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Pancreatic Neoplasms: HELP
Articles by Mokenge P. Malafa
Based on 67 articles published since 2008
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Between 2008 and 2019, Mokenge Malafa wrote the following 67 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. 2017

Tempero, Margaret A / Malafa, Mokenge P / Al-Hawary, Mahmoud / Asbun, Horacio / Bain, Andrew / Behrman, Stephen W / Benson, Al B / Binder, Ellen / Cardin, Dana B / Cha, Charles / Chiorean, E Gabriela / Chung, Vincent / Czito, Brian / Dillhoff, Mary / Dotan, Efrat / Ferrone, Cristina R / Hardacre, Jeffrey / Hawkins, William G / Herman, Joseph / Ko, Andrew H / Komanduri, Srinadh / Koong, Albert / LoConte, Noelle / Lowy, Andrew M / Moravek, Cassadie / Nakakura, Eric K / O'Reilly, Eileen M / Obando, Jorge / Reddy, Sushanth / Scaife, Courtney / Thayer, Sarah / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer / Darlow, Susan. · ·J Natl Compr Canc Netw · Pubmed #28784865.

ABSTRACT: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

2 Guideline Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. 2012

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen W / Ben-Josef, Edgar / Benson, Al B / Casper, Ephraim S / Cohen, Steven J / Czito, Brian / Ellenhorn, Joshua D I / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Ma, Wen Wee / Malafa, Mokenge P / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Sasson, Aaron R / Tally, Anitra / Thayer, Sarah P / Whiting, Samuel / Wolff, Robert A / Wolpin, Brian M / Freedman-Cass, Deborah A / Shead, Dorothy A / Anonymous1061005. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

3 Guideline Pancreatic adenocarcinoma. 2010

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen / Ben-Josef, Edgar / Benson, Al B / Berlin, Jordan D / Cameron, John L / Casper, Ephraim S / Cohen, Steven J / Duff, Michelle / Ellenhorn, Joshua D I / Hawkins, William G / Hoffman, John P / Kuvshinoff, Boris W / Malafa, Mokenge P / Muscarella, Peter / Nakakura, Eric K / Sasson, Aaron R / Thayer, Sarah P / Tyler, Douglas S / Warren, Robert S / Whiting, Samuel / Willett, Christopher / Wolff, Robert A / Anonymous3820673. · ·J Natl Compr Canc Netw · Pubmed #20876541.

ABSTRACT: -- No abstract --

4 Editorial Partnering to advance early detection and prevention efforts for pancreatic cancer: the Florida Pancreas Collaborative. 2016

Permuth, Jennifer B / Trevino, Jose / Merchant, Nipun / Malafa, Mokenge / Anonymous50858. ·Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, FL, USA. · Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, FL, USA. ·Future Oncol · Pubmed #26863203.

ABSTRACT: -- No abstract --

5 Editorial MiRNAs as biomarkers of high-risk pancreatic cysts: a possible holy grail for the early detection of pancreatic cancer. 2015

Permuth, Jennifer B / Georgeades, Christina / Malafa, Mokenge. ·Department of Cancer Epidemiology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Morsani College of Medicine, University of South Florida, Tampa, FL, USA. ·Future Oncol · Pubmed #26549701.

ABSTRACT: -- No abstract --

6 Editorial MicroRNAs in pancreatic ductal adenocarcinoma. 2011

Park, Jong Y / Helm, James / Coppola, Domenico / Kim, Donghwa / Malafa, Mokenge / Kim, Seung Joon. · ·World J Gastroenterol · Pubmed #21412491.

ABSTRACT: Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done. Therefore, biomarkers for early detection and new therapeutic strategies are urgently needed. miRNAs are a recently discovered class of small endogenous non-coding RNAs of about 22 nucleotides that have gained attention for their role in downregulation of mRNA expression at the post-transcriptional level. miRNAs regulate proteins involved in critical cellular processes such as differentiation, proliferation, and apoptosis. Evidence suggests that deregulated miRNA expression is involved in carcinogenesis at many sites, including the pancreas. Aberrant expression of miRNAs may upregulate the expression of oncogenes or downregulate the expression of tumor suppressor genes, as well as play a role in other mechanisms of carcinogenesis. The purpose of this review is to summarize our knowledge of deregulated miRNA expression in pancreatic cancer and discuss the implication for potential translation of this knowledge into clinical practice.

7 Editorial New insights and gains in pancreatic cancer. 2008

Malafa, Mokenge P. · ·Cancer Control · Pubmed #18813194.

ABSTRACT: -- No abstract --

8 Review Systematic Review and Case Series Report of Acinar Cell Carcinoma of the Pancreas. 2016

Glazer, Evan S / Neill, Kevin G / Frakes, Jessica M / Coppola, Domenico / Hodul, Pamela J / Hoffe, Sara E / Pimiento, Jose M / Springett, Gregory M / Malafa, Mokenge P. ·Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA. Mokenge.Malafa@Moffitt.org. ·Cancer Control · Pubmed #27842335.

ABSTRACT: BACKGROUND: Acinar cell carcinoma of the pancreas is a rare malignancy representing less than 1% of all pancreatic malignancies. METHODS: We report on a case series of 21 patients with acinar cell carcinoma of the pancreas treated at a high-volume quaternary center. A systematic review of the medical literature was performed that described typical therapeutic management approaches for acinar cell carcinoma of the pancreas and reported on disease control and survival rates. Data for the case series were obtained from a prospective database. RESULTS: In our systematic review of 6 articles, study patients had a median age of 61 years, 66% were male, 52% had stage I/II disease, and 55% of lesions were located in the pancreatic head. The rates of median survival were approximately 47 months after resection with adjuvant therapy, 38 months for nonmetastatic, locally unresectable disease, and 17 months for metastatic disease treated with chemotherapy. Combination fluoropyrimidine-based chemotherapy regimens had better rates of disease control than other therapies. Our case series included 21 study patients, 14 of whom required resection and 7 who had metastatic disease. The rates of median survival were 40.2 ± 31.9 months in those who underwent surgery and were treated with adjuvant therapy and 13.8 ± 11.3 months for patients with metastatic disease. CONCLUSIONS: Multidisciplinary treatment for acinar cell carcinoma of the pancreas should be considered due to the rarity of the disease and its lack of high-level therapeutic data. Progress in the molecular analysis of this tumor may improve outcomes through the use of personalized therapy based on underlying tumor mutations.

9 Review Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications. 2015

Davis-Yadley, Ashley H / Malafa, Mokenge P. ·Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL; and Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL. · Department of Gastrointestinal Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL Mokenge.malafa@moffitt.org. ·Adv Nutr · Pubmed #26567201.

ABSTRACT: Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer.

10 Review Robotic Whipple Procedure for Pancreatic Cancer: The Moffitt Cancer Center Pathway. 2015

Rashid, Omar M / Mullinax, John E / Pimiento, Jose M / Meredith, Kenneth L / Malafa, Mokenge P. ·Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. Mokenge.Malafa@Moffitt.org. ·Cancer Control · Pubmed #26351891.

ABSTRACT: BACKGROUND: Resection of malignancies in the head and uncinate process of the pancreas (Whipple procedure) using a robotic approach is emerging as a surgical option. Although several case series of the robotic Whipple procedure have been reported, detailed descriptions of operative techniques and a clear pathway for adopting this technology are lacking. METHODS: We present a focused review of the procedure as it applies to pancreatic cancer and describe our clinical pathway for the robotic Whipple procedure used in pancreatic cancer and review the outcomes of our early experience. A systematic review of the literature is provided, focusing on the indications, variations in surgical techniques, complications, and oncological results of the robotic Whipple procedure. RESULTS: A clinical pathway has been defined for preoperative training of surgeons, the requirements for hospital privileges, patient selection, and surgical techniques for the robotic Whipple procedure. The robotic technique for managing malignant lesions of the pancreas head is safe when following well-established guidelines for adopting the technology. Preliminary data demonstrate that perioperative convalescence may exceed end points when compared with the open technique. CONCLUSIONS: The robotic Whipple procedure is a minimally invasive approach for select patients as part of multidisciplinary management of periampullary lesions in tertiary centers where clinicians have developed robotic surgical programs. Prospective trials are needed to define the short- and long-term benefits of the robotic Whipple procedure.

11 Review Early detection of pancreatic cancer: why, who, and how to screen. 2008

Klapman, Jason / Malafa, Mokenge P. ·Gastrointestinal Tumor Program, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. jason.klapman@moffitt.org ·Cancer Control · Pubmed #18813195.

ABSTRACT: BACKGROUND: Pancreatic cancer represents the fourth-leading cause of cancer death in the United States, with a dismal 5-year survival rate of less than 5%. Despite advancements in screening and early detection of other cancers such as breast and colon cancer, no reliable screening test exists for pancreatic cancer. Subsequently, the majority of patients present with advanced-stage disease leading to a poor prognosis. Because of the relatively low incidence, current efforts are focused on early detection and screening only in patients at high risk for the development of the disease. METHODS: We discuss the practical considerations encountered when determining if an individual should be screened for pancreatic cancer. The current literature was reviewed regarding risk factors, genetic syndromes, screening modalities, and screening studies of pancreatic cancer. The current high-risk pancreatic screening program at our institute is also summarized. RESULTS: Current efforts to detect pancreatic cancer at a curative phase are focused on screening individuals at high risk for the development of this disease. They include kindreds with two or more first-degree relatives affected with this disease and those with known hereditary pancreatic cancer syndromes. Hereditary pancreatic cancer syndromes include Peutz-Jeghers syndrome, familial breast cancer syndrome, and familial atypical multiple mole melanoma syndrome. Of all the screening modalities available, endoscopic ultrasound is the most sensitive and specific screening tool to evaluate the pancreas and has been proven to detect early precancerous and cancerous changes in clinical studies. CONCLUSIONS: Early detection and screening for pancreatic cancer in the current state should be limited to high-risk patients, although hereditary/familial factors account for only 10% of patients with pancreatic cancer. Continued efforts are needed to discover effective test to identify patients with nonhereditary risk factors who will benefit from screening and also to develop less invasive and more cost-effective screening modalities aimed at controlling pancreatic cancer.

12 Clinical Trial A Phase I Safety, Pharmacokinetic, and Pharmacodynamic Presurgical Trial of Vitamin E δ-tocotrienol in Patients with Pancreatic Ductal Neoplasia. 2015

Springett, Gregory M / Husain, Kazim / Neuger, Anthony / Centeno, Barbara / Chen, Dung-Tsa / Hutchinson, Tai Z / Lush, Richard M / Sebti, Saïd / Malafa, Mokenge P. ·Department of Gastrointestinal Oncology, Tampa, FL, USA. · Translational Research Core, Tampa, FL, USA. · Department of Cytopathology, Tampa, FL, USA. · Biostatistics Core, Tampa, FL, USA. · Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. ·EBioMedicine · Pubmed #26844278.

ABSTRACT: BACKGROUND: Vitamin E δ-tocotrienol (VEDT), a natural vitamin E from plants, has shown anti-neoplastic and chemoprevention activity in preclinical models of pancreatic cancer. Here, we investigated VEDT in patients with pancreatic ductal neoplasia in a window-of-opportunity preoperative clinical trial to assess its safety, tolerability, pharmacokinetics, and apoptotic activity. METHODS: Patients received oral VEDT at escalating doses (from 200 to 3200 mg) daily for 13 days before surgery and one dose on the day of surgery. Dose escalation followed a three-plus-three trial design. Our primary endpoints were safety, VEDT pharmacokinetics, and monitoring of VEDT-induced neoplastic cell apoptosis (ClinicalTrials.gov number NCT00985777). FINDINGS: In 25 treated patients, no dose-limiting toxicity was encountered; thus no maximum-tolerated dose was reached. One patient had a drug-related adverse event (diarrhea) at a 3200-mg daily dose level. The effective half-life of VEDT was ~ 4 h. VEDT concentrations in plasma and exposure profiles were quite variable but reached levels that are bioactive in preclinical models. Biological activity, defined as significant induction of apoptosis in neoplastic cells as measured by increased cleaved caspase-3 levels, was seen in the majority of patients at the 400-mg to 1600-mg daily dose levels. INTERPRETATION: VEDT from 200 to 1600 mg daily taken orally for 2 weeks before pancreatic surgery was well tolerated, reached bioactive levels in blood, and significantly induced apoptosis in the neoplastic cells of patients with pancreatic ductal neoplasia. These promising results warrant further clinical investigation of VEDT for chemoprevention and/or therapy of pancreatic cancer.

13 Article Recognition of Tumor Invasion of a Pancreatic Head Biliary Stent During Stereotactic Body Radiation Therapy. 2019

Song, Ethan / Segarra, Daniel / Latifi, Kujtim / Leuthold, Susan / Belinc, Dalila / Pena, Luis / Malafa, Mokenge P / Frakes, Jessica M / Hoffe, Sarah E. ·University of South Florida Health Morsani College of Medicine, Tampa, Florida. Electronic address: esong@health.usf.edu. · University of South Florida Health Morsani College of Medicine, Tampa, Florida. · Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Surgical Oncology, Moffitt Cancer Center, Tampa, Florida. ·Pract Radiat Oncol · Pubmed #30708132.

ABSTRACT: -- No abstract --

14 Article Identification of nonalcoholic fatty liver disease following pancreatectomy for noninvasive intraductal papillary mucinous neoplasm. 2018

Luu, Carrie / Thapa, Ram / Rose, Trevor / Woo, Katherine / Jeong, Daniel / Thomas, Kerry / Chen, Dung-Tsa / Friedman, Mark / Malafa, Mokenge P / Hodul, Pamela J. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. · Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. · Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. Electronic address: Pamela.Hodul@moffitt.org. ·Int J Surg · Pubmed #30218781.

ABSTRACT: BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) following pancreatectomy is a potential cause of long term morbidity in patients undergoing pancreatic resection with curative intent. Prior studies have reported an incidence of NAFLD up to 30% following pancreatectomy but the investigated cohorts were typically a mix of benign and malignant disease. Here we examined the incidence of NAFLD in a homogenous cohort of patients following pancreatectomy for benign intraductal papillary mucinous neoplasm (IPMN). METHODS: A retrospective review of patients who underwent pancreatic resection for IPMN from 2000 to 2016 was performed. Post pancreatectomy CT/MRI scans were obtained as standard surveillance. We investigated changes in the liver parenchymal density on post surgical imaging to estimate the frequency with which NAFLD occurred. Radiographic criteria for NAFLD included Hounsfield units less than 40 on CT or liver:spleen ratio <0.9 on CT or MRI. Fischer's exact test, Kruskal-Wallis test, and logistic regression were performed. RESULTS: Our study cohort included 109 patients who underwent pancreatectomy for nonmalignant intraductal papillary mucinous neoplasm with no evidence of NAFLD preoperatively and at least 6 months follow-up. Mean follow-up was 52 months (range 8-130/months). The incidence of postoperative NAFLD was 17/109 (15.6%). Most cases occurred within 12 months of pancreatectomy. On multivariate analysis, proximal pancreatectomy (pancreaticoduodenectomy) and development of atrophy of the pancreas remnant were significant risk factors for development of hepatic steatosis (p < 0.05). CONCLUSION: Patients undergoing pancreatectomy for benign disease have a significant risk of developing NAFLD but the frequency is lower than previously reported in cohorts that included individuals with malignant disease. Highest risk was observed in individuals who underwent pancreaticoduodenectomy or developed pancreatic atrophy. Further investigations to define the mechanisms that promote steatosis and interventions to prevent subsequent morbidity from NAFLD are warranted.

15 Article EGFR L861Q Mutation in a Metastatic Solid-pseudopapillary Neoplasm of the Pancreas. 2018

Neill, Kevin G / Saller, James / Al Diffalha, Sameer / Centeno, Barbara A / Malafa, Mokenge P / Coppola, Domenico. ·Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. · Department of Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. · Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. Domenico.coppola@moffitt.org. · Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. · Department of Oncological Sciences, University of South Florida, Tampa, FL, U.S.A. ·Cancer Genomics Proteomics · Pubmed #29695402.

ABSTRACT: Solid-pseudopapillary neoplasm of the pancreas (SPN) is a rare neoplasm that is typically indolent in nature. Surgical resection is the preferred method of treatment and often associated with a good prognosis. Local invasion and metastasis have been reported in a small subset of patients. Currently, there are limited data on the molecular mutation profile of invasive and metastatic SPN. In this report, we present the case of a 38-year-old female with a locally-invasive and unresectable SPN that, despite exhaustive chemoradiotherapy, progressed to liver metastasis. Pyrosequencing of the primary pancreatic tumor antecedent to metastasis showed an uncommon EGFR mutation at L861Q in the kinase domain of exon 21. This finding, if confirmed in additional cases of metastatic SPN, would support preoperative testing for EGFR mutation analysis to detect aggressive SPNs.

16 Article Endoscopic Ultrasound-Based Pancreatic Cancer Screening of High-Risk Individuals: A Prospective Observational Trial. 2018

Gangi, Alexandra / Malafa, Mokenge / Klapman, Jason. · ·Pancreas · Pubmed #29683970.

ABSTRACT: OBJECTIVES: Pancreatic cancer (PC), a common cause of cancer death, is rarely diagnosed at an early stage. Early detection of PC may improve outcomes in affected patients. This study evaluated the utility of screening of high-risk individuals (HRIs) using an endoscopic ultrasound (EUS)-only approach to detect early malignant changes. METHODS: A prospective PC screening program for HRIs was opened in 2007. Fifty-eight patients have enrolled to date. Patients with normal EUS examinations underwent repeat EUS annually for 5 years. Patients with abnormal EUS underwent fine-needle aspiration (FNA) if a mass/cyst 1 cm or longer was found. Those with cysts/mass shorter than 1 cm or benign FNA underwent repeat EUS in 3 months. If unchanged, patients were followed with magnetic resonance imaging. RESULTS: Thirty-nine patients (67%) had initial normal EUS examinations, and 16 patients completed the 5-year trial. Five patients who initially had a normal EUS developed cysts on subsequent examinations. Of the 24 subjects (41%) with abnormal findings, 3 underwent FNA: 2 consistent with intraductal papillary mucinous neoplasm, 1 with benign cytology. The 21 remaining patients had 1 subcentimeter cyst or more followed by magnetic resonance imaging. No PCs have been detected. CONCLUSIONS: Precancerous cysts are frequently detected with EUS in HRI. Whether screening impacts survival in HRIs remains unclear and requires further evaluation in larger multicenter trials.

17 Article Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience. 2017

Ambe, Chenwi M / Nguyen, Phuong / Centeno, Barbara A / Choi, Junsung / Strosberg, Jonathan / Kvols, Larry / Hodul, Pamela / Hoffe, Sarah / Malafa, Mokenge P. ·1 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · 2 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · 3 Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. ·Cancer Control · Pubmed #28975822.

ABSTRACT: BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. METHODS: We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. RESULTS: Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). CONCLUSIONS: A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

18 Article Linc-ing Circulating Long Non-coding RNAs to the Diagnosis and Malignant Prediction of Intraductal Papillary Mucinous Neoplasms of the Pancreas. 2017

Permuth, Jennifer B / Chen, Dung-Tsa / Yoder, Sean J / Li, Jiannong / Smith, Andrew T / Choi, Jung W / Kim, Jongphil / Balagurunathan, Yoganand / Jiang, Kun / Coppola, Domenico / Centeno, Barbara A / Klapman, Jason / Hodul, Pam / Karreth, Florian A / Trevino, Jose G / Merchant, Nipun / Magliocco, Anthony / Malafa, Mokenge P / Gillies, Robert. ·Departments of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. jenny.permuth@moffitt.org. · Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. jenny.permuth@moffitt.org. · Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Molecular Genomics Core Facility, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, Florida, USA. · Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, USA. ·Sci Rep · Pubmed #28874676.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective biomarkers for early detection. We hypothesized that circulating long non-coding RNAs (lncRNAs) may act as diagnostic markers of incidentally-detected cystic PDAC precursors known as intraductal papillary mucinous neoplasms (IPMNs) and predictors of their pathology/histological classification. Using NanoString nCounter® technology, we measured the abundance of 28 candidate lncRNAs in pre-operative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Results showed that two lncRNAs (GAS5 and SRA) aided in differentiating IPMNs from controls. An 8-lncRNA signature (including ADARB2-AS1, ANRIL, GLIS3-AS1, LINC00472, MEG3, PANDA, PVT1, and UCA1) had greater accuracy than standard clinical and radiologic features in distinguishing 'aggressive/malignant' IPMNs that warrant surgical removal from 'indolent/benign' IPMNs that can be observed. When the 8-lncRNA signature was combined with plasma miRNA data and quantitative 'radiomic' imaging features, the accuracy of predicting IPMN pathological classification improved. Our findings provide novel information on the ability to detect lncRNAs in plasma from patients with IPMNs and suggest that an lncRNA-based blood test may have utility as a diagnostic adjunct for identifying IPMNs and their pathology, especially when incorporated with biomarkers such as miRNAs, quantitative imaging features, and clinical data.

19 Article Patterns of recurrence and long-term outcomes in patients who underwent pancreatectomy for intraductal papillary mucinous neoplasms with high grade dysplasia: implications for surveillance and future management guidelines. 2017

Blackham, Aaron U / Doepker, Matthew P / Centeno, Barbara A / Springett, Gregory / Pimiento, Jose M / Malafa, Mokenge / Hodul, Pamela J. ·Department of Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, 12901 Magnolia Drive, Tampa, FL 33612, USA. · Department of Anatomic Pathology, Moffitt Cancer Center and Research Institute, 12901 Magnolia Drive, Tampa, FL 33612, USA. · Department of Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, 12901 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: Pamela.Hodul@moffitt.org. ·HPB (Oxford) · Pubmed #28495434.

ABSTRACT: BACKGROUND: While intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia (HGD) are thought to represent non-invasive, high-risk lesions, its natural history following resection is unknown. METHODS: A retrospective review of HGD-IPMN patients (1999-2015) was performed. Recurrence patterns and clinical outcomes following pancreatectomy were analyzed and the indications for surgery were explored based on current guidelines. RESULTS: HGD was diagnosed in 100 of 314 patients (32%) following pancreatectomy for IPMN. IPMNs were classified as main duct, branch duct, or mixed in 15, 58 and 27 patients, respectively. Following resection, 25 patients had low-risk residual disease in the remnant pancreas. With a median follow-up of 35 months (range 1-129), 9 patients developed progressive or recurrent disease, 4 of whom underwent additional pancreatectomy. Three patients developed invasive adenocarcinoma. Median time to recurrence was 15 months (range 7-72). Based on the management algorithm from the international consensus guidelines, resection was indicated in 76 patients (76%). Other indications for surgery included mixed-duct IPMN(13), increased cyst size(7) and other(4). CONCLUSION: The prognosis of HGD-IPMN following resection is good; however, HGD may be a marker for developing IPMN recurrence or adenocarcinoma. Current guidelines regarding surgical indications for IPMN can miss a significant number of patients with HGD.

20 Article δ-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis. 2017

Husain, Kazim / Centeno, Barbara A / Coppola, Domenico / Trevino, Jose / Sebti, Said M / Malafa, Mokenge P. ·Departments of Gastrointestinal Oncology, Tampa, FL, USA. · Departments of Pathology, Tampa, FL, USA. · Department of Surgery, University of Florida, Gainesville, FL, USA. · Departments of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. ·Oncotarget · Pubmed #28404939.

ABSTRACT: The growth, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC) is characterized by the activation and growth of tumor-initiating cells in distant organs that have stem-like properties. Thus, inhibiting growth of these cells may prevent PDAC growth and metastases. We have demonstrated that δ-tocotrienol, a natural form of vitamin E (VEDT), is bioactive against cancer, delays progression, and prevents metastases in transgenic mouse models of PDAC. In this report, we provide the first evidence that VEDT selectively inhibits PDAC stem-like cells. VEDT inhibited the viability, survival, self-renewal, and expression of Oct4 and Sox2 transcription factors in 3 models of PDAC stem-like cells. In addition, VEDT inhibited the migration, invasion, and several biomarkers of epithelial-to-mesenchymal transition and angiogenesis in PDAC cells and tumors. These processes are critical for tumor metastases. Furthermore, in the L3.6pl orthotopic model of PDAC metastases, VEDT significantly inhibited growth and metastases of these cells. Finally, in an orthotopic xenograft model of human PDAC stem-like cells, we showed that VEDT significantly retarded the growth and metastases of gemcitabine-resistant PDAC human stem-like cells. Because VEDT has been shown to be safe and to reach bioactive levels in humans, this work supports investigating VEDT for chemoprevention of PDAC metastases.

21 Article Endoscopic ultrasonography complements computed tomography in predicting portal or superior mesenteric vein resection in patients with borderline resectable pancreatic carcinoma. 2017

Glazer, Evan S / Rashid, Omar M / Klapman, Jason B / Harris, Cynthia L / Hodul, Pamela J / Pimiento, Jose M / Malafa, Mokenge P. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address: Mokenge.malafa@moffitt.org. ·Pancreatology · Pubmed #28043760.

ABSTRACT: BACKGROUND: Current guidelines recommend computed tomographic (CT) scans for vascular staging of patients with pancreatic carcinoma; however, endoscopic ultrasonography (EUS) in these patients is not required and its utility in combination with CT scan is less well-defined. The purpose of this study is to explore the utility of EUS in addition to CT in identifying patients with borderline resectable pancreatic carcinoma (BRPC). METHODS: We reviewed our database of patients with BRPC who went to surgery with curative intent. Inclusion criteria were preoperative staging with CT scan and EUS, completion of neoadjuvant chemotherapy and radiotherapy, and surgical resection. RESULTS: We identified 62 patients (average age of 65 ± 9 years, 60% male); 97% of patients underwent R0 resections. We found that 29% of patients were classified as BRPC by EUS alone, 23% by CT alone, and 48% by both modalities. Of 34 patients who required vein resection, EUS alone preoperatively identified 88% of these patients while CT alone identified 67%. EUS identified 11 patients who required vein resection that CT did not identify as BRPC, whereas CT identified 4 patients that EUS did not identify as BRPC. On multivariate analysis, EUS was associated with vein resection (P < 0.02), but CT scan findings, tumor size, and CA19-9 values were not associated (each P > 0.1). CONCLUSIONS: EUS complemented CT in identifying BRPC patients requiring vein resection, with nearly one-third of patients identified with EUS alone, supporting EUS use in addition to CT scan for vascular staging of patients with pancreatic carcinoma.

22 Article TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma. 2017

Glazer, Evan S / Welsh, Eric / Pimiento, Jose M / Teer, Jamie K / Malafa, Mokenge P. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Surgery, University of Tennessee Health Sciences Center, Memphis, TN, USA. · Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. ·Oncotarget · Pubmed #27895310.

ABSTRACT: The role of transforming growth factor beta-type-1 (TGFβ1) in pancreatic ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that TGFβ1 expression is associated with survival and proliferation markers in patients with early-stage PDAC. We acquired clinicopathologic, treatment, and mRNA expression data from The Cancer Genome Atlas data set for 106 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients were categorized as high expression when mRNA expression was ≥75th percentile for each gene. Average log2 mRNA expression of TGFβ1 in patients with high expression was 11.6 ± 0.2 and 10.5 ± 0.6 in patients with low expression (P<0.001). Low TGFβ1 expression is associated with shorter median survival compared with high TGFβ1 expression (17 versus at least 60 months; P=0.005). Patients with tumors demonstrating high MKI67 (the gene encoding Ki-67) expression have shorter median survival versus those with lowerMKI67 expression (16 versus 20 months; P=0.026). TGFβ1 and MKI67 are inversely associated (P=0.009). On multivariate analysis, improved survival is associated with TGFβ1 overexpression (P=0.017), adjuvant chemotherapy (P=0.001), and adjuvant radiotherapy (P=0.017), whereas positive surgical margins are associated with worse survival (P=0.002). In patients who undergo pancreaticoduodenectomy for PDAC, high TGFβ1 expression may counteract the worse survival associated with high proliferation.

23 Article Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy. 2017

Mellon, Eric A / Jin, William H / Frakes, Jessica M / Centeno, Barbara A / Strom, Tobin J / Springett, Gregory M / Malafa, Mokenge P / Shridhar, Ravi / Hodul, Pamela J / Hoffe, Sarah E. ·a Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA. · b Department of Radiation Oncology , University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center , Miami , Florida , USA. · c Department of Pathology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA. · d Gastrointestinal Tumor Program , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA. · e Department of Radiation Oncology , Florida Hospital Cancer Institute , Orlando , Florida , USA. ·Acta Oncol · Pubmed #27885876.

ABSTRACT: BACKGROUND: Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival. MATERIALS AND METHODS: We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19-9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT. They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression-free (PFS) survival were estimated and compared by Kaplan-Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, restaging and change in CA19-9 and the PET maximum standardized uptake value (SUVmax). RESULTS: Restaging level and decrease in CA19-9 correlated with improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30). The TRG groups had similar OS and PFS except the TRG 0 (complete response) group. Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS 13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual isolated tumor cells had similar outcomes to the other TRG 1-3 patients. CONCLUSION: Pre-operative PET-CT and CA19-9 response correlate with histopathologic tumor regression. Patients with complete pathologic response have superior outcomes, suggesting a rationale for intensification and personalization of neoadjuvant therapy in BRPC and LAPC.

24 Article Cancer Antigen 125 (CA125, MUC16) Protein Expression in the Diagnosis and Progression of Pancreatic Ductal Adenocarcinoma. 2017

Jiang, Kun / Tan, Elaine / Sayegh, Zena / Centeno, Barbara / Malafa, Mokenge / Coppola, Domenico. ·*Department of Anatomic Pathology †Tissue Core ‡Gastrointestinal Surgical Oncology Program §Tumor Biology and Chemical Biology & Molecular Medicine Programs, Moffitt Cancer Center and Research Institute, Tampa, FL. ·Appl Immunohistochem Mol Morphol · Pubmed #27093451.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive carcinoma, with most patients diagnosed at an advanced stage, with a 5-year survival rate of around 5%. An urgent need exists for identifying better diagnostic, prognostic, and therapeutic markers for this lethal disease. Recently, CA125 has been identified in PDAC, and the aim of this research is to study the changes in CA125 expression during the progression of benign pancreatic tissue (BPT) to PDAC and to assess its value as a biomarker of tumor growth. To address these questions, the cellular levels of CA125 in BPT and PDAC were measured using immunohistochemistry and compared on the basis of tumor staging, and the tissue microarray technology were constructed using resected pancreatic tissues. The staining reactions for each case were evaluated semiquantitatively using the histologic score system. Our investigation demonstrates a consistent and significant upregulation of CA125 during the transition from BPT to PDAC. We also found a direct correlation between CA125 immunohistochemistry score and tumor stage (P=0.02). In conclusion, our data indicate that CA125 plays a direct role in pancreatic carcinogenesis and suggests that it may eventually be used as a diagnostic and/or prognostic biomarker of pancreatic cancer. Prospective studies are recommended to evaluate further the diagnostic and prognostic capabilities of CA125 in PDAC, and further studies are warranted to assess the use of CA125 as a therapeutic marker.

25 Article Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors. 2016

Hall, MacLean / Liu, Hao / Malafa, Mokenge / Centeno, Barbara / Hodul, Pamela J / Pimiento, José / Pilon-Thomas, Shari / Sarnaik, Amod A. ·Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA. · Gastrointestinal Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA. · Cutaneous Oncology Program, H Lee Moffitt Cancer Center and Research Institute, 10920 N. McKinley Dr, Tampa, FL 33612 USA. ·J Immunother Cancer · Pubmed #27777771.

ABSTRACT: BACKGROUND: We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. METHODS: Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. RESULTS: TIL expansion was measured in 19 patient samples. The majority of these TIL were CD4 CONCLUSIONS: TIL expanded from pancreatic tumors are functional and able to respond to pancreatic tumor associated antigens. PD-1 blockade, 41BB stimulation, and CD8

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