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Pancreatic Neoplasms: HELP
Articles by Peter Muscarella
Based on 21 articles published since 2009
(Why 21 articles?)
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Between 2009 and 2019, Peter Muscarella wrote the following 21 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 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 --

3 Review Biomarkers as predictors of recurrence following curative resection for pancreatic ductal adenocarcinoma: a review. 2014

Osayi, Sylvester N / Bloomston, Mark / Schmidt, Carl M / Ellison, E Christopher / Muscarella, Peter. ·Department of Surgery and Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. ·Biomed Res Int · Pubmed #25050350.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is the fourth most common cancer causing death in the United States. Early tumor recurrence is an important contributor to the dismal prognosis. The availability of an accurate prognostic biomarker for predicting disease recurrence following curative resection will be beneficial for patient care. Most of the currently studied biomarkers remain in the investigational phase, with CA 19-9 being the only biomarker currently approved by the FDA. Herein, we review the utility of CA 19-9 and other investigational cellular, gene, and molecular tumor markers for predicting PDA recurrence following curative surgical resection.

4 Review A review of 130 humans enrolled in transgastric NOTES protocols at a single institution. 2011

Nau, Peter / Ellison, E Christopher / Muscarella, Peter / Mikami, Dean / Narula, Vimal K / Needleman, Bradley / Melvin, W Scott / Hazey, Jeffrey W. ·Division of General Surgery, The Ohio State University School of Medicine and Public Health, 410 West 10th Avenue, Columbus, OH 43210-1228, USA. ·Surg Endosc · Pubmed #20976500.

ABSTRACT: BACKGROUND: The methodology of Natural Orifice Translumenal Endoscopic Surgery (NOTES) has been validated in both human and animal models. Herein is a discussion of our experience gained from the initial 130 patients enrolled in transgastric pre-NOTES and NOTES protocols at our institution. METHODS: A retrospective review of our research database was performed for all patients enrolled in NOTES protocols. The infectious risk of a gastrotomy with and without a NOTES procedure was assessed in 100 patients. Eighty patients completed a true NOTES protocol looking at staging, access, and insufflation with select patients evaluating the potential for bacterial contamination of the abdominal compartment. RESULTS: A total of 130 patients have completed pre-NOTES and NOTES protocols at our institution. We observed no clinically significant contamination of the abdomen secondary to transgastric procedures in 100 patients. Diagnostic transgastric endoscopic peritoneoscopy (DTEP) was completed in 20 patients with pancreatic head masses and found to have a 95% concordance with laparoscopic exploration for assessment of peritoneal metastases. Blind endoscopic gastrotomy and DTEP were evaluated in 40 patients who underwent laparoscopic Roux-en-Y gastric bypass procedures (LSRYGB) and were found to be safe, reliable, and without a clinically significant risk of contamination. Endoscopic peritoneal insufflation was successfully established and correlated with standard laparoscopic insufflation in 20 patients. CONCLUSIONS: Transgastric NOTES is a safe alternative approach to accessing the peritoneal cavity in humans. The risk of bacterial contamination secondary to peroral and transgastric access is clinically insignificant. A device for the facile closure of the gastric defect is the sole factor limiting institution of this methodology as a standalone technique.

5 Clinical Trial Diagnostic transgastric endoscopic peritoneoscopy: extension of the initial human trial for staging of pancreatic head masses. 2010

Nau, Peter / Anderson, Joel / Yuh, Benjamin / Muscarella, Peter / Christopher Ellison, E / Happel, Lynn / Narula, Vimal K / Melvin, W Scott / Hazey, Jeffrey W. ·Division of General Surgery, The Ohio State University School of Medicine and Public Health, 410 West 10th Avenue, Columbus, OH 43210-1228, USA. ·Surg Endosc · Pubmed #20054581.

ABSTRACT: BACKGROUND: The validity of natural orifice transluminal endoscopic surgery (NOTES) was confirmed in a human trial of 10 patients undergoing diagnostic transgastric endoscopic peritoneoscopy (DTEP) for staging of pancreatic head masses. This report is an update with 10 additional patients in the series and includes bacterial contamination data. METHODS: The patients in this human trial were scheduled to undergo diagnostic laparoscopy for abdominal staging of a pancreatic head mass. A second surgeon, blinded to the laparoscopic findings, performed a transgastric endoscopic peritoneoscopy (TEP). The findings of laparoscopic exploration were compared with that those of the TEP. Diagnostic findings, operative times, and clinical course were recorded. Bacterial contamination data were collected for the second cohort of 10 patients. Bacterial samples were collected from the scope before use and the abdominal cavity before and after creation of the gastrotomy. Samples were assessed for bacterial counts and species identification. Definitive care was rendered based on the findings from laparoscopy. RESULTS: In this study, 20 patients underwent diagnostic laparoscopy followed by DTEP. The average time for completion of diagnostic laparoscopy was 10 min compared with 21 min for TEP. The experience acquired during the initial 10 procedures translated to a 7-min decrease in TEP time for the second 10 cases. For 19 of the 20 patients, DTEP corroborated laparoscopic findings for surgical decision making. One endoscopic and five laparoscopic biopsies were performed. Pancreaticoduodenectomy was performed for 14 patients and palliative gastrojejunostomy for 6 patients. No cross-contamination of the peritoneum or infectious complications were noted. No significant complications related to either the endoscopic or laparoscopic approach occurred. CONCLUSIONS: This study supports the authors' previous conclusions that the transgastric approach to diagnostic peritoneoscopy is feasible, safe, and accurate. The lack of documented bacterial contamination further supports the use of this technique. Technical issues, including intraabdominal manipulation and gastric closure, require further investigation.

6 Article Primary Pancreatic Secretinoma: Further Evidence Supporting Secretin as a Diarrheogenic Hormone. 2017

Chey, William Y / Frankel, Wendy L / Roy, Sashwati / Datta, Soma / Sen, Chandan K / Dillhoff, Mary / Muscarella, Peter / Soergel, Konrad H / Tompkins, Ronald K / Chang, Ta-Min / Bradley, Edward L / Ellison, Edwin Christopher. ·*Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH †Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH ‡Department of Surgery, Center for Regenerative Medicine and Cell Based Therapies, Comprehensive Wound Center, Laser Capture Molecular Core, The Ohio State University Wexner Medical Center, Columbus, OH §Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI ¶Department of Surgery, University of California at Los Angeles, School of Medicine, Los Angeles, CA ||Department of Surgery, Florida State University, Tallahassee, FL **William and Sheila Konar Center for Digestive and Liver Diseases, Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY. ·Ann Surg · Pubmed #27501174.

ABSTRACT: OBJECTIVES: To document the existence of primary pancreatic secretinoma in patients with watery diarrhea syndrome (WDS) and achlorhydria and establish secretin as a diarrheogenic hormone. BACKGROUND: Vasoactive intestinal peptide (VIP) has been widely accepted as the main mediator of WDS. However, in 1968, Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors, WDS, and achlorhydria. During surgery on the first, a 24-year-old patient, they noticed distended duodenum filled with fluid and a dilated gallbladder containing dilute bile with high bicarbonate concentration. After excision of the tumor, WDS ceased and gastric acid secretion returned. The second, a 47-year-old, patient's metastatic tumor extract given intravenously in dogs, produced significantly increased pancreatic and biliary fluid rich in bicarbonate. They suggested a secretin-like hormone of islet cell origin explains WDS and achlorhydria. These observations, however, predated radioimmunoassay, immunohistochemical staining, and other molecular studies. METHODS: The first patient's tumor tissue was investigated for secretin and VIP. Using both immunohistochemistry and laser microdissection and pressure catapulting technique for RNA isolation and subsequent reverse transcription polymerase chain reaction, the expression levels of secretin, and VIP were measured. RESULTS: Immunoreactive secretin and its mRNA were predominantly found in the tumor tissue whereas VIP and its mRNA were scarce. CONCLUSIONS: The findings strongly support that the WDS and achlorhydria in this patient may have been caused by secretin as originally proposed in 1968 and that secretin may act as a diarrheogenic hormone.

7 Article Novel techniques for diagnosis of serous cystadenoma: fern pattern of vascularity confirmed by in vivo and ex vivo confocal laser endomicroscopy. 2017

Modi, Rohan M / Swanson, Benjamin / Muscarella, Peter / Conwell, Darwin L / Krishna, Somashekar G. ·Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Division of General and Gastrointestinal Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. ·Gastrointest Endosc · Pubmed #27449195.

ABSTRACT: -- No abstract --

8 Article Routine Cyst Fluid Cytology Is Not Indicated in the Evaluation of Pancreatic Cystic Lesions. 2016

Shirley, Lawrence A / Walker, Jon / Krishna, Somashekar / El-Dika, Samer / Muscarella, Peter / Ellison, E Christopher / Schmidt, Carl R / Bloomston, Mark. ·Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 410 W. 10th Ave, N924 Doan Hall, Columbus, OH, 43210, USA. lawrence.shirley@osumc.edu. · Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Department of Surgery, Montefiore Medical Center, Bronx, NY, USA. · Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 410 W. 10th Ave, N924 Doan Hall, Columbus, OH, 43210, USA. · Division of Surgical Oncology, 21st Century Oncology, Ft. Myers, FL, USA. ·J Gastrointest Surg · Pubmed #27230996.

ABSTRACT: BACKGROUND: The work-up of cystic lesions of the pancreas often involves endoscopic ultrasound (EUS) with fine needle aspiration (FNA). In addition to CEA and amylase measurement, fluid is routinely sent for cytologic examination. We evaluated the utility of cytologic findings in clinical decision-making. MATERIALS AND METHODS: Records of patients who underwent EUS-guided pancreatic cyst aspiration were reviewed. Findings from axial imaging and EUS were compared to cyst fluid cytology as well as fluid amylase and CEA. All results were then compared to final diagnosis, determined by clinical analysis for those patients not resected, and surgical pathology report for those who underwent resection. RESULTS: A total of 167 patients were reviewed. Of 48 patients with suspicious findings on imaging, cytology yielded diagnostic information in 89.6 % of cases (43 patients). However, in the 119 patients where no suspicious components were revealed on imaging, fluid cytology yielded no significant diagnostic results in any case. In all cases where mucin was noted on cytologic review, thick fluid was also seen at the time of aspiration. DISCUSSION: In our cohort of patients with cystic pancreatic lesions, cytologic analysis of pancreatic cyst fluid yielded no diagnostic benefit over radiologic findings alone. In such cases where fluid is to be aspirated, specimens that would otherwise be sent for cytologic evaluation would be better served for other purposes, such as molecular analysis or banking for future research.

9 Article Intraoperative Use of a Portable Large Field of View Gamma Camera and Handheld Gamma Detection Probe for Radioguided Localization and Prediction of Complete Surgical Resection of Gastrinoma: Proof of Concept. 2015

Hall, Nathan C / Nichols, Shawnn D / Povoski, Stephen P / James, Iyore A O / Wright, Chadwick L / Harris, Randall / Schmidt, Carl R / Muscarella, Peter / Latchana, Nicholas / Martin, Edward W / Ellison, E Christopher. ·Department of Radiology, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH; Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA. Electronic address: nathan.hall@uphs.upenn.edu. · Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH; Department of Surgery, San Antonio Military Medical Center, Fort Sam Houston, TX. · Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH. · Department of Radiology, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH. · Division of Epidemiology, The Ohio State University, Wexner Medical Center, Columbus, OH. ·J Am Coll Surg · Pubmed #26206636.

ABSTRACT: BACKGROUND: Surgical management of Zollinger-Ellison syndrome (ZES) relies on localization and resection of all tumor foci. We describe the benefit of combined intraoperative use of a portable large field of view gamma camera (LFOVGC) and a handheld gamma detection probe (HGDP) for indium-111 ((111)In)-pentetreotide radioguided localization and confirmation of gastrinoma resection in ZES. STUDY DESIGN: Five patients (6 cases) with (111)In-pentetreotide-avid ZES were evaluated. Patients were injected with (111)In-pentetreotide for diagnostic imaging the day before surgery. Intraoperatively, an HGDP and LFOVGC were used to localize (111)In-pentetreotide-avid lesions, guide resection, assess specimens for (111)In-pentetreotide activity, and to verify lack of abnormal post-resection surgical field activity. RESULTS: Large field of view gamma camera imaging and HGDP-assisted detection were helpful for localization and guided resection of tumor and removal of (111)In-pentetreotide-avid tumor foci in all cases. In 3 of 5 patients (3 of 6 cases), these techniques led to detection and resection of additional tumor foci beyond those detected by standard surgical techniques. The (111)In-pentetreotide-positive or-negative specimens correlated with neuroendocrine tumors or benign pathology, respectively. In one patient with mild residual focal activity on post-resection portable LFOVGC imaging, thought to be artifact, had recurrence of disease in the same area 5 months after surgery. CONCLUSIONS: Real-time LFOVGC imaging and HGDP use for surgical management of gastrinoma improve success of localizing and resecting all neuroendocrine tumor-positive tumor foci, providing instantaneous navigational feedback. This approach holds potential for improving long-term patient outcomes in patients with ZES.

10 Article In vivo and ex vivo needle-based confocal endomicroscopy of intraductal papillary mucinous neoplasm of the pancreas. 2015

Krishna, Somashekar G / Swanson, Benjamin / Conwell, Darwin L / Muscarella, Peter. ·Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Division of General and Gastrointestinal Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. ·Gastrointest Endosc · Pubmed #26005013.

ABSTRACT: -- No abstract --

11 Article Groove Pancreatitis, a Masquerading Yet Distinct Clinicopathological Entity: Analysis of Risk Factors and Differentiation. 2015

Oza, Veeral M / Skeans, Jacob M / Muscarella, Peter / Walker, Jon P / Sklaw, Brett C / Cronley, Kevin M / El-Dika, Samer / Swanson, Benjamin / Hinton, Alice / Conwell, Darwin L / Krishna, Somashekar G. ·From the *Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, †Department of Surgery, and ‡Department of Pathology, The Ohio State University Wexner Medical Center; and §Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH. ·Pancreas · Pubmed #25899649.

ABSTRACT: OBJECTIVES: Our objective was to delineate predictive factors differentiating groove pancreatitis (GP) from other lesions involving the head of the pancreas (HOP). METHODS: A case-control study of patients older than 10 years was performed comparing patients with GP to those with other surgically resected HOP lesions. RESULTS: Thirteen patients with GP (mean ± SD age, 51.9 ± 10.5 years; 11 males [84.6%]), all with a history of smoking (mean, 37.54 ± 17.8 pack-years), were identified. Twelve patients (92.3%) had a history of heavy alcohol drinking (heavy alcohol [EtOH]). The mean lesion size was 2.6 ± 1.1 cm, and the CA 19-9 was elevated (>37 IU/mL) in 5 patients (45.5%). The most common histopathologic condition was duodenal wall cyst with myofibroblastic proliferation and changes of chronic pancreatitis in the HOP.Univariate analysis revealed decreasing age, male sex, weight loss, nausea/vomiting, heavy EtOH, smoking, and a history of chronic pancreatitis were predictive of GP. A multivariate analysis among smokers demonstrated that weight loss (P = 0.006; odds ratio, 11.96; 95% confidence interval, 2.1-70.2), and heavy EtOH (P < 0.001; odds ratio, 82.2; 95% confidence interval, 9.16-738.1) were most predictive of GP. Compared to pancreatic adenocarcinoma (n = 183), weight loss and heavy EtOH remained predictive of GP. CONCLUSION: Groove pancreatitis in the HOP is associated with a history of heavy EtOH and weight loss. In the absence of these symptoms, it is essential to rule out a malignant lesion.

12 Article Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. 2015

Blazer, Marlo / Wu, Christina / Goldberg, Richard M / Phillips, Gary / Schmidt, Carl / Muscarella, Peter / Wuthrick, Evan / Williams, Terrence M / Reardon, Joshua / Ellison, E Christopher / Bloomston, Mark / Bekaii-Saab, Tanios. ·James Cancer Hospital, The Ohio State University, Columbus, OH, USA. ·Ann Surg Oncol · Pubmed #25358667.

ABSTRACT: BACKGROUND: For patients with metastatic pancreatic cancer, FOLFIRINOX (fluorouracil [5-FU], leucovorin [LV], irinotecan [IRI], and oxaliplatin) has shown improved survival rates compared with gemcitabine but with significant toxicity, particularly in patients with a high tumor burden. Because of reported response rates exceeding 30 %, the authors began to use a modified (m) FOLFIRINOX regimen for patients with advanced nonmetastatic disease aimed at downstaging for resection. This report describes their experience with mFOLFIRINOX and aggressive surgical resection. METHODS: Between January 2011 and August of 2013, 43 patients with borderline resectable pancreatic cancer (BRPC, n = 18) or locally advanced pancreatic cancer (LAPC, n = 25) were treated with mFOLFIRINOX (no bolus 5-FU, no LV, and decreased IRI). Radiation was used based on response and intended surgery. Charts were retrospectively reviewed to assess response, toxicities, and extent of resection when possible. RESULTS: The most common grade 3/4 toxicity was diarrhea in six patients (14 %) with no grade 3/4 neutropenia or thrombocytopenia. Resection was attempted in 31 cases (72 %) and accomplished in 22 cases (51.1 %) including 11 of 25 LAPC cases (44 %). Vascular resection was required in 4 cases (18 %), with R0 resection in 86.4 % of the resections. Complications occurred in 6 cases (27 %), with no perioperative deaths. The median progression-free survival period was 18 months if the resection was achieved compared with 8 months if no resection was performed (p < 0.001). CONCLUSION: Neoadjuvant mFOLFIRINOX is an effective, well-tolerated regimen for patients with advanced nonmetastatic pancreatic cancer. When mFOLFIRINOX is coupled with aggressive surgery, high resection rates are possible even when the initial imaging shows locally advanced disease. Although data are still maturing, resection appears to offer at least a progression-free survival advantage.

13 Article Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. 2014

Tempero, Margaret A / Malafa, Mokenge P / Behrman, Stephen W / Benson, Al B / Casper, Ephraim S / Chiorean, E Gabriela / Chung, Vincent / Cohen, Steven J / Czito, Brian / Engebretson, Anitra / Feng, Mary / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Lowy, Andrew M / Ma, Wen Wee / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Reddy, Sushanth / Sasson, Aaron R / Thayer, Sarah P / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer L / Freedman-Cass, Deborah A. ·From UCSF Helen Diller Family Comprehensive Cancer Center; Moffitt Cancer Center; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; City of Hope Comprehensive Cancer Center; Fox Chase Cancer Center; Duke Cancer Institute; Pancreatic Cancer Action Network (PanCAN); University of Michigan Comprehensive Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Stanford Cancer Institute; UC San Diego Moores Cancer Center; Roswell Park Cancer Institute; Vanderbilt-Ingram Cancer Center; Huntsman Cancer Institute at the University of Utah; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; Massachusetts General Hospital Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; University of Colorado Cancer Center; The University of Texas MD Anderson Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #25099441.

ABSTRACT: The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.

14 Article Deletions of RDINK4/ARF enhancer in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors. 2014

Poi, Ming J / Drosdeck, Joe / Frankel, Wendy L / Muscarella, Peter / Li, Junan. ·From the *Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, †College of Pharmacy, ‡Comprehensive Cancer Center, Departments of §Surgery and ∥Pathology, College of Medicine, and ¶Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH. ·Pancreas · Pubmed #25003221.

ABSTRACT: OBJECTIVE: The presence of an enhancer element, RD (RD), in the prominent INK4-ARF locus provides a novel en bloc mechanism to simultaneously regulate the transcription of p15, p14ARF, and p16 genes. However, knowledge about RD alterations and its potential contributions to cancer progression remains limited. In this study, we aimed to evaluate the incidence of RD alterations in pancreatic tumors. METHODS: DNAs from 14 gastrinomas and 6 nonfunctioning pancreatic neuroendocrine tumors were subjected to quantitative real-time polymerase chain reaction-based assays to determine deletions in p15, p14ARF, and p16 (both exons 1 and 2). RESULTS: RD was frequently deleted in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors with an incidence of 30% (6/20 samples). In comparison, the incidences of deletions of p15 (exon 1), p14ARF (exon 1β), and p16 (exon 1α) are 10% (2/20 samples), 10% (2/20 samples), and 45% (9/20 samples), respectively. Whereas some RD deletion events arose from deletions of the entire INK4-ARF locus, RD deletions in some specimens seemed to be independent of genetic alterations in any of the p15, p14ARF, and p16 genes. CONCLUSIONS: Our results strongly support that the deletion of RD may represent a novel mechanism to simultaneously downregulate p15, p14ARF, and p16, thus contributing to the development of human pancreatic cancers.

15 Article The addition of radiation to chemotherapy does not improve outcome when compared to chemotherapy in the treatment of resected pancreas cancer: the results of a single-institution experience. 2014

Martin, Ludmila Katherine / Luu, Dai Chu / Li, Xiaobai / Muscarella, Peter / Ellison, E Christopher / Bloomston, Mark / Bekaii-Saab, Tanios. ·Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH. · Department of Internal Medicine, The Ohio State University, Columbus, OH. · Center for Biostatistics, The Ohio State University, Columbus, OH. · Department of Surgery, The Ohio State University, Columbus, OH. · Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH. ·Ann Surg Oncol · Pubmed #24046122.

ABSTRACT: BACKGROUND: Pancreas cancer is highly lethal even at early stages. Adjuvant therapy with chemotherapy (CT) or chemoradiation (CRT) is standard following surgery to delay recurrence and improve survival. There is no consensus on the added value of radiotherapy (RT). We conducted a retrospective analysis of clinical outcomes in pancreas cancer patients treated with CT or CRT following surgery. METHODS: Patients with resected pancreas adenocarcinoma were identified in our institutional database. Relevant clinicopathologic and demographic data were collected. Patients were grouped according to adjuvant treatment: group A: no treatment; group B: CT; group C: CRT. The primary endpoint of overall survival was compared between groups B vs. C. Univariate and multivariate analyses of potential prognostic factors were conducted including all patients. RESULTS: A total of 146 evaluable patients were included (group A: n = 33; group B: n = 45; group C: n = 68). Demographics and pathologic characteristics were comparable. There was no significant survival benefit for CRT compared with CT (mOS 16.8 months vs. 21.5 months, respectively, p = 0.76). Local recurrence rates were similar in all three groups. Univariate analyses identified absence of lymph node involvement (hazards ratio [HR] 1.43, p = 0.0082) and administration of adjuvant therapy (HR 0.496, p = 0.0008) as significant predictors for improved survival. Multivariate analyses suggested that patients without nodal involvement derived the most benefit from adjuvant treatment. CONCLUSIONS: The addition of RT to CT did not improve survival over CT. Lymph node involvement predicts inferior clinical outcome.

16 Article NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia. 2013

He, Wei A / Berardi, Emanuele / Cardillo, Veronica M / Acharyya, Swarnali / Aulino, Paola / Thomas-Ahner, Jennifer / Wang, Jingxin / Bloomston, Mark / Muscarella, Peter / Nau, Peter / Shah, Nilay / Butchbach, Matthew E R / Ladner, Katherine / Adamo, Sergio / Rudnicki, Michael A / Keller, Charles / Coletti, Dario / Montanaro, Federica / Guttridge, Denis C. · ·J Clin Invest · Pubmed #24084740.

ABSTRACT: Cachexia is a debilitating condition characterized by extreme skeletal muscle wasting that contributes significantly to morbidity and mortality. Efforts to elucidate the underlying mechanisms of muscle loss have predominantly focused on events intrinsic to the myofiber. In contrast, less regard has been given to potential contributory factors outside the fiber within the muscle microenvironment. In tumor-bearing mice and patients with pancreatic cancer, we found that cachexia was associated with a type of muscle damage resulting in activation of both satellite and nonsatellite muscle progenitor cells. These muscle progenitors committed to a myogenic program, but were inhibited from completing differentiation by an event linked with persistent expression of the self-renewing factor Pax7. Overexpression of Pax7 was sufficient to induce atrophy in normal muscle, while under tumor conditions, the reduction of Pax7 or exogenous addition of its downstream target, MyoD, reversed wasting by restoring cell differentiation and fusion with injured fibers. Furthermore, Pax7 was induced by serum factors from cachectic mice and patients, in an NF-κB-dependent manner, both in vitro and in vivo. Together, these results suggest that Pax7 responds to NF-κB by impairing the regenerative capacity of myogenic cells in the muscle microenvironment to drive muscle wasting in cancer.

17 Article Pancreatic resection in the octogenarian: a safe option for pancreatic malignancy. 2011

Hatzaras, Ioannis / Schmidt, Carl / Klemanski, Dori / Muscarella, Peter / Melvin, W Scott / Ellison, E Christopher / Bloomston, Mark. ·Department of Surgery, The Ohio State University, Columbus, OH, USA. ·J Am Coll Surg · Pubmed #21227721.

ABSTRACT: BACKGROUND: The incidence of pancreatic cancer is age related; patients older than the age of 65 represent 60% of all cases. We assessed our institution's experience and outcomes with pancreatic resection for malignancy in patients in their ninth decade. STUDY DESIGN: We reviewed records of patients undergoing pancreatic resection for malignancy at our institution between 1990 and 2007. Demographics, laboratory, treatment, and outcomes data were gathered. Comparisons were made between patients older and younger than the age of 80. Survival was analyzed using the Kaplan-Meier method and comparisons between groups were performed using the log-rank test. Regression methods were used to evaluate predictors of outcomes. RESULTS: There were 517 pancreatic resections for cancer reviewed. Of these, 27 patients were 80 years or older (age range 80 to 91 years), compared with 490 patients less than 80 (range 20 to 79 years). The distribution of clinical characteristics was similar between the 2 groups. The majority of patients undergoing pancreatic resection harbored a mass in the head of the pancreas, so the most common procedure was pancreaticoduodenectomy (n = 398, 78%). There were no significant differences in complication rates for younger and older groups (59% vs 52%, respectively, p = 0.4), median length of stay (11 vs 12 days, p = 0.33), or perioperative mortality rates (3.7% vs 3.7%, p = 1.0). Overall survival between the 2 groups was similar (21.9 vs 33.3 months, p = 0.18). CONCLUSIONS: Pancreatectomy for malignancy is a safe option for the elderly. Patients older than age 80 achieved similar results, with similar rates of perioperative complications and mortality. Pancreatectomy for cancer offers a similar survival benefit in both groups.

18 Article Failure of normalization of CA19-9 following resection for pancreatic cancer is tantamount to metastatic disease. 2011

Abdel-Misih, Sherif R Z / Hatzaras, Ioannis / Schmidt, Carl / Saab, Tanios-Bekaii / Klemanski, Dori / Muscarella, Peter / Melvin, W Scott / Ellison, E Christopher / Bloomston, Mark. ·Division of Surgical Oncology, The Ohio State University Medical Center/James Cancer Hospital, Columbus, OH, USA. ·Ann Surg Oncol · Pubmed #21042945.

ABSTRACT: BACKGROUND: Multidisciplinary therapy for pancreatic cancer involves radical resection followed by gemcitabine-based chemotherapy. Carbohydrate antigen 19-9 (CA19-9), when elevated preoperatively, is a useful marker to monitor disease status following resection. However, little has been reported on outcomes of patients in whom CA19-9 never normalizes. We hypothesize that failure of CA19-9 normalization within 6 months is prognostically equivalent to metastatic disease. METHODS: From our pancreatectomy database, we identified 93 patients with pancreatic adenocarcinoma and elevated CA19-9 prior to resection with levels recorded postoperatively. Patients were grouped based on normalization or persistent elevation of CA19-9 at 6 months after resection. CA19-9 levels normalized (≤35 u/ml) after resection in 38 (41%) and remained elevated in 55 (59%). Clinicopathologic characteristics were compared using Student's t-test and contingency table analyses. Survival curves were constructed using Kaplan-Meier method and compared by log-rank analysis. Cox regression was used to determine predictors of survival. RESULTS: The two groups had comparable clinicopathologic characteristics except for nodal status and perineural invasion, which were higher in patients with persistently elevated CA19-9. Persistent CA19-9 conferred shorter median overall survival of 10.8 months compared with 23.8 months in patients with normalization (p < 0.001), which persisted when controlling for nodal status. Multivariate analysis demonstrated persistently elevated CA19-9 as the sole statistically significant negative predictor of survival [hazard ratio (HR) 2.20, p = 0.002]. CONCLUSIONS: Persistent CA19-9 elevation after pancreatectomy correlates with shorter survival analogous to unresected or metastatic disease and should be regarded as persistent disease regardless of radiographic findings. These patients should be considered for accrual to clinical trials or initiation of alternative therapy.

19 Article Predictors of survival in periampullary cancers following pancreaticoduodenectomy. 2010

Hatzaras, Ioannis / George, Nathaniel / Muscarella, Peter / Melvin, W Scott / Ellison, E Christopher / Bloomston, Mark. ·Department of Surgery, The Ohio State University, Columbus, OH, USA. ·Ann Surg Oncol · Pubmed #20108122.

ABSTRACT: BACKGROUND: Cancers of the ampulla of Vater, distal common bile duct, and pancreas are known to have dismal prognosis. It is often reported that ampullary cancers are less aggressive relative to the other periampullary carcinomas. We sought to evaluate predictors of survival for periampullary cancers following pancreaticoduodenectomy to identify biologic behavior. METHODS: We reviewed the records of all patients who underwent pancreaticoduodenectomy for periampullary carcinoma between 1992 and 2007 at the Ohio State University Medical Center. Demographics, treatment, and outcome/survival data were analyzed. Kaplan-Meier survival curves were created and compared by log-rank analysis. Multivariate analysis was undertaken using Cox proportional-hazards method. RESULTS: 346 consecutive periampullary malignancies (249 pancreatic cancers, 79 ampullary carcinomas, 18 extrahepatic cholangiocarcinomas) treated by pancreaticoduodenectomy were identified. Pancreatic cancer histology correlated with the shortest median survival (17.1 months), followed by cholangiocarcinoma (17.9 months) and ampullary carcinoma (44.3 months) (P < 0.001). Potential predictors of decreased survival on univariate analysis included site of origin, preoperative jaundice, microscopic positive margin, nodal metastasis, lymphovascular invasion, neural invasion, and poor differentiation. Only nodal metastasis (median 16.2 versus 29.9 months, P < 0.001) and neural invasion (median 17.7 versus 47.9 months, P < 0.00001) significantly predicted outcome on multivariate analysis. CONCLUSIONS: Although ampullary cancers have the best prognosis overall, when controlled for tumor stage, only presence of neural invasion and nodal metastasis predict poor survival following pancreaticoduodenectomy. Biological behavior remains the most important prognostic indicator in periampullary cancers amenable to resection, regardless of site of origin.

20 Article Coordinate loss of fragile gene expression in pancreatobiliary cancers: correlations among markers and clinical features. 2009

Bloomston, Mark / Kneile, Jeffrey / Butterfield, Matthew / Dillhoff, Mary / Muscarella, Peter / Ellison, E Christopher / Melvin, W Scott / Croce, Carlo M / Pichiorri, Flavia / Huebner, Kay / Frankel, Wendy L. ·Department of Surgery, The Ohio State University, Columbus, OH, USA. mark.bloomston@osumc.edu ·Ann Surg Oncol · Pubmed #19434452.

ABSTRACT: BACKGROUND: Loss of expression of fragile gene products, Fhit and Wwox, occurs in many cancer types, with loss exhibited early in the neoplastic process in some. Wwox has been understudied in pancreatobiliary cancers, especially in relation to other involved tumor suppressors. We have assessed the status of the Fhit and Wwox proteins encoded by DNA damage susceptible chromosome fragile sites encompassed by FHIT and WWOX tumor suppressor genes. METHODS: Pancreatic, gallbladder and ampullary cancers, normal pancreas, chronic pancreatitis, and benign gallbladder specimens were stained for expression of Fhit, Fhit effector protein Fdxr, Wwox, and other tumor suppressors by immunohistochemistry, and comparisons were made between benign and malignant tissue. Correlations of expression among proteins and clinicopathologic features were sought using Spearman's rank order. Survival curves were created using the Kaplan-Meier method and compared by log-rank analysis. Predictors of survival were determined using multivariate Cox proportional hazards analysis. RESULTS: Fhit and Wwox were ubiquitously expressed in benign samples and significantly and coordinately reduced in pancreatic, gallbladder, and ampullary cancers. In pancreatic cancers, Fdxr expression was positively correlated with Fhit and Wwox expression. Neither Fhit nor Wwox expression correlated with expression of other tumor suppressors or with clinicopathologic characteristics measured. CONCLUSION: Loss of Fhit and Wwox expression does not predict tumor progression or patient survival, suggesting that loss of expression of genes at the exquisitely replication stress sensitive chromosome fragile regions is an early event in the pathogenesis of cancers of the gallbladder, pancreas, and ampulla.

21 Article Intraoperative assessment of pancreatic neck margin at the time of pancreaticoduodenectomy increases likelihood of margin-negative resection in patients with pancreatic cancer. 2009

Dillhoff, Mary / Yates, Robert / Wall, Kristian / Muscarella, Peter / Melvin, W Scott / Ellison, E Christopher / Bloomston, Mark. ·Department of Surgery, Ohio State University, 410 W. 10th Ave., N924 Doan Hall, Columbus, OH 43210, USA. ·J Gastrointest Surg · Pubmed #19277793.

ABSTRACT: BACKGROUND: The utility of intraoperative assessment of surgical margins is often debated by experienced pancreatic surgeons. We sought to review our experience with pancreaticoduodenectomy (PD) for pancreatic cancer to determine the impact of intraoperative frozen section (FS) analysis on margin-negative resection and long-term outcome. MATERIAL AND METHODS: Between 1992 and 2007, 310 consecutive patients underwent PD at our institution; 223 of these were for pancreatic cancer. Seven patients who underwent R2 resection were excluded. Charts were reviewed to determine demographics, final pathology, perioperative course, and long-term outcome. Data were compared by Fisher's exact and Student's t tests. Survival curves were created using the Kaplan-Meier method and compared by log-rank analysis. Predictors of margin-negative resection were determined by logistic regression analysis and predictors of survival determined by Cox proportional hazards analysis. RESULTS: FS analysis of pancreatic neck resection margins was obtained in 75, while no intraoperative assessment was done in 141. Although patients who underwent FS were younger (median, 62 vs. 67 years, p = 0.01), the two groups were similar in terms of gender, comorbidities, preoperative stenting, pylorus preservation, tumor differentiation, nodal status, tumor size, length of stay, and complication rate. Margin-negative resection was more common when FS was undertaken (99% vs. 81%, p = 0.0001). However, intraoperative FS did not significantly increase overall survival (median, 21.7 vs. 14.6, p = 0.20). Only nodal metastasis was predictive of poor survival (median, 21.7 vs. 13.3 months, p = 0.001). CONCLUSIONS: Intraoperative assessment of the pancreatic neck margin status at the time of PD for pancreatic cancer increases the likelihood of obtaining a margin-negative resection. Noteworthy is that final margin status was not predictive of survival, while only nodal metastasis was, suggesting that tumor biology is the most important factor in patients with pancreatic cancer.