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Pancreatic Neoplasms: HELP
Articles from South Carolina
Based on 69 articles published since 2008
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These are the 69 published articles about Pancreatic Neoplasms that originated from South Carolina during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial The Countdown to a Paradigm Shift in Diagnosing Pancreatic Ductal Adenocarcinoma. 2017

Coté, Gregory A. ·Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina. ·Clin Gastroenterol Hepatol · Pubmed #28300695.

ABSTRACT: -- No abstract --

2 Review Dietary patterns and risk of pancreatic cancer: a systematic review. 2017

Zheng, Jiali / Guinter, Mark A / Merchant, Anwar T / Wirth, Michael D / Zhang, Jiajia / Stolzenberg-Solomon, Rachael Z / Steck, Susan E. ·Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA. · Cancer Prevention and Control Program, University of South Carolina, Columbia, South Carolina, USA. · Connecting Health Innovations LLC, Columbia, South Carolina, USA. · Division of Cancer Epidemiology and Genetics, Nutritional Epidemiology Branch, National Cancer Institute, Rockville, Maryland, USA. ·Nutr Rev · Pubmed #29025004.

ABSTRACT: Context: Pancreatic cancer has the highest case fatality rate of all major cancers. Objective: A systematic review using PRISMA guidelines was conducted to summarize the associations between dietary patterns and risk of pancreatic cancer. Data Sources: PubMed and Web of Science databases were searched for case-control and cohort studies published up to June 15, 2016. Study Selection: Eligible studies included a dietary pattern as exposure and pancreatic cancer incidence or mortality as outcome and reported odds ratios, hazard ratios, or relative risks, along with corresponding 95%CIs. Data Extraction: Important characteristics of each study, along with the dietary assessment instrument, the component foods or nutrients included in each dietary pattern or the scoring algorithm of a priori dietary patterns, were presented. For each dietary pattern identified, the estimate of association and the 95%CI comparing the highest versus the lowest category from the model with the most covariate adjustment were reported. Results: A total of 16 studies were identified. Among the 8 studies that examined data-driven dietary patterns, significant positive associations were found between pancreatic cancer risk and the Animal Products, Starch Rich, and Western dietary patterns, with effect estimates ranging from 1.69 to 2.40. Significant inverse relationships were found between risk of pancreatic cancer and dietary patterns designated as Fruits and Vegetables, Vitamins and Fiber, and Prudent, with effect estimates ranging from 0.51 to 0.55. Eight studies of a priori dietary patterns consistently suggested that improved dietary quality was associated with reduced risk of pancreatic cancer. Conclusions: Better diet quality is associated with reduced risk of pancreatic cancer. The associations between dietary patterns and pancreatic cancer were stronger in case-control studies than in cohort studies and were stronger among men than among women.

3 Review Update on the Management of Pancreatic Cancer in Older Adults. 2016

Lee, Shin Yin / Sissoko, Moussa / Hartshorn, Kevan L. ·Section of Hematology/Oncology, Boston University School of Medicine, Boston Medical Center, 820 Harrison Avenue, Boston, MA, 02118, USA. shinyin.lee@bmc.org. · Charleston Area Medical Center Cancer Center, 3415 MacCorkle Avenue, SE, Charleston, WV, 25304, USA. · Section of Hematology/Oncology, Boston University School of Medicine, Boston Medical Center, 820 Harrison Avenue, Boston, MA, 02118, USA. ·Curr Oncol Rep · Pubmed #27492426.

ABSTRACT: Pancreatic cancer is more common in older adults, who are underrepresented in clinical trials and frequently under treated. Chronological age alone should not deter clinicians from offering treatment to geriatric patients, as they are a heterogeneous population. Geriatric assessment, frailty assessment tools, and toxicity risk scores help clinicians select appropriate patients for therapy. For resectable disease, surgery can be safe but should be done at a high-volume center. Adjuvant therapy is important; though there remains controversy on the role of radiation, chemotherapy is well studied and efficacious. In locally advanced unresectable disease, chemoradiation or chemotherapy alone is an option. Neoadjuvant therapy improves the chances of resectability in borderline resectable disease. Chemotherapy extends survival in metastatic disease, but treatment goals and risk-benefit ratios have to be clarified. Adequate symptom management and supportive care are important. There are now many new treatment strategies and novel therapies for this disease.

4 Review Non-neoplastic pancreatic lesions that may mimic malignancy. 2016

Okun, Sherry D / Lewin, David N. ·Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Ave MSC 908, Charleston, South Carolina 29425-9080. Electronic address: okuns@musc.edu. · Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Ave MSC 908, Charleston, South Carolina 29425-9080. ·Semin Diagn Pathol · Pubmed #26602569.

ABSTRACT: The widespread use of abdominal ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) has resulted in an increased identification of asymptomatic pancreatic lesions. Preoperative diagnoses of pancreatic lesions can be difficult. Solid and cystic lesions and anatomic variants of normal can all mimic tumor clinically and radiologically. Newer imaging modalities have increased the likelihood of the accurate diagnosis of non-neoplastic pancreatic disease, however, despite the many advances; it still remains a challenge to differentiate rarer non-neoplastic entities and inflammatory masses from adenocarcinoma, preoperatively. Adding to the challenge is the fact that a variety of inflammatory, solid and cystic non-neoplastic lesions have significant clinical and radiological overlap with malignancies. About 5-10% of pancreatectomies performed with the primary clinical diagnosis of pancreatic carcinoma are later proved to be essentially non-neoplastic lesions. It is vital to include these non-neoplastic entities in the differential diagnosis while working up abnormal clinical and radiological pancreatic findings because it may drastically alter therapeutic options for the patients. The significance of recognizing these lesions preoperatively is to help to guide the clinical decision-making process and the avoidance of an unnecessary pancreatectomy. Examples of such entities include chronic pancreatitis, sarcoidosis, intrapancreatic accessory spleen (IPAS), lymphoid hyperplasia, lipomatous pseudohypertrophy (LPH), lymphangioma, lymphoepithelial cyst (LEC) and endometriosis.

5 Review Palliative chemotherapy for pancreatic malignancies. 2010

Mehta, Sharmila P. ·Palmetto Hematology/Oncology Internal Medicine, Marsha and Jimmy Gibbs Regional Cancer Center, Spartanburg Regional Health Systems, 380 Serpentine Drive, Suite 200, Spartanburg, SC 29303, USA. smehta@srhs.com ·Surg Clin North Am · Pubmed #20362792.

ABSTRACT: Metastatic pancreatic cancer is often one of the most challenging malignancies a medical oncologist faces. Although the primary endpoint of many studies remains overall survival, palliation and quality of life are now more commonly being addressed. The author discusses the most common chemotherapeutic modalities for the treatment of metastatic pancreatic cancer, such as single agent chemotherapy, combination therapy, targeted therapy, and second line treatment.

6 Review Solid tumors of the body and tail of the pancreas. 2010

Morgan, Katherine A / Adams, David B. ·Section of Gastrointestinal and Laparoscopic Surgery, Medical University of South Carolina, 25 Courtenay Drive Suite 7018, MSC 290, Charleston, SC 29425, USA. morganka@musc.edu ·Surg Clin North Am · Pubmed #20362787.

ABSTRACT: Solid lesions of the body and tail of the pancreas challenge all the diagnostic and technical skills of the modern gastrointestinal surgeon. The information available from modern computed tomography (CT), magnetic resonance (MR), and endoscopic ultrasound (EUS) imaging provide diagnostic and anatomic data that give the surgeon precise information with which to plan an operation and to discuss with the patient during the preoperative visit. A preoperative evaluation includes a thorough history and a pancreas protocol CT scan, supplemented by MR imaging and EUS when needed, to differentiate between the various potential diagnoses. These same modalities can be essential in proper staging in the case of malignant lesions, thus aiding in management decisions. Most lesions ultimately require operative resection, barring metastatic disease, with the notable exception of autoimmune pancreatitis.

7 Review Outcomes in pancreatic cancer surgery. 2010

Orr, Richard K. ·Marsha and Jimmy Gibbs Regional Cancer Center - 3rd Floor, Spartanburg Regional Medical Center, Spartanburg, SC 29303, USA. Rick1841@yahoo.com ·Surg Clin North Am · Pubmed #20362783.

ABSTRACT: The increase in surgery for pancreatic cancer during the last 3 decades can be correlated with a gradual decline in operative mortality and postoperative complications. Although not all surgeons (nor all hospitals) can have equal outcomes, the definition and tabulation of these outcomes have been difficult. This article asks several pertinent questions: (1) what is the scientific rationale for pancreatic resection? (2) what are the best available results at this time? (3) who should be performing pancreatic resections? The article analyzes results of resection for adenocarcinoma of the exocrine pancreas, and excludes duodenal and ampullary cancers, pancreatic endocrine tumors, and tumors of less malignant potential.

8 Review The pancreatic anastomosis: the danger of a leak, which anastomotic technique is better? 2009

Adams, David B. ·Division of Gastrointestinal & Laparoscopic Surgery, Medical University of South Carolina, Ashley River Tower, 25 Courtenay Drive, Charleston, SC 29403, USA. adamsdav@musc.edu ·J Gastrointest Surg · Pubmed #19333663.

ABSTRACT: -- No abstract --

9 Clinical Trial A Phase 2 Study of PCI-27483, a Factor VIIa Inhibitor in Combination with Gemcitabine for Advanced Pancreatic Cancer. 2019

Ramanathan, Ramesh K / Thomas, Gary W / Khorana, Alok A / Shah, Satish / Zhou, Cathy / Wong, Sofia / Cole, George / James, Danelle / Gabrail, Nashat Y. ·Honor Health Research Institute/Translational Genomics Research Institute, Scottsdale, Arizona, USA. · South Carolina Cancer Specialists, Hilton Head Island, South Carolina, USA. · University of Rochester, Rochester, New York, USA. · Gettysburg Cancer Center, Gettysburg, Pennsylvania, USA. · Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California, USA. · Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California, USA, gecole@pcyc.com. · Gabrail Cancer Center, Canton, Ohio, USA. ·Oncology · Pubmed #30844808.

ABSTRACT: OBJECTIVES: Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may contribute to tumor invasiveness by promoting cell migration and angiogenesis. The study objective was to evaluate safety, pharmacokinetics, and efficacy of PCI-27483, a selective FVIIa inhibitor. METHODS: This was an open-label, multicenter phase 2 trial of patients with advanced pancreatic cancer. Part A of the study was an intrapatient dose escalation lead-in portion in patients concurrently receiving gemcitabine, and in part B, patients were randomized 1: 1 to the recommended phase 2 dose combination PCI-27483-gemcitabine versus gemcitabine alone. RESULTS: Target international normalized ratio (between 2.0-3.0) was achieved following PCI-27483 treatment. Overall safety of PCI-27483-gemcitabine (n = 26) was similar to gemcitabine alone (n = 16), with a higher incidence of mostly low-grade bleeding events (65% vs. 19%). Progression-free survival (PFS) and overall survival (OS) were not significantly different between patients treated with PCI-27483-gemcitabine (PFS: 3.7 months, OS: 5.7 months) and those treated with gemcitabine alone (PFS: 1.9 months, OS: 5.6 months). CONCLUSIONS: Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483-gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated.

10 Clinical Trial A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent. 2017

Fountzilas, Christos / Chhatrala, Ravi / Khushalani, Nikhil / Tan, Wei / LeVea, Charles / Hutson, Alan / Tucker, Chris / Ma, Wen Wee / Warren, Graham / Boland, Patrick / Iyer, Renuka. ·Roswell Park Cancer Institute, Buffalo, Elm and Carlton Streets, Buffalo, NY, 14263, USA. · The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. · Virginia Commonwealth University, Richmond, VA, USA. · Moffitt Cancer Center, Tampa, FL, USA. · Astellas Pharmaceuticals Inc., Long Island, NY, USA. · Mayo Clinic, Rochester, MN, USA. · Medical University of South Carolina, Charleston, SC, USA. · Roswell Park Cancer Institute, Buffalo, Elm and Carlton Streets, Buffalo, NY, 14263, USA. Renuka.Iyer@roswellpark.org. ·Cancer Chemother Pharmacol · Pubmed #28702772.

ABSTRACT: INTRODUCTION: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy. METHODS: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS). Correlations of clinical response with smoking, rash, steady-state concentration of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite cotinine were performed. RESULTS: The trial was terminated early for futility. Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and 95 days, respectively. Best response was stable disease (21%). There was a trend for improved PFS and OS in never smokers compared to current and past smokers (128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers had lower steady-state concentrations of erlotinib and OSI-420 compared to never smokers. There was evidence of recent smoking exposure in 30% of patients self-identified as past smokers. Rash was infrequent, with no cases of grade III/IV rash and it was not related to treatment outcomes. CONCLUSIONS: Overall, erlotinib monotherapy failed to improve outcomes compared to historical controls in patients with APC after 0-1 prior systemic therapies. There was a trend for improved PFS and OS in never smokers.

11 Clinical Trial Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer. 2017

Mehrotra, Shikhar / Britten, Carolyn D / Chin, Steve / Garrett-Mayer, Elizabeth / Cloud, Colleen A / Li, Mingli / Scurti, Gina / Salem, Mohamed L / Nelson, Michelle H / Thomas, Melanie B / Paulos, Chrystal M / Salazar, Andres M / Nishimura, Michael I / Rubinstein, Mark P / Li, Zihai / Cole, David J. ·Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, 29425, USA. mehrotr@musc.edu. · Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. mehrotr@musc.edu. · Present address: Gibbs Cancer Center and Research Institute, 380 Serpentine Drive, Spartanburg, SC, 29303, USA. mehrotr@musc.edu. · Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA. · Present address: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. · Departmet of Population Sciences, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA. · Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, 29425, USA. · Department of Surgery, Loyola University Medical Center, Maywood, IL, 60153, USA. · Center of Excellence in Cancer Research and Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt. · Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. · Present address: Gibbs Cancer Center and Research Institute, 380 Serpentine Drive, Spartanburg, SC, 29303, USA. · Oncovir Inc., 3202 Cleaveland Avenue NW, Washington, DC, 20008, USA. · Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, 29425, USA. coledj@musc.edu. · Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. coledj@musc.edu. ·J Hematol Oncol · Pubmed #28388966.

ABSTRACT: BACKGROUND: Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). METHODS: We generated autologous DCs from the peripheral blood of HLA-A2 RESULTS: Twelve patients underwent apheresis: nine patients with metastatic disease, and three patients with locally advanced unresectable disease. Vaccines were successfully manufactured from all individuals. We found that this treatment was well-tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms. Among the eight patients who underwent imaging on day 56, four patients experienced stable disease while four patients had disease progression. The median overall survival was 7.7 months. One patient survived for 28 months post leukapheresis. MHC class I -tetramer analysis before and after vaccination revealed effective generation of antigen-specific T cells in three patients with stable disease. CONCLUSION: Vaccination with peptide-pulsed DCs in combination with poly-ICLC is safe and induces a measurable tumor specific T cell population in patients with advanced PC. TRIAL REGISTRATION: NCT01410968 ; Name of registry: clinicaltrials.gov; Date of registration: 08/04/2011).

12 Clinical Trial A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma. 2017

Benson, Al B / Wainberg, Zev A / Hecht, J Randolph / Vyushkov, Dmitry / Dong, Hua / Bendell, Johanna / Kudrik, Fred. ·Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA a-benson@northwestern.edu. · David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA. · Budgetary Healthcare Institution of Omsk Region, Clinical Oncologic Dispensary, Omsk, Russia. · Gilead Sciences, Inc., Foster City, California, USA. · Sarah Cannon Research Institute, Nashville, Tennessee, USA. · South Carolina Oncology Associates, Columbia, South Carolina, USA. ·Oncologist · Pubmed #28246206.

ABSTRACT: LESSONS LEARNED: The safety profile in the gemcitabine/simtuzumab group was similar to that in the gemcitabine/placebo group.The addition of simtuzumab to gemcitabine does not improve clinical outcomes in patients with metastatic pancreatic adenocarcinoma ABSTRACT: Background.The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. METHODS: Adult patients with metastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m RESULTS: Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median follow-up of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI], CONCLUSION: The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.

13 Clinical Trial Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer. 2015

Borad, Mitesh J / Reddy, Shantan G / Bahary, Nathan / Uronis, Hope E / Sigal, Darren / Cohn, Allen L / Schelman, William R / Stephenson, Joe / Chiorean, E Gabriela / Rosen, Peter J / Ulrich, Brian / Dragovich, Tomislav / Del Prete, Salvatore A / Rarick, Mark / Eng, Clarence / Kroll, Stew / Ryan, David P. ·Mitesh J. Borad, Mayo Clinic, Scottsdale · Tomislav Dragovich, Arizona Cancer Center, Tucson, AZ · Shantan G. Reddy, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA · Nathan Bahary, University of Pittsburgh Medical Center, Pittsburgh, PA · Hope E. Uronis, Duke University Medical Center, Durham, NC · Darren Sigal, Scripps Clinic, La Jolla · Peter J. Rosen, Disney Family Cancer Center, Burbank · Clarence Eng and Stew Kroll, Threshold Pharmaceuticals, South San Francisco, CA · Allen L. Cohn, Rocky Mountain Cancer Center, Denver, CO · William R. Schelman, University of Wisconsin Carbone Cancer Center, Madison, WI · Joe Stephenson Jr, Institute for Translational Oncology Research, Greenville, SC · E. Gabriela Chiorean, Indiana University Simon Cancer Center, Indianapolis, IN · Brian Ulrich, Texas Oncology, Wichita Falls, TX · Salvatore A. Del Prete, Hematology Oncology PC, Stamford, CT · Mark Rarick, Kaiser Permanente Northwest Region Oncology Hematology, Portland, OR · and David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA. ·J Clin Oncol · Pubmed #25512461.

ABSTRACT: PURPOSE: TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m(2)), gemcitabine plus TH-302 240 mg/m(2) (G+T240), or gemcitabine plus TH-302 340 mg/m(2) (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. RESULTS: Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (-5,398 v -549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302-related AEs but were not associated with treatment discontinuation. CONCLUSION: PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979).

14 Clinical Trial Phase 2 trial of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer. 2014

Esnaola, Nestor F / Chaudhary, Uzair B / O'Brien, Paul / Garrett-Mayer, Elizabeth / Camp, E Ramsay / Thomas, Melanie B / Cole, David J / Montero, Alberto J / Hoffman, Brenda J / Romagnuolo, Joseph / Orwat, Kelly P / Marshall, David T. ·Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina. · Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina. · Division of Biostatistics and Epidemiology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina. · Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina. · Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina. Electronic address: marshadt@musc.edu. ·Int J Radiat Oncol Biol Phys · Pubmed #24606850.

ABSTRACT: PURPOSE: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). METHODS AND MATERIALS: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; "downstaged" patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. RESULTS: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. CONCLUSIONS: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.

15 Clinical Trial Comparison of radiation treatment delivery for pancreatic cancer: Linac intensity-modulated radiotherapy versus helical tomotherapy. 2012

Taylor, Robert / Opfermann, Krisha / Jones, Brian D / Terwilliger, Lacy E / McDonald, Daniel G / Ashenafi, Michael S / Garrett-Meyer, Elizabeth / Marshall, David T. ·Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina 29464, USA. ·J Med Imaging Radiat Oncol · Pubmed #22697333.

ABSTRACT: INTRODUCTION: Intensity-modulated radiotherapy (IMRT) has been shown to reduce dose to organs at risk (OAR) while adequately treating tumour volume. This study quantitatively compares the dosimetric differences from step-and-shoot IMRT compared with helical tomotherapy (HT) for pancreatic head cancer. METHODS: Twelve consecutive patients with non-metastatic, stage T3 or T4, unresectable pancreatic head cancer were planned for step-and-shoot IMRT as well as HT. Radiotherapy was planned to deliver 45.9 Gy to the clinical target volume in 30 fractions with an integrated boost to 54 Gy to the gross tumour volume (planning target volume 5400 including a 1-cm set-up margin). The uniformity index (UI) and conformity index (CI) were used to compare the quality of target coverage, while the quality index (QI) compared the dosimetric performance for OAR. RESULTS: Both methods were effective at covering the tumour with no significant difference in UI or CI. However, HT dosimetry exhibited superior sparing of OAR with significantly less stomach (mean QI(StomV30) = 0.84, P = 0.006) and small bowel dosing (mean small bowel QI(SBV30) = 0.84, P = 0.005). HT reduced dose to the kidney receiving the highest dose but the overall volume of kidney receiving 18 Gy was not significantly different between the two systems, indicating that HT spread the dose more uniformly through the kidneys. CONCLUSIONS: Target coverage is equivalent between the two systems; however, HT shows significantly better sparing of the stomach and small bowel. The decreased dose to OAR with HT is likely to improve the therapeutic ratio in the radiotherapy of pancreatic head cancers.

16 Article Loss of PDPK1 abrogates resistance to gemcitabine in label-retaining pancreatic cancer cells. 2018

Li, Dandan / Mullinax, John E / Aiken, Taylor / Xin, Hongwu / Wiegand, Gordon / Anderson, Andrew / Thorgeirsson, Snorri / Avital, Itzhak / Rudloff, Udo. ·Rare Tumor Initiative, Cancer for Cancer Research, National Cancer Institute, Building 10, Room 2B-38E, Bethesda, MD, USA. · Sarcoma Department, Moffitt Cancer Center, Tampa, FL, USA. · Thoracic & GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. · Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. · Laboratory of Oncology, Center for Molecular Medicine and Department of Molecular Biology and Biochemistry, School of Basic Medicine, Yangtze University, Jingzhou, Hubei, China. · Flow Cytometry Core, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA. · Gilead Sciences, Foster City, CA, USA. · Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, USA. · St. Peter's Hospital, Rutgers University, Robert Wood Johnson School of Medicine, New Brunswick, NJ, USA. · Rare Tumor Initiative, Cancer for Cancer Research, National Cancer Institute, Building 10, Room 2B-38E, Bethesda, MD, USA. rudloffu@mail.nih.gov. ·BMC Cancer · Pubmed #30064387.

ABSTRACT: BACKGROUND: Label-retaining cancer cells (LRCC) have been proposed as a model of slowly cycling cancer stem cells (CSC) which mediate resistance to chemotherapy, tumor recurrence, and metastasis. The molecular mechanisms of chemoresistance in LRCC remain to-date incompletely understood. This study aims to identify molecular targets in LRCC that can be exploited to overcome resistance to gemcitabine, a standard chemotherapy agent for the treatment of pancreas cancer. METHODS: LRCC were isolated following Cy5-dUTP staining by flow cytometry from pancreatic cancer cell lines. Gene expression profiles obtained from LRCC, non-LRCC (NLRCC), and bulk tumor cells were used to generate differentially regulated pathway networks. Loss of upregulated targets in LRCC on gemcitabine sensitivity was assessed via RNAi experiments and pharmacological inhibition. Expression patterns of PDPK1, one of the upregulated targets in LRCC, was studied in patients' tumor samples and correlated with pathological variables and clinical outcome. RESULTS: LRCC are significantly more resistant to gemcitabine than the bulk tumor cell population. Non-canonical EGF (epidermal growth factor)-mediated signal transduction emerged as the top upregulated network in LRCC compared to non-LRCC, and knock down of EGF signaling effectors PDPK1 (3-phosphoinositide dependent protein kinase-1), BMX (BMX non-receptor tyrosine kinase), and NTRK2 (neurotrophic receptor tyrosine kinase 2) or treatment with PDPK1 inhibitors increased growth inhibition and induction of apoptosis in response to gemcitabine. Knockdown of PDPK1 preferentially increased growth inhibition and reduced resistance to induction of apoptosis upon gemcitabine treatment in the LRCC vs non-LRCC population. These findings are accompanied by lower expression levels of PDPK1 in tumors compared to matched uninvolved pancreas in surgical resection specimens and a negative association of membranous localization on IHC with high nuclear grade (p < 0.01). CONCLUSION: Pancreatic cancer cell-derived LRCC are relatively resistant to gemcitabine and harbor a unique transcriptomic profile compared to bulk tumor cells. PDPK1, one of the members of an upregulated EGF-signaling network in LRCC, mediates resistance to gemcitabine, is found to be dysregulated in pancreas cancer specimens, and might be an attractive molecular target for combination therapy studies.

17 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.

18 Article Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues. 2018

Pusceddu, Sara / Vernieri, Claudio / Di Maio, Massimo / Marconcini, Riccardo / Spada, Francesca / Massironi, Sara / Ibrahim, Toni / Brizzi, Maria Pia / Campana, Davide / Faggiano, Antongiulio / Giuffrida, Dario / Rinzivillo, Maria / Cingarlini, Sara / Aroldi, Francesca / Antonuzzo, Lorenzo / Berardi, Rossana / Catena, Laura / De Divitiis, Chiara / Ermacora, Paola / Perfetti, Vittorio / Fontana, Annalisa / Razzore, Paola / Carnaghi, Carlo / Davì, Maria Vittoria / Cauchi, Carolina / Duro, Marilina / Ricci, Sergio / Fazio, Nicola / Cavalcoli, Federica / Bongiovanni, Alberto / La Salvia, Anna / Brighi, Nicole / Colao, Annamaria / Puliafito, Ivana / Panzuto, Francesco / Ortolani, Silvia / Zaniboni, Alberto / Di Costanzo, Francesco / Torniai, Mariangela / Bajetta, Emilio / Tafuto, Salvatore / Garattini, Silvio Ken / Femia, Daniela / Prinzi, Natalie / Concas, Laura / Lo Russo, Giuseppe / Milione, Massimo / Giacomelli, Luca / Buzzoni, Roberto / Delle Fave, Gianfranco / Mazzaferro, Vincenzo / de Braud, Filippo. ·Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. Electronic address: sara.pusceddu@istitutotumori.mi.it. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy. · Dipartimento di Oncologia, Università degli Studi di Torino, A. O. Ordine Mauriziano, Turin, Italy. · Dipartimento di Oncologia, Santa Chiara Hospital, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. · IEO - Istituto Europeo di Oncologia, ENETS Center of Excellence, Milan, Italy. · Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. · Centro di Osteoncologia e Tumori Rari, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy. · Policlinico Sant'Orsola Malpighi, Bologna, Italy. · Unità di chirurgia tiroidea e paratiroidea, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy. · IOM- Istituto Oncologico del Mediterraneo, Catania, Italy. · Azienda Ospedaliera Universitaria Sant'Andrea, ENETS Center of Excellence, Rome, Italy. · Azienda Ospedaliera Universitaria, Verona, Italy. · Fondazione Poliambulanza, Brescia, Italy. · A. O. U. Careggi, Firenze, Italy. · Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy. · Policlinico di Monza, Monza, Italy. · IRCCS Fondazione Pascale, ENETS Center of Excellence, Naples, Italy. · Azienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine, Italy. · Fondazione IRCCS Policlinico San Matteo, SC oncologia, Pavia, Italy. · Policlinico di Modena, Italy. · Unit of Endocrinology, Ospedale Mauriziano, Torino, Italy. · Istituto Clinico Humanitas, Rozzano, ENETS Center of Excellence, Italy. · Ospedale Policlinico Borgo Roma, Verona, Italy. · Ospedale S Croce e Carle, Cuneo, Italy. · Ospedale Valduce Como, Italy. · Endocrinology Section, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Medical-Surgical Science and Traslational Medicine Departement, Sapienza University, Rome, Italy. · Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Universita' degli Studi di Milano, Milan, Italy. ·Gastroenterology · Pubmed #29655834.

ABSTRACT: BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS: PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS: In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.

19 Article Inflammatory potential of diet and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. 2018

Zheng, Jiali / Merchant, Anwar T / Wirth, Michael D / Zhang, Jiajia / Antwi, Samuel O / Shoaibi, Azza / Shivappa, Nitin / Stolzenberg-Solomon, Rachael Z / Hebert, James R / Steck, Susan E. ·Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC. · Cancer Prevention and Control Program, University of South Carolina, Columbia, SC. · Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX. · Connecting Health Innovations, LLC, Columbia, SC. · Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Jacksonville, FL. · Biomedical Informatics Center, Medical University of South Carolina, Charleston, SC. · Division of Cancer Epidemiology and Genetics, Metabolic Epidemiology Branch, National Cancer Institute (NCI/DCEG), Rockville, MD. ·Int J Cancer · Pubmed #29355939.

ABSTRACT: Inflammation plays a central role in pancreatic cancer etiology and can be modulated by diet. We aimed to examine the association between the inflammatory potential of diet, assessed with the Dietary Inflammatory Index (DII®), and pancreatic cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial prospective cohort. Our study included 101,449 participants aged 52-78 years at baseline who completed both baseline questionnaire and a diet history questionnaire. Energy-adjusted DII (E-DII) scores were computed based on food and supplement intake. Cox proportional hazards models and time dependent Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with participants in the lowest E-DII quintile (most anti-inflammatory scores) as referent. After a median 8.5 years of follow-up, 328 pancreatic cancer cases were identified. E-DII scores were not associated with pancreatic cancer risk in the multivariable model (HR

20 Article Microwave ablation of pancreatic tumors. 2018

Vogl, Thomas J / Panahi, Bita / Albrecht, Moritz H / Naguib, Nagy Naguib Naeem / Nour-Eldin, Nour-Eldin A / Gruber-Rouh, Tatjana / Thompson, Zachary M / Basten, Lajos M. ·a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany. · b Department of Radiology and Radiological Science , Medical University of South Carolina , Charleston , SC , USA. ·Minim Invasive Ther Allied Technol · Pubmed #29278340.

ABSTRACT: OBJECTIVES: To evaluate the clinical performance of percutaneous microwave ablation (MWA) for treatment of locally-advanced-pancreatic-cancer (LAPC). MATERIAL AND METHODS: Twenty-two MWA sessions (August 2015-March 2017) in 20 patients with primary pancreatic cancer (13 men, 7 women, mean-age: 59.9 ± 8.6 years, range: 46-73 years), who had given informed consent, were retrospectively evaluated. All procedures were performed percutaneously under CT-guidance using the same high-frequency (2.45-GHz) MWA device. Tumor location and diameter, ablation diameter and volume, roundness, duration, technical success and efficacy, output energy, complications, and local tumor progression defined as a tumor focus connected to the edge of a previously technically efficient ablation zone were collected. RESULTS: Seventeen pancreatic malignant tumors (77.3%) were located in the pancreatic head and five (22.7%) in the pancreatic tail. Initial Mean Tumor Diameter was 30 ± 6 mm. Technical success and efficacy were idem (100%). No major complications occurred. Two patients (9.1%) showed minor complications of severe local pain related to MWA. Post-ablation diameter was on average 34.4 ± 5.8 mm. Mean ablation volume was 7.8 ± 3.8 cm³. The mean transverse roundness index was 0.74 ± 0.14. Mean ablation time was 2.6 ± 0.96 min. The mean applied energy per treatment was 9627 ± 3953 J. Local tumor progression was documented in one case (10%) of the 10/22 available three-month follow-up imaging studies. CONCLUSION: High-frequency (2.45 GHz) microwave ablation (MWA) for treatment of unresectable and non-metastatic locally-advanced-pancreatic-cancer (LAPC) shows promising results regarding feasibility and safety of percutaneous approach after short-term follow-up and should be further evaluated.

21 Article Transarterial chemoembolization in pancreatic adenocarcinoma with liver metastases: MR-based tumor response evaluation, apparent diffusion coefficient (ADC) patterns, and survival rates. 2018

Vogl, Thomas J / Mohamed, Sherif A / Albrecht, Moritz H / Gruber-Roh, Tatjana / Lin, Han / Nour Eldin, Nour Eldin A / Bednarova, Iliana / Naguib, Nagy N / Panahi, Bita. ·University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt, Germany. · University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt, Germany. Electronic address: sherifabdou90@gmail.com. · University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt, Germany; Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston SC, USA. · Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston SC, USA. · University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt, Germany; Institute of Diagnostic Radiology, Department of Medical and Biological Science, Udine, Italy. ·Pancreatology · Pubmed #29221632.

ABSTRACT: PURPOSE: To retrospectively investigate the effectiveness of triple drug combination transarterial chemoembolization (TACE) on local tumor response and survival in patients with liver metastases from pancreatic cancer. Also, this study will evaluate the variances in response regarding the number of metastases, assess the correlation between tumor response and the changes in the apparent diffusion coefficients (ADC) in diffusion weighted (DW) MRI. MATERIALS AND METHODS: One hundred and twelve patients (58 men and 54 women; mean age 57) with malignant liver metastases from pancreatic adenocarcinoma underwent at least one session of TACE with a chemotherapeutic combination of mitomycin C, cisplatin, and gemcitabine. A size-based evaluation of tumor response (response evaluation criteria in solid tumors (RECIST)) was conducted, along with ADC values, and survival indices as related to treatment pattern. RESULTS: Four weeks following the end of the treatment, 78.26% of patients showed stable disease and 11.59% showed partial response. The median survival time was 19 months and for the stable disease group, 26 months. Low pretreatment ADC values showed no significant correlation to poor response to treatment (r = 0.347,p = 0.146). CONCLUSION: The triple drug TACE technique showed improvements in median survival times in patients with hepatic metastases from pancreatic carcinoma and helped control disease progression, whereas the number of hepatic lesions was not a statistically significant factor in patients' response to TACE. The data suggest that pre-treatment ADC values in DW-MRI have no statistical correlation with tumor response.

22 Article Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. 2018

Fan, Xiaozhou / Alekseyenko, Alexander V / Wu, Jing / Peters, Brandilyn A / Jacobs, Eric J / Gapstur, Susan M / Purdue, Mark P / Abnet, Christian C / Stolzenberg-Solomon, Rachael / Miller, George / Ravel, Jacques / Hayes, Richard B / Ahn, Jiyoung. ·Department of Population Health, New York University School of Medicine, New York, New York, USA. · Departments of Public Health Sciences and Oral Health Sciences, Biomedical Informatics Center, Program for Human Microbiome Research, Medical University of South Carolina, Charleston, South Carolina, USA. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Surgery, New York University School of Medicine, New York, New York, USA. · Department of Cell Biology, New York University School of Medicine, New York, New York, USA. · NYU Perlmutter Cancer Center, New York, New York, USA. · Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA. ·Gut · Pubmed #27742762.

ABSTRACT: OBJECTIVE: A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. DESIGN: We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression. RESULTS: Carriage of oral pathogens, CONCLUSIONS: This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.

23 Article Generation of a pancreatic cancer model using a Pdx1-Flp recombinase knock-in allele. 2017

Wu, Jinghai / Liu, Xin / Nayak, Sunayana G / Pitarresi, Jason R / Cuitiño, Maria C / Yu, Lianbo / Hildreth, Blake E / Thies, Katie A / Schilling, Daniel J / Fernandez, Soledad A / Leone, Gustavo / Ostrowski, Michael C. ·Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America. · Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio, United States of America. · Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, United States of America. · Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, United States of America. · Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America. ·PLoS One · Pubmed #28934293.

ABSTRACT: The contribution of the tumor microenvironment to the development of pancreatic adenocarcinoma (PDAC) is unclear. The LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre (KPC) tumor model, which is widely utilized to faithfully recapitulate human pancreatic cancer, depends on Cre-mediated recombination in the epithelial lineage to drive tumorigenesis. Therefore, specific Cre-loxP recombination in stromal cells cannot be applied in this model, limiting the in vivo investigation of stromal genetics in tumor initiation and progression. To address this issue, we generated a new Pdx1FlpO knock-in mouse line, which represents the first mouse model to physiologically express FlpO recombinase in pancreatic epithelial cells. This mouse specifically recombines Frt loci in pancreatic epithelial cells, including acinar, ductal, and islet cells. When combined with the Frt-STOP-Frt KrasG12D and p53Frt mouse lines, simultaneous Pdx1FlpO activation of mutant Kras and deletion of p53 results in the spectrum of pathologic changes seen in PDAC, including PanIN lesions and ductal carcinoma. Combination of this KPF mouse model with any stroma-specific Cre can be used to conditionally modify target genes of interest. This will provide an excellent in vivo tool to study the roles of genes in different cell types and multiple cell compartments within the pancreatic tumor microenvironment.

24 Article The CA19-9 and Sialyl-TRA Antigens Define Separate Subpopulations of Pancreatic Cancer Cells. 2017

Barnett, Daniel / Liu, Ying / Partyka, Katie / Huang, Ying / Tang, Huiyuan / Hostetter, Galen / Brand, Randall E / Singhi, Aatur D / Drake, Richard R / Haab, Brian B. ·Van Andel Research Institute, Grand Rapids, MI, USA. · Michigan State University, East Lansing, MI, USA. · Fred Hutchinson Cancer Research Center, Seattle, WA, USA. · University of Pittsburgh Medical Center, Pittsburgh, PA, USA. · Medical University of South Carolina, Charleston, SC, USA. · Van Andel Research Institute, Grand Rapids, MI, USA. brian.haab@vai.org. ·Sci Rep · Pubmed #28642461.

ABSTRACT: Molecular markers to detect subtypes of cancer cells could facilitate more effective treatment. We recently identified a carbohydrate antigen, named sTRA, that is as accurate a serological biomarker of pancreatic cancer as the cancer antigen CA19-9. We hypothesized that the cancer cells producing sTRA are a different subpopulation than those producing CA19-9. The sTRA glycan was significantly elevated in tumor tissue relative to adjacent pancreatic tissue in 3 separate tissue microarrays covering 38 patients. The morphologies of the cancer cells varied in association with glycan expression. Cells with dual staining of both markers tended to be in well-to-moderately differentiated glands with nuclear polarization, but exclusive sTRA staining was present in small clusters of cells with poor differentiation and large vacuoles, or in small and ill-defined glands. Patients with higher dual-staining of CA19-9 and sTRA had statistically longer time-to-progression after surgery. Patients with short time-to-progression (<2 years) had either low levels of the dual-stained cells or high levels of single-stained cells, and such patterns differentiated short from long time-to-progression with 90% (27/30) sensitivity and 80% (12/15) specificity. The sTRA and CA19-9 glycans define separate subpopulations of cancer cells and could together have value for classifying subtypes of pancreatic adenocarcinoma.

25 Article Pancreatic Polypeptide Cell Proliferation in the Pancreas and Duodenum Coexisting in a Patient With Pancreatic Adenocarcinoma Treated With a GLP-1 Analog. 2017

Talmon, Geoffrey A / Wren, J David / Nguyen, Christophe L / Pour, Parviz M. ·From the *Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE; †Department of Pathology, Spartanburg Medical Center; ‡Gibbs Cancer Center, Spartanburg Regional Hospital System; and §Department of Surgery, Gibbs Cancer Center, Spartanburg, SC; and ∥UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE. ·Pancreas · Pubmed #28609372.

ABSTRACT: A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells. Among the etiological factors, the possible long-lasting effects of the GLP-1 analog, with which the patient was treated, are discussed. This is the first report in the literature of both the coexistence of a pancreatic adenocarcinoma and invasive PPoma and the occurrence of PP and insulin cells in human duodenal mucosa.

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