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Pancreatic Neoplasms: HELP
Articles by Jeffrey E. Lee
Based on 74 articles published since 2009
(Why 74 articles?)
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Between 2009 and 2019, Jeffery E. Lee wrote the following 74 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Borderline resectable pancreatic cancer: what have we learned and where do we go from here? 2011

Katz, Matthew H G / Pisters, Peter W T / Lee, Jeffrey E / Fleming, Jason B. · ·Ann Surg Oncol · Pubmed #21136179.

ABSTRACT: -- No abstract --

2 Clinical Trial Outpatient virtual clinical encounters after complex surgery for cancer: a prospective pilot study of "TeleDischarge". 2016

Katz, Matthew H G / Slack, Rebecca / Bruno, Morgan / McMillan, Jermaine / Fleming, Jason B / Lee, Jeffrey E / Bednarski, Brian / Papadopoulos, John / Matin, Surena F. ·The Minimally Invasive New Technologies in Oncologic Surgery (MINTOS) Cooperative Group, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: mhgkatz@mdanderson.org. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · The Minimally Invasive New Technologies in Oncologic Surgery (MINTOS) Cooperative Group, The University of Texas MD Anderson Cancer Center, Houston, Texas. · The Minimally Invasive New Technologies in Oncologic Surgery (MINTOS) Cooperative Group, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · The Minimally Invasive New Technologies in Oncologic Surgery (MINTOS) Cooperative Group, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas. ·J Surg Res · Pubmed #27083967.

ABSTRACT: BACKGROUND: Outpatient clinical encounters are used to promote recovery after complex surgical procedures for cancer. These care episodes are resource intensive. Virtual clinical encounters (VCEs) can now be conducted using widely available videoconferencing technologies. However, whether these technologies may be used to monitor postoperative recovery is unknown. METHODS: In this pilot study, we provided care using a comprehensive "TeleDischarge" protocol to 15 patients after pancreatectomy. In addition to routine follow-up, all patients participated in two scheduled and an unlimited number of unscheduled VCEs using mobile hardware and secure videoconferencing software. We evaluated feasibility, patient satisfaction, postoperative adverse events, and health care human resource utilization. RESULTS: The median age of enrolled patients was 63 y (range, 52-83 y) and 93% underwent pancreatoduodenectomy. Twenty-eight scheduled VCEs (93%) were completed successfully, and only one unscheduled VCE was requested. Twelve patients (80%) felt their postoperative care was enhanced by VCEs and 14 (93%) felt that VCEs should be a regular part of postoperative care. Minor interventions in four patients (27%) were performed on the basis of clinical data gathered during a VCE. On a per patient basis, the TeleDischarge pathway was estimated to take 36 min longer and to have a direct labor cost $39 greater than the standard pathway. CONCLUSIONS: Secure VCEs can be conducted using widely available hardware and software solutions. Although cancer patients support the introduction of mobile technology into postoperative care, further studies are needed to identify ways in which such technology can be used most effectively and efficiently to reduce barriers to recovery.

3 Clinical Trial Neoadjuvant therapy is associated with a reduced lymph node ratio in patients with potentially resectable pancreatic cancer. 2015

Roland, Christina L / Yang, Anthony D / Katz, Matthew H G / Chatterjee, Deyali / Wang, Huamin / Lin, Heather / Vauthey, Jean N / Pisters, Peter W / Varadhachary, Gauri R / Wolff, Robert A / Crane, Christopher H / Lee, Jeffrey E / Fleming, Jason B. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. ·Ann Surg Oncol · Pubmed #25352267.

ABSTRACT: BACKGROUND: The use of neoadjuvant therapy (NAC) for the treatment of potentially resectable pancreatic cancer remains controversial. In this study, we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first (SF) approach with specific emphasis on lymph node metastases. METHODS: A total of 222 patients who underwent NAC and 85 patients who underwent SF were identified from 1990 to 2008 and compared for cancer-related endpoints. Peripancreatic lymph nodes from 135 neoadjuvant therapy patients were evaluated for histologic tumor regression. RESULTS: Patients who underwent NAC followed by surgery had improved overall survival and time to local recurrence compared with the SF approach. NAC patients were less likely to have lymph node metastases (p = 0.001), lymphovascular invasion (LVI), and had smaller tumors. On multivariate analysis, lymph node positivity was associated with SF, tumor size, and the presence of LVI. NAC patients with N0 disease had equivalent outcomes to patients with a low-LNR (0.01-0.15), whereas patients with a LNR >0.15 had reduced survival, and time to local and distant recurrence. Ten of 135 (7.4 %) NAC patients had evidence of tumor regression in at least one lymph node. CONCLUSIONS: Patients with potentially resectable PDAC selected to undergo NAC had improved survival and longer time to recurrence. Although some of these differences may be related to improvements in multimodality therapy completion rates, tumor regression in lymph node metastases exists and may demonstrate a biologic benefit of NAC compared with a SF approach.

4 Clinical Trial Transport properties of pancreatic cancer describe gemcitabine delivery and response. 2014

Koay, Eugene J / Truty, Mark J / Cristini, Vittorio / Thomas, Ryan M / Chen, Rong / Chatterjee, Deyali / Kang, Ya'an / Bhosale, Priya R / Tamm, Eric P / Crane, Christopher H / Javle, Milind / Katz, Matthew H / Gottumukkala, Vijaya N / Rozner, Marc A / Shen, Haifa / Lee, Jeffery E / Wang, Huamin / Chen, Yuling / Plunkett, William / Abbruzzese, James L / Wolff, Robert A / Varadhachary, Gauri R / Ferrari, Mauro / Fleming, Jason B. · ·J Clin Invest · Pubmed #24614108.

ABSTRACT: BACKGROUND: The therapeutic resistance of pancreatic ductal adenocarcinoma (PDAC) is partly ascribed to ineffective delivery of chemotherapy to cancer cells. We hypothesized that physical properties at vascular, extracellular, and cellular scales influence delivery of and response to gemcitabine-based therapy. METHODS: We developed a method to measure mass transport properties during routine contrast-enhanced CT scans of individual human PDAC tumors. Additionally, we evaluated gemcitabine infusion during PDAC resection in 12 patients, measuring gemcitabine incorporation into tumor DNA and correlating its uptake with human equilibrative nucleoside transporter (hENT1) levels, stromal reaction, and CT-derived mass transport properties. We also studied associations between CT-derived transport properties and clinical outcomes in patients who received preoperative gemcitabine-based chemoradiotherapy for resectable PDAC. RESULTS: Transport modeling of 176 CT scans illustrated striking differences in transport properties between normal pancreas and tumor, with a wide array of enhancement profiles. Reflecting the interpatient differences in contrast enhancement, resected tumors exhibited dramatic differences in gemcitabine DNA incorporation, despite similar intravascular pharmacokinetics. Gemcitabine incorporation into tumor DNA was inversely related to CT-derived transport parameters and PDAC stromal score, after accounting for hENT1 levels. Moreover, stromal score directly correlated with CT-derived parameters. Among 110 patients who received preoperative gemcitabine-based chemoradiotherapy, CT-derived parameters correlated with pathological response and survival. CONCLUSION: Gemcitabine incorporation into tumor DNA is highly variable and correlates with multiscale transport properties that can be derived from routine CT scans. Furthermore, pretherapy CT-derived properties correlate with clinically relevant endpoints. TRIAL REGISTRATION: Clinicaltrials.gov NCT01276613. FUNDING: Lustgarten Foundation (989161), Department of Defense (W81XWH-09-1-0212), NIH (U54CA151668, KCA088084).

5 Clinical Trial Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. 2011

Crane, Christopher H / Varadhachary, Gauri R / Yordy, John S / Staerkel, Gregg A / Javle, Milind M / Safran, Howard / Haque, Waqar / Hobbs, Bridgett D / Krishnan, Sunil / Fleming, Jason B / Das, Prajnan / Lee, Jeffrey E / Abbruzzese, James L / Wolff, Robert A. ·Dept of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX. ccrane@mdanderson.org ·J Clin Oncol · Pubmed #21709185.

ABSTRACT: PURPOSE: This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. RESULTS: Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). CONCLUSION: This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.

6 Clinical Trial Survival and quality of life of patients with resected pancreatic adenocarcinoma treated with adjuvant interferon-based chemoradiation: a phase II trial. 2011

Katz, Matthew H G / Wolff, Robert / Crane, Christopher H / Varadhachary, Gauri / Javle, Milind / Lin, E / Evans, Douglas B / Lee, Jeffrey E / Fleming, Jason B / Pisters, Peter W T. ·Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA. ·Ann Surg Oncol · Pubmed #21701927.

ABSTRACT: PURPOSE: We conducted a phase II trial to assess the survival duration and quality of life of patients who received adjuvant interferon-based chemoradiation for pancreatic adenocarcinoma after pancreaticoduodenectomy. METHODS: Patients with a performance status of 0 or 1 were enrolled to receive interferon-alfa-2b (3 million units MWF), cisplatin (30 mg/m(2), 6 doses) and 5-fluorouracil (5-FU; 175 mg/m(2)/day), concurrent with external-beam radiation (50.4 Gy) and followed by 2 courses of systemic 5-FU. The protocol was modified to include an optional 9 day break in the middle of chemoradiation. Quality of life was assessed by use of validated instruments. RESULTS: Twenty-eight patients were eligible for analysis. The operation of 15 (54%) patients was performed at other institutions. All patients had T3 tumors, 22 (79%) had positive lymph nodes and 4 (14%) had positive (R1) margins. 24 (86%) patients completed therapy. In all, 25 (89%) patients experienced grade 3 toxicity and 3 (11%) patients were hospitalized. The most common grade 3 events were leukopenia (15, 54%) and neutropenia (12, 43%). No grade 4 toxicity occurred. Overall quality of life decreased during chemoradiation but returned to baseline thereafter and was stable throughout surveillance. 19 patients have died; the median follow-up of the 9 survivors is 62 months. The median OS duration of treated patients was 42.3 (95% confidence interval 30.5-54.2) months. CONCLUSIONS: Adjuvant interferon-based chemoradiation can be delivered safely and tolerably-though with substantial reversible toxicity-to patients of good performance status at an experienced cancer center. Therapy may be associated with an improvement in overall survival.

7 Article Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation. 2019

Kano, Yoshihito / Gebregiworgis, Teklab / Marshall, Christopher B / Radulovich, Nikolina / Poon, Betty P K / St-Germain, Jonathan / Cook, Jonathan D / Valencia-Sama, Ivette / Grant, Benjamin M M / Herrera, Silvia Gabriela / Miao, Jinmin / Raught, Brian / Irwin, Meredith S / Lee, Jeffrey E / Yeh, Jen Jen / Zhang, Zhong-Yin / Tsao, Ming-Sound / Ikura, Mitsuhiko / Ohh, Michael. ·Department of Laboratory Medicine and Pathobiology, University of Toronto, 661 University Avenue, Toronto, ON, M5G 1M1, Canada. · Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, ON, M5G 1M1, Canada. · Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada. · Princess Margaret Cancer Centre, University Health Network and Department of Pathology, University of Toronto, Toronto, ON, M5G 1L7, Canada. · Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Toronto, ON, 5G OA4, Canada. · Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA. · Department of Medicinal Chemistry and Molecular Pharmacology, Center for Cancer Research and Institute for Drug Discovery, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, USA. · Department of Surgery, University of North Carolina, Chapel Hill, NC, 27599, USA. · Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA. · Department of Laboratory Medicine and Pathobiology, University of Toronto, 661 University Avenue, Toronto, ON, M5G 1M1, Canada. michael.ohh@utoronto.ca. · Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, ON, M5G 1M1, Canada. michael.ohh@utoronto.ca. ·Nat Commun · Pubmed #30644389.

ABSTRACT: Deregulation of the RAS GTPase cycle due to mutations in the three RAS genes is commonly associated with cancer development. Protein tyrosine phosphatase SHP2 promotes RAF-to-MAPK signaling pathway and is an essential factor in RAS-driven oncogenesis. Despite the emergence of SHP2 inhibitors for the treatment of cancers harbouring mutant KRAS, the mechanism underlying SHP2 activation of KRAS signaling remains unclear. Here we report tyrosyl-phosphorylation of endogenous RAS and demonstrate that KRAS phosphorylation via Src on Tyr32 and Tyr64 alters the conformation of switch I and II regions, which stalls multiple steps of the GTPase cycle and impairs binding to effectors. In contrast, SHP2 dephosphorylates KRAS, a process that is required to maintain dynamic canonical KRAS GTPase cycle. Notably, Src- and SHP2-mediated regulation of KRAS activity extends to oncogenic KRAS and the inhibition of SHP2 disrupts the phosphorylation cycle, shifting the equilibrium of the GTPase cycle towards the stalled 'dark state'.

8 Article Chemotherapy Versus Chemoradiation as Preoperative Therapy for Resectable Pancreatic Ductal Adenocarcinoma: A Propensity Score Adjusted Analysis. 2019

Cloyd, Jordan M / Chen, Hsiang-Chun / Wang, Xuemei / Tzeng, Ching-Wei D / Kim, Michael P / Aloia, Thomas A / Vauthey, Jean-Nicolas / Lee, Jeffrey E / Katz, Matthew H G. ·From the Departments of Surgical Oncology and. · Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX. ·Pancreas · Pubmed #30629022.

ABSTRACT: OBJECTIVES: Although the use of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma is increasing, the optimal preoperative treatment regimen remains poorly defined. METHODS: All patients with resectable pancreatic ductal adenocarcinoma who received preoperative chemotherapy alone (12%) or chemoradiation therapy (CRT) alone (88%) before pancreatectomy between 1999 and 2014 were included. Propensity score matching with inverse probability weighting was conducted based on age, baseline carbohydrate antigen 19-9, and procedure type. RESULTS: Patients who received preoperative CRT were more likely to undergo a margin negative (91% vs 79%, P < 0.01) and node negative (53% vs 23%, P < 0.01) resection and experience less locoregional recurrence (LR; 16% vs 33%, P < 0.01) but similar median overall survival (OS; 33.6 vs 26.4 months, P = 0.09). On multivariate analysis, carbohydrate antigen 19-9 (hazard ratio, 1.2; 95% confidence interval [CI], 1.1-1.3) and positive lymph nodes (hazard ratio, 1.5; 95% CI, 1.0-2.2) were associated with OS, whereas tumor size (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), positive lymph nodes (OR, 3.1; 95% CI, 1.8-5.6), and preoperative chemotherapy (OR, 1.8; 95% CI, 1.1-2.9) were associated with LR. CONCLUSIONS: Preoperative CRT is associated with less margin and lymph node positivity, reduced LR, and similar OS compared with preoperative chemotherapy.

9 Article Pancreaticoduodenectomy with Mesocaval Shunt for Locally Advanced Pancreatic Adenocarcinoma. 2019

Simoneau, Eve / Goumard, Claire / Lee, Jeffrey E / Vauthey, Jean-Nicolas / Aloia, Thomas A / Chun, Yun Shin / Kim, Michael P / Katz, Matthew H G / Tzeng, Ching-Wei D. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler, Unit 1484, Houston, TX, USA. · Department of Hepatobiliary Surgery and Liver Transplantation, La Pitié Salpetrière Hospital, Université Pierre et Marie Curie (UPMC), Assistance Publique-Hôpitaux de Paris, Paris, France. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler, Unit 1484, Houston, TX, USA. CDTzeng@mdanderson.org. ·Ann Surg Oncol · Pubmed #30539487.

ABSTRACT: INTRODUCTION: Patients with locally advanced pancreatic cancer (LAPC) represent a challenging group to treat, given the involvement of major vascular structures. In selected patients with favorable biology, temporary mesocaval shunt can facilitate the resection and allow for a safer procedure with enhanced exposure to the superior mesenteric vessels. METHODS: We present a video of a pancreaticoduodenectomy (PD) with temporary mesocaval shunt with left internal jugular (LIJ) vein conduit. RESULTS: A 65-year-old woman presented with LAPC in the uncinate, causing total occlusion of the superior mesenteric vein (SMV) and encasement of the first jejunal artery. After neoadjuvant therapy and evidence of disease stability, a decision was made to perform a PD with a temporary mesocaval shunt to divert mesenteric flow to reduce blood loss and prevent bowel ischemia. During the procedure, the main mesenteric collateral (ileocolic vein) was divided to create the shunt to the inferior vena cava (IVC) with LIJ interposition. The remaining mesenteric tributaries involved by the tumor were divided. The uncinate dissection was performed using a superior mesenteric artery-first approach. Once the resection was completed, the shunt was stapled from the IVC and the graft transposed to the upper SMV. Standard reconstruction was performed. Total operative time was 536 min, and estimated blood loss was 250 cc without transfusions. No perioperative complications occurred. CONCLUSION: In selected patients with LAPC, PD with temporary mesocaval shunt can facilitate resection and venous reconstruction in patients with complete portal vein/SMV occlusion.

10 Article Physical activity and exercise during preoperative pancreatic cancer treatment. 2019

Parker, Nathan H / Ngo-Huang, An / Lee, Rebecca E / O'Connor, Daniel P / Basen-Engquist, Karen M / Petzel, Maria Q B / Wang, Xuemei / Xiao, Lianchun / Fogelman, David R / Schadler, Keri L / Simpson, Richard J / Fleming, Jason B / Lee, Jeffrey E / Varadhachary, Gauri R / Sahai, Sunil K / Katz, Matthew H G. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. nhparker@mdanderson.org. · Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Unit 1330, CPB 3.3278, PO Box 301439, Houston, TX, 77030-1439, USA. nhparker@mdanderson.org. · Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · College of Nursing and Health Innovation, Center for Health Promotion and Disease Prevention, Arizona State University, Phoenix, AZ, USA. · Department of Health and Human Performance, University of Houston, Houston, TX, USA. · Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Unit 1330, CPB 3.3278, PO Box 301439, Houston, TX, 77030-1439, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Nutritional Sciences, The University of Arizona Cancer Center, Phoenix, AZ, USA. · Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Support Care Cancer · Pubmed #30334105.

ABSTRACT: PURPOSE: Guidelines recommend exercise to cancer survivors, but limited data exists regarding exercise among patients undergoing preoperative cancer treatment. We examined differences in weekly self-reported exercise and accelerometer-measured physical activity among participants in a home-based exercise program administered during preoperative treatment for pancreatic cancer. METHODS: Participants were encouraged to perform at least 60 min/week of moderate-intensity aerobic exercise and at least 60 min/week of full-body strengthening exercises concurrent with chemotherapy, chemoradiation therapy or both sequentially and received resistance equipment, program instruction, and biweekly follow-up calls to encourage adherence. Self-reported aerobic and strengthening exercise minutes were measured using daily logs, and physical activity was measured objectively using accelerometers. RESULTS: Fifty participants (48% female, mean age 66 ± 8 years) participated for an average of 16 ± 9 preoperative weeks. Participants reported overall means of 126 ± 83 weekly minutes of aerobic exercise and 39 ± 33 weekly minutes of strengthening exercise in daily logs. Participants performed 158.7 ± 146.7 weekly minutes of accelerometer-measured moderate-to-vigorous physical activity. There were no significant differences in exercise or physical activity between treatment phases. CONCLUSIONS: These findings suggest that it is feasible to target the entire preoperative course for exercise prescription. Although participants exceeded aerobic exercise recommendations on average, we observed low strengthening exercise adherence and wide variability in self-reported exercise and accelerometer physical activity variables. These findings suggest that additional support, including program adaptations, may be necessary to overcome barriers to exercise or improve motivation when prescribing exercise in this clinical scenario.

11 Article First-Line Gemcitabine and Nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. 2019

Gulhati, Pat / Prakash, Laura / Katz, Matthew H G / Wang, Xuemei / Javle, Milind / Shroff, Rachna / Fogelman, David / Lee, Jeffrey E / Tzeng, Ching-Wei D / Lee, Jeffrey H / Weston, Brian / Tamm, Eric / Bhosale, Priya / Koay, Eugene J / Maitra, Anirban / Wang, Huamin / Wolff, Robert A / Varadhachary, Gauri R. ·Hematology/Oncology Fellowship Program, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Surgery, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, TX, 77030, USA. · Division of Internal Medicine, Department of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Pathology/Lab Medicine, Department of Anatomic Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, TX, 77030, USA. gvaradha@mdanderson.org. ·Ann Surg Oncol · Pubmed #30324485.

ABSTRACT: BACKGROUND: Preoperative chemotherapy provides early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy for localized pancreatic ductal adenocarcinoma (PDAC). For locally advanced (LA) PDAC, induction chemotherapy is the standard of care. This study evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy for localized PDAC. METHODS: Clinicopathologic features, treatment, and outcomes were evaluated for 99 patients with localized PDAC. The patients were staged using previously published criteria as follows: potentially resectable (PR), borderline type A (BR-A) (anatomy amenable to vascular resection), BR-B (biology suspicious for metastatic disease including high CA19-9), BR-C (comorbidities requiring medical optimization), and LA. RESULTS: The 99 patients (PR/BR/LA: 45/14/40) were treated with Gem/nab-P. Clinical staging showed that 20 patients had PR or BR-A disease, whereas 39 patients had BR-B or BR-C disease. The BR-B+C cases included one or more of the following: age of 80 years or older (13%), Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or more (13%), moderate to severe comorbidities (55%), CA19-9 of 1000 or higher (28%), and suspicion for metastases (21%). The majority of the patients received biweekly Gem/nab-P dosing, which was well tolerated. Pancreatectomy was performed for 12 (60%) of 20 patients with PR+BR-A, 2 (5%) of 39 patients with BR-B+C, and 1 (3%) of 40 patients with LA disease. During a median follow-up period of 26 months, the median overall survival (OS) period was 18 months (95% confidence interval [CI], 15.6-20.5 months) for all the patients, 17 months (95% CI, 14.6-19.5 months) for the unresected patients, and not reached for the resected patients (p = 0.028 for resected vs unresected patients). CONCLUSIONS: A significant number of patients with radiographically resectable PDAC albeit aggressive biology (BR-B), medically inoperable conditions (BR-C), or both received biweekly first-line Gem/nab-P. The resection rates were lower for the BR-B/BR-C patients than for the PR/BR-A patients (hazard ratio [HR], 0.43; 95% CI, 0.19-1.00; p = 0.05).

12 Article Vein resection during pancreaticoduodenectomy for pancreatic adenocarcinoma: Patency rates and outcomes associated with thrombosis. 2018

Snyder, Rebecca A / Prakash, Laura R / Nogueras-Gonzalez, Graciela M / Kim, Michael P / Aloia, Thomas A / Vauthey, Jean-Nicolas / Lee, Jeffrey E / Fleming, Jason B / Katz, Matthew H G / Tzeng, Ching-Wei D. ·Department of Surgery, University of South Carolina School of Medicine-Greenville, Greenville, South Carolina. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida. ·J Surg Oncol · Pubmed #29723419.

ABSTRACT: BACKGROUND AND OBJECTIVES: Venous patency rates after pancreaticoduodenectomy (PD) with portal vein (PV) resection are not well established, and the oncologic impact of portal vein thrombosis (PVT) is unknown. The primary aim of this study was to determine rates and predictors of PVT after PD with PV resection for pancreatic adenocarcinoma (PDAC). METHODS: A retrospective cohort study was performed on PDAC patients treated with preoperative therapy and PD with PV resection at a high-volume institution (2008-15). Primary outcomes were early and late PVT (≤ or >90 days of surgery). Secondary outcomes included major complications and OS. RESULTS: Patients undergoing vein resection (N = 120) included 41.7% (N = 50) primary repair or patch venoplasty, 29.2% (N = 35) primary anastomosis, and 29.2% (N = 35) interposition graft. Thirty-four (28.3%) patients developed PVT (early 7.5% [N = 9]; late 20.8% [N = 25]). Late PVT was often detected concurrently with local recurrence (76.0%; N = 19). There was no association of PVT with vascular resection extent or complications (P > 0.05). On multivariable analysis, PVT was associated with worse OS (HR 2.2 [95% CI 1.34-3.5], P < 0.001). CONCLUSIONS: Overall postoperative patency rates following PV resection PDAC were high. PVT is associated with worse OS, which appears less likely related to technical issues, but rather representative of disease biology.

13 Article Preoperative Fluorouracil, Doxorubicin, and Streptozocin for the Treatment of Pancreatic Neuroendocrine Liver Metastases. 2018

Cloyd, Jordan M / Omichi, Kiyohiko / Mizuno, Takashi / Kawaguchi, Yoshikuni / Tzeng, Ching-Wei D / Conrad, Claudius / Chun, Yun Shin / Aloia, Thomas A / Katz, Matthew H G / Lee, Jeffrey E / Halperin, Daniel / Yao, James / Vauthey, Jean-Nicolas / Dasari, Arvind. ·Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. jvauthey@mdanderson.org. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. adasari@mdanderson.org. ·Ann Surg Oncol · Pubmed #29626307.

ABSTRACT: INTRODUCTION: While preoperative chemotherapy is frequently utilized before resection of non-neuroendocrine liver metastases, patients with resectable neuroendocrine liver metastases typically undergo surgery first. FAS is a cytotoxic chemotherapy regimen that is associated with substantial response rates in locally advanced and metastatic pancreatic neuroendocrine tumors. METHODS: All patients who underwent R0/R1 resection of pancreatic neuroendocrine liver metastases at a single institution between 1998 and 2015 were included. The outcomes of patients treated with preoperative FAS were compared with those of patients who were not. RESULTS: Of the 67 patients included, 27 (40.3%) received preoperative FAS, whereas 40 (59.7%) did not. Despite being associated with higher rates of synchronous disease, lymph node metastases, and larger tumor size, patients who received preoperative FAS had similar overall survival [overall survival (OS), 108.2 months (95% confidence interval (CI) 78.0-136.0) vs. 107.0 months (95% CI 78.0-136.0), p = 0.64] and recurrence-free survival [RFS, 25.1 months (95% CI 23.2-27.0) vs. 18.0 months (95% CI 13.8-22.2), p = 0.16] as patients who did not. Among patients who presented with synchronous liver metastases (n = 46), the median OS [97.3 months (95% CI 65.9-128.6) vs. 65.0 months (95% CI 28.1-101.9), p = 0.001] and RFS [24.8 months (95% CI 22.6-26.9) vs. 12.1 months (2.2-22.0), p = 0.003] were significantly greater among patients who received preoperative FAS compared with those who did not. CONCLUSIONS: The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.

14 Article Anthropometric Changes in Patients with Pancreatic Cancer Undergoing Preoperative Therapy and Pancreatoduodenectomy. 2018

Cloyd, Jordan M / Nogueras-González, Graciela M / Prakash, Laura R / Petzel, Maria Q B / Parker, Nathan H / Ngo-Huang, An T / Fogelman, David / Denbo, Jason W / Garg, Naveen / Kim, Michael P / Lee, Jeffrey E / Tzeng, Ching-Wei D / Fleming, Jason B / Katz, Matthew H G. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1484, PO Box 301402, Houston, TX, 77230-1402, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1484, PO Box 301402, Houston, TX, 77230-1402, USA. mhgkatz@mdanderson.org. ·J Gastrointest Surg · Pubmed #29230694.

ABSTRACT: BACKGROUND: The changes in body composition that occur in response to therapy for localized pancreatic ductal adenocarcinoma (PDAC) and during the early survivorship period, as well as their clinical significance, are poorly understood. METHODS: One hundred twenty-seven consecutive patients with PDAC who received preoperative therapy followed by pancreatoduodenectomy (PD) at a single institution between 2009 and 2012 were longitudinally evaluated. Changes in skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured on serial computed tomography images obtained upon presentation, prior to pancreatectomy, and approximately 3 and 12 months after surgery. RESULTS: Prior to therapy, patients' mean baseline BMI was 26.5 ± 4.7 kg/m CONCLUSIONS: In contrast to the minor changes that occur during preoperative therapy for PDAC, significant losses in key anthropometric parameters tend to occur over the first year following PD. Ongoing SKM loss in the postoperative period may represent an early marker for worse outcomes.

15 Article Genotype-phenotype pancreatic neuroendocrine tumor relationship in multiple endocrine neoplasia type 1 patients: A 23-year experience at a single institution. 2018

Christakis, Ioannis / Qiu, Wei / Hyde, Samuel M / Cote, Gilbert J / Grubbs, Elizabeth G / Perrier, Nancy D / Lee, Jeffrey E. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatobiliary Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China. · Department of Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: jelee@mdanderson.org. ·Surgery · Pubmed #29122330.

ABSTRACT: BACKGROUND: The aim of this study was to investigate the genotype-phenotype relationship of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 treated at our institution. METHODS: We conducted a retrospective chart review of all patients with multiple endocrine neoplasia type 1 treated at our center from January 1993 to December 2015. Presence of a pancreatic neuroendocrine tumor was determined based on imaging performed at any time from presentation to conclusion of follow-up. RESULTS: We reviewed 188 patients. The most common site of multiple endocrine neoplasia type 1 mutation was in exon 2 (34/188; 18%). Of 188 patients, 125 had a pancreatic neuroendocrine tumor (61%). Among all patients, 30 of 34 (88%) with an exon 2 mutation had a pancreatic neuroendocrine tumor compared with 95 of 154 (62%) with a mutation in exons 3-10 (P = .002). In the age group of 20 to 40 years, 8 of 9 patients with an exon 2 mutation had a pancreatic neuroendocrine tumor, compared with 24 of 52 patients (46%) with a mutation in exons 3-10 (P = .028). Patients with an exon 2 mutation had a greater frequency of pancreatic neuroendocrine tumor distant metastasis (53% vs 23%, P = .049). CONCLUSION: Young patients with multiple endocrine neoplasia type 1 and an exon 2 mutation appear to have a 2-fold greater risk for developing a pancreatic neuroendocrine tumor, and patients with an exon 2 mutation may be at greater risk for developing distant metastasis. Consideration should be given to more intensive screening and more liberal application of primary operative intervention in this potentially high-risk group.

16 Article Open Pancreaticoduodenectomy Case Volume Predicts Outcome of Laparoscopic Approach: A Population-based Analysis. 2018

Kutlu, Onur C / Lee, Jeffrey E / Katz, Matthew H / Tzeng, Ching-Wei D / Wolff, Robert A / Varadhachary, Gauri R / Vauthey, Jean-Nicolas / Fleming, Jason B / Conrad, Claudius. ·Department of Surgery, University of Miami, Miller School of Medicine, Miami, FL. · Department of Surgical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX. · Department of Surgical Oncology, University of Kentucky, Lexington, KY. · Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX. ·Ann Surg · Pubmed #28045744.

ABSTRACT: OBJECTIVE: To determine if laparoscopic pancreaticoduodenectomy (LPD) is safe and offers benefits over open pancreaticoduodenectomy (OPD) at institutions with lower pancreaticoduodenectomy (PD) volume. BACKGROUND: Although a hospital-based case volume-outcome relationship for morbidity, mortality, and oncologic quality has been reported for OPD, comparative trends for LPD have yet to be investigated. METHODS: A total of 4739 patients with complete data were identified in National Cancer Data Base between 2010 and 2011; 4309 patients had OPD and 430 patients had LPD. Institutions were categorized into quartiles based on PD case volume. For the entire cohort and within each quartile, LPD and OPD were compared for 30-day and 90-day mortality, length of hospital stay, 30-day unplanned readmission rate, and margin status. Binary logistic regression, linear regression, and propensity score matching was performed. RESULTS: Hospitals with low PD case volume (≤25 PDs per year; 91% of all hospitals in the US and 25% of cases) had the highest 30- and 90-day mortality, highest margin positivity rates, and lowest lymph node counts. These trends were more pronounced in the LPD group. Only in the highest-volume hospitals was LPD associated with shorter hospital stay and lower readmission compared with OPD. CONCLUSIONS: These findings confirm that risks of postoperative mortality and suboptimal oncologic surgical quality following PD are higher in low-volume hospitals. Furthermore, these risks are more profound with LPD compared with OPD. These data suggest that the putative benefits of LPD are unlikely to be observed in institutions performing ≤25 PDs per year.

17 Article Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Chemotherapy. 2017

Nejati, Reza / Goldstein, Jennifer B / Halperin, Daniel M / Wang, Hua / Hejazi, Nazila / Rashid, Asif / Katz, Matthew H / Lee, Jeffrey E / Fleming, Jason B / Rodriguez-Canales, Jaime / Blando, Jorge / Wistuba, Ignacio I / Maitra, Anirban / Wolff, Robert A / Varadhachary, Gauri R / Wang, Huamin. ·From the Departments of *Pathology, †Gastrointestinal Medical Oncology, ‡Surgical Oncology, and §Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. ·Pancreas · Pubmed #28902789.

ABSTRACT: OBJECTIVES: The aim of this study was to examine tumor-infiltrating lymphocytes (TILs) and their prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy. METHODS: Intratumoral CD4, CD8, and FOXP3 lymphocytes were examined by immunohistochemistry using a computer-assisted quantitative analysis in 136 PDAC patients who received neoadjuvant therapy and pancreaticoduodenectomy. The results were correlated with clinicopathological parameters and survival. RESULTS: High CD4 TILs in treated PDAC were associated with high CD8 TILs (P = 0.003), differentiation (P = 0.04), and a lower frequency of recurrence (P = 0.02). Patients with high CD4 TILs had longer disease-free survival and overall survival (OS) than did patients with low CD4 TILs (P < 0.01). The median OS of patients with a high CD8/FOXP3 lymphocyte ratio (39.5 [standard deviation, 6.1] months) was longer than that of patients with a low CD8/FOXP3 lymphocyte ratio (28.3 [standard deviation, 2.3] months; P = 0.01). In multivariate analysis, high CD4 TILs were an independent prognostic factor for disease-free survival (hazard ratio, 0.49; 95% confidence interval, 0.30-0.81; P = 0.005) and OS (hazard ratio, 0.54; 95% confidence interval, 0.33-0.89; P = 0.02). CONCLUSIONS: High level of CD4 lymphocytes is associated with tumor differentiation and lower recurrence and is an independent prognostic factor for survival in PDAC patients treated with neoadjuvant therapy.

18 Article Home-based exercise during preoperative therapy for pancreatic cancer. 2017

Ngo-Huang, An / Parker, Nathan H / Wang, Xuemei / Petzel, Maria Q B / Fogelman, David / Schadler, Keri L / Bruera, Eduardo / Fleming, Jason B / Lee, Jeffrey E / Katz, Matthew H G. ·Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1414, Houston, TX, 77030, USA. ango2@mdanderson.org. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Health and Human Performance, University of Houston, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Clinical Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1414, Houston, TX, 77030, USA. ·Langenbecks Arch Surg · Pubmed #28710540.

ABSTRACT: PURPOSE: Exercise concurrent with neoadjuvant chemotherapy and/or chemoradiation for pancreatic adenocarcinoma (PDAC) may mitigate the decline in function that may occur as a result of the disease or its treatment in the preoperative period. The primary objective of this single-arm prospective trial was to determine adherence to a home-based exercise program administered during preoperative therapy. METHODS: Twenty patients from a quaternary cancer center with potentially resectable PDAC were enrolled. Patients were prescribed a minimum of 120 min of moderate-intensity exercise weekly: at least 60 min of aerobic exercise and 60 min of resistance exercise. Self-reported exercise was recorded in daily logs. Functional and survey measures were collected upon enrollment, following preoperative therapy, and 1 month after surgery. RESULTS: Fifteen out of 20 patients participated in the program. They reported a mean (standard deviation (SD)) of 98.6 (69.8) min of aerobic exercise weekly and 57.4 (36.0) min of strengthening exercise weekly over a median of 17 weeks (range, 5-35 weeks) of preoperative therapy, for a mean (SD) of 156.0 (64.5) min of total exercise weekly. Eighty percent reported a mean of least 120 min of total exercise weekly during preoperative therapy. Patients with low baseline physical activity based on the International Physical Activity Questionnaire significantly increased their preoperative physical activity (p = .01). There were no adverse events associated with the exercise program. CONCLUSIONS: Patients with PDAC will participate in a home-based exercise program of aerobic and strengthening exercise and will increase physical activity, concurrent with preoperative chemotherapy and/or chemoradiation.

19 Article Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma. 2017

Cloyd, Jordan M / Wang, Huamin / Egger, Michael E / Tzeng, Ching-Wei D / Prakash, Laura R / Maitra, Anirban / Varadhachary, Gauri R / Shroff, Rachna / Javle, Milind / Fogelman, David / Wolff, Robert A / Overman, Michael J / Koay, Eugene J / Das, Prajnan / Herman, Joseph M / Kim, Michael P / Vauthey, Jean-Nicolas / Aloia, Thomas A / Fleming, Jason B / Lee, Jeffrey E / Katz, Matthew H G. ·Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston. · Department of Pathology; University of Texas MD Anderson Cancer Center, Houston. · Department of Gastrointestinal Medical Oncology; University of Texas MD Anderson Cancer Center, Houston. · Department of Radiation Oncology; University of Texas MD Anderson Cancer Center, Houston. ·JAMA Surg · Pubmed #28700784.

ABSTRACT: Importance: We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined. Objective: To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma. Design, Setting, and Participants: Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015. Exposures: Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%). Main Outcomes and Measures: Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression. Results: Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P < .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009). Conclusions and Relevance: Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.

20 Article Prognostic Significance of New AJCC Tumor Stage in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Therapy. 2017

Chatterjee, Deyali / Katz, Matthew H / Foo, Wai Chin / Sundar, Manonmani / Wang, Hua / Varadhachary, Gauri R / Wolff, Robert A / Lee, Jeffrey E / Maitra, Anirban / Fleming, Jason B / Rashid, Asif / Wang, Huamin. ·Departments of *Pathology †Surgical Oncology ‡Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX. ·Am J Surg Pathol · Pubmed #28614206.

ABSTRACT: The American Joint Committee for Cancer has adopted a size-based T stage system (eighth edition) for pancreatic ductal adenocarcinoma (PDAC), defined as follows: pT1≤2 cm (pT1a≤0.5 cm, pT1b>0.5 and<1 cm, and pT1c 1-2 cm); pT2>2 and ≤4 cm; and pT3> 4 cm. However, the prognostic value of this new T staging system has not been validated in patients who underwent pancreaticoduodenectomy (PD) after neoadjuvant therapy. In this study, we analyzed 398 PDAC patients who underwent neoadjuvant therapy and PD at our institution from 1999 to 2012. The results were correlated with clinicopathologic parameters and survival. The new T stage correlated with lymph nodes metastasis (P<0.001), tumor response grade (P<0.001), disease-free survival (DFS, P<0.001) and overall survival (OS, P<0.001). None of the patients with ypT0 had recurrence or died of disease. Among the patients with ypT1 disease, patients with ypT1a and ypT1b had better DFS (P=0.046) and OS (P=0.03) than those with ypT1c. However, there was no significant difference in either DFS or OS between ypT1c and ypT2 or between ypT2 and ypT3 groups (P>0.05). In multivariate analysis, new ypT3 stage was associated with shorter OS (P=0.04), but not DFS (P=0.16). Our results show that the new ypT stage better stratify survival than the ypT stage in American Joint Committee for Cancer seventh edition for PDAC patients who received PD after neoadjuvant therapy, and that tumor size cutoff of 1.0 cm work better for ypT2 than the proposed tumor size cutoff of 2.0 cm in this group of patients.

21 Article Is estrogen exposure a protective factor for pancreatic neuroendocrine tumours in female patients with multiple endocrine neoplasia syndrome type 1? 2017

Qiu, Wei / Christakis, Ioannis / Stewart, Ashley A / Vodopivec, Danica M / Silva-Figueroa, Angelica / Chen, Huiqin / Woodard, Terri L / Halperin, Daniel M / Lee, Jeffrey E / Yao, James C / Perrier, Nancy D. ·Department of Hepatobiliary Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgery, Levine Cancer Institute, Charlotte, NC, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Clin Endocrinol (Oxf) · Pubmed #28273369.

ABSTRACT: OBJECTIVE: Pancreatic neuroendocrine tumours (PNETs) are the most common cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Women have been shown to have improved survival, which may suggest a possible protective effect of female sex hormones. The aim of this study was to evaluate the relationship between estrogen exposure and PNET tumourigenesis, tumour growth and survival in female MEN1 patients with these tumours. DESIGN: We performed a retrospective chart review of the existing MEN1 database in our institution. Detailed information about female patients' menstrual and reproductive history, and PNET clinicopathologic characteristics was collected. Questionnaires regarding estrogen exposure were used to collect information that was missing in the database. PATIENTS: Of 293 confirmed MEN1 cases, 141 women met the inclusion criteria. MEASUREMENTS: We used measures of cumulative estrogen exposure time (CEET), parity, live birth pregnancies and bilateral oophorectomy to estimate estrogen exposure. RESULTS: There was no significant association between CEET and time to PNET diagnosis (hazard ratio = 0·966, P = 0·380). For the correlation between estrogen exposure and PNET type, size, numbers, distant metastasis, lymph node metastasis, lymphovascular invasion, AJCC (American Joint Committee on Cancer) stage and overall survival, only CEET was significantly correlated with PNET size (P = 0·043). CONCLUSIONS: In female patients with MEN1, estrogen exposure may inhibit PNET growth. A demonstrable protective effect against PNET tumourigenesis, tumour growth and survival of patients with these tumours may require a larger cohort.

22 Article Reduced expression of argininosuccinate synthetase 1 has a negative prognostic impact in patients with pancreatic ductal adenocarcinoma. 2017

Liu, Qingqing / Stewart, John / Wang, Hua / Rashid, Asif / Zhao, Jun / Katz, Matthew H / Lee, Jeffrey E / Fleming, Jason B / Maitra, Anirban / Wolff, Robert A / Varadhachary, Gauri R / Krishnan, Sunil / Wang, Huamin. ·Department of Pathology, the University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Surgical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. ·PLoS One · Pubmed #28187218.

ABSTRACT: Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme for arginine biosynthesis, is expressed in many types of human malignancies. Recent studies showed that ASS1 may have tumor suppressor function and that ASS1 deficiency is associated with clinical aggressiveness in nasopharyngeal carcinoma, myxofibrosarcomas and bladder cancer. The goal of this study was to evaluate the prognostic impact of ASS1 expression in patients with pancreatic ductal adenocarcinoma (PDAC). Our study included two independent cohorts: untreated cohort, which was comprised of 135 patients with PDAC who underwent pancreatoduodenectomy (PD) without pre-operative neoadjuvant therapy, and treated cohort, which was comprised of 122 patients with PDAC who have completed neoadjuvant therapy and PD. The expression level of ASS1 was evaluated by immunohistochemistry and the results were correlated with clinicopathologic parameters and survival using SPSS statistics. Our study showed that 12% of PDAC in untreated cohort and 15% of PDAC in treated cohort has low expression of ASS1 (ASS1-low). ASS1-low was associated with higher recurrence (p = 0.045), shorter disease-free survival (DFS, 4.8 ± 1.6 months vs 15.3 ± 2.2 months, p = 0.001) and shorter overall survival (OS, 14.6 ± 6.4 months vs 26.5 ± 3.5 months, p = 0.005) in untreated cohort and shorter OS in treated cohort compared to ASS1-high tumors. In multivariate analysis, ASS1-low (HR: 0.45, 95% CI: 0.26-0.79, p = 0.005) was an independent prognostic factor for DFS in untreated cohort and an independent prognostic factor for OS (HR: 0.56, 95% CI: 0.32-0.97, p = 0.04) in treated cohort. Our results provide supporting evidence for future clinical trial using arginine deprivation agents either alone or in combination with conventional chemotherapy in treating pancreatic cancer.

23 Article Impact of pancreatectomy on long-term patient-reported symptoms and quality of life in recurrence-free survivors of pancreatic and periampullary neoplasms. 2017

Cloyd, Jordan M / Tran Cao, Hop S / Petzel, Maria Q B / Denbo, Jason W / Parker, Nathan H / Nogueras-González, Graciela M / Liles, Joseph S / Kim, Michael P / Lee, Jeffrey E / Vauthey, Jean-Nicolas / Aloia, Thomas A / Fleming, Jason B / Katz, Matthew H G. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Division of Surgical Oncology, Michael E. DeBakey VA Medical Center, Baylor College Medicine, Houston, Texas. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Division of Surgical Oncology, Department of Surgery, University of South Alabama, Mobile, Alabama. ·J Surg Oncol · Pubmed #27859270.

ABSTRACT: BACKGROUND: Long term patient-reported symptoms and quality of life (QOL) are important outcome metrics following cancer operations, but have been poorly described in patients who have previously undergone pancreatectomy. METHODS: We conducted a cross-sectional survey of recurrence-free survivors of pancreatic ductal adenocarcinoma, periampullary carcinomas, and pancreatic neuroendocrine tumors who had undergone prior pancreatectomy. QOL and symptom burden were measured using the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire, and psychosocial distress was measured using the Hospital Anxiety and Depression Scale. RESULTS: Of 331 eligible patients surveyed, 217 (66%) participated at a median of 53.3 (range, 7.6-214.8) months following pancreatoduodenectomy (PD, n = 165) or distal pancreatectomy (DP, n = 52). Among all patients, overall QOL scores were favorable and influenced by race, histology, and type of surgery. The most common significant symptoms reported were fatigue (82%), back pain (32%), and difficulty with digestion (31%). In general, PD survivors reported better QOL, lower levels of anxiety/depression, greater levels of diarrhea, and improved appetite, constipation, fatigue, anxiety, and depression (P < 0.05) than DP survivors. On both univariate and multivariate regression analysis, DP was negatively associated with QOL. CONCLUSIONS: Most disease-free survivors of pancreatic neoplasms report favorable QOL, but gastrointestinal and psychosocial symptoms may exist long after pancreatectomy. J. Surg. Oncol. 2017;115:144-150. © 2016 Wiley Periodicals, Inc.

24 Article Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience. 2017

Cloyd, Jordan M / Katz, Matthew H G / Prakash, Laura / Varadhachary, Gauri R / Wolff, Robert A / Shroff, Rachna T / Javle, Milind / Fogelman, David / Overman, Michael / Crane, Christopher H / Koay, Eugene J / Das, Prajnan / Krishnan, Sunil / Minsky, Bruce D / Lee, Jeffrey H / Bhutani, Manoop S / Weston, Brian / Ross, William / Bhosale, Priya / Tamm, Eric P / Wang, Huamin / Maitra, Anirban / Kim, Michael P / Aloia, Thomas A / Vauthey, Jean-Nicholas / Fleming, Jason B / Abbruzzese, James L / Pisters, Peter W T / Evans, Douglas B / Lee, Jeffrey E. ·Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1484, Houston, TX, 77030, USA. · Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gasteroenterology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA. · University Health Network, Toronto, ON, Canada. · Division of Surgical Oncology, Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1484, Houston, TX, 77030, USA. jelee@mdanderson.org. ·J Gastrointest Surg · Pubmed #27778257.

ABSTRACT: BACKGROUND: The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to pancreatoduodenectomy (PD). METHODS: Consecutive patients (622) with PDAC who underwent PD following chemotherapy and/or chemoradiation between 1990 and 2014 were retrospectively reviewed. Preoperative treatment regimens, clinicopathologic characteristics, operative details, and long-term outcomes in four successive time periods (1990-1999, 2000-2004, 2005-2009, 2010-2014) were evaluated and compared. RESULTS: The average number of patients per year who underwent PD following preoperative therapy as well as the proportion of operations performed for borderline resectable and locally advanced (BR/LA) tumors increased over time. The use of induction systemic chemotherapy, as well as postoperative adjuvant chemotherapy, also increased over time. Throughout the study period, the mean EBL decreased while R0 margin rates and vascular resection rates increased overall. Despite the increase in BR/LA resections, locoregional recurrence (LR) rates remained similar over time, and overall survival (OS) improved significantly (median 24.1, 28.1, 37.3, 43.4 months, respectively, p < 0.0001). CONCLUSIONS: Despite increases in case complexity, relatively low rates of LR have been maintained while significant improvements in OS have been observed. Further improvements in patient outcomes will likely require disruptive advances in systemic therapy.

25 Article Role of Fluorouracil, Doxorubicin, and Streptozocin Therapy in the Preoperative Treatment of Localized Pancreatic Neuroendocrine Tumors. 2017

Prakash, Laura / Bhosale, Priya / Cloyd, Jordan / Kim, Michael / Parker, Nathan / Yao, James / Dasari, Arvind / Halperin, Daniel / Aloia, Thomas / Lee, Jeffrey E / Vauthey, Jean Nicolas / Fleming, Jason B / Katz, Matthew H G. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1484, PO Box 301402, Houston, TX, 77230-1402, USA. · Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1484, PO Box 301402, Houston, TX, 77230-1402, USA. mhgkatz@mdanderson.org. ·J Gastrointest Surg · Pubmed #27634306.

ABSTRACT: INTRODUCTION: 5-Fluorouracil, doxorubicin, and streptozocin (FAS) leads to a 39 % response rate in advanced pancreatic neuroendocrine tumors (pNETs). We sought to validate our hypothesis that preoperative FAS may facilitate resection of locoregionally advanced pNETs by reducing the anatomic extent of the primary tumor. PATIENTS: All patients who received FAS between 2000 and 2012 as initial therapy for a localized pNET were reviewed. Tumor size and vascular relationships were compared on pretreatment and posttreatment imaging studies to quantify treatment response. RESULTS: Twenty-nine patients received a median 4 cycles of FAS (range 2-15). Rates of RECIST progressive disease (PD), stable disease (SD), and partial response (PR) were 3, 90, and 7 %, respectively. An interface was observed between the tumor and a major mesenteric artery and/or vein in 19 (66 %) and 24 (83 %) patients, respectively; after therapy with FAS, 17 (59 %) and 22 (76 %) had persistent interface with artery and/or vein. Fourteen (48 %) patients underwent pancreatectomy, 7 (50 %) required vascular management, and 9 (64 %) operations were R0. The median overall survival of unresected and resected patients was 41 months (95 % CI, 16-66) and 112 months (95 % CI, 104-120) (P = 0.04). CONCLUSIONS: Although patients receiving FAS for locoregionally advanced pNETs are unlikely to progress during systemic therapy, significant "downstaging" appears uncommon.

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