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Pancreatic Neoplasms: HELP
Articles by Mary E. Dillhoff
Based on 14 articles published since 2008
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Between 2008 and 2019, Mary Dillhoff wrote the following 14 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
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 Clinical Trial None 2017

Krishna, Somashekar G / Modi, Rohan M / Kamboj, Amrit K / Swanson, Benjamin J / Hart, Phil A / Dillhoff, Mary E / Manilchuk, Andrei / Schmidt, Carl R / Conwell, Darwin L. ·Somashekar G Krishna, Phil A Hart, Darwin L Conwell, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States. ·World J Gastroenterol · Pubmed #28566895.

ABSTRACT: AIM: To investigate the reproducibility of the METHODS: In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an RESULTS: A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic

3 Article Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer. 2019

Ramsey, Mitchell L / Talbert, Erin / Ahn, Daniel / Bekaii-Saab, Tanios / Badi, Niharika / Bloomston, P Mark / Conwell, Darwin L / Cruz-Monserrate, Zobeida / Dillhoff, Mary / Farren, Matthew R / Hinton, Alice / Krishna, Somashekar G / Lesinski, Gregory B / Mace, Thomas / Manilchuk, Andrei / Noonan, Anne / Pawlik, Timothy M / Rajasekera, Priyani V / Schmidt, Carl / Guttridge, Denis / Hart, Phil A. ·Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Department of Cancer Biology and Genetics and The Ohio State University Comprehensive Cancer Center Cachexia Program, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Division of Hematology/Medical Oncology, Mayo Clinic, Phoenix, AZ, USA. · Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · 21st Century Oncology, Inc., Fort Meyers, FL, USA. · Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA. · Division of Biostatistics, The Ohio State University, Columbus, OH, USA. · Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: philip.hart@osumc.edu. ·Pancreatology · Pubmed #30497874.

ABSTRACT: BACKGROUND: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression. METHODS: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models. RESULTS: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p < 0.001 for multiplex and p = 0.007 for ELISA). Further, while >5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was. CONCLUSION: Circulating IL-6 levels do not correlate with cachexia (when defined by weight loss), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia.

4 Article Perioperative cytokine levels portend early death after pancreatectomy for ductal adenocarcinoma. 2018

Lewis, Heather L / Chakedis, Jeff M / Talbert, Erin / Haverick, Ericka / Rajasekera, Priyani / Hart, Philip / Bloomston, Mark / Dillhoff, Mary / Pawlik, Timothy M / Guttridge, Denis / Schmidt, Carl R. ·Division of Surgical Oncology, Department of Surgery, Wexner Medical Center, Ohio State University, Columbus, Ohio. · Center for Regenerative Medicine and Cell Based Therapies, College of Medicine, Ohio State University, Columbus, Ohio. · Department of Gastroenterology, Wexner Medical Center, Ohio State University, Columbus, Ohio. · 21st Century Oncology, Inc., Fort Meyers, Florida. ·J Surg Oncol · Pubmed #29205349.

ABSTRACT: BACKGROUND: Soluble signaling molecules may play an important role in malignant pathogenesis. We hypothesize that perioperative cytokine levels are associated with outcomes in patients with pancreatic adenocarcinoma (PDAC) undergoing surgical resection. METHODS: One hundered and eighteen patients with benign or malignant pancreatic disease were enrolled in a prospective study through a protocol for banking biologic samples. Peripheral blood was drawn at time of operation, and a multiplex cytokine assay was performed. Statistical analysis was via χ RESULTS: Of 118 patients enrolled, 85 (72%) had a diagnosis of PDAC, and 60 (70%) ultimately underwent partial pancreatectomy. Cytokine levels were not associated with postoperative complications in this initial cohort. A plasma level of monocyte chemoattractant protein-1 (MCP-1) pg/mL ≤118 was associated with better overall survival (OS) (median survival 21 months vs 12.8 months, P = 0.023), as was non-detectable interleukin-8 (IL-8) (19 months) versus detectable IL-8 (12.8 months, P = 0.05). Patients with both MCP-1 >118 pg/mL and detectable IL-8 had a median survival of 10.6 months (P = 0.028). CONCLUSIONS: MCP-1 and IL-8 cytokine levels are associated with decreased survival following pancreatectomy for PDAC, and may be useful biomarkers. Measurement of these cytokine levels at different time points in future investigations will be important to validate these findings.

5 Article Predictors of Pancreatic Cancer-Associated Weight Loss and Nutritional Interventions. 2017

Nemer, Laura / Krishna, Somashekar G / Shah, Zarine K / Conwell, Darwin L / Cruz-Monserrate, Zobeida / Dillhoff, Mary / Guttridge, Denis C / Hinton, Alice / Manilchuk, Andrei / Pawlik, Timothy M / Schmidt, Carl R / Talbert, Erin E / Bekaii-Saab, Tanios / Hart, Phil A. ·From the *Division of Gastroenterology, Hepatology, and Nutrition, †Department of Radiology, ‡Division of Surgical Oncology, §Department of Cancer Biology and Genetics, ∥Division of Biostatistics, College of Public Health, ¶Division of General Surgery, #Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH; and **Division of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ. ·Pancreas · Pubmed #28902785.

ABSTRACT: OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is often accompanied by weight loss. We sought to characterize factors associated with weight loss and observed nutritional interventions, as well as define the effect of weight loss on survival. METHODS: Consecutive subjects diagnosed with PDAC (N = 123) were retrospectively evaluated. Univariate analysis was used to compare subjects with and without substantial (>5%) weight loss. Multivariate logistic regression was performed to identify factors associated with weight loss, and survival analyses were performed using Kaplan-Meier curves and Cox survival models. RESULTS: Substantial weight loss at diagnosis was present in 71.5% of subjects and was independently associated with higher baseline body mass index, longer symptom duration, and increased tumor size. Recommendations for nutrition consultation and pancreatic enzyme replacement therapy occurred in 27.6% and 36.9% of subjects, respectively. Weight loss (>5%) was not associated with worse survival on multivariate analysis (hazard ratio, 1.32; 95% confidence interval, 0.76-2.30), unless a higher threshold (>10%) was used (hazard ratio, 1.77; 95% confidence interval, 1.09-2.87). CONCLUSIONS: Despite the high prevalence of weight loss at PDAC diagnosis, there are low observed rates of nutritional interventions. Weight loss based on current criteria for cancer cachexia is not associated with poor survival in PDAC.

6 Article NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development. 2017

Ratnam, Nivedita M / Peterson, Jennifer M / Talbert, Erin E / Ladner, Katherine J / Rajasekera, Priyani V / Schmidt, Carl R / Dillhoff, Mary E / Swanson, Benjamin J / Haverick, Ericka / Kladney, Raleigh D / Williams, Terence M / Leone, Gustavo W / Wang, David J / Guttridge, Denis C. ·Department of Cancer Biology and Genetics. · Molecular, Cellular and Developmental Biology Graduate Program. · Arthur G. James Comprehensive Cancer Center. · Division of Surgical Oncology. · Department of Pathology, and. · Department of Radiation Oncology, The Ohio State University (OSU), Columbus, Ohio, USA. ·J Clin Invest · Pubmed #28891811.

ABSTRACT: Macrophages are attracted to developing tumors and can participate in immune surveillance to eliminate neoplastic cells. In response, neoplastic cells utilize NF-κB to suppress this killing activity, but the mechanisms underlying their self-protection remain unclear. Here, we report that this dynamic interaction between tumor cells and macrophages is integrally linked by a soluble factor identified as growth and differentiation factor 15 (GDF-15). In vitro, tumor-derived GDF-15 signals in macrophages to suppress their proapoptotic activity by inhibiting TNF and nitric oxide (NO) production. In vivo, depletion of GDF-15 in Ras-driven tumor xenografts and in an orthotopic model of pancreatic cancer delayed tumor development. This delay correlated with increased infiltrating antitumor macrophages. Further, production of GDF-15 is directly regulated by NF-κB, and the colocalization of activated NF-κB and GDF-15 in epithelial ducts of human pancreatic adenocarcinoma supports the importance of this observation. Mechanistically, we found that GDF-15 suppresses macrophage activity by inhibiting TGF-β-activated kinase (TAK1) signaling to NF-κB, thereby blocking synthesis of TNF and NO. Based on these results, we propose that the NF-κB/GDF-15 regulatory axis is important for tumor cells in evading macrophage immune surveillance during the early stages of tumorigenesis.

7 Article Hospital Volume and the Costs Associated with Surgery for Pancreatic Cancer. 2017

Gani, Faiz / Johnston, Fabian M / Nelson-Williams, Howard / Cerullo, Marcelo / Dillhoff, Mary E / Schmidt, Carl R / Pawlik, Timothy M. ·Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Wexner Medical Center at The Ohio State University, Columbus, OH, USA. · Department of Surgery, Wexner Medical Center at The Ohio State University, Columbus, OH, USA. tim.pawlik@osumc.edu. · Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Wexner Medical Center at The Ohio State University, 395 W. 12th Avenue, Suite 670, Columbus, OH, 43210, USA. tim.pawlik@osumc.edu. ·J Gastrointest Surg · Pubmed #28664254.

ABSTRACT: BACKGROUND: Data evaluating the financial implications of volume-based referral are lacking. This study sought to compare in-hospital costs for pancreatic surgery by annual hospital volume. METHODS: Eleven thousand and eighty-one patients aged ≥18 years undergoing an elective pancreatic resection for cancer were identified using the Nationwide Inpatient Sample 2002-2011. Multivariable regression analysis was performed to compare length-of-stay (LOS), postoperative morbidity and mortality, failure-to-rescue (FTR), and inpatient costs by annual hospital volume group. RESULTS: Patients undergoing surgery at high-volume hospitals (HVH) demonstrated 23% lower odds (odds ratio [OR] = 0.77, 95% confidence interval [95%CI] 0.63-0.95) of developing a postoperative complication, 59% lower odds of experiencing an LOS > 14 days (OR = 0.41, 95%CI 0.34-0.50), 51% lower odds of postoperative mortality (OR = 0.49, 95%CI 0.34-0.71), and 47% lower odds of FTR (OR = 0.53, 95%CI 0.37-0.76; all p<0.05). The overall mean in-hospital cost was $39,012 (SD = $15,214) with minimal differences observed across hospital volume groups. Rather, postoperative complications (no complication vs. complication $26,686 [SD = $5762] vs. $44,633 [SD = $11,637]) and FTR (rescue vs. FTR $42,413 [SD = $8481] vs. $69,546 [SD = $13,131]) were determinant of higher in-hospital costs. While this pattern was observed at all hospital volume groups, costs varied minimally between hospital volume groups after this stratification. CONCLUSIONS: Annual hospital surgical volume was not associated with in-hospital costs among patients undergoing pancreatic surgery.

8 Article Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos). 2017

Krishna, Somashekar G / Brugge, William R / Dewitt, John M / Kongkam, Pradermchai / Napoleon, Bertrand / Robles-Medranda, Carlos / Tan, Damien / El-Dika, Samer / McCarthy, Sean / Walker, Jon / Dillhoff, Mary E / Manilchuk, Andrei / Schmidt, Carl / Swanson, Benjamin / Shah, Zarine K / Hart, Phil A / Conwell, Darwin L. ·Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Pancreas Biliary Center, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. · Division of Gastroenterology, Department of Medicine, Indiana University Hospital, Indianapolis, Indiana, USA. · Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand. · Department of Gastroenterology, Ramsay Générale de Santé, Hôpital privé Jean Mermoz, Lyon, France. · Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas, University Hospital OMNI, Guayaquil, Ecuador. · Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore. · Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Department of General Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. ·Gastrointest Endosc · Pubmed #28286093.

ABSTRACT: BACKGROUND AND AIMS: EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis. METHODS: Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used. RESULTS: A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively. CONCLUSIONS: EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.).

9 Article Pancreatic neuroendocrine microadenomatosis: A case report of cytology and histology correlation. 2017

Vo, Nguyen / Cohen, David W / Dillhoff, Mary E / Jin, Ming. ·Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio. · Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio. ·Diagn Cytopathol · Pubmed #27670143.

ABSTRACT: Pancreatic neuroendocrine neoplasia is categorized by grade, size, and functional status. Neuroendocrine microadenoma (NEMA) is defined as a neuroendocrine tumor (NET) that measures less than 0.5 cm in diameter. Multiple NEMAs are termed neuroendocrine adenomatosis (NEMAtosis). The surgical pathology and clinical aspects of pancreatic NEMAtosis have been reported, but there has been no report regarding EUS-FNA cytology of NEMAtosis. We report a case of NEMAtosis with cytologic correlation and illustrate the diagnostic challenges and potential pitfalls. The pre-operative cytology can be problematic. The main differential diagnosis of the EUS-FNA specimen includes NET, normal pancreas, and islet cell hyperplasia/aggregation associated with chronic pancreatitis. The helpful cytopathologic feature of NEMAtosis is the presence of two intermingled populations of loosely-cohesive neuroendocrine cell clusters and tight acinar cell groups arranged in microacinar and/or grape-like structures. Although neuroendocrine cells and acinar cells possess different cytomorphology, the distinction is not always straightforward because both types of cells are small and cytologically bland. Cytologic assessment of both architecture and individual cell morphology is imperative to avoid interpretation error and further guide appropriate clinical management. Diagn. Cytopathol. 2017;45:143-147. © 2016 Wiley Periodicals, Inc.

10 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.

11 Article Cystic pancreatic neuroendocrine tumors: correlation of in vivo needle-based confocal endomicroscopic findings by ex vivo analysis. 2017

Kamboj, Amrit K / Swanson, Benjamin / Dillhoff, Mary E / Conwell, Darwin L / Krishna, Somashekar G. ·Ohio State University College of Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Division of Surgical Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Division of Gastroenterology, Hepatology, and Nutrition, Ohio State University Wexner Medical Center, Columbus, Ohio, USA. ·Gastrointest Endosc · Pubmed #27492715.

ABSTRACT: -- No abstract --

12 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.

13 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.

14 Article MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. 2008

Dillhoff, Mary / Liu, James / Frankel, Wendy / Croce, Carlo / Bloomston, Mark. ·Department of Surgery, The Ohio State University, 410 W. 10th Ave., N924 Doan Hall, Columbus, OH 43210, USA. ·J Gastrointest Surg · Pubmed #18642050.

ABSTRACT: BACKGROUND: MicroRNAs are small (18-22 nucleotides) noncoding RNAs involved in posttranscriptional modification of many target genes. One of these, microRNA-21 (miR-21), has been shown to play a role in multiple hematologic and solid organ malignancies. We sought to determine the expression pattern of miR-21 in pancreatic cancers and its impact on clinicopathologic characteristics. METHODS: Eighty resected pancreatic cancer specimens were microdissected and tissue microarrays (TMA) created in duplicate. TMAs were also created for benign pancreas (N = 12) and chronic pancreatitis (N = 45). In situ hybridization (ISH) was undertaken utilizing locked nucleic acid probes for miR-21. RNA U6 and scrambled RNA served as positive and negative control, respectively. ISH was scored as 0 (absent), 1+ (faint/focal expression), or 2+ (strong expression). Kaplan-Meier survival curves were constructed and compared by log-rank analysis. RESULTS: MiR-21 expression was demonstrated in 63 (79%) pancreatic cancers (1+ in 49, 2+ in 14) compared to one of 12 (8%, p < 0.0001) benign pancreas and 12/45 (27%, p < 0.0001) chronic pancreatitis. None of the benign tissues demonstrated strong miR-21 expression. Although miR-21 expression did not correlate with tumor size, differentiation, nodal status, or T stage, strong miR-21 expression was predictive of poorer outcome compared to absent or faint/focal miR-21 expression in patients with node-negative disease (median 27.7 months vs. 15.2, p = 0.037). Nodal status was also predictive of survival (p = 0.029). CONCLUSIONS: MicroRNA-21 is significantly overexpressed in pancreatic cancers as detected by in situ hybridization. Its strong expression predicts limited survival in patients with node-negative disease and may be an important biologic marker for outcome.