiving regionalized care far from home, we must be mindful of patients at increased risk for readmission. The development of strategies to minimize the complications that necessitate reoperation and readmission is critical to improving patient care. © 2013 by the American College of Surgeons.

Authors
Barbas, AS; Turley, RS; Mallipeddi, MK; Lidsky, ME; Reddy, SK; White, RR; Clary, BM
MLA Citation
Barbas, AS, Turley, RS, Mallipeddi, MK, Lidsky, ME, Reddy, SK, White, RR, and Clary, BM. "Examining reoperation and readmission after hepatic surgery." Journal of the American College of Surgeons 216.5 (2013): 915-923.
Source
scival
Published In
Journal of The American College of Surgeons
Volume
216
Issue
5
Publish Date
2013
Start Page
915
End Page
923
DOI
10.1016/j.jamcollsurg.2013.01.008

Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease: A Propensity Score-Adjusted, Population-Based Trend Analysis Involving 10 206 Patients.

OBJECTIVE To assess trends in the frequency of concomitant vascular reconstructions (VRs) from 2000 through 2009 among patients who underwent pancreatectomy, as well as to compare the short-term outcomes between patients who underwent pancreatic resection with and without VR. DESIGN Single-center series have been conducted to evaluate the short-term and long-term outcomes of VR during pancreatic resection. However, its effectiveness from a population-based perspective is still unknown. Unadjusted, multivariable, and propensity score-adjusted generalized linear models were performed. SETTING Nationwide Inpatient Sample from 2000 through 2009. PATIENTS A total of 10 206 patients were involved. MAIN OUTCOME MEASURES Incidence of VR during pancreatic resection, perioperative in-hospital complications, and length of hospital stay. RESULTS Overall, 10 206 patients were included in this analysis. Of these, 412 patients (4.0%) underwent VR, with the rate increasing from 0.7% in 2000 to 6.0% in 2009 (P < .001). Patients who underwent pancreatic resection with VR were at a higher risk for intraoperative (propensity score-adjusted odds ratio, 1.94; P = .001) and postoperative (propensity score-adjusted odds ratio, 1.36; P = .008) complications, while the mortality and median length of hospital stay were similar to those of patients without VR. Among the 25% of hospitals with the highest surgical volume, patients who underwent pancreatic surgery with VR had significantly higher rates of postoperative complications and mortality than patients without VR. CONCLUSIONS The frequency of VR during pancreatic surgery is increasing in the United States. In contrast with most single-center analyses, this population-based study demonstrated that patients who underwent VR during pancreatic surgery had higher rates of adverse postoperative outcomes than their counterparts who underwent pancreatic resection only. Prospective studies incorporating long-term outcomes are warranted to further define which patients benefit from VR.

Authors
Worni, M; Castleberry, AW; Clary, BM; Gloor, B; Carvalho, E; Jacobs, DO; Pietrobon, R; Scarborough, JE; White, RR
MLA Citation
Worni, M, Castleberry, AW, Clary, BM, Gloor, B, Carvalho, E, Jacobs, DO, Pietrobon, R, Scarborough, JE, and White, RR. "Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease: A Propensity Score-Adjusted, Population-Based Trend Analysis Involving 10 206 Patients." Arch Surg (December 17, 2012): 1-8.
PMID
23247767
Source
pubmed
Published In
Archives of Surgery
Publish Date
2012
Start Page
1
End Page
8
DOI
10.1001/jamasurg.2013.1058

The impact of vascular resection on early postoperative outcomes after pancreaticoduodenectomy: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: Several single-center reports suggest that vascular resection (VR) during pancreaticoduodenectomy (PD) for patients with pancreatic adenocarcinoma is feasible without affecting early postoperative mortality or morbidity. Our objective is to review the outcomes associated with VR during PD using a large multicenter data source. METHODS: A retrospective cohort analysis was performed using the National Surgical Quality Improvement Program Participant User Files for 2005-2009. All patients undergoing PD for a postoperative diagnosis of malignant neoplasm of the pancreas were included. Forward stepwise multivariate regression analysis was used to determine the association between VR during PD and 30-day postoperative mortality and morbidity after adjustment for patient demographics and comorbidities. RESULTS: 3,582 patients were included for analysis, 281 (7.8 %) of whom underwent VR during PD. VR during PD was associated with significantly greater risk-adjusted 30-day postoperative mortality [5.7 % with VR versus 2.9 % without VR, adjusted odds ratio (AOR) 2.1, 95 % confidence interval (CI) 1.22-3.73, P = 0.008] and overall morbidity (39.9 % with VR versus 33.3 % without VR, AOR 1.36, 95 % CI 1.05-1.75, P = 0.02). There was no significant difference in risk-adjusted postoperative mortality or morbidity between those patients undergoing VR by the primary surgical team versus those patients undergoing VR by a vascular surgical team. CONCLUSIONS: Contrary to the findings of several previously published single-center analyses, the current study demonstrates increased 30-day postoperative morbidity and mortality in PD with VR when compared with PD alone.

Authors
Castleberry, AW; White, RR; De La Fuente, SG; Clary, BM; Blazer, DG; McCann, RL; Pappas, TN; Tyler, DS; Scarborough, JE
MLA Citation
Castleberry, AW, White, RR, De La Fuente, SG, Clary, BM, Blazer, DG, McCann, RL, Pappas, TN, Tyler, DS, and Scarborough, JE. "The impact of vascular resection on early postoperative outcomes after pancreaticoduodenectomy: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database." Annals of surgical oncology 19.13 (December 2012): 4068-4077.
PMID
22932857
Source
epmc
Published In
Annals of Surgical Oncology
Volume
19
Issue
13
Publish Date
2012
Start Page
4068
End Page
4077
DOI
10.1245/s10434-012-2585-y

Aptamer-mediated delivery of chemotherapy to pancreatic cancer cells.

Gemcitabine is a nucleoside analog that is currently the best available single-agent chemotherapeutic drug for pancreatic cancer. However, efficacy is limited by our inability to deliver sufficient active metabolite into cancer cells without toxic effects on normal tissues. Targeted delivery of gemcitabine into cancer cells could maximize effectiveness and concurrently minimize toxic side effects by reducing uptake into normal cells. Most pancreatic cancers overexpress epidermal growth factor receptor (EGFR), a trans-membrane receptor tyrosine kinase. We utilized a nuclease resistant RNA aptamer that binds and is internalized by EGFR on pancreatic cancer cells to deliver gemcitabine-containing polymers into EGFR-expressing cells and inhibit cell proliferation in vitro. This approach to cell type-specific therapy can be adapted to other targets and to other types of therapeutic cargo.

Authors
Ray, P; Cheek, MA; Sharaf, ML; Li, N; Ellington, AD; Sullenger, BA; Shaw, BR; White, RR
MLA Citation
Ray, P, Cheek, MA, Sharaf, ML, Li, N, Ellington, AD, Sullenger, BA, Shaw, BR, and White, RR. "Aptamer-mediated delivery of chemotherapy to pancreatic cancer cells." Nucleic Acid Ther 22.5 (October 2012): 295-305.
PMID
23030589
Source
pubmed
Published In
Nucleic Acid Therapeutics
Volume
22
Issue
5
Publish Date
2012
Start Page
295
End Page
305
DOI
10.1089/nat.2012.0353

Targeting eNOS in pancreatic cancer.

Mortality from pancreatic ductal adenocarcinoma cancer (PDAC) is among the highest of any cancer and frontline therapy has changed little in years. Activation of endothelial nitric oxide synthase (eNOS, NOS3, or NOS III) has been implicated recently in the pathogenesis of PDACs. In this study, we used genetically engineered mouse and human xenograft models to evaluate the consequences of targeting eNOS in PDACs. Genetic deficiency in eNOS limited the development of preinvasive pancreatic lesions and trended toward an extended lifespan in mice with advanced pancreatic cancer. These effects were also observed upon oral administration of the clinically evaluated NOS small molecule inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME). Similarly, other transgenic models of oncogenic KRas-driven tumors responded to l-NAME treatment. Finally, these results were recapitulated in xenograft models of human pancreatic cancer, in which l-NAME was found to broadly inhibit tumorigenic growth. Taken together, our findings offer preclinical proof-of-principle to repurpose l-NAME for clinical investigations in treatment of PDACs and possibly other KRas-driven human cancers.

Authors
Lampson, BL; Kendall, SD; Ancrile, BB; Morrison, MM; Shealy, MJ; Barrientos, KS; Crowe, MS; Kashatus, DF; White, RR; Gurley, SB; Cardona, DM; Counter, CM
MLA Citation
Lampson, BL, Kendall, SD, Ancrile, BB, Morrison, MM, Shealy, MJ, Barrientos, KS, Crowe, MS, Kashatus, DF, White, RR, Gurley, SB, Cardona, DM, and Counter, CM. "Targeting eNOS in pancreatic cancer." Cancer Res 72.17 (September 1, 2012): 4472-4482.
PMID
22738914
Source
pubmed
Published In
Cancer Research
Volume
72
Issue
17
Publish Date
2012
Start Page
4472
End Page
4482
DOI
10.1158/0008-5472.CAN-12-0057

Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy.

PURPOSE: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic disease. Little is known regarding the use of radiotherapy in the prevention of local recurrence after resection. To better define the role of radiotherapy, we performed an analysis of resected patients at our institution. METHODS: Between 1994 and 2009, 33 patients with NET of the pancreatic head and neck underwent treatment with curative intent at Duke University Medical Center. Sixteen patients were treated with surgical resection alone while an additional 17 underwent resection with adjuvant or neoadjuvant radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. RESULTS: Thirteen patients (39%) experienced treatment failure. Eleven of the initial failures were distant, one was local only and one was local and distant. Two-year overall survival was 77% for all patients. Two-year local control for all patients was 87%: 85% for the CMT group and 90% for the surgery alone group (p = 0.38). Two-year distant metastasis-free survival was 56% for all patients: 46% and 69% for the CMT and surgery patients, respectively (p = 0.10). CONCLUSIONS: The primary mode of failure is distant which often results in mortality, with local failure occurring much less commonly. The role of radiotherapy in the adjuvant management of NET remains unclear.

Authors
Zagar, TM; White, RR; Willett, CG; Tyler, DS; Papavassiliou, P; Papalezova, KT; Guy, CD; Broadwater, G; Clough, RW; Czito, BG
MLA Citation
Zagar, TM, White, RR, Willett, CG, Tyler, DS, Papavassiliou, P, Papalezova, KT, Guy, CD, Broadwater, G, Clough, RW, and Czito, BG. "Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy." Int J Radiat Oncol Biol Phys 83.4 (July 15, 2012): 1126-1131.
PMID
22270161
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
83
Issue
4
Publish Date
2012
Start Page
1126
End Page
1131
DOI
10.1016/j.ijrobp.2011.09.041

Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?

The objective of this study was to compare survival between all patients with radiographically resectable adenocarcinoma of the proximal pancreas who underwent preoperative chemoradiation therapy (PRE-OP CRT) or surgical exploration first (SURGERY) with "intention to resect." Pancreatic cancer patients who undergo resection after PREOP CRT live longer than patients who undergo resection without PREOP CRT, a difference that may be attributable to patient selection. We retrospectively identified 236 patients with pancreatic head adenocarcinoma seen between 1999 and 2007 with sufficient data to be confirmed medically and radiographically resectable. The outcomes of 144 patients who underwent PREOP CRT were compared to those of 92 patients who proceeded straight to SURGERY. The groups were similar in age and gender. Tumors were slightly larger in the PREOP CRT group (mean 2.5 cm vs. 2.1 cm, P < 0.01), and there were trends toward more venous abutment (54% vs. 39%, P = 0.06) and a higher Charlson comorbidity index (P = 0.1). In the PREOP CRT group, 76 patients (53%) underwent resection, 28 (19%) had metastatic and 17 (12%) locally unresectable disease after PREOP CRT, and 23 (16%) were not explored due to performance status or loss to follow-up. In the SURGERY group, 68 patients (74%) underwent resection. Sixteen patients (17%) had metastatic and eight patients (9%) locally unresectable disease at exploration. In patients who underwent resection, the PREOP CRT group had smaller pathologic tumor size and lower incidence of positive lymph nodes than the SURGERY group but no difference in positive margins or need for vascular resection. Median overall survival (OS) in patients undergoing resection was 27 months in the PREOP CRT group and 17 months in the SURGERY group (P = 0.04). Median OS in all patients treated with PREOP CRT or surgically explored with intention to resect was 15 and 13 months, respectively, with superimposable survival curves. Despite a lower resection rate, the PREOP CRT group as a whole had a similar OS to the SURGERY group as a whole. For patients who underwent resection, those in the PREOP CRT had longer survival than those in the SURGERY group, suggesting that PREOP CRT allows better patient selection for resection. PREOP CRT should be considered an acceptable alternative for most patients with resectable pancreatic cancer.

Authors
Papalezova, KT; Tyler, DS; Blazer, DG; Clary, BM; Czito, BG; Hurwitz, HI; Uronis, HE; Pappas, TN; Willett, CG; White, RR
MLA Citation
Papalezova, KT, Tyler, DS, Blazer, DG, Clary, BM, Czito, BG, Hurwitz, HI, Uronis, HE, Pappas, TN, Willett, CG, and White, RR. "Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?." J Surg Oncol 106.1 (July 1, 2012): 111-118.
PMID
22311829
Source
pubmed
Published In
Journal of Surgical Oncology
Volume
106
Issue
1
Publish Date
2012
Start Page
111
End Page
118
DOI
10.1002/jso.23044

Vascular surgery collaboration during pancreaticoduodenectomy with vascular reconstruction.

BACKGROUND: Once thought to have unresectable disease, pancreatic cancer patients with portal venous involvement are now reported to have comparable survival after pancreaticoduodenectomy (PD) with vascular reconstruction (VR) as compared with patients without vascular involvement. We hypothesize that a multidisciplinary approach involving a vascular surgeon will minimize morbidity and improve patency of VRs. METHODS: We identified 204 patients who underwent PD for pancreatic adenocarcinoma from 1997 to 2008. Patients who underwent PD with VR (N = 42) were compared with those who underwent standard PD (N = 162). VRs were performed by a vascular surgeon and involved primary repair (N = 8), vein patch (N = 25), or interposition grafting (N = 9) with femoral or other venous conduit. RESULTS: Patients undergoing PD with VR had larger tumors (3.0 cm vs. 2.5 cm, P < 0.01) but did not have different rates of tumor-free margins (73% vs. 72%, P = 0.84) or lymph nodes metastases (50% vs. 38%, P = 0.14). The VR group had higher median blood loss (875 mL vs. 550 mL, P = 0<0.01), but no differences in mortality, complication rates, length of stay, or readmission rates were found in a median follow-up of 29 months. Overall survival rates were similar. Predictors of mortality on multivariate analysis included increasing histological grade (P = 0.01), positive lymph nodes (P = 0.01), and increasing tumor size (P = 0.01), but not VR (P = 0.28). When evaluated by computed tomography scans within 6 months postoperatively, 97% of reconstructions remained patent. CONCLUSIONS: The need for VR is not a contraindication to potentially curative resection in patients with pancreatic adenocarcinoma. Assistance of a vascular surgeon during VR may allow moderate-volume centers to achieve outcomes comparable with high-volume centers.

Authors
Turley, RS; Peterson, K; Barbas, AS; Ceppa, EP; Paulson, EK; Blazer, DG; Clary, BM; Pappas, TN; Tyler, DS; McCann, RL; White, RR
MLA Citation
Turley, RS, Peterson, K, Barbas, AS, Ceppa, EP, Paulson, EK, Blazer, DG, Clary, BM, Pappas, TN, Tyler, DS, McCann, RL, and White, RR. "Vascular surgery collaboration during pancreaticoduodenectomy with vascular reconstruction." Ann Vasc Surg 26.5 (July 2012): 685-692.
PMID
22305864
Source
pubmed
Published In
Annals of Vascular Surgery
Volume
26
Issue
5
Publish Date
2012
Start Page
685
End Page
692
DOI
10.1016/j.avsg.2011.11.009

Neoadjuvant chemoradiation for potentially resectable gastric cancer.

Authors
Barfield, ME; Untch, BR; Arcury, JT; Czito, BG; Willett, C; Pappas, TN; White, RR; Tyler, DS; Blazer, DG
MLA Citation
Barfield, ME, Untch, BR, Arcury, JT, Czito, BG, Willett, C, Pappas, TN, White, RR, Tyler, DS, and Blazer, DG. "Neoadjuvant chemoradiation for potentially resectable gastric cancer." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

Survival trends of patients with metastatic pancreatic cancer: A Surveillance Epidemiology and End Results registry trend analysis from 1988 to 2008

Authors
Worni, M; Guller, U; White, RR; Pietrobon, R; Cerny, T; Gloor, B; Koeberle, D
MLA Citation
Worni, M, Guller, U, White, RR, Pietrobon, R, Cerny, T, Gloor, B, and Koeberle, D. "Survival trends of patients with metastatic pancreatic cancer: A Surveillance Epidemiology and End Results registry trend analysis from 1988 to 2008." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

Authors
Ray, P; Rialon-Guevara, KL; Veras, E; Sullenger, BA; White, RR
MLA Citation
Ray, P, Rialon-Guevara, KL, Veras, E, Sullenger, BA, and White, RR. "Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker." The Journal of clinical investigation 122.5 (May 2012): 1734-1741.
PMID
22484812
Source
epmc
Published In
Journal of Clinical Investigation
Volume
122
Issue
5
Publish Date
2012
Start Page
1734
End Page
1741
DOI
10.1172/jci62385

Comparison of outcomes and the use of multimodality therapy in young and elderly people undergoing surgical resection of pancreatic cancer.

OBJECTIVES: To compare outcomes and the use of multimodality therapy in young and elderly people with pancreatic cancer undergoing surgical resection. DESIGN: Retrospective, single-institution study. SETTING: National Cancer Institute/National Comprehensive Cancer Network cancer center. PARTICIPANTS: Two hundred three individuals who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma at Duke University Medical Center comprised the study population. Participants were divided into three groups based on age (<65, n = 97; 65-74, n = 74; ≥75, N = 32). MEASUREMENTS: Perioperative outcomes, the use of multimodality therapy, and overall survival of the different age groups were compared. RESULTS: Similar rates of perioperative mortality and morbidity were observed in all age groups, but elderly adults were more likely to be discharged to a rehabilitation or skilled nursing facility. A similar proportion of participants received neoadjuvant therapy, but a smaller proportion of elderly participants received adjuvant therapy. Overall survival was similar between the age groups. Predictors of poorer overall survival included coronary artery disease, positive resection margin, and less-differentiated tumor histology. Treatment with neoadjuvant and adjuvant therapy were predictors of better overall survival. CONCLUSION: Carefully selected elderly individuals experience similar perioperative outcomes and overall survival to those of younger individuals after resection of pancreatic cancer. There appears to be a significant disparity in the use of adjuvant therapy between young and elderly individuals.

Authors
Barbas, AS; Turley, RS; Ceppa, EP; Reddy, SK; Blazer, DG; Clary, BM; Pappas, TN; Tyler, DS; White, RR; Lagoo, SA
MLA Citation
Barbas, AS, Turley, RS, Ceppa, EP, Reddy, SK, Blazer, DG, Clary, BM, Pappas, TN, Tyler, DS, White, RR, and Lagoo, SA. "Comparison of outcomes and the use of multimodality therapy in young and elderly people undergoing surgical resection of pancreatic cancer." J Am Geriatr Soc 60.2 (February 2012): 344-350.
PMID
22211710
Source
pubmed
Published In
Journal of American Geriatrics Society
Volume
60
Issue
2
Publish Date
2012
Start Page
344
End Page
350
DOI
10.1111/j.1532-5415.2011.03785.x

The Impact of Vascular Reconstruction on Early Postoperative Outcomes after Pancreaticoduodenectomy: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program Database

Authors
Castleberry, AW; White, RR; De la Fuente, SG; Tyler, DS; Pappas, TN; Scarborough, JE
MLA Citation
Castleberry, AW, White, RR, De la Fuente, SG, Tyler, DS, Pappas, TN, and Scarborough, JE. "The Impact of Vascular Reconstruction on Early Postoperative Outcomes after Pancreaticoduodenectomy: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program Database." February 2012.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
19
Publish Date
2012
Start Page
S10
End Page
S10

A decision model of therapy for potentially resectable pancreatic cancer

Background: Optimal treatment for potentially resectable pancreatic cancer is controversial. Resection is considered the only curative treatment, but neoadjuvant chemoradiotherapy may offer significant advantages. Materials and Methods: We developed a decision model for potentially resectable pancreatic cancer. Initial therapeutic choices were surgery, neoadjuvant chemoradiotherapy, or no treatment; subsequent decisions offered a second intervention if not prohibited by complications or death. Payoffs were calculated as the median expected survival. We gathered evidence for this model through a comprehensive MEDLINE search. One-way sensitivity analyses were performed. Results: Neoadjuvant chemoradiation is favored over initial surgery, with expected values of 18.6 and 17.7 mo, respectively. The decision is sensitive to the probabilities of treatment mortality and tumor resectability. Threshold probabilities are 7.0% mortality of neoadjuvant chemoradiotherapy, 69.2% resectability on imaging after neoadjuvant therapy, and 73.7% resectability at exploration after neoadjuvant therapy, 92.2% resectability at initial resection, and 9.9% surgical mortality following chemoradiotherapy. The decision is sensitive to the utility of time spent in chemoradiotherapy, with surgery favored for utilities less than 0.3 and -0.8, for uncomplicated and complicated chemoradiotherapy, respectively. Conclusions: The ideal treatment for potentially resectable pancreatic cancer remains controversial, but recent evidence supports a slight benefit for neoadjuvant therapy. Our model shows that the decision is sensitive to the probability of tumor resectability and chemoradiation mortality, but not to rates of other treatment complications. With minimal benefit of one treatment over another based on survival alone, patient preferences will likely play an important role in determining best treatment.

Authors
VanHouten, JP; White, RR; Jackson, GP
MLA Citation
VanHouten, JP, White, RR, and Jackson, GP. "A decision model of therapy for potentially resectable pancreatic cancer." Journal of Surgical Research 174.2 (2012): 222-230.
PMID
22079845
Source
scival
Published In
Journal of Surgical Research
Volume
174
Issue
2
Publish Date
2012
Start Page
222
End Page
230
DOI
10.1016/j.jss.2011.08.022

Neuroendocrine tumors: Clinical practice guidelines in oncology

Neuroendocrine tumors comprise a broad family of tumors, the most common of which are carcinoid and pancreatic neuroendocrine tumors. The NCCN Neuroendocrine Tumors Guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine tumors. Most of the recommendations pertain to well-differentiated, low- to intermediate-grade tumors. This updated version of the NCCN Guidelines includes a new section on pathology for diagnosis and reporting and revised recommendations for the surgical management of neuroendocrine tumors of the pancreas. © JNCCN - Journal of the National Comprehensive Cancer Network.

Authors
Kulke, MH; III, ABB; Bergsland, E; Berlin, JD; Blaszkowsky, LS; Choti, MA; Clark, OH; Doherty, GM; Eason, J; Emerson, L; Engstrom, PF; Goldner, WS; Heslin, MJ; Kandeel, F; Kunz, PL; II, BWK; Moley, JF; Pillarisetty, VG; Saltz, L; Schteingart, DE; Shah, MH; Shibata, S; Strosberg, JR; Vauthey, J-N; White, R; Yao, JC
MLA Citation
Kulke, MH, III, ABB, Bergsland, E, Berlin, JD, Blaszkowsky, LS, Choti, MA, Clark, OH, Doherty, GM, Eason, J, Emerson, L, Engstrom, PF, Goldner, WS, Heslin, MJ, Kandeel, F, Kunz, PL, II, BWK, Moley, JF, Pillarisetty, VG, Saltz, L, Schteingart, DE, Shah, MH, Shibata, S, Strosberg, JR, Vauthey, J-N, White, R, and Yao, JC. "Neuroendocrine tumors: Clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 10.6 (2012): 724-764.
PMID
22679117
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
6
Publish Date
2012
Start Page
724
End Page
764

Carcinoma of the Ampulla of Vater: Patterns of Failure Following Resection and Benefit of Chemoradiotherapy.

BACKGROUND: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. METHODS: A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. RESULTS: A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. CONCLUSIONS: Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.

Authors
Palta, M; Patel, P; Broadwater, G; Willett, C; Pepek, J; Tyler, D; Zafar, SY; Uronis, H; Hurwitz, H; White, R; Czito, B
MLA Citation
Palta, M, Patel, P, Broadwater, G, Willett, C, Pepek, J, Tyler, D, Zafar, SY, Uronis, H, Hurwitz, H, White, R, and Czito, B. "Carcinoma of the Ampulla of Vater: Patterns of Failure Following Resection and Benefit of Chemoradiotherapy." Annals of surgical oncology (November 2011). (Academic Article)
PMID
22045467
Source
manual
Published In
Annals of Surgical Oncology
Publish Date
2011
DOI
10.1245/s10434-011-2117-1

AN RNA APTAMER IS A POTENTIAL BIOMARKER FOR PANCREATIC CANCER

Authors
Ray, P; Sullenger, BA; White, RR
MLA Citation
Ray, P, Sullenger, BA, and White, RR. "AN RNA APTAMER IS A POTENTIAL BIOMARKER FOR PANCREATIC CANCER." October 2011.
Source
wos-lite
Published In
Nucleic Acid Therapeutics
Volume
21
Issue
5
Publish Date
2011
Start Page
A40
End Page
A41

Aptamers: potential applications to pancreatic cancer therapy.

There is an unquestionable need for more effective therapies for pancreatic cancer. Aptamers are single-stranded DNA or RNA oligonucleotide ligands whose 3-dimensional structures are dictated by their sequences. Aptamers have been generated against numerous purified protein targets using an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Several biochemical properties make them attractive tools for use in an array of biological research applications and as potential pharmacologic agents. Isolated aptamers may directly affect target protein function, or they may also be modified for use as delivery agents for other therapeutic cargo or as imaging agents. More complex selections, using whole cancer cells or tumor tissue, may simultaneously identify novel or unexpected targets and aptamers to inhibit them. This review summarizes recent advances in the field of aptamers and discusses aptamer targets that have relevance to pancreatic cancer.

Authors
Rialon, KL; White, RR
MLA Citation
Rialon, KL, and White, RR. "Aptamers: potential applications to pancreatic cancer therapy." Anticancer Agents Med Chem 11.5 (June 2011): 434-441. (Review)
PMID
21492073
Source
pubmed
Published In
Anti-Cancer Agents in Medicinal Chemistry
Volume
11
Issue
5
Publish Date
2011
Start Page
434
End Page
441

Pancreatic neuroendocrine tumors: selection, selection, selection….

Authors
White, RR
MLA Citation
White, RR. "Pancreatic neuroendocrine tumors: selection, selection, selection…." J Surg Res 167.2 (May 15, 2011): 211-213.
PMID
20855087
Source
pubmed
Published In
Journal of Surgical Research
Volume
167
Issue
2
Publish Date
2011
Start Page
211
End Page
213
DOI
10.1016/j.jss.2010.07.024

Resected pancreatic neuroendocrine tumors: Patterns of failure and disease-related outcomes with or without radiotherapy

Authors
Zagar, TM; White, RR; Willett, CG; Papavassiliou, P; Tyler, DS; Papalezova, K; Guy, C; Clough, R; Czito, BG
MLA Citation
Zagar, TM, White, RR, Willett, CG, Papavassiliou, P, Tyler, DS, Papalezova, K, Guy, C, Clough, R, and Czito, BG. "Resected pancreatic neuroendocrine tumors: Patterns of failure and disease-related outcomes with or without radiotherapy." February 1, 2011.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
4
Publish Date
2011

Aptamer applications for targeted cancer therapy.

Aptamers are single-stranded DNA or RNA oligonucleotides that assume specific 3D structures and bind to target molecules with high affinity. The unique specificity of aptamers has made them attractive agents for targeted cancer therapy. Aptamers have been developed against a variety of cancer targets, including extracellular ligands and cell surface proteins. In addition, aptamers have been incorporated into novel constructs involving siRNAs, chemotherapeutic agents, cell toxins and nanoparticles, in which they function as delivery agents for therapeutic cargo. In this article, we review recent developments in the use of aptamers for targeted cancer therapy, particularly focusing on novel applications of aptamers targeting the cell surface.

Authors
Barbas, AS; Mi, J; Clary, BM; White, RR
MLA Citation
Barbas, AS, Mi, J, Clary, BM, and White, RR. "Aptamer applications for targeted cancer therapy." Future Oncol 6.7 (July 2010): 1117-1126. (Review)
PMID
20624124
Source
pubmed
Published In
Future oncology (London, England)
Volume
6
Issue
7
Publish Date
2010
Start Page
1117
End Page
1126
DOI
10.2217/fon.10.67

Percutaneous abscess drainage in patients with perforated acute appendicitis: effectiveness, safety, and prediction of outcome.

OBJECTIVE: The purposes of this study were to retrospectively investigate the effectiveness and safety of CT-guided percutaneous drainage in the treatment of patients with acute appendicitis complicated by perforation and to identify CT findings and procedure-related factors predictive of clinical and procedure outcome. MATERIALS AND METHODS: From March 2005 through December 2008, 41 consecutively registered patients (24 men, 17 women; age range, 18-75 years) underwent CT-guided percutaneous drainage for the management of acute appendicitis complicated by perforation and abscess. Three board-certified radiologists independently reviewed preprocedure CT images. Patients were assigned to one of three risk categories on the basis of the CT findings. Success and failure of percutaneous drainage were defined on a per-patient (i.e., clinical outcome) and per-procedure (i.e., technical outcome) basis. Immediate, periprocedure, and delayed complications were recorded. The association between candidate predictive variables, including demographic characteristics, preprocedure CT findings, and procedure-related factors and clinical or technical outcome was assessed with logistic regression models. RESULTS: Fifty-two CT-guided procedures were performed on 41 patients. Percutaneous drainage had clinical and technical success rates of 90% (37 of 41 patients, 47 of 52 procedures) with no procedure-related complications. In seven patients (19%) clinical success required repeated drainage procedures. A large, poorly defined periappendiceal abscess and an extraluminal appendicolith on preprocedure CT images were independent predictors of clinical failure of percutaneous drainage. CONCLUSION: CT-guided percutaneous drainage is both effective and safe in the treatment of patients with acute appendicitis complicated by perforation and abscess. The clinical and technical success rates are high.

Authors
Marin, D; Ho, LM; Barnhart, H; Neville, AM; White, RR; Paulson, EK
MLA Citation
Marin, D, Ho, LM, Barnhart, H, Neville, AM, White, RR, and Paulson, EK. "Percutaneous abscess drainage in patients with perforated acute appendicitis: effectiveness, safety, and prediction of outcome." AJR Am J Roentgenol 194.2 (February 2010): 422-429.
PMID
20093605
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
194
Issue
2
Publish Date
2010
Start Page
422
End Page
429
DOI
10.2214/AJR.09.3098

Defining criteria for selective operative management of pancreatic cystic lesions: does size really matter?

INTRODUCTION: Proposed criteria for resection of pancreatic cystic lesions have included symptoms, size (>3 cm), and suspicious features by endoscopic ultrasound (EUS). The objective of this study was to evaluate risk factors for malignancy in a large series of patients undergoing resection of suspected pancreatic cystic neoplasms. METHODS: Medical records of patients selected for resection of pancreatic cystic lesions at Duke University Medical Center from 2000 to 2008 were reviewed. Lesions with solid components on cross-sectional imaging were excluded. Malignancy was defined as invasive or in situ carcinoma. RESULTS: After review, 101 patients were confirmed to have undergone resection for suspected cystic neoplasms of the pancreas. Preoperative EUS was performed in 71 patients. Sixteen patients (16%) had malignant lesions (preoperative size 1.5-5.9 cm). There was no clear association between size and malignancy. Male gender, biliary ductal dilatation (BDD), pancreatic ductal dilatation (PDD), and suspicious cytology (but not age, symptoms, or size) were associated with increased risk of malignancy. When factors available for all patients were incorporated into a multivariate model, only BDD and PDD were independent risk factors for malignancy. Only one patient with malignancy had neither BDD nor PDD but did have solid components by EUS. CONCLUSIONS: In patients selected for resection, size was not an independent risk factor for malignancy. While size might be appropriate for stratification of asymptomatic patients with simple cysts, size should not be used as a selection criterion for patients who have cysts with solid components or with associated BDD or PDD.

Authors
Ceppa, EP; De la Fuente, SG; Reddy, SK; Stinnett, SS; Clary, BM; Tyler, DS; Pappas, TN; White, RR
MLA Citation
Ceppa, EP, De la Fuente, SG, Reddy, SK, Stinnett, SS, Clary, BM, Tyler, DS, Pappas, TN, and White, RR. "Defining criteria for selective operative management of pancreatic cystic lesions: does size really matter?." J Gastrointest Surg 14.2 (February 2010): 236-244.
PMID
19911240
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
14
Issue
2
Publish Date
2010
Start Page
236
End Page
244
DOI
10.1007/s11605-009-1078-1

Does neoadjuvant therapy improve survival in patients with resectable pancreatic cancer?

Authors
Papalezova, KT; Kim, VM; Stinnett, SS; III, BDG; Clary, BM; Pappas, TN; Tyler, DS; White, RR
MLA Citation
Papalezova, KT, Kim, VM, Stinnett, SS, III, BDG, Clary, BM, Pappas, TN, Tyler, DS, and White, RR. "Does neoadjuvant therapy improve survival in patients with resectable pancreatic cancer?." February 2010.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
17
Publish Date
2010
Start Page
S70
End Page
S71

Notch promotes radioresistance of glioma stem cells.

Radiotherapy represents the most effective nonsurgical treatments for gliomas. However, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we show that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) renders the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhance radiation-induced cell death and impair clonogenic survival of glioma stem cells but not non-stem glioma cells. Expression of the constitutively active intracellular domains of Notch1 or Notch2 protect glioma stem cells against radiation. Notch inhibition with GSIs does not alter the DNA damage response of glioma stem cells after radiation but rather reduces Akt activity and Mcl-1 levels. Finally, knockdown of Notch1 or Notch2 sensitizes glioma stem cells to radiation and impairs xenograft tumor formation. Taken together, our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment.

Authors
Wang, J; Wakeman, TP; Lathia, JD; Hjelmeland, AB; Wang, X-F; White, RR; Rich, JN; Sullenger, BA
MLA Citation
Wang, J, Wakeman, TP, Lathia, JD, Hjelmeland, AB, Wang, X-F, White, RR, Rich, JN, and Sullenger, BA. "Notch promotes radioresistance of glioma stem cells." Stem Cells 28.1 (January 2010): 17-28.
PMID
19921751
Source
pubmed
Published In
Stem Cells
Volume
28
Issue
1
Publish Date
2010
Start Page
17
End Page
28
DOI
10.1002/stem.261

Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy

BACKGROUND: During chemotherapy, some colorectal liver metastases (LMs) disappear on serial imaging. This disappearance may represent a complete response (CR) or a reduction in the sensitivity of imaging during chemotherapy. The objective of the current study was to determine the fate of disappearing LMs (DLMs) and the factors that predict a true CR. METHODS: Between 2000 and 2003, 435 patients who were evaluated by hepatobiliary surgeons received chemotherapy before they were considered for resection. Inclusion criteria were <12 LMs before chemotherapy, at least 1 DLM on a computed tomography (CT) scan, and either surgical resection or 1 year of clinical follow-up after the disappearance of LMs. A true CR was defined as either a pathologic CR (no tumor detected in the resection specimen) or a durable clinical CR (did not reappear on follow-up imaging). Clinical and pathologic factors were analyzed to identify those associated with a true CR. RESULTS: During chemotherapy, 39 patients (9%) had a total of 118 DLMs on follow-up CT scans. Sixty-eight DLMs were resected, and 50 were followed clinically. Overall, 75 DLMs (64%) were true CRs, including 44 pathologic CRs and 31 durable clinical CRs. On multivariate analysis, the use of hepatic arterial infusion (HAI) chemotherapy (odds ratio [OR], 6.2; P = .02), the inability to observe the DLM on a magnetic resonance image (OR, 4.7; P = .005), and normalization of serum carcinoembryonic antigen levels (OR, 4.6; P = .006) were associated independently with a true CR. CONCLUSIONS: Approximately 66% of DLMs represented a true CR according to assessment by resection or radiologic follow-up. Predictive factors may help to stratify patients who are likely to harbor residual disease. © 2010 American Cancer Society.

Authors
Auer, RC; White, RR; Kemeny, NE; Schwartz, LH; Shia, J; Blumgart, LH; Dematteo, RP; Fong, Y; Jarnagin, WR; D'Angelica, MI
MLA Citation
Auer, RC, White, RR, Kemeny, NE, Schwartz, LH, Shia, J, Blumgart, LH, Dematteo, RP, Fong, Y, Jarnagin, WR, and D'Angelica, MI. "Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy." Cancer 116.6 (2010): 1502-1509.
PMID
20120032
Source
scival
Published In
Cancer
Volume
116
Issue
6
Publish Date
2010
Start Page
1502
End Page
1509
DOI
10.1002/cncr.24912

Aptamers for targeted drug delivery

Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer- mediated delivery. © 2010 by the authors.

Authors
Ray, P; White, RR
MLA Citation
Ray, P, and White, RR. "Aptamers for targeted drug delivery." Pharmaceuticals 3.6 (2010): 1761-1778.
PMID
27713328
Source
scival
Published In
Pharmaceuticals
Volume
3
Issue
6
Publish Date
2010
Start Page
1761
End Page
1778
DOI
10.3390/ph3061761

Resected Pancreatic Neuroendocrine Tumors: Patterns of Failure and Disease-related Outcomes with or without Radiotherapy

Authors
Zagar, TM; White, RR; Willett, CG; Papavassiliou, P; Tyler, DS; Papalezova, KT; Guy, CD; Clough, R; Czito, BG
MLA Citation
Zagar, TM, White, RR, Willett, CG, Papavassiliou, P, Tyler, DS, Papalezova, KT, Guy, CD, Clough, R, and Czito, BG. "Resected Pancreatic Neuroendocrine Tumors: Patterns of Failure and Disease-related Outcomes with or without Radiotherapy." 2010.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S309
End Page
S310

Pancreaticoduodenectomy: frequency and outcome of post-operative imaging-guided percutaneous drainage.

BACKGROUND: To study the frequency and outcomes of percutaneous imaging-guided drainage following pancreaticoduodenectomy and to assess if fluid collection location correlates with pancreatic duct leak. METHODS: IRB approval was obtained. Three hundred and seventy-three subjects (age 21-84 years) who underwent pancreaticoduodenectomy were included in this retrospective study. Eighty-three of these subjects underwent post-operative imaging-guided drainage (CT 77; US 6). Medical and imaging records were reviewed. Procedural details including collection location, size, catheter size, drain duration, fluid type, fluid chemistry, and fluid culture were recorded. Collection location was correlated with fluid amylase. RESULTS: The frequency of imaging-guided percutaneous drainage following Whipple was 22.2%. The immediate technical and overall success rates for fluid collection drainage were 97.6% and 79.6%, respectively. Rate of complication was 4.8% (4/83). 74.7% (62/83) of fluid collections were proven abscesses, and 61.4% (51/83) were complicated by pancreatic fistula. Collections near the pancreatic resection site were more likely to have elevated fluid amylase. CONCLUSION: Approximately one-fifth of subjects requires percutaneous drainage following pancreaticoduodenectomy. Percutaneous imaging-guided drainage is an effective means of managing post-pancreaticoduodenectomy fluid collections. Collections near the pancreas resection site often have a pancreatic duct leak.

Authors
Zink, SI; Soloff, EV; White, RR; Clary, BM; Tyler, DS; Pappas, TN; Paulson, EK
MLA Citation
Zink, SI, Soloff, EV, White, RR, Clary, BM, Tyler, DS, Pappas, TN, and Paulson, EK. "Pancreaticoduodenectomy: frequency and outcome of post-operative imaging-guided percutaneous drainage." Abdom Imaging 34.6 (November 2009): 767-771.
PMID
18758847
Source
pubmed
Published In
Abdominal Imaging
Volume
34
Issue
6
Publish Date
2009
Start Page
767
End Page
771
DOI
10.1007/s00261-008-9455-x

Evaluation of peri-operative chemotherapy using a prognostic nomogram for survival after resection of colorectal liver metastases.

INTRODUCTION: Nomograms are statistical tools designed to predict outcomes. This study evaluates the effects of peri-operative chemotherapy on the accuracy of a prognostic nomogram for disease-specific survival (DSS) after resection of colorectal liver metastases (CRLM) established at Memorial-Sloan Kettering Cancer Center (MSKCC). METHODS: An external cohort of 203 patients who underwent resection of CRLM between 1996 and 2006 was used to assess the nomogram. RESULTS: After median follow-up of 30.4 months (range 0.33-150), Kaplan-Meier (KM) estimates for 3-, 5- and 8-year post-resection DSS were 56%, 41%, and 32%, respectively; similar to nomogram-predicted probabilities for DSS. The concordance index for the nomogram was higher (0.602) than for the Fong colorectal risk score (CRS; 0.533). KM DSS was longer for patients (n= 50) treated with at least 6 months of peri-operative irinotecan or oxaliplatin compared with all other patients (median 66 vs. 40 months, P= 0.06). KM DSS was greater than nomogram predicted DSS for treated patients and less than nomogram predicted DSS for all other patients. CONCLUSIONS: The CRLM nomogram was validated by an external cohort and more accurately predicted post-resection survival than the commonly used CRS. Differences in observed and nomogram-predicted survival may reflect the effect of treatment factors, such as peri-operative chemotherapy.

Authors
Reddy, SK; Kattan, MW; Yu, C; Ceppa, EP; de la Fuente, SG; Fong, Y; Clary, BM; White, RR
MLA Citation
Reddy, SK, Kattan, MW, Yu, C, Ceppa, EP, de la Fuente, SG, Fong, Y, Clary, BM, and White, RR. "Evaluation of peri-operative chemotherapy using a prognostic nomogram for survival after resection of colorectal liver metastases." HPB (Oxford) 11.7 (November 2009): 592-599.
PMID
20495712
Source
pubmed
Published In
HPB
Volume
11
Issue
7
Publish Date
2009
Start Page
592
End Page
599
DOI
10.1111/j.1477-2574.2009.00106.x

Timing of multimodality therapy for resectable synchronous colorectal liver metastases: a retrospective multi-institutional analysis.

The optimal timing of chemotherapy relative to resection of synchronous colorectal liver metastases (SCRLM) is not known. The objective of this retrospective multi-institutional study was to assess the influence of chemotherapy administered before and after hepatic resection on long-term outcomes among patients with initially resectable SCRLM treated from 1995 to 2005. Clinicopathologic data, treatments, and long-term outcomes from patients with initially resectable SCRLM who underwent partial hepatectomy at three hepatobiliary centers were reviewed. Four hundred ninety-nine consecutive patients underwent resection; 297 (59.5%) and 264 (52.9%) were treated with chemotherapy before and after resection. Chemotherapy strategies included pre-hepatectomy alone (n = 148, 24.7%), post-hepatectomy alone (n = 115, 23.0%), perioperative (n = 149, 29.0%), and no chemotherapy (n = 87, 17.4%). Male gender (p = 0.0029, HR = 1.41 [1.12-1.77]), node-positive primary tumor (p = 0.0046, HR = 1.40 [1.11-1.77]), four or more SCRLM (p = 0.0005, HR = 1.65 [1.24-2.18]), and post-hepatectomy chemotherapy treatment for 6 months or longer (p = 0.039, HR = 0.75 [0.57-0.99]) were associated with recurrence-free survival after discovery of SCRLM. Carcinoembryonic antigen >200 ng/ml (p = 0.0003, HR = 2.33 [1.48-3.69]), extrahepatic metastatic disease (p = 0.0025, HR = 2.34 [1.35-4.05]), four or more SCRLM (p = 0.033, HR = 1.43 [1.03-2.00]), and post-hepatectomy chemotherapy treatment for 2 months or longer (p < 0.0001, HR = 0.59 [0.45-0.76]) were associated with overall survival. Pre-hepatectomy chemotherapy was not associated with recurrence-free or overall survival. Patients treated with perioperative chemotherapy had similar outcomes as patients treated with post-hepatectomy chemotherapy only. We conclude that chemotherapy administered after but not before resection of SCRLM was associated with improved recurrence-free and overall survival. However, prospective randomized trials are needed to determine the optimal timing of chemotherapy.

Authors
Reddy, SK; Zorzi, D; Lum, YW; Barbas, AS; Pawlik, TM; Ribero, D; Abdalla, EK; Choti, MA; Kemp, C; Vauthey, J-N; Morse, MA; White, RR; Clary, BM
MLA Citation
Reddy, SK, Zorzi, D, Lum, YW, Barbas, AS, Pawlik, TM, Ribero, D, Abdalla, EK, Choti, MA, Kemp, C, Vauthey, J-N, Morse, MA, White, RR, and Clary, BM. "Timing of multimodality therapy for resectable synchronous colorectal liver metastases: a retrospective multi-institutional analysis." Ann Surg Oncol 16.7 (July 2009): 1809-1819.
PMID
18979139
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
16
Issue
7
Publish Date
2009
Start Page
1809
End Page
1819
DOI
10.1245/s10434-008-0181-y

The development and testing of aptamers for cancer.

Aptamers are single-stranded DNA or RNA oligonucleotides that have specific three-dimensional structures and bind to target molecules. Several unique properties of aptamers, including high binding specificity, low immunogenicity, structural stability and ease of synthesis, have made aptamers promising agents for directed therapy against cancer targets. Aptamers with anti-neoplastic activity against extracellular, cell membrane and intracellular targets have been developed. Aptamers also have been incorporated into novel constructs as tools for delivering therapeutic agents. This review discusses the most recent advances in the application of aptamer technology for cancer therapy.

Authors
Barbas, AS; White, RR
MLA Citation
Barbas, AS, and White, RR. "The development and testing of aptamers for cancer." Curr Opin Investig Drugs 10.6 (June 2009): 572-578. (Review)
PMID
19513946
Source
pubmed
Published In
Current Opinion in Investigational Drugs
Volume
10
Issue
6
Publish Date
2009
Start Page
572
End Page
578

Crystal structure of an RNA aptamer bound to thrombin.

Aptamers, an emerging class of therapeutics, are DNA or RNA molecules that are selected to bind molecular targets that range from small organic compounds to large proteins. All of the determined structures of aptamers in complex with small molecule targets show that aptamers cage such ligands. In structures of aptamers in complex with proteins that naturally bind nucleic acid, the aptamers occupy the nucleic acid binding site and often mimic the natural interactions. Here we present a crystal structure of an RNA aptamer bound to human thrombin, a protein that does not naturally bind nucleic acid, at 1.9 A resolution. The aptamer, which adheres to thrombin at the binding site for heparin, presents an extended molecular surface that is complementary to the protein. Protein recognition involves the stacking of single-stranded adenine bases at the core of the tertiary fold with arginine side chains. These results exemplify how RNA aptamers can fold into intricate conformations that allow them to interact closely with extended surfaces on non-RNA binding proteins.

Authors
Long, SB; Long, MB; White, RR; Sullenger, BA
MLA Citation
Long, SB, Long, MB, White, RR, and Sullenger, BA. "Crystal structure of an RNA aptamer bound to thrombin." RNA 14.12 (December 2008): 2504-2512.
PMID
18971322
Source
pubmed
Published In
RNA (New York, N.Y.)
Volume
14
Issue
12
Publish Date
2008
Start Page
2504
End Page
2512
DOI
10.1261/rna.1239308

Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer.

BACKGROUND: Cellular events mediated by the Tie2 receptor are important to tumor neovascularization. Despite the complex interplay of the best-characterized Tie2 ligands, angiopoietins 1 and 2, Ang2 is purportedly "proangiogenic" in the presence of vascular endothelial growth factor. We examined whether in vivo administration of an RNA aptamer that specifically blocks Ang 2 would inhibit tumor angiogenesis and growth. METHODS: Ang2-mediated Tie2 receptor phosphorylation was assessed in vitro in the absence and presence of aptamer coupled to polyethylene glycol. IN VIVO ANGIOGENESIS ASSAY: CT26 murine colon carcinoma cells expressing green fluorescent protein were delivered into mouse dorsal skinfold window chambers. Animals received daily intraperitoneal injections of phosphate-buffered saline, low-dose (Ang2 aptamer-LD; 1 mg/kg/d), or high-dose aptamer (Ang2 aptamer-HD; 10 mg/kg/d). Vascular length density was measured under fluorescence microscopy. PRIMARY TUMOR GROWTH: CT26 cells expressing luciferase were injected into flanks of BALB/c mice to allow tumor growth monitoring by bioluminescence imaging. Animals received continuous phosphate-buffered saline or aptamer (1 mg/kg/d) via ALZET pumps. Tumors were assessed for CD31/PECAM-1 immunostaining and Hoechst dye uptake. RESULTS: Pegylated aptamer inhibited Tie2 phosphorylation. Systemic aptamer administration reduced vascular length density (P < or = 0.03) and decreased bioluminescence emission (P < 0.04), corresponding to 50% decrease in tumor volume (P = 0.04). Control tumors displayed abundant vascular marker staining, in contrast to tumors from aptamer-treated animals. CONCLUSIONS: in vivo administration of a clinically relevant, pegylated RNA aptamer specifically designed against Ang2 inhibited tumor angiogenesis and growth. These findings support targeted Ang2 inhibition as a relevant anti-angiogenic, anti-neoplastic strategy.

Authors
Sarraf-Yazdi, S; Mi, J; Moeller, BJ; Niu, X; White, RR; Kontos, CD; Sullenger, BA; Dewhirst, MW; Clary, BM
MLA Citation
Sarraf-Yazdi, S, Mi, J, Moeller, BJ, Niu, X, White, RR, Kontos, CD, Sullenger, BA, Dewhirst, MW, and Clary, BM. "Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer." J Surg Res 146.1 (May 1, 2008): 16-23.
PMID
17950331
Source
pubmed
Published In
Journal of Surgical Research
Volume
146
Issue
1
Publish Date
2008
Start Page
16
End Page
23
DOI
10.1016/j.jss.2007.04.028

A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function.

Tie2 is a receptor tyrosine kinase that is expressed predominantly in the endothelium and plays key roles in both physiological and pathological angiogenesis. The ligands for Tie2, the angiopoietins (Ang), perform opposing functions in vascular maintenance and angiogenesis; Ang1 regulates vascular quiescence, while Ang2 is thought to promote vascular destabilization and facilitate angiogenesis. However, the mechanisms responsible for these differences are not understood. To begin to elucidate the molecular differences between the angiopoietins, we previously developed a specific RNA aptamer inhibitor of Ang2. Here, we used the same iterative in vitro selection process, termed SELEX (Systematic Evolution of Ligands by EXponential enrichment), to screen a library of 2'-fluoro-modified ribonucleotides for Ang1-binding aptamers. After nine rounds of selection, we identified a single clone, ANG9-4, that bound with high affinity to human Ang1 (K ( d ) 2.8 nM) but not Ang2 (K ( d ) > 1 microM), demonstrating specificity for Ang1. ANG9-4 blocked Ang1-mediated Tie2 phosphorylation and downstream Akt activation. Moreover, ANG9-4 inhibited Ang1-induced endothelial cell survival. Together, these findings demonstrate the feasibility of developing an Ang1-inhibitory aptamer. ANG9-4 and its derivatives may provide useful tools for elucidating the biology of Ang1 and for treating certain angiogenic diseases.

Authors
White, RR; Roy, JA; Viles, KD; Sullenger, BA; Kontos, CD
MLA Citation
White, RR, Roy, JA, Viles, KD, Sullenger, BA, and Kontos, CD. "A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function." Angiogenesis 11.4 (2008): 395-401.
PMID
19037734
Source
pubmed
Published In
Angiogenesis
Volume
11
Issue
4
Publish Date
2008
Start Page
395
End Page
401
DOI
10.1007/s10456-008-9122-4

Assessing the optimal duration of chemotherapy in patients with colorectal liver metastases

Background and Objectives: Few studies have addressed the optimal duration of chemotherapy, particularly prior to liver resection for colorectal liver metastases (CLM). The purpose of this retrospective analysis was to evaluate time to maximal response in patients receiving systemic ± hepatic arterial infusion (HAI) chemotherapy alone for the treatment of CLM. Methods: We reviewed 35 patients with CLM on clinical trials of HAI floxuridine/ dexamethasone plus systemic oxaliplatin with 5-fluorouracil/leucovorin or irinotecan (PUMP + SYSTEMIC). We retrospectively identified 35 patients with CLM who received first-line systemic 5FU/leucovorin/oxaliplatin (FOLFOX) ± bevacizumab (SYSTEMIC) during the same time period. Measurable disease was evaluated on CT scans performed at 2-month intervals. The sum of the products of bi-dimensional tumor measurements for representative lesions was compared both to baseline imaging and between consecutive time points. Results: In responders to therapy, mean cumulative tumor reduction increased from 61% at 2 months to 73% at 4 months in the PUMP + SYSTEMIC group (P < 0.01) and from 39% to 56% in the SYSTEMIC group (P < 0.01). No significant incremental tumor reduction occurred between 4 and 6 months in either group. Conclusions: In responders to preoperative therapy, surgical resection should be considered after 2-4 months, when most patients have achieved maximal response. © 2008 Wiley-Liss, Inc.

Authors
White, RR; Schwartz, LH; Munoz, JA; Raggio, G; Jarnagin, WR; Fong, Y; D'Angelica, MI; Kemeny, NE
MLA Citation
White, RR, Schwartz, LH, Munoz, JA, Raggio, G, Jarnagin, WR, Fong, Y, D'Angelica, MI, and Kemeny, NE. "Assessing the optimal duration of chemotherapy in patients with colorectal liver metastases." Journal of Surgical Oncology 97.7 (2008): 601-604.
PMID
18449915
Source
scival
Published In
Journal of Surgical Oncology
Volume
97
Issue
7
Publish Date
2008
Start Page
601
End Page
604
DOI
10.1002/jso.21042

Current Utility of Staging Laparoscopy for Pancreatic and Peripancreatic Neoplasms

Background: The routine use of staging laparoscopy in patients with radiographically resectable pancreatic and peripancreatic neoplasms remains controversial. Study Design: We reviewed a prospective database that identified 1,045 patients who underwent staging laparoscopy for radiographically resectable pancreatic or peripancreatic tumors between 1995 and 2005. Radiographic resectability was determined by review of radiographic reports, surgeons' notes, and cross-sectional imaging studies. Factors were assessed for their association with the laparoscopic identification of radiographically occult unresectable disease. Recursive partitioning was used to build a decision tree, with laparoscopic identification of unresectable disease as the outcomes, including only patients since 1999 (modern imaging) and factors available preoperatively. Results: Unresectable disease was identified laparoscopically in 145 of the 1,045 radiographically resectable patients (14%). Factors associated with radiographically occult unresectable disease included the time period of the study, whether imaging was performed at our institution (internal versus external imaging), primary site, histology, weight loss, and jaundice. Primary site (pancreatic versus nonpancreatic) was identified as the strongest predictor of yield. In patients with nonpancreatic tumors, the yield of laparoscopy was 4%. In patients with pancreatic tumors, the yield of laparoscopy was 14% overall, but was 8.4% in patients with internal imaging versus 17% in patients with external imaging (p < 0.01). This higher-risk subgroup was partitioned by the presence of weight loss, then by primary site within the pancreas. Conclusions: During the time period of this study, the yield of staging laparoscopy decreased and exceeded 10% only for patients with pancreatic adenocarcinoma. When high-quality cross-sectional imaging reveals no evidence of unresectable disease, routine staging laparoscopy may not be warranted for pancreatic or peripancreatic tumors other than presumed pancreatic adenocarcinoma. © 2008 American College of Surgeons.

Authors
White, R; Winston, C; Gonen, M; D'Angelica, M; Jarnagin, W; Fong, Y; Conlon, K; Brennan, M; Allen, P
MLA Citation
White, R, Winston, C, Gonen, M, D'Angelica, M, Jarnagin, W, Fong, Y, Conlon, K, Brennan, M, and Allen, P. "Current Utility of Staging Laparoscopy for Pancreatic and Peripancreatic Neoplasms." Journal of the American College of Surgeons 206.3 (2008): 445-450.
PMID
18308214
Source
scival
Published In
Journal of The American College of Surgeons
Volume
206
Issue
3
Publish Date
2008
Start Page
445
End Page
450
DOI
10.1016/j.jamcollsurg.2007.09.021

The role of aggressive regional therapy for colorectal liver metastases

Surgical resection is the most effective treatment modality for liver metastases from colorectal cancer. However, most patients with liver metastases are not candidates for resection due to extensive intrahepatic disease. Approximately one-half of the patients who are able to undergo resection will eventually recur within the remnant liver. Hepatic arterial infusion (HAI) chemotherapy takes advantage of the arterial blood supply of colorectal liver metastases to increase tumor exposure to chemotherapy while minimizing systemic toxicity. HAI chemotherapy has been utilized in patients with unresectable disease in the neoadjuvant setting in an effort to convert them to resectability as well as in patients with resectable disease in the adjuvant setting in an effort to prevent recurrence. This article reviews the roles of HAI chemotherapy in an aggressive approach toward colorectal liver metastases. Copyright © Informa Healthcare USA, Inc.

Authors
White, RR; Jarnagin, WR
MLA Citation
White, RR, and Jarnagin, WR. "The role of aggressive regional therapy for colorectal liver metastases." Cancer Investigation 25.6 (2007): 458-463.
PMID
17882658
Source
scival
Published In
Cancer Investigation (Informa)
Volume
25
Issue
6
Publish Date
2007
Start Page
458
End Page
463
DOI
10.1080/07357900701508561

Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis

The purpose of this study was to compare rates and patterns of disease progression following percutaneous, image-guided radiofrequency ablation (RFA) and nonanatomic wedge resection for solitary colorectal liver metastases. We identified 30 patients who underwent nonanatomic wedge resection for solitary liver metastases and 22 patients who underwent percutaneous RFA because of prior major hepatectomy (50%), major medical comorbidities (41%), or relative unresectability (9%). Serial imaging studies were retrospectively reviewed for evidence of local tumor progression. Patients in the RFA group were more likely to have undergone prior liver resection, to have a disease-free interval greater than 1 year, and to have had an abnormal carcinoembryonic antigen (CEA) level before treatment. Two-year local tumor progression-free survival (PFS) was 88% in the Wedge group and 41% in the RFA group. Two patients in the RFA group underwent re-ablation, and two patients underwent resection to improve the 2-year local tumor disease-free survival to 55%. Approximately 30% of patients in each group presented with distant metastasis as a component of their first recurrence. Median overall survival from the time of resection was 80 months in the Wedge group vs 31 months in the RFA group. However, overall survival from the time of treatment of the colorectal primary was not significantly different between the two groups. Local tumor progression is common after percutaneous RFA. Surgical resection remains the gold standard treatment for patients who are candidates for resection. For patients who are poor candidates for resection, RFA may help to manage local disease, but close follow-up and retreatment are necessary to achieve optimal results. . © The Society for Surgery of the Alimentary Tract 2007.

Authors
White, RR; Avital, I; Sofocleous, CT; Brown, KT; Brody, LA; Covey, A; Getrajdman, GI; Jarnagin, WR; Dematteo, RP; Fong, Y; Blumgart, LH; D'Angelica, M
MLA Citation
White, RR, Avital, I, Sofocleous, CT, Brown, KT, Brody, LA, Covey, A, Getrajdman, GI, Jarnagin, WR, Dematteo, RP, Fong, Y, Blumgart, LH, and D'Angelica, M. "Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis." Journal of Gastrointestinal Surgery 11.3 (2007): 256-263.
PMID
17458595
Source
scival
Published In
Journal of Gastrointestinal Surgery
Volume
11
Issue
3
Publish Date
2007
Start Page
256
End Page
263
DOI
10.1007/s11605-007-0100-8

Fate of the Remnant Pancreas after Resection of Noninvasive Intraductal Papillary Mucinous Neoplasm

Background: The risk of local recurrence in the pancreatic remnant after resection of noninvasive intraductal papillary mucinous neoplasm (IPMN) is not well defined. Study Design: We performed a retrospective review of a prospectively maintained pancreatic resection database that identified 78 patients who underwent resection for noninvasive IPMN between 1983 and 2006. Local recurrence was determined radiographically and confirmed either pathologically or clinically. Results: At a median followup of 40 months, 6 patients (7.7%) have recurred locally, with a median interval of 22 months (range 8 to 62 months) from the time of resection. Three patients did not undergo additional operative treatment and died of disease progression. Three patients underwent additional resection and are alive without evidence of disease. The estimated 5-year local recurrence-free survival for all patients with noninvasive IPMN is 87%. One of 50 patients (2%) with margins negative for IPMN recurred versus 4 of 23 patients (17%) with margins positive for IPMN (p = 0.02). Conclusions: Patients who have undergone resection for noninvasive IPMN require indefinite surveillance because local recurrences may be identified several years from the initial operation and be resected while still noninvasive. Although the risk of local recurrence appears to increase in the setting of positive margins, the majority of patients with positive margins have not developed local recurrence. Negative margins should be the goal of the operation when achievable with partial pancreatectomy, but the risk of local recurrence is not high enough to mandate total pancreatectomy for microscopic positive margins. © 2007 American College of Surgeons.

Authors
White, R; D'Angelica, M; Katabi, N; Tang, L; Klimstra, D; Fong, Y; Brennan, M; Allen, P
MLA Citation
White, R, D'Angelica, M, Katabi, N, Tang, L, Klimstra, D, Fong, Y, Brennan, M, and Allen, P. "Fate of the Remnant Pancreas after Resection of Noninvasive Intraductal Papillary Mucinous Neoplasm." Journal of the American College of Surgeons 204.5 (2007): 987-993.
PMID
17481526
Source
scival
Published In
Journal of The American College of Surgeons
Volume
204
Issue
5
Publish Date
2007
Start Page
987
End Page
993
DOI
10.1016/j.jamcollsurg.2006.12.040

Evaluation of preoperative therapy for pancreatic cancer using a prognostic nomogram.

BACKGROUND: Theoretical benefits of preoperative chemoradiation therapy (preop CRT) for pancreatic cancer include improved efficacy, resectability, and patient selection. The goal of this study was to evaluate the applicability of a nomogram, which was developed for patients undergoing resection without preop CRT and which incorporates several post-resection pathological factors, to a population of patients who received preop CRT prior to resection. METHODS: From 1994 to 2004, 82 patients with biopsy-proven, radiographically localized adenocarcinoma of the pancreatic head underwent preop CRT followed by pancreaticoduodenectomy (PD); 50 concurrent patients underwent PD without preop CRT. Mean nomogram-predicted disease-specific survival (DSS) rates were compared with observed DSS rates from the time of resection. RESULTS: Despite having more locally advanced tumors on initial staging (21 vs. 8%; P < .05), patients who received preop CRT had smaller resected tumors (mean 2.3 vs. 3.1 cm; P < .01), were less likely to have T3 tumors (54 vs. 80%, P < .01), were less likely to have positive lymph nodes (29 vs. 58%, P < .01), and had fewer positive lymph nodes (mean .4 vs. 1.9, P < .01), all factors that imply treatment effect and favorably impact on nomogram-predicted DSS. Observed DSS was similar to predicted DSS in both groups. CONCLUSIONS: The similarity in observed and predicted DSS following resection in patients who received preop CRT suggests that the effects of preop CRT-whether treatment, selection, or no effect-are reflected by the nomogram. The ability of the nomogram to evaluate the effects of preop CRT on survival is limited by the potential effects of preop CRT on factors within the nomogram.

Authors
White, RR; Kattan, MW; Haney, JC; Clary, BM; Pappas, TN; Tyler, DS; Brennan, MF
MLA Citation
White, RR, Kattan, MW, Haney, JC, Clary, BM, Pappas, TN, Tyler, DS, and Brennan, MF. "Evaluation of preoperative therapy for pancreatic cancer using a prognostic nomogram." Ann Surg Oncol 13.11 (November 2006): 1485-1492.
PMID
17013688
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
13
Issue
11
Publish Date
2006
Start Page
1485
End Page
1492
DOI
10.1245/s10434-006-9104-y

Effect of neoadjuvant chemoradiation on operative mortality and morbidity for pancreaticoduodenectomy.

BACKGROUND: Neoadjuvant chemoradiotherapy (neo-CRT) is being used with increasing frequency for periampullary tumors, but how it alters the complication rate of pancreaticoduodenectomy (PD) is unclear. METHODS: A retrospective analysis was conducted of 79 patients with periampullary malignancies who received 5-fluorouracil-based neo-CRT followed by PD. RESULTS: There was no difference in mortality between PD after neo-CRT (3.8%) and conventional PD for either malignant (4.5%) or benign (2.2%) disease. Focusing only on patients with malignancy, the neo-CRT group had a significantly lower pancreatic leak rate than the conventional group (10% vs. 43%; P < .001). Intra-abdominal abscesses were less common in the neo-CRT group (8.8% vs. 21%; P = .019), and there was one (1.2%) amylase-rich abscess in neo-CRT group, compared with eight (12%) in the conventional group. In addition, two patients in the conventional group died of leak-associated sepsis, compared with none in the neo-CRT group. Multivariate analysis revealed that neoadjuvant chemoradiation (odds ratio, .15) was the most significant factor associated with a reduced risk of pancreatic leak. CONCLUSIONS: Neo-CRT does not increase the mortality or morbidity of PD. In contrast, neo-CRT was associated with a marked reduction in the incidence of pancreatic leak, as well as leak-associated morbidity and mortality.

Authors
Cheng, T-Y; Sheth, K; White, RR; Ueno, T; Hung, C-F; Clary, BM; Pappas, TN; Tyler, DS
MLA Citation
Cheng, T-Y, Sheth, K, White, RR, Ueno, T, Hung, C-F, Clary, BM, Pappas, TN, and Tyler, DS. "Effect of neoadjuvant chemoradiation on operative mortality and morbidity for pancreaticoduodenectomy." Ann Surg Oncol 13.1 (January 2006): 66-74.
PMID
16372154
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
13
Issue
1
Publish Date
2006
Start Page
66
End Page
74
DOI
10.1245/ASO.2006.02.003

Liver resection. State of the art.

Authors
White, R; D'Angelica, M; Blumgart, LH
MLA Citation
White, R, D'Angelica, M, and Blumgart, LH. "Liver resection. State of the art." Chirurgia italiana. 58.2 (2006): 137-140.
PMID
16734161
Source
scival
Published In
Chirurgia Italiana
Volume
58
Issue
2
Publish Date
2006
Start Page
137
End Page
140

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.

BACKGROUND: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. METHODS: Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods. RESULTS: The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation. CONCLUSIONS: Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Authors
White, RR; Xie, HB; Gottfried, MR; Czito, BG; Hurwitz, HI; Morse, MA; Blobe, GC; Paulson, EK; Baillie, J; Branch, MS; Jowell, PS; Clary, BM; Pappas, TN; Tyler, DS
MLA Citation
White, RR, Xie, HB, Gottfried, MR, Czito, BG, Hurwitz, HI, Morse, MA, Blobe, GC, Paulson, EK, Baillie, J, Branch, MS, Jowell, PS, Clary, BM, Pappas, TN, and Tyler, DS. "Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer." Annals of surgical oncology 12.3 (March 3, 2005): 214-221.
PMID
15827813
Source
epmc
Published In
Annals of Surgical Oncology
Volume
12
Issue
3
Publish Date
2005
Start Page
214
End Page
221
DOI
10.1245/aso.2005.03.105

The role of chemoradiation therapy in locally advanced pancreatic cancer.

The majority of patients with pancreatic cancer present with disease that is unresectable due to local invasion. This article reviews the evidence (or lack thereof) that chemoradiation therapy (CRT) helps these patients in four areas: survival, tumor downstaging, palliation of obstructive symptoms, and pain control. We believe that CRT allows a small percentage of patients with locally advanced disease to undergo potentially curative resection while providing effective palliative treatment.

Authors
White, RR; Reddy, S; Tyler, DS
MLA Citation
White, RR, Reddy, S, and Tyler, DS. "The role of chemoradiation therapy in locally advanced pancreatic cancer." HPB (Oxford) 7.2 (2005): 109-113.
PMID
18333172
Source
pubmed
Published In
HPB
Volume
7
Issue
2
Publish Date
2005
Start Page
109
End Page
113
DOI
10.1080/13651820510016506

Laparoscopic staging for hepatobiliary carcinoma.

Authors
White, RR; Pappas, TN
MLA Citation
White, RR, and Pappas, TN. "Laparoscopic staging for hepatobiliary carcinoma." J Gastrointest Surg 8.8 (December 2004): 920-922.
PMID
15702520
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
8
Issue
8
Publish Date
2004
Start Page
920
End Page
922

Antidote-mediated control of an anticoagulant aptamer in vivo.

Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.

Authors
Rusconi, CP; Roberts, JD; Pitoc, GA; Nimjee, SM; White, RR; Quick, G; Scardino, E; Fay, WP; Sullenger, BA
MLA Citation
Rusconi, CP, Roberts, JD, Pitoc, GA, Nimjee, SM, White, RR, Quick, G, Scardino, E, Fay, WP, and Sullenger, BA. "Antidote-mediated control of an anticoagulant aptamer in vivo." Nat Biotechnol 22.11 (November 2004): 1423-1428.
PMID
15502817
Source
pubmed
Published In
Nature Biotechnology
Volume
22
Issue
11
Publish Date
2004
Start Page
1423
End Page
1428
DOI
10.1038/nbt1023

Neoadjuvant therapy for pancreatic cancer: the Duke experience.

The advantages of neoadjuvant (preoperative) chemoradiation therapy for pancreatic cancer include the assurance that all resected patients receive multimodality therapy; the opportunity for patients with occult metastatic disease to manifest themselves; and the potential to improve resectability. Since 1994, Duke University Medical Center has treated over 180 patients with localized pancreatic cancer using neoadjuvant 5-fluorouracil (5FU)-based chemoradiation therapy (CRT). Approximately 20% of patients demonstrate distant disease progression during CRT and avoid the morbidity of laparotomy. Almost 20% of locally advanced tumors on initial-staging CT can be resected following CRT. Patients who have successfully undergone resection have experienced favorable survival with an estimated 5-year survival rate of 36%. This article reviews the authors' experience and the lessons learned from it.

Authors
White, RR; Tyler, DS
MLA Citation
White, RR, and Tyler, DS. "Neoadjuvant therapy for pancreatic cancer: the Duke experience." Surg Oncol Clin N Am 13.4 (October 2004): 675-x. (Review)
PMID
15350941
Source
pubmed
Published In
Surgical Oncology Clinics of North America
Volume
13
Issue
4
Publish Date
2004
Start Page
675
End Page
x
DOI
10.1016/j.soc.2004.06.001

RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins.

We studied the RNA aptamer Toggle-25/thrombin interaction during inhibition by antithrombin (AT), heparin cofactor II (HCII) and protein C inhibitor (PCI). Thrombin inhibition was reduced 3-fold by Toggle-25 for AT and HCII, but it was slightly enhanced for PCI. In the presence of glycosaminoglycans, AT and PCI had significantly reduced thrombin inhibition with Toggle-25, but it was only reduced 3-fold for HCII. This suggested that the primary effect of aptamer binding was through the heparin-binding site of thrombin, anion-binding exosite-2 (exosite-2). We localized the Toggle-25 binding site to Arg 98, Glu 169, Lys 174, Asp 175, Arg 245, and Lys 248 of exosite-2. We conclude that a RNA aptamer to thrombin exosite-2 might provide an effective clinical reagent to control heparin's anticoagulant action.

Authors
Jeter, ML; Ly, LV; Fortenberry, YM; Whinna, HC; White, RR; Rusconi, CP; Sullenger, BA; Church, FC
MLA Citation
Jeter, ML, Ly, LV, Fortenberry, YM, Whinna, HC, White, RR, Rusconi, CP, Sullenger, BA, and Church, FC. "RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins." FEBS Lett 568.1-3 (June 18, 2004): 10-14.
PMID
15196911
Source
pubmed
Published In
FEBS Letters
Volume
568
Issue
1-3
Publish Date
2004
Start Page
10
End Page
14
DOI
10.1016/j.febslet.2004.04.087

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Authors
Gerke, H; White, R; Byrne, MF; Stiffier, H; Mitchell, RM; Hurwitz, HI; Morse, MA; Branch, MS; Jowell, PS; Czito, B; Clary, B; Pappas, TN; Tyler, DS; Baillie, J
MLA Citation
Gerke, H, White, R, Byrne, MF, Stiffier, H, Mitchell, RM, Hurwitz, HI, Morse, MA, Branch, MS, Jowell, PS, Czito, B, Clary, B, Pappas, TN, Tyler, DS, and Baillie, J. "Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage." Dig Liver Dis 36.6 (June 2004): 412-418.
PMID
15248382
Source
pubmed
Published In
Digestive and Liver Disease
Volume
36
Issue
6
Publish Date
2004
Start Page
412
End Page
418

Pelvic sarcomas

The differential diagnosis of a presacral soft tissue mass includes a heterogeneous list of benign and malignant tumors. Preoperative imaging is helpful in judging resectability, but core-needle biopsy is generally recommended for tissue diagnosis and to facilitate decision-making about neoadjuvant therapy. Malignant tumors (sarcomas) frequently require resection of involved adjacent structures to achieve a complete gross resection. Data for extremity and retroperitoneal sarcoma suggest that radiation therapy - pre-, intra-, or postoperative - improves local control and that postoperative chemotherapy may improve survival for high-risk tumors. Pelvic sarcomas are uncommon but challenging tumors to treat and require a multidisciplinary and individualized approach. © 2004 Elsevier Inc. All rights reserved.

Authors
White, RR; Tyler, DS
MLA Citation
White, RR, and Tyler, DS. "Pelvic sarcomas." Seminars in Colon and Rectal Surgery 15.1 SPEC.ISS. (2004): 33-40.
Source
scival
Published In
Seminars in Colon and Rectal Surgery
Volume
15
Issue
1 SPEC.ISS.
Publish Date
2004
Start Page
33
End Page
40
DOI
10.1053/j.scrs.2004.06.006

Pancreatic cancer since Halsted: how far have we come and where are we going?

Authors
White, RR; Shah, AS; Tyler, DS
MLA Citation
White, RR, Shah, AS, and Tyler, DS. "Pancreatic cancer since Halsted: how far have we come and where are we going?." Ann Surg 238.6 Suppl (December 2003): S132-S144. (Review)
PMID
14703755
Source
pubmed
Published In
Annals of Surgery
Volume
238
Issue
6 Suppl
Publish Date
2003
Start Page
S132
End Page
S144

Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA.

Studies have suggested an increased risk of peritoneal seeding in patients with pancreatic cancer diagnosed by percutaneous FNA. EUS-FNA is an alternate method of diagnosis. The aim of this study was to compare the frequency of peritoneal carcinomatosis as a treatment failure pattern in patients with pancreatic cancer diagnosed by EUS-FNA vs. percutaneous FNA.Retrospective review of patients with non-metastatic pancreatic cancer identified 46 patients in whom the diagnosis was made by EUS-FNA and 43 with the diagnosis established by percutaneous FNA. All had neoadjuvant chemoradiation. Patients underwent restaging CT after completion of therapy, followed by attempted surgical resection if there was no evidence of disease progression.There were no significant differences in tumor characteristics between the two study groups. In the EUS-FNA group, one patient had developed peritoneal carcinomatosis compared with 7 in the percutaneous FNA group (2.2% vs. 16.3%; p<0.025). No patient with a potentially resectable tumor in the EUS-FNA group had developed peritoneal carcinomatosis.Peritoneal carcinomatosis may occur more frequently in patients who undergo percutaneous FNA compared with those who have EUS-FNA for the diagnosis of pancreatic cancer. A concern for peritoneal seeding of pancreatic cancer via percutaneous FNA is warranted. EUS-guided FNA is recommended as the method of choice for diagnosis in patients with potentially resectable pancreatic cancer.

Authors
Micames, C; Jowell, PS; White, R; Paulson, E; Nelson, R; Morse, M; Hurwitz, H; Pappas, T; Tyler, D; McGrath, K
MLA Citation
Micames, C, Jowell, PS, White, R, Paulson, E, Nelson, R, Morse, M, Hurwitz, H, Pappas, T, Tyler, D, and McGrath, K. "Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA." Gastrointestinal endoscopy 58.5 (November 2003): 690-695.
PMID
14595302
Source
epmc
Published In
Gastrointestinal Endoscopy
Volume
58
Issue
5
Publish Date
2003
Start Page
690
End Page
695
DOI
10.1016/s0016-5107(03)02009-1

Thin melanomas: predictive lethal characteristics from a 30-year clinical experience.

OBJECTIVE: To guide treatment and clinical follow-up by defining the natural history of thin melanomas and identifying negative prognostic characteristics that may delineate high-risk patients. SUMMARY BACKGROUND DATA: In following > 10,000 patients with cutaneous melanoma over the past 30 years, our institution has observed nodal or metastatic disease in approximately 15% of patients with a thin (<1 mm) primary lesion. METHODS: A database query of patients with cutaneous melanoma returned 1158 patients with primary lesion < or = 1 mm thick and who received their initial treatment at a single institution. Median follow-up was 11 years (range, 1 to 34 years). Patient and melanoma characteristics as well as outcomes were recorded and statistically analyzed. RESULTS: 6.6% of patients had nodal or distant disease at presentation. Over time, an additional 9.4% developed metastases, including nodal and distal recurrences. Overall incidence of advanced disease was 15.3%. Univariate analysis identified male gender (P = 0.01), advanced age (>45 years; P = 0.05), and Breslow thickness (>0.75 mm; P = 0.008) as significant negative prognostic characteristics. Of patients with these 3 high-risk characteristics, 19.7% developed advanced disease (likelihood ratio 6.3; P = 0.007 versus nonhigh-risk patients). This group had more than twice the incidence of nodal recurrences. Patients with recurrence had significantly decreased 10-year survival (82% versus 45%; P < 0.0001). Surprisingly, neither ulceration nor Clark level predicted advanced disease. CONCLUSIONS: Thin melanomas are potentially lethal lesions. Long-term follow-up identified a high-risk population of older males with tumors between 0.75 mm and 1.0 mm whose risk of recurrent disease approaches 20%. Traditionally accepted negative prognostic factors such as ulceration and discordant Clark levels are not predictive for metastasis in this population. Given the poor prognosis associated with recurrent disease, we recommend close clinical evaluation and follow-up to maximize accurate staging and therapeutic options.

Authors
Kalady, MF; White, RR; Johnson, JL; Tyler, DS; Seigler, HF
MLA Citation
Kalady, MF, White, RR, Johnson, JL, Tyler, DS, and Seigler, HF. "Thin melanomas: predictive lethal characteristics from a 30-year clinical experience." Ann Surg 238.4 (October 2003): 528-535.
PMID
14530724
Source
pubmed
Published In
Annals of Surgery
Volume
238
Issue
4
Publish Date
2003
Start Page
528
End Page
535
DOI
10.1097/01.sla.0000090446.63327.40

Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.

Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability. Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangiogenic growth factors. To investigate the specific role of Ang2 in the adult vasculature, we generated a nuclease-resistant RNA aptamer that binds and inhibits Ang2 but not the related Tie2 agonist, angiopoietin-1. Local delivery of this aptamer but not a partially scrambled mutant aptamer inhibited basic fibroblast growth factor-mediated neovascularization in the rat corneal micropocket angiogenesis assay. These in vivo data directly demonstrate that a specific inhibitor of Ang2 can act as an antiangiogenic agent.

Authors
White, RR; Shan, S; Rusconi, CP; Shetty, G; Dewhirst, MW; Kontos, CD; Sullenger, BA
MLA Citation
White, RR, Shan, S, Rusconi, CP, Shetty, G, Dewhirst, MW, Kontos, CD, and Sullenger, BA. "Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2." Proc Natl Acad Sci U S A 100.9 (April 29, 2003): 5028-5033.
PMID
12692304
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
100
Issue
9
Publish Date
2003
Start Page
5028
End Page
5033
DOI
10.1073/pnas.0831159100

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

Therapeutic aptamers and antidotes: a novel approach to safer drug design.

Authors
Sullenger, BA; White, RR; Rusconi, CP
MLA Citation
Sullenger, BA, White, RR, and Rusconi, CP. "Therapeutic aptamers and antidotes: a novel approach to safer drug design." Ernst Schering Res Found Workshop 43 (2003): 217-223. (Review)
PMID
12894459
Source
pubmed
Published In
Ernst Schering Research Foundation workshop
Issue
43
Publish Date
2003
Start Page
217
End Page
223

Long-term survival in 2,505 patients with melanoma with regional lymph node metastasis.

OBJECTIVE: To examine the long-term outcomes of patients with melanoma metastatic to regional lymph nodes. SUMMARY BACKGROUND DATA: Regional lymph node metastasis is a major determinant of outcome for patients with melanoma, and the presence of regional lymph node metastasis has been commonly used as an indication for systemic, often intensive, adjuvant therapy. However, the risk of recurrence varies greatly within this heterogeneous group of patients. METHODS: Database review identified 2,505 patients, referred to the Duke University Melanoma Clinic between 1970 and 1998, with histologic confirmation of regional lymph node metastasis before clinical evidence of distant metastasis and with documentation of full lymph node dissection. Recurrence and survival after lymph node dissection were analyzed. RESULTS: Estimated overall survival rates at 5, 10, 15, and 20 years were 43%, 35%, 28%, and 23%, respectively. This population included 792 actual 5-year survivors, 350 10-year survivors, and 137 15-year survivors. The number of positive lymph nodes was the most powerful predictor of both overall survival and recurrence-free survival; 5-year overall survival rates ranged from 53% for one positive node to 25% for greater than four nodes. Primary tumor ulceration and thickness were also powerful predictors of both overall and recurrence-free survival in multivariate analyses. The most common site of first recurrence after lymph node dissection was distant (44% of all patients). CONCLUSIONS: Patients with regional lymph node metastasis can enjoy significant long-term survival after lymph node dissection. Therefore, aggressive surgical therapy of regional lymph node metastases is warranted, and each individual's risk of recurrence should be weighed against the potential risks of adjuvant therapy.

Authors
White, RR; Stanley, WE; Johnson, JL; Tyler, DS; Seigler, HF
MLA Citation
White, RR, Stanley, WE, Johnson, JL, Tyler, DS, and Seigler, HF. "Long-term survival in 2,505 patients with melanoma with regional lymph node metastasis." Ann Surg 235.6 (June 2002): 879-887.
PMID
12035046
Source
pubmed
Published In
Annals of Surgery
Volume
235
Issue
6
Publish Date
2002
Start Page
879
End Page
887

Regulation of thrombin-serpin inhibition reactions by a thrombin-specific RNA aptamer

Authors
Jeter, ML; White, RR; Sullenger, BA; Rusconi, CP; Church, FC
MLA Citation
Jeter, ML, White, RR, Sullenger, BA, Rusconi, CP, and Church, FC. "Regulation of thrombin-serpin inhibition reactions by a thrombin-specific RNA aptamer." March 22, 2002.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
5
Publish Date
2002
Start Page
A1193
End Page
A1193

Generation of species cross-reactive aptamers using "toggle" SELEX.

Species cross-reactivity facilitates the preclinical evaluation of potentially therapeutic molecules in animal models. Here we describe an in vitro selection strategy in which RNA ligands (aptamers) that bind both human and porcine thrombin were selected by "toggling" the protein target between human and porcine thrombin during alternating rounds of selection. The "toggle" selection process yielded a family of aptamers, all of which bound both human and porcine thrombin with high affinity. Toggle-25, a characteristic member, inhibited two of thrombin's most important functions: plasma clot formation and platelet activation. If appropriate targets are available, the toggle strategy is a simple measure that promotes cross-reactivity and may be generalizable to related proteins of the same species as well as to other combinatorial library screening strategies. This strategy should facilitate the isolation of ligands with needed properties for gene therapy and other therapeutic and diagnostic applications.

Authors
White, R; Rusconi, C; Scardino, E; Wolberg, A; Lawson, J; Hoffman, M; Sullenger, B
MLA Citation
White, R, Rusconi, C, Scardino, E, Wolberg, A, Lawson, J, Hoffman, M, and Sullenger, B. "Generation of species cross-reactive aptamers using "toggle" SELEX." Mol Ther 4.6 (December 2001): 567-573.
PMID
11735341
Source
pubmed
Published In
Molecular Therapy
Volume
4
Issue
6
Publish Date
2001
Start Page
567
End Page
573
DOI
10.1006/mthe.2001.0495

Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.

BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy (EBRT; median, 4500 cGy) with 5-flourouracil-based chemotherapy. Tumors were defined as potentially resectable (PR, n = 53) in the absence of arterial involvement and venous occlusion and locally advanced (LA, n = 58) with arterial involvement or venous occlusion by CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3) or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors (53%) and 11 patients with initially LA tumors (19%) were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant (postoperative) CRT.

Authors
White, RR; Hurwitz, HI; Morse, MA; Lee, C; Anscher, MS; Paulson, EK; Gottfried, MR; Baillie, J; Branch, MS; Jowell, PS; McGrath, KM; Clary, BM; Pappas, TN; Tyler, DS
MLA Citation
White, RR, Hurwitz, HI, Morse, MA, Lee, C, Anscher, MS, Paulson, EK, Gottfried, MR, Baillie, J, Branch, MS, Jowell, PS, McGrath, KM, Clary, BM, Pappas, TN, and Tyler, DS. "Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas." Ann Surg Oncol 8.10 (December 2001): 758-765.
PMID
11776488
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
8
Issue
10
Publish Date
2001
Start Page
758
End Page
765

Staging of pancreatic cancer before and after neoadjuvant chemoradiation.

Neoadjuvant chemoradiation therapy is used at many institutions for treatment of localized adenocarcinoma of the pancreas. Accurate staging before neoadjuvant therapy identifies patients with distant metastatic disease, and restaging after neoadjuvant therapy selects patients for laparotomy and attempted resection. The aims of this study were to (1) determine the utility of staging laparoscopy in candidates for neoadjuvant therapy and (2) evaluate the accuracy of restaging CT following chemoradiation. Staging laparoscopy was performed in 98 patients with radiographically potentially resectable (no evidence of arterial abutment or venous occlusion) or locally advanced (arterial abutment or venous occlusion) adenocarcinoma of the pancreas. Unsuspected distant metastasis was identified in 8 (18%) of 45 patients with potentially resectable tumors and 13 (24%) of 55 patients with locally advanced tumors by CT. Neoadjuvant chemoradiation therapy and restaging CT were completed in a total of 103 patients. Thirty-three patients with potentially resectable tumors by restaging CT underwent surgical exploration and resections were performed in 27 (82%). Eleven (22%) of 49 patients with locally advanced tumors by restaging CT were resected, with negative margins in 55%; the tumors in these 11 patients had been considered locally advanced because of arterial involvement on restaging CT. Staging laparoscopy is useful for the exclusion of patients with unsuspected metastatic disease from aggressive neoadjuvant chemoradiation protocols. Following neoadjuvant chemoradiation, restaging CT guides the selection of patients for laparotomy but may overestimate unresectability to a greater extent than does prechemoradiation CT.

Authors
White, RR; Paulson, EK; Freed, KS; Keogan, MT; Hurwitz, HI; Lee, C; Morse, MA; Gottfried, MR; Baillie, J; Branch, MS; Jowell, PS; McGrath, KM; Clary, BM; Pappas, TN; Tyler, DS
MLA Citation
White, RR, Paulson, EK, Freed, KS, Keogan, MT, Hurwitz, HI, Lee, C, Morse, MA, Gottfried, MR, Baillie, J, Branch, MS, Jowell, PS, McGrath, KM, Clary, BM, Pappas, TN, and Tyler, DS. "Staging of pancreatic cancer before and after neoadjuvant chemoradiation." J Gastrointest Surg 5.6 (November 2001): 626-633.
PMID
12086901
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
5
Issue
6
Publish Date
2001
Start Page
626
End Page
633

A novel inhibitor of Angiopoietin-1 disrupts Tie2-mediated endothelial cell survival

Authors
White, RR; Rusconi, CP; Sullenger, BA; Kontos, CD
MLA Citation
White, RR, Rusconi, CP, Sullenger, BA, and Kontos, CD. "A novel inhibitor of Angiopoietin-1 disrupts Tie2-mediated endothelial cell survival." October 23, 2001.
Source
wos-lite
Published In
Circulation
Volume
104
Issue
17
Publish Date
2001
Start Page
315
End Page
315

Impact of core-needle breast biopsy on the surgical management of mammographic abnormalities.

OBJECTIVE: To evaluate the accuracy of percutaneous, image-guided core-needle breast biopsy (CNBx) and to compare the surgical management of patients with breast cancer diagnosed by CNBx with patients diagnosed by surgical needle-localization biopsy (SNLBx). SUMMARY BACKGROUND DATA: Percutaneous, image-guided CNBx is a less invasive alternative to SNLBx for the diagnosis of nonpalpable mammographic abnormalities. CNBx potentially spares patients with benign lesions from unnecessary surgery, although false-negative results can occur. For patients with malignant lesions, preoperative diagnosis by CNBx allows definitive treatment decisions to be made before surgery and may affect surgical outcomes. METHODS: Between 1992 and 1999, 939 patients with 1,042 mammographically detected lesions underwent biopsy by stereotactic CNBx or ultrasound-guided CNBx. Results were categorized pathologically as benign or malignant and, further, as invasive or noninvasive malignancies. Only biopsy results confirmed by excision or 1-year-minimum mammographic follow-up were included in the analysis. Patients with breast cancer diagnosed by CNBx were compared with a matched control group of patients with breast cancer diagnosed by SNLBx. RESULTS: Benign results were obtained in 802 lesions (77%), 520 of which were in patients with adequate follow-up. Ninety-five of the 520 evaluable lesions (18%) were subsequently excised because of atypical hyperplasia, mammographic-histologic discordance, or other clinical indications. There were 17 false-negative CNBx results in this group; 15 of these lesions were correctly diagnosed by excisional biopsy within 4 months of CNBx. In two patients (0.9%), delayed diagnoses of ductal carcinoma in situ were made at 15 and 19 months after CNBx. Malignant results were obtained in 240 lesions (23%), 220 of which were surgically excised from 202 patients at our institution. Two lesions diagnosed as ductal carcinoma in situ were reclassified as atypical ductal hyperplasia and considered false-positive results (0.4%). For malignant lesions, the sensitivity and specificity of CNBx for the detection of invasion were 89% and 96%, respectively. During the first surgical procedure, 115 of 199 patients (58%) diagnosed by CNBx underwent local excision; 194 of 199 patients (97%) evaluated by SNLBx underwent local excision. For patients whose initial surgery was local excision, those diagnosed before surgery by CNBx had larger excision specimens and were more likely to have negative surgical margins than were patients initially evaluated by SNLBx. Overall, patients diagnosed by CNBx required fewer surgical procedures for definitive treatment than did patients diagnosed by SNLBx. CONCLUSIONS: Diagnosis by CNBx spares most patients with benign mammographic abnormalities from unnecessary surgery. With the selective use of SNLBx to confirm discordant results, missed diagnoses are rare. When compared with SNLBx, preoperative diagnosis of breast cancer by CNBx facilitates wider initial margins of excision, fewer positive margins, and fewer surgical procedures to accomplish definitive treatment than diagnosis by SNLBx.

Authors
White, RR; Halperin, TJ; Olson, JA; Soo, MS; Bentley, RC; Seigler, HF
MLA Citation
White, RR, Halperin, TJ, Olson, JA, Soo, MS, Bentley, RC, and Seigler, HF. "Impact of core-needle breast biopsy on the surgical management of mammographic abnormalities." Ann Surg 233.6 (June 2001): 769-777.
PMID
11371735
Source
pubmed
Published In
Annals of Surgery
Volume
233
Issue
6
Publish Date
2001
Start Page
769
End Page
777

Management of node-positive melanoma in the era of sentinel node biopsy.

Regional lymph node metastasis is a powerful predictor of decreased overall survival from malignant melanoma. However, the therapeutic value of elective node dissections and the role of adjuvant therapy for node-positive disease have been highly controversial. Sentinel lymph node biopsy has reshaped the debate by allowing for staging of the regional lymph nodes with less morbidity and greater accuracy. This review summarizes the current consensus on the management of node-positive melanoma in the era of sentinel lymph node biopsy.

Authors
White, RR; Tyler, DS
MLA Citation
White, RR, and Tyler, DS. "Management of node-positive melanoma in the era of sentinel node biopsy." Surg Oncol 9.3 (November 2000): 119-125. (Review)
PMID
11356340
Source
pubmed
Published In
Surgical Oncology
Volume
9
Issue
3
Publish Date
2000
Start Page
119
End Page
125

Developing aptamers into therapeutics.

Authors
White, RR; Sullenger, BA; Rusconi, CP
MLA Citation
White, RR, Sullenger, BA, and Rusconi, CP. "Developing aptamers into therapeutics." J Clin Invest 106.8 (October 2000): 929-934.
PMID
11032851
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
106
Issue
8
Publish Date
2000
Start Page
929
End Page
934
DOI
10.1172/JCI11325

Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas.

BACKGROUND: Improved resectability is a major theoretical benefit of preoperative chemoradiation for pancreatic cancer. Since 1994, patients at Duke University Medical Center with locally advanced pancreatic cancer have been treated with multimodality preoperative therapy. The purpose of this study was to review our experience with preoperative therapy for locally advanced pancreatic cancer and determine if an aggressive neoadjuvant regimen would not only downstage these tumors pathologically but also improve the odds of complete surgical resection. METHODS: The charts of 25 patients treated with neoadjuvant chemoradiation at Duke University Medical Center with biopsy-proven, locally advanced adenocarcinoma of the pancreas were reviewed. Tumors were defined as locally advanced based on radiographic or intraoperative evidence of disease that abuts the superior mesenteric artery or vein (n = 22) or involves lymph nodes that are within the proposed radiation field (n = 3). All 25 patients received external beam radiotherapy (median dose 4500 cGy) in daily fractions of 180 cGy over 5 weeks. All patients concurrently received 5-fluorouracil (FU), and many also received mitomycin C or cisplatin, or both. Patients were given a 3- to 4-week break before a restaging computed tomographic (CT) scan was performed. Three patients were not restaged: one died from metastatic disease; one was reclassified as having a neuroendocrine tumor; and one was lost to follow-up. RESULTS: On restaging after neoadjuvant therapy, 64% of patients had stable or decreased primary tumor size. Radiographically, two patients appeared potentially resectable, and seven others developed evidence of metastatic disease. Eight patients underwent exploration, but only five could be resected. Of the five patients resected, only one had negative margins and negative lymph nodes. This patient had significant pancreatitis on initial exploration. After neoadjuvant therapy, he had a complete response radiographically, and there was no residual cancer in his resection specimen. Pathologic examination of the other resection specimens suggested that despite significant tumor fibrosis, malignant cells persist even at the periphery of the lesions. CONCLUSION: Although neoadjuvant chemoradiation has many theoretical advantages in managing pancreatic malignancy, true pathologic downstaging of locally advanced lesions into tumors that can be removed with negative nodes and margins appears to be a rare event with currently used therapeutic regimens.

Authors
White, R; Lee, C; Anscher, M; Gottfried, M; Wolff, R; Keogan, M; Pappas, T; Hurwitz, H; Tyler, D
MLA Citation
White, R, Lee, C, Anscher, M, Gottfried, M, Wolff, R, Keogan, M, Pappas, T, Hurwitz, H, and Tyler, D. "Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas." Ann Surg Oncol 6.1 (January 1999): 38-45.
PMID
10030414
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
6
Issue
1
Publish Date
1999
Start Page
38
End Page
45

Neoadjuvant chemoradiation for adenocarcinoma of the pancreas.

Adjuvant 5-fluorouracil and concurrent radiation may improve survival following complete surgical resection in patients with pancreatic adenocarcinoma. However, the morbidity and prolonged recovery associated with pancreaticoduodenectomy frequently prevents the timely delivery of postoperative chemoradiation. Therefore, the University of Texas M.D. Anderson Cancer Center (MDACC) has investigated the use of neoadjuvant chemoradiation in potentially resectable pancreatic cancer. We have incorporated a standardized approach to pretreatment staging, operative technique and pathologic evaluation. Our initial experience suggests that preoperative chemoradiation is well tolerated and may reduce loco-regional recurrence. Patients treated with rapid-fractionation preoperative chemoradiation had a significantly shorter duration of treatment compared with patients who received postoperative chemoradiation or standard-fractionation preoperative chemoradiation. New and more potent radiation-sensitizing agents such as gemcitabine may further enhance local control. Novel therapies directed at specific molecular events involved in pancreatic tumorigenesis may be incorporated into preoperative and postoperative regimens to attempt to reduce systemic relapse.

Authors
Breslin, TM; Janjan, NA; Lee, JE; Pisters, PW; Wolff, RA; Abbruzzese, JL; Evans, DB
MLA Citation
Breslin, TM, Janjan, NA, Lee, JE, Pisters, PW, Wolff, RA, Abbruzzese, JL, and Evans, DB. "Neoadjuvant chemoradiation for adenocarcinoma of the pancreas." November 1998.
PMID
9792895
Source
epmc
Published In
Frontiers in bioscience : a journal and virtual library
Volume
3
Publish Date
1998
Start Page
E193
End Page
E203

Molecules involved in mammalian sperm-egg interaction.

To achieve fertilization, sperm and egg are equipped with specific molecules which mediate the steps of gamete interaction. In mammals, the first interaction between sperm and egg occurs at an egg-specific extracellular matrix, the zona pellucida (zp). The three glycoproteins, ZP1, ZP2, and ZP3, that comprise the zp have been characterized from many species and assigned different roles in gamete interaction. A large number of candidate-binding partners for the zp proteins have been described; a subset of these have been characterized structurally and functionally. Galactosyltransferase, sp56, zona receptor kinase, and spermadhesins are thought to participate in the primary binding between sperm and zp and may initiate the exocytotic release of hydrolytic enzymes in the sperm head, the acrosome reaction. Digestion of the zp by these enzymes enables sperm to traverse the zp, at which time the proteins PH20, proacrosin, sp38, and Sp17 are thought to participate in secondary binding between the acrosome-reacted sperm and zp. Once through the zp, sperm and egg plasma membranes meet and fuse in a process reported to involve the egg integrin alpha 6 beta 1 and the sperm proteins DE and fertilin. These molecules and the processes involved in gamete interaction are reviewed in this chapter within a physiological context.

Authors
McLeskey, SB; Dowds, C; Carballada, R; White, RR; Saling, PM
MLA Citation
McLeskey, SB, Dowds, C, Carballada, R, White, RR, and Saling, PM. "Molecules involved in mammalian sperm-egg interaction." Int Rev Cytol 177 (1998): 57-113. (Review)
PMID
9378618
Source
pubmed
Published In
International review of cytology
Volume
177
Publish Date
1998
Start Page
57
End Page
113
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