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Pancreatic Neoplasms: HELP
Articles by C. Max Schmidt
Based on 63 articles published since 2010
(Why 63 articles?)
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Between 2010 and 2020, C. Max Schmidt wrote the following 63 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Postbrushing and fine-needle aspiration biopsy follow-up and treatment options for patients with pancreatobiliary lesions: the Papanicolaou Society of Cytopathology guidelines. 2014

Kurtycz, Daniel / Tabatabai, Z Laura / Michaels, Claire / Young, Nancy / Schmidt, C Max / Farrell, James / Gopal, Deepak / Simeone, Diane / Merchant, Nipun B / Field, Andrew / Pitman, Martha Bishop / Anonymous3070788. ·Department of Pathology, University of Wisconsin, Wisconsin State Laboratory of Hygiene, Madison, Wisconsin. ·Diagn Cytopathol · Pubmed #24639399.

ABSTRACT: The papanicolaou society of cytopathology (PSC) has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) biopsy, techniques of EUS-FNA, terminology and nomenclature for pancreatobiliary cytology, ancillary testing, and postprocedure management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18 month period and synthesis of online comments of the draft document on the PSC web site [www.papsociety.org]. This document selectively presents the results of these discussions and focuses on the follow-up and treatment options for patients after procedures performed for obtaining cytology samples for the evaluation of biliary strictures and solid and cystic masses in the pancreas. These recommendations follow the six-tiered terminology and nomenclature scheme proposed by Committee III.

2 Guideline International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. 2012

Tanaka, Masao / Fernández-del Castillo, Carlos / Adsay, Volkan / Chari, Suresh / Falconi, Massimo / Jang, Jin-Young / Kimura, Wataru / Levy, Philippe / Pitman, Martha Bishop / Schmidt, C Max / Shimizu, Michio / Wolfgang, Christopher L / Yamaguchi, Koji / Yamao, Kenji / Anonymous6680728. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. masaotan@med.kyushu-u.ac.jp ·Pancreatology · Pubmed #22687371.

ABSTRACT: The international consensus guidelines for management of intraductal papillary mucinous neoplasm and mucinous cystic neoplasm of the pancreas established in 2006 have increased awareness and improved the management of these entities. During the subsequent 5 years, a considerable amount of information has been added to the literature. Based on a consensus symposium held during the 14th meeting of the International Association of Pancreatology in Fukuoka, Japan, in 2010, the working group has generated new guidelines. Since the levels of evidence for all items addressed in these guidelines are low, being 4 or 5, we still have to designate them "consensus", rather than "evidence-based", guidelines. To simplify the entire guidelines, we have adopted a statement format that differs from the 2006 guidelines, although the headings are similar to the previous guidelines, i.e., classification, investigation, indications for and methods of resection and other treatments, histological aspects, and methods of follow-up. The present guidelines include recent information and recommendations based on our current understanding, and highlight issues that remain controversial and areas where further research is required.

3 Clinical Trial Vascular endothelial growth factor, a novel and highly accurate pancreatic fluid biomarker for serous pancreatic cysts. 2014

Yip-Schneider, Michele T / Wu, Huangbing / Dumas, Ryan P / Hancock, Brad A / Agaram, Narasimhan / Radovich, Milan / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Electronic address: maxschmi@iupui.edu. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Pathology, Indiana University School of Medicine, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN; Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN; Indiana University Cancer Center, Indianapolis, IN; Richard L Roudebush VA Medical Center, Indianapolis, IN. ·J Am Coll Surg · Pubmed #24491241.

ABSTRACT: BACKGROUND: Mucinous pancreatic cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) have the potential to progress to invasive pancreatic adenocarcinoma, presenting an opportunity for early detection, prevention, and cure. Serous cystic neoplasms (SCN) have no malignant potential, but can mimic mucinous pancreatic cysts on imaging. Therefore, identification of biomarkers that can distinguish between cystic lesions is critically important. We hypothesize that vascular endothelial growth factor (VEGF)-A levels in pancreatic fluid correlate with pathologic diagnosis. STUDY DESIGN: Pancreatic cyst/duct fluid samples were prospectively collected from patients undergoing pancreatic resection and correlated with surgical pathology. VEGF levels were detected by ELISA. VEGF-A and VEGF receptor 2 expression in pancreatic tissue was localized by immunohistochemistry. Genetic alterations of the von Hippel-Lindau gene were determined by targeted next-generation sequencing. RESULTS: Eighty-seven patients met inclusion criteria for enrollment. Final pathologic diagnoses included pseudocyst (n = 9), SCN (n = 17), mucinous cystic neoplasm (n = 24), low/moderate grade intraductal papillary mucinous neoplasm (n = 16), high-grade/invasive intraductal papillary mucinous neoplasm (n = 10), and pancreatic ductal adenocarcinoma (n = 11). VEGF-A was significantly upregulated in SCN cyst fluid compared with all other diagnoses (p < 0.0001). With a cut-off of 8,500 pg/mL, VEGF-A has 100% sensitivity and 97% specificity as an SCN biomarker. VEGF-A and VEGF receptor 2 are overexpressed in SCN cyst tissue. VEGF-C was also significantly elevated in SCN cyst fluid (p < 0.0001). With a cut-off set at 200 pg/mL, VEGF-C identifies SCN with 100% sensitivity and 90% specificity. The presence of a von Hippel-Lindau mutation in SCN cyst tissue correlates with elevated cyst fluid VEGF levels. CONCLUSIONS: This is the first report of a cyst fluid protein biomarker that can positively identify SCN. The ability to distinguish SCN from premalignant/malignant pancreatic cysts can spare the cost and risk of surveillance and surgical intervention in select patients.

4 Article Performance of candidate urinary biomarkers for pancreatic cancer - Correlation with pancreatic cyst malignant progression? 2019

Yip-Schneider, Michele T / Soufi, Mazhar / Carr, Rosalie A / Flick, Katelyn F / Wu, Huangbing / Colgate, Cameron L / Schmidt, C Max. ·Departments of Surgery, USA; Departments of Walther Oncology Center, USA; Departments of Indiana University Simon Cancer Center, USA; Departments of Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA. · Departments of Surgery, USA; Departments of Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA. · Departments of Center for Outcomes Research in Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. · Departments of Surgery, USA; Departments of Biochemistry/Molecular Biology, USA; Departments of Walther Oncology Center, USA; Departments of Indiana University Simon Cancer Center, USA; Departments of Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA. Electronic address: maxschmi@iupui.edu. ·Am J Surg · Pubmed #31554598.

ABSTRACT: BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are precursors of pancreatic cancer. Potential biomarkers of IPMN progression have not been identified in urine. A few urinary biomarkers were reported to be predictive of pancreatic ductal adenocarcinoma (PDAC). Here, we seek to assess their ability to detect high-risk IPMN. METHODS: Urine was collected from patients undergoing pancreatic resection and healthy controls. TIMP-1(Tissue Inhibitor of Metalloproteinase-1), LYVE-1(Lymphatic Vessel Endothelial Receptor 1), and PGEM(Prostaglandin E Metabolite) levels were determined by ELISA and analyzed by Kruskal-Wallis. RESULTS: Median urinary TIMP-1 levels were significantly lower in healthy controls (n = 9; 0.32 ng/mg creatinine) compared to PDAC (n = 13; 1.95) but not significantly different between low/moderate-grade (n = 20; 0.71) and high-grade/invasive IPMN (n = 20; 1.12). No significant difference in urinary LYVE-1 was detected between IPMN low/moderate (n = 16; 0.37 ng/mg creatinine) and high/invasive grades (n = 21; 0.09). Urinary PGEM levels were not significantly different between groups. CONCLUSIONS: Urinary TIMP-1, LYVE-1, and PGEM do not correlate with malignant potential of pancreatic cysts.

5 Article The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy. 2019

Zhong, Xiaoling / Pons, Marianne / Poirier, Christophe / Jiang, Yanlin / Liu, Jianguo / Sandusky, George E / Shahda, Safi / Nakeeb, Attila / Schmidt, C Max / House, Michael G / Ceppa, Eugene P / Zyromski, Nicholas J / Liu, Yunlong / Jiang, Guanglong / Couch, Marion E / Koniaris, Leonidas G / Zimmers, Teresa A. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. · IUPUI Center for Cachexia Innovation, Research and Therapy, Indianapolis, IN, USA. · Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. · IU Simon Cancer Center, Indianapolis, IN, USA. · Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. · Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA. · Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. ·J Cachexia Sarcopenia Muscle · Pubmed #31286691.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy partly due to frequent, severe cachexia. Serum activin correlates with cachexia and mortality, while exogenous activin causes cachexia in mice. METHODS: Isoform-specific activin expression and activities were queried in human and murine tumours and PDAC models. Activin inhibition was by administration of soluble activin type IIB receptor (ACVR2B/Fc) and by use of skeletal muscle specific dominant negative ACVR2B expressing transgenic mice. Feed-forward activin expression and muscle wasting activity were tested in vivo and in vitro on myotubes. RESULTS: Murine PDAC tumour-derived cell lines expressed activin-βA but not activin-βB. Cachexia severity increased with activin expression. Orthotopic PDAC tumours expressed activins, induced activin expression by distant organs, and produced elevated serum activins. Soluble factors from PDAC elicited activin because conditioned medium from PDAC cells induced activin expression, activation of p38 MAP kinase, and atrophy of myotubes. The activin trap ACVR2B/Fc reduced tumour growth, prevented weight loss and muscle wasting, and prolonged survival in mice with orthotopic tumours made from activin-low cell lines. ACVR2B/Fc also reduced cachexia in mice with activin-high tumours. Activin inhibition did not affect activin expression in organs. Hypermuscular mice expressing dominant negative ACVR2B in muscle were protected for weight loss but not mortality when implanted with orthotopic tumours. Human tumours displayed staining for activin, and expression of the gene encoding activin-βA (INHBA) correlated with mortality in patients with PDAC, while INHBB and other related factors did not. CONCLUSIONS: Pancreatic adenocarcinoma tumours are a source of activin and elicit a systemic activin response in hosts. Human tumours express activins and related factors, while mortality correlates with tumour activin A expression. PDAC tumours also choreograph a systemic activin response that induces organ-specific and gene-specific expression of activin isoforms and muscle wasting. Systemic blockade of activin signalling could preserve muscle and prolong survival, while skeletal muscle-specific activin blockade was only protective for weight loss. Our findings suggest the potential and need for gene-specific and organ-specific interventions. Finally, development of more effective cancer cachexia therapy might require identifying agents that effectively and/or selectively inhibit autocrine vs. paracrine activin signalling.

6 Article Cystic pancreatic neuroendocrine tumors: A more favorable lesion? 2019

Carr, Rosalie A / Bletsis, Panagiotis / Roch, Alexandra M / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max / Ceppa, Eugene P. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: eceppa@iupui.edu. ·Pancreatology · Pubmed #30704851.

ABSTRACT: BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are predominantly solid lesions with malignant potential. Cystic PNETs are a small subset in which data are scarce. The aim of this study was to compare clinical and biologic differences between cystic and solid PNETs. METHODS: Patients with PNETs undergoing pancreatectomy between 1988 and 2016 at a high-volume center were reviewed retrospectively. Demographic, clinical, and histopathologic data were collected and analyzed. RESULTS: 347 patients with PNETs were identified; 27% (n = 91) were cystic. Patients with cystic PNETs were generally older (59 vs. 55 years, p = 0.05). Cystic PNETs were more commonly non-functional (95% vs. 82%, p = 0.004), asymptomatic (44% vs. 28%, p = 0.009), and located in the pancreatic body/tail (81% vs. 60%, p < 0.001) than solid PNETs. Although cystic and solid PNETs had similar sizes and pathologic stage at the time of resection, Ki-67 proliferation index (Ki-67 ≤ 9%: 98% vs. 85%; p = 0.007), and histologic grade (grade I: 84% vs. 59%; p = 0.009) had less aggressive features in cystic PNETs. CONCLUSION: In addition to reporting a higher than previously published incidence of cystic PNET (27%), this study found significant differences in multiple clinicopathologic variables between cystic and solid PNETs. Cystic PNET may be a distinct and possibly less aggressive subtype of PNET yet have similar pathologic stage, recurrence, and survival to solid PNETs. Cystic PNETs require further attention to better understand the true natural history.

7 Article Are BRCA1 and BRCA2 gene mutation patients underscreened for pancreatic adenocarcinoma? 2019

Roch, Alexandra M / Schneider, Justine / Carr, Rosalie A / Lancaster, William P / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max / Ceppa, Eugene P. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. ·J Surg Oncol · Pubmed #30636051.

ABSTRACT: BACKGROUND: Breast cancer (BRCA) mutations account for the highest proportion of hereditary causes of pancreatic ductal adenocarcinoma (PDAC). Screening is currently recommended only for patients with one first-degree relative or two family members with PDAC. We hypothesized that screening all BRCA1/2 patients would identify a higher rate of pancreatic abnormalities. METHODS: All BRCA1/2 patients at a single academic center were retrospectively reviewed (2005-2015). Pancreatic abnormalities were defined on cross-sectional imaging as pancreatic neoplasm (cystic/solid) or main-duct dilation. RESULTS: Two hundred and four patients were identified with BRCA mutations. Forty-seven (40%) had abdominal imaging (20 computerized tomography and 27 magnetic resonance imaging). Twenty-one percent had pancreatic abnormalities (PDAC [n = 2] and intraductal papillary mucinous neoplasm [IPMN; n = 8]). The prevalence of pancreatic abnormalities and IPMN was higher in BRCA2 patients than in the general population (21% vs 8% and 17% vs 1%; P = 0.0007 and P < 0.0001, respectively), with no influence of family history. Similarly, BRCA1 patients had an increased prevalence of IPMN (8.3% vs 1%; P < 0.0001). CONCLUSIONS: In this series, 4% and 17% of BRCA2 patients developed PDAC and IPMN, respectively. Eight percent of BRCA1 patients developed IPMN. Under current recommended screening, 60% of BRCA1/2 patients had incompletely pancreatic assessment. With no influence of family history, this study suggests all BRCA1/2 patients should undergo a high-risk screening protocol that will identify a higher rate of precancerous pancreatic neoplasms amenable to curative resection.

8 Article The Dilemma of the Dilated Main Pancreatic Duct in the Distal Pancreatic Remnant After Proximal Pancreatectomy for IPMN. 2019

Simpson, Rachel E / Ceppa, Eugene P / Wu, Howard H / Akisik, Fatih / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Al-Haddad, Mohammad A / DeWitt, John M / Sherman, Stuart / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 129, Indianapolis, IN, 46202, USA. · Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA. · Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 129, Indianapolis, IN, 46202, USA. maxschmi@iupui.edu. · Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA. maxschmi@iupui.edu. · Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. maxschmi@iupui.edu. · Walther Oncology Center, Indianapolis, IN, USA. maxschmi@iupui.edu. · Indiana University Simon Cancer Center, Indianapolis, IN, USA. maxschmi@iupui.edu. ·J Gastrointest Surg · Pubmed #30603862.

ABSTRACT: OBJECTIVE(S): A dilated main pancreatic duct in the distal remnant after proximal pancreatectomy for intraductal papillary mucinous neoplasms (IPMN) poses a diagnostic dilemma. We sought to determine parameters predictive of remnant main-duct IPMN and malignancy during surveillance. METHODS: Three hundred seventeen patients underwent proximal pancreatectomy for IPMN (Indiana University, 1991-2016). Main-duct dilation included those ≥ 5 mm or "dilated" on radiographic reports. Statistics compared groups using Student's T/Mann-Whitney U tests for continuous variables or chi-square/Fisher's exact test for categorical variables with P < 0.05 considered significant. RESULTS: High-grade/invasive IPMN or adenocarcinoma at proximal pancreatectomy predicted malignant outcomes (100.0% malignant outcomes; P < 0.001) in remnant surveillance. Low/moderate-grade lesions revealed benign outcomes at last surveillance regardless of duct diameter. Twenty of 21 patients undergoing distal remnant reoperation had a dilated main duct. Seven had main-duct IPMN on remnant pathology; these patients had greater mean maximum main-duct diameter prior to reoperation (9.5 vs 6.2 mm, P = 0.072), but this did not reach statistical significance. Several features showed high sensitivity/specificity for remnant main-duct IPMN. CONCLUSIONS: Remnant main-duct dilation after proximal pancreatectomy for IPMN remains a diagnostic dilemma. Several parameters show a promise in accurately diagnosing main-duct IPMN in the remnant.

9 Article Circulating Thrombospondin-2 enhances prediction of malignant intraductal papillary mucinous neoplasm. 2019

Simpson, Rachel E / Yip-Schneider, Michele T / Wu, Huangbing / Fan, Hao / Liu, Ziyue / Korc, Murray / Zhang, Jianjun / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Walther Oncology Center, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA. · Department of Biostatistics, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA. · Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; The Pancreatic Cancer Signature Center at IUPUI, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA. · Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA. Electronic address: JZ21@iu.edu. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Walther Oncology Center, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: maxschmi@iupui.edu. ·Am J Surg · Pubmed #30293901.

ABSTRACT: BACKGROUND: IPMNs are cystic pancreatic lesions with variable malignant potential. Thrombospondin-2 (THBS2)-an endogenous, anti-angiogenic matrix glycoprotein-may modulate tumor progression. We hypothesized that circulating levels of THBS2 could aid in preoperative prediction of malignant IPMN. METHODS: Preoperative serum/plasma samples were procured from patients undergoing surgery. Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and compared to surgical pathology IPMN dysplastic grade. RESULTS: 164 patients underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN). Circulating THBS2 (mean ± SD) was greater in High-Grade/Invasive-IPMN than Low/Moderate-grade IPMN (26.6 ± 12.7 ng/mL vs. 20.4 ± 8.2 ng/mL; P < 0.001). THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main-duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction model for IPMN grade. CONCLUSION: Circulating THBS2 is correlated with IPMN dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather strengthened prediction models for High-Grade/Invasive IPMN when combined with other clinical/biomarker data.

10 Article DNA profile components predict malignant outcomes in select cases of intraductal papillary mucinous neoplasm with negative cytology. 2018

Simpson, Rachel E / Cockerill, Nathan J / Yip-Schneider, Michele T / Ceppa, Eugene P / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Al-Haddad, Mohammad A / Schmidt, C Max. ·From the Department of Surgery, Indiana University School of Medicine, Indianapolis. · From the Department of Surgery, Indiana University School of Medicine, Indianapolis; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis. · Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis; Department of Medicine, Division of Gastroenterology, Indiana University Hospital, Indianapolis. · From the Department of Surgery, Indiana University School of Medicine, Indianapolis; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis; Indiana University Simon Cancer Center, Indianapolis; Walther Oncology Center, Indianapolis, IN; and; Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis. Electronic address: maxschmi@iupui.edu. ·Surgery · Pubmed #30139561.

ABSTRACT: BACKGROUND: Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. METHODS: We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology. A total 225 patients had 283 DNA profiles (98 followed by surgery, 185 followed by ≥23-month surveillance). High-grade dysplasia/invasive outcomes were high-grade dysplasia, intraductal papillary mucinous neoplasm-invasive, and adenocarcinoma on surgical pathology or mesenteric or vascular invasion, metastases, or biopsy with high-grade dysplasia or adenocarcinoma during surveillance. RESULTS: High-quantity DNA predicted (P = .004) high-grade dysplasia/invasive disease outcomes with sensitivity of 78.3%, but 52.7% specificity, indicating benign cases may exhibit high-quantity DNA. High clonality loss of heterozygosity of tumor suppressor genes was 98.0% specific, strongly predicted high-grade dysplasia/invasive disease but lacked sensitivity (20.0%). High-quantity DNA + high clonality loss of heterozygosity had 99.0% specificity for high-grade dysplasia/invasive disease. KRAS mutation alone did not predict high-grade dysplasia/invasive disease, but, when combined with high-quantity DNA (specificity 84.7%) and high clonality loss of heterozygosity (specificity 99.0%) strongly predicted high-grade dysplasia/invasive outcomes. CONCLUSION: Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails.

11 Article Pancreatic cyst fluid glucose: rapid, inexpensive, and accurate diagnosis of mucinous pancreatic cysts. 2018

Carr, Rosalie A / Yip-Schneider, Michele T / Simpson, Rachel E / Dolejs, Scott / Schneider, Justine G / Wu, Huangbing / Ceppa, Eugene P / Park, Walter / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Cancer Center, Indianapolis, IN. Electronic address: myipschn@iupui.edu. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN; Indiana University Cancer Center, Indianapolis, IN. · Department of Medicine, Stanford University, Stanford, CA. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Cancer Center, Indianapolis, IN; Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN. Electronic address: maxschmi@iupui.edu. ·Surgery · Pubmed #29241991.

ABSTRACT: BACKGROUND: The most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen. However, the diagnostic accuracy of carcinoembryonic antigen ranges from 70% to 86%. Based on previous work, we hypothesize that pancreatic cyst fluid glucose may be an attractive alternative to carcinoembryonic antigen. METHODS: Pancreatic cyst fluid was collected during endoscopic or operative intervention. Diagnoses were pathologically confirmed. Glucose and carcinoembryonic antigen were measured using a patient glucometer and automated analyzer/enzyme-linked immunosorbent assay. Sensitivity, specificity, accuracy, and receiver operator characteristic analyses were performed. RESULTS: Cyst fluid samples from 153 patients were evaluated (mucinous: 25 mucinous cystic neoplasms, 77 intraductal papillary mucinous neoplasms, 4 ductal adenocarcinomas; nonmucinous: 21 serous cystic neoplasms, 9 cystic neuroendocrine tumors, 14 pseudocysts, 3 solid pseudopapillary neoplasms). Median cyst fluid glucose was lower in mucinous versus nonmucinous cysts (19 vs 96 mg/dL; P < .0001). With a threshold of ≤ 50 mg/dL, cyst fluid glucose was 92% sensitive, 87% specific, and 90% accurate in diagnosing mucinous pancreatic cysts. In comparison, cyst fluid carcinoembryonic antigen with a threshold of >192 ng/mL was 58% sensitive, 96% specific, and 69% accurate. Area under the curve for glucose and CEA were similar at 0.91 and 0.92. CONCLUSION: Cyst fluid glucose has significant advantages over carcinoembryonic antigen and should be considered for use as a routine diagnostic test for pancreatic mucinous cysts.

12 Article Cancer history: A predictor of IPMN subtype and dysplastic status? 2018

Carr, Rosalie A / Kiel, Brandon A / Roch, Alexandra M / Ceppa, Eugene P / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: maxschmi@iupui.edu. ·Am J Surg · Pubmed #29174163.

ABSTRACT: INTRODUCTION: The aim of this study was to determine the association of PMH and FH of pancreatic (PDAC) and non-pancreatic cancers with IPMN malignant risk. METHODS: A retrospective review of a prospective database of IPMN patients undergoing resection was performed to assess FH and PMH. RESULTS: FH of PDAC was present in 13% of 362 included patients. Of these, 8% had at least one first degree relative (FDR) with PDAC. The rate of PDAC positive FH in non-invasive versus invasive IPMN patients was 14% and 8%, respectively (p = 0.3). In main duct IPMN patients, FH (44%) and PMH of non-pancreatic cancer (16%) was higher than that seen in branch duct IPMN (FH 29%; PMH 6%; p = 0.004 and 0.008). CONCLUSIONS: FH of PDAC is not associated with IPMN malignant progression. FH and PMH of non-pancreatic cancer is associated with main duct IPMN, the subtype with the highest rate of invasive transformation.

13 Article Indication for en bloc pancreatectomy with colectomy: when is it safe? 2018

Schwartz, Patrick B / Roch, Alexandra M / Han, Jane S / Vaicius, Alex V / Lancaster, William P / Kilbane, E Molly / House, Michael G / Zyromski, Nicholas J / Schmidt, C Max / Nakeeb, Atilla / Ceppa, Eugene P. ·Department of Surgery, Indiana University School of Medicine, 545 Barnhill Dr. EH541, Indianapolis, IN, 46202, USA. · Department of Surgery, Indiana University School of Medicine, 545 Barnhill Dr. EH541, Indianapolis, IN, 46202, USA. eceppa@iupui.edu. ·Surg Endosc · Pubmed #28664444.

ABSTRACT: INTRODUCTION: Aggressive en bloc resection of adjacent organs is often necessary to resect pancreatic or colonic lesions. However, it is debated whether simultaneous pancreatectomy with colectomy (P+C) is warranted as it potentially increases morbidity and mortality (MM). We hypothesized that MM would be increased in P+C, especially in cases of pancreatitis. METHODS: All patients who underwent pancreatectomy (P) and simultaneous pancreatectomy with colectomy (P+C) at a high-volume center from November 2006 to 2015 were prospectively collected using ACS-NSQIP at our institution. Patients with additional multivisceral or enucleation procedures were excluded. Data were augmented to 90-day outcomes using our institutional database. RESULTS: Forty-three patients with a mean age of 62 years (27:16 male: female) underwent P+C, accounting for 2.39% (43/1797) of pancreatectomies performed. Pancreatoduodenectomy (PD) was performed in 61% (n = 26), distal pancreatectomy (DP) in 37% (n = 16), and total pancreatectomy (TP) in 2% (n = 1) of patients. The 30- and 90-day MM were higher in P+C than P (30-day: 54 vs. 37%, p = 0.037 and 9 vs. 2%, p = 0.022; 90-day: 61 vs. 42%, p = 0.019 and 14 vs. 3%, p = 0.002). Logistical regression modeling revealed an association between 90-day mortality and colectomy (p = 0.013, OR = 3.556). When P+C MM were analyzed according to intraoperative factors, there was no significant difference according to type of pancreatectomy (PD vs. DP vs. TP), origin of primary lesion (pancreas vs. colon), surgical indication (malignant vs. non-malignant), or case status (planned colectomy vs. intraoperative decision). CONCLUSIONS: Addition of colectomy to pancreatectomy substantially increased MM. Subanalysis revealed that type of resection performed, etiology, and planning status did not account for increased risk when performing P+C. However, colectomy was found to be an independent risk factor for mortality. Therefore, patients should be informed of the risk of increased postoperative complications until a further study can identify potential patients or perioperative factors that can be used for risk stratification.

14 Article Laparoscopic distal pancreatectomy for pancreatic cancer is safe and effective. 2018

Bauman, Marita D / Becerra, David G / Kilbane, E Molly / Zyromski, Nicholas J / Schmidt, C Max / Pitt, Henry A / Nakeeb, Attila / House, Michael G / Ceppa, Eugene P. ·Department of Surgery, Indiana University School of Medicine, 545 Barnhill Dr, EH 541, Indianapolis, IN, 46202, USA. eceppa@iupui.edu. · Department of Surgery, Indiana University School of Medicine, 545 Barnhill Dr, EH 541, Indianapolis, IN, 46202, USA. ·Surg Endosc · Pubmed #28643065.

ABSTRACT: PURPOSE: To compare the short-term and oncologic outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) undergoing laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP). METHODS: Consecutive cases of distal pancreatectomy (DP) (n = 422) were reviewed at a single high-volume institution over a 10-year period (2005-2014). Inclusion criteria consisted of any patient with PDAC by surgical pathology. Ninety-day outcomes were monitored through a prospectively maintained pancreatic resection database. The Social Security Death Index was used for 5-year survival. Two-way statistical analyses were used to compare categories; variance was reported with standard error of the mean; * indicates P value <0.05. RESULTS: Seventy-nine patients underwent DP for PDAC. Thirty-three underwent LDP and 46 ODP. There were no statistical differences in demographics, BMI, and ASA classification. Intraoperative and surgical pathology variables were comparable for LDP versus ODP: operative time (3.9 ± 0.2 vs. 4.2 ± 0.2 h), duct size, gland texture, stump closure, tumor size (3.3 ± 0.3 vs. 4.0 ± 0.4 cm), lymph node harvest (14.5 ± 1.1 vs. 17.5 ± 1.2), tumor stage (see table), and negative surgical margins (77 vs. 87%). Patients who underwent LDP experienced lower blood loss (310 ± 68 vs. 597 ± 95 ml; P = 0.016*) and required fewer transfusions (0 vs. 13; P = 0.0008*). Patients who underwent LDP had fewer positive lymph nodes (0.8 ± 0.2 vs. 1.6 ± 0.3; P = 0.04*) and a lower incidence of type C pancreatic fistula (0 vs. 13%; P = 0.03*). Median follow-up for all patients was 11.4 months. Long-term oncologic outcomes revealed similar outcomes including distant or local recurrence (30 vs. 52%; P = 0.05) and median survival (18 vs. 15 months), as well as 1-year (73 vs. 59%), 3-year (22 vs. 21%), and 5-year (20 vs. 15%) survival for LDP and ODP, respectively. CONCLUSIONS: The results of this series suggest that LDP is a safe surgical approach that is comparable from an oncologic standpoint to ODP for the management of pancreatic adenocarcinoma.

15 Article Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. 2017

Cohen, Joshua D / Javed, Ammar A / Thoburn, Christopher / Wong, Fay / Tie, Jeanne / Gibbs, Peter / Schmidt, C Max / Yip-Schneider, Michele T / Allen, Peter J / Schattner, Mark / Brand, Randall E / Singhi, Aatur D / Petersen, Gloria M / Hong, Seung-Mo / Kim, Song Cheol / Falconi, Massimo / Doglioni, Claudio / Weiss, Matthew J / Ahuja, Nita / He, Jin / Makary, Martin A / Maitra, Anirban / Hanash, Samir M / Dal Molin, Marco / Wang, Yuxuan / Li, Lu / Ptak, Janine / Dobbyn, Lisa / Schaefer, Joy / Silliman, Natalie / Popoli, Maria / Goggins, Michael G / Hruban, Ralph H / Wolfgang, Christopher L / Klein, Alison P / Tomasetti, Cristian / Papadopoulos, Nickolas / Kinzler, Kenneth W / Vogelstein, Bert / Lennon, Anne Marie. ·The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Howard Hughes Medical Institute, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Sidney Kimmel Cancer Center at Johns Hopkins, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Division of Systems Biology and Personalized Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3021, Australia. · Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3010, Australia. · Department of Medical Oncology, Western Health, Melbourne, VIC 3021, Australia. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202. · Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260. · Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260. · Department of Epidemiology, Mayo Clinic, Rochester, MN 55902. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. · Department of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. · Division of Pancreatic Surgery, Department of Surgery, San Raffaele Scientific Institute Research Hospital, 20132 Milan, Italy. · Department of Pathology, San Raffaele Scientific Institute Research Hospital, 20132 Milan, Italy. · The Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. · Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. · Division of Biostatistics and Bioinformatics, Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287; bertvog@gmail.com amlennon@jhmi.edu. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287; bertvog@gmail.com amlennon@jhmi.edu. ·Proc Natl Acad Sci U S A · Pubmed #28874546.

ABSTRACT: The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for

16 Article Prospective Evaluation of Associations between Cancer-Related Pain and Perineural Invasion in Patients with Resectable Pancreatic Adenocarcinoma. 2017

Carr, Rosalie A / Roch, Alexandra M / Zhong, Xin / Ceppa, Eugene P / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max / House, Michael G. ·Department of General Surgery, Indiana University School of Medicine, 515 Barnhill Drive, Indianapolis, IN, 46202, USA. · Department of General Surgery, Indiana University School of Medicine, 515 Barnhill Drive, Indianapolis, IN, 46202, USA. michouse@iupui.edu. ·J Gastrointest Surg · Pubmed #28785934.

ABSTRACT: INTRODUCTION: Perineural invasion is a unique characteristic of pancreatic adenocarcinoma biology and is present in the majority of resected pathologic specimens. The purpose of this study was to understand the relationships between preoperative pain and perineural invasion in patients with pancreatic adenocarcinoma. METHODS: Fifty-two chemotherapy naive patients undergoing resection for pancreatic adenocarcinoma from 2012 to 2014 completed a previously validated Brief Pain Inventory survey for preoperative clinical pain scoring. Preoperative pain was correlated with multiple clinicopathologic features. RESULTS: Preoperative pain was not associated with pathologic cancer stage, lymph node status, lymph node positivity ratio, resection margin status, or tumor location within the pancreas. In the subgroup of pancreatic head cancers, pain interference with affect was associated with the absence of perineural invasion (p = 0.02). Patients with stage I cancer had higher pain interference scores than those with stage II cancer (p = 0.02). CONCLUSIONS: Preoperative pain does not predict the presence of perineural invasion or other pathologic prognostic factors in patients with resectable pancreatic adenocarcinoma. Higher pain scores in pancreatic head cancers correlated with absence of perineural invasion and early cancer stage. The effects of preoperative pain on quality and interference of daily life deserve further investigation in larger prospective studies involving patients with pancreatic cancer.

17 Article Prostaglandin E 2017

Yip-Schneider, Michele T / Carr, Rosalie A / Wu, Huangbing / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Cancer Center, Indianapolis, IN; Indiana University Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Indiana University Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Cancer Center, Indianapolis, IN; Indiana University Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN. Electronic address: maxschmi@iupui.edu. ·J Am Coll Surg · Pubmed #28739154.

ABSTRACT: BACKGROUND: With the increased frequency of diagnostic imaging, pancreatic cysts are now detected in >3% of American adults. Most of these are intraductal papillary mucinous neoplasms (IPMNs) with well-established but variable malignant potential. A biomarker that predicts malignant potential or dysplastic grade would help determine which IPMNs require removal and which can be observed safely. We previously reported that pancreatic fluid prostaglandin E STUDY DESIGN: Pancreatic cyst/duct fluid was prospectively collected from 100 patients with IPMN undergoing pancreatic resection. Surgical pathology revealed 47 low-/moderate-grade, 34 high-grade, and 20 invasive IPMNs. The PGE RESULTS: Mean pancreatic cyst fluid PGE CONCLUSIONS: Our results validate pancreatic cyst fluid PGE

18 Article Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm. 2017

Carr, Rosalie A / Yip-Schneider, Michele T / Dolejs, Scott / Hancock, Bradley A / Wu, Huangbing / Radovich, Milan / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine; Department of Walther Oncology Center; Indiana University Cancer Center; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine. · Department of Surgery, Indiana University School of Medicine; Department of Walther Oncology Center; Indiana University Cancer Center. · Department of Surgery, Indiana University School of Medicine; Department of Biochemistry/Molecular Biology, Indiana University School of Medicine; Department of Walther Oncology Center; Indiana University Cancer Center; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN. Electronic address: maxschmi@iupui.edu. ·J Am Coll Surg · Pubmed #28633941.

ABSTRACT: BACKGROUND: Accurate differentiation of pancreatic cystic lesions is important for pancreatic cancer early detection and prevention as well as avoidance of unnecessary surgical intervention. Serous cystic neoplasms (SCN) have no malignant potential, but may mimic premalignant mucinous cystic lesions: mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN). We recently identified vascular endothelial growth factor (VEGF)-A as a novel pancreatic fluid biomarker for SCN. We hypothesize that combining cyst fluid carcinoembryonic antigen (CEA) with VEGF-A will improve the diagnostic accuracy of VEGF-A. METHODS: Pancreatic cyst/duct fluid was collected from consenting patients undergoing surgical cyst resection with corresponding pathologic diagnoses. Pancreatic fluid VEGF-A and CEA levels were detected by ELISA. RESULTS: One hundred forty-nine patients with pancreatic cystic lesions met inclusion criteria. Pathologic diagnoses included pseudocyst (n=14), SCN (n=26), MCN (n=40), low/moderate grade IPMN (n=34), high grade IPMN (n=20), invasive IPMN (n=10) and solid pseudopapillary neoplasm (n=5). VEGF-A was significantly elevated in SCN cyst fluid compared to all other diagnoses (p<0.001). With a threshold of >5,000 pg/ml, VEGF-A alone has 100% sensitivity and 83.7% specificity to distinguish SCN from other cystic lesions. With a threshold of ≤10ng/ml, CEA alone identifies SCN with 95.5% sensitivity and 81.5% specificity. Sensitivity and specificity of the VEGF-A/CEA combination are 95.5% and 100% respectively. The c-statistic increased from 0.98 to 0.99 when CEA was added to VEGF-A alone in the ROC analysis. CONCLUSIONS: Although VEGF-A alone is a highly accurate test for SCN, the combination of VEGF-A with CEA approaches the gold-standard of pathologic diagnosis, thus importantly avoiding false positives. Patients with a positive test indicating benign SCN can be spared a high risk surgical pancreatic resection.

19 Article Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic Cysts. 2017

Ivry, Sam L / Sharib, Jeremy M / Dominguez, Dana A / Roy, Nilotpal / Hatcher, Stacy E / Yip-Schneider, Michele T / Schmidt, C Max / Brand, Randall E / Park, Walter G / Hebrok, Matthias / Kim, Grace E / O'Donoghue, Anthony J / Kirkwood, Kimberly S / Craik, Charles S. ·Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California. · Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, San Francisco, California. · Department of Surgery, University of California, San Francisco, San Francisco, California. · Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, California. · Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. · Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Medicine, Stanford University School of Medicine, Stanford, California. · Department of Pathology, University of California, San Francisco, San Francisco, California. · Skaggs School of Pharmacy and Pharmaceutical Chemistry, University of California, San Diego, La Jolla, California. · Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California. Charles.Craik@ucsf.edu. ·Clin Cancer Res · Pubmed #28424202.

ABSTRACT:

20 Article Management of Undifferentiated Solitary Mucinous Cystic Lesion of the Pancreas: A Clinical Dilemma. 2017

Roch, Alexandra M / Bigelow, Katherine / Schmidt, Christian M / Carr, Rosalie A / Jester, Andrea L / Ceppa, Eugene P / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Electronic address: maxschmi@iupui.edu. ·J Am Coll Surg · Pubmed #28126546.

ABSTRACT: BACKGROUND: Management of solitary mucinous cystic lesions of the pancreas (MCLs) relies on correct differentiation between branch duct intraductal papillary mucinous neoplasm (BD-IPMN) and mucinous cystic neoplasm (MCN). Current international consensus guidelines recommend resection for MCN, and unifocal BD-IPMN can be followed in the absence of worrisome features/high-risk stigmata. We hypothesized that preoperative differentiation of solitary MCLs is suboptimal, and that all solitary MCLs should be treated similarly. STUDY DESIGN: A retrospective review of an institutional database (2003 to 2016) identified 711 patients who underwent resection for pancreatic cyst. Only lesions that met cytologic or biochemical criteria for diagnosis of MCLs were included. Mucinous cystic neoplasms were defined by presence of ovarian stroma on pathology. Patients with formal preoperative diagnosis of BD-IPMN (multifocality, GNAS mutation) were excluded. RESULTS: One hundred and eighty solitary MCLs were identified on preoperative imaging (mean age 54 years, 24% men). On surgical pathology, 108 were MCNs and 72 BD-IPMNs. There was no difference in invasive rate (7 of 108 [6.5%] MCNs vs 4 of 72 [5.6%] BD-IPMN; p ≈ 1). Pancreatic ductal connectivity was reported on imaging/endoscopy in 10 of 108 (9%) MCNs and 22 of 72 (31%) BD-IPMNs, representing 67% accuracy in differentiating MCNs from BD-IPMNs. On multivariate analysis, typical risk factors failed to predict invasiveness in either MCNs or BD-IPMNs. When all undifferentiated solitary MCLs were analyzed together, older age (p = 0.03) and cyst size (p = 0.04) were associated with increased invasive rate in multivariate analysis. CONCLUSIONS: Unreliable differentiation and limited ability to predict invasiveness make solitary MCLs clinically challenging. With similar invasive rates, MCN and unifocal BD-IPMNs should be merged into one new entity for management, the undifferentiated solitary MCL.

21 Article MicroRNA Expression in a Readily Accessible Common Hepatic Artery Lymph Node Predicts Time to Pancreatic Cancer Recurrence Postresection. 2016

Nguyen, Hai V / Gore, Jesse / Zhong, Xin / Savant, Sudha S / Deitz-McElyea, Samantha / Schmidt, C Max / House, Michael G / Korc, Murray. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. · Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. · The Pancreatic Cancer Signature Center, Indiana University Simon Cancer Center, Indianapolis, IN, 46202, USA. · Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. · Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. mkorc@iu.edu. · The Pancreatic Cancer Signature Center, Indiana University Simon Cancer Center, Indianapolis, IN, 46202, USA. mkorc@iu.edu. · Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. mkorc@iu.edu. · IU Simon Cancer Center, Indiana University School of Medicine, 980 West Walnut Street, Rm 528, Indianapolis, IN, 46202, USA. mkorc@iu.edu. ·J Gastrointest Surg · Pubmed #27456015.

ABSTRACT: Lymph node involvement in pancreatic adenocarcinoma (PAC) predicts postresection survival, but early lymph node metastasis detection is not easily accomplished. We assessed a panel of microRNAs (miRNAs) in a common hepatic artery lymph node (station 8) that is readily accessible during pancreatoduodenectomy (PD) to determine if increased miRNA levels correlate with postresection recurrence. Station 8 lymph nodes overlying the common hepatic artery collected during PD were assayed for miRNA-10b, miRNA-30c, miRNA-21, and miRNA-155 and cytokeratin-19 (CK19), an epithelial cell marker, using quantitative PCR. Expression was correlated with disease recurrence, recurrence-free survival (RFS), and overall survival (OS). Station 8 lymph nodes from 37 patients (30 periampullary carcinomas (PCs), 2 chronic pancreatitis, 5 other cancers) exhibited increased miRNA-10b levels in 14/30 PCs, and in 10 of these 14 patients, cancer recurred during the study period (2012-2015). High miRNA-10b was also associated with shorter RFS (42.5 vs. 92.4 weeks, p < 0.05) but not OS, whereas miRNA-30c, miRNA-21, and miRNA-155 levels and CK19 mRNA levels in station 8 nodes were variable and did not correlate with RFS or OS. We conclude that elevated miRNA-10b levels in station 8 lymph nodes could be utilized to assess risk for early disease progression in patients with periampullary tumors.

22 Article Management of branch-duct intraductal papillary mucinous neoplasms: a large single-center study to assess predictors of malignancy and long-term outcomes. 2016

Ridtitid, Wiriyaporn / DeWitt, John M / Schmidt, C Max / Roch, Alexandra / Stuart, Jennifer Schaffter / Sherman, Stuart / Al-Haddad, Mohammad A. ·Indiana University School of Medicine, Indianapolis, Indiana, USA; Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. · Indiana University School of Medicine, Indianapolis, Indiana, USA. · Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates. ·Gastrointest Endosc · Pubmed #26905937.

ABSTRACT: BACKGROUND AND AIMS: Management of branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging. We determined factors associated with malignancy in BD-IPMNs and long-term outcomes. METHODS: This retrospective cohort study included all patients with established BD-IPMNs by the International Consensus Guidelines (ICG) 2012 and/or pathologically confirmed BD-IPMNs in a tertiary care referral center between 2001 and 2013. Main outcome measures were the association between high-risk stigmata (HRS)/worrisome features (WFs) of the ICG 2012 and malignant BD-IPMNs, performance characteristics of EUS-FNA for the diagnosis of malignant BD-IPMNs, and recurrence and long-term outcomes of BD-IPMN patients undergoing surgery or imaging surveillance. RESULTS: Of 364 BD-IPMN patients, 229 underwent imaging surveillance and 135 underwent surgery. Among the 135 resected BD-IPMNs, HRS/WFs on CT/magnetic resonance imaging (MRI) were similar between the benign and malignant groups, but main pancreatic duct (MPD) dilation (5-9 mm) was more frequently identified in malignant lesions. On EUS-FNA, mural nodules, MPD features suspicious for involvement, and suspicious/positive malignant cytology were more frequently detected in the malignant group with a sensitivity, specificity, and accuracy of 33%, 94%, and 86%; 42%, 91%, and 83%; and 33% 91%, and 82%, respectively. Mural nodules identified by EUS were missed by CT/MRI in 28% in the malignant group. Patients with malignant lesions had a higher risk of any IPMN recurrence during a mean follow-up period of 131 months (P = .01). CONCLUSIONS: Among HRS and WFs of the ICG 2012, an MPD size of 5 to 9 mm on CT/MRI was associated with malignant BD-IPMNs. EUS features including mural nodules, MPD features suspicious for involvement, and suspicious/malignant cytology were accurate and highly specific for malignant BD-IPMNs. Our study highlights the incremental value of EUS-FNA over imaging in identifying malignant BD-IPMNs, particularly in patients without WFs and those with smaller cysts. Benign IPMN recurrence was observed in some patients up to 8 years after resection.

23 Article Intraductal papillary mucinous neoplasm of the pancreas, one manifestation of a more systemic disease? 2016

Roch, Alexandra M / Rosati, Carlo Maria / Cioffi, Jessica L / Ceppa, Eugene P / DeWitt, John M / Al-Haddad, Mohammad A / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, 980 West Walnut Street C522, Indianapolis, IN, 46202, USA. · Division of Gastroenterology, Department of Medicine, Indiana University Hospital, Indianapolis, IN, USA. · Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates. · Department of Surgery, Indiana University School of Medicine, 980 West Walnut Street C522, Indianapolis, IN, 46202, USA. Electronic address: maxschmi@iupui.edu. ·Am J Surg · Pubmed #26830712.

ABSTRACT: BACKGROUND: Several studies have demonstrated a high prevalence of extrapancreatic malignancies, and an association with autoimmune pancreatitis in patients with intraductal papillary mucinous neoplasm (IPMN). We hypothesized that IPMNs were associated with an increase rate of systemic diseases. METHODS: From 1996 to 2013, a retrospective analysis of a prospectively collected database was performed and supplemented with electronic medical charts review. RESULTS: Two hundred twenty extrapancreatic malignancies were found in 185 patients (22%) compared with expected 5% in the general population. Colorectal, lung, and renal cell carcinoma had significant observed/expected ratios (P < .0001). One hundred ten synchronous autoimmune diseases were found in 96 patients (11%). Systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease showed statistically significant observed/expected ratios (P < .0001, .01, and <.0001, respectively). There was no impact of immunosuppressive treatment on the IPMN subtype and malignancy rate. CONCLUSIONS: IPMN are associated with surprisingly high rates of autoimmune diseases suggesting that IPMN might be 1 manifestation of a more systemic disease.

24 Article Significance of Portal Vein Invasion and Extent of Invasion in Patients Undergoing Pancreatoduodenectomy for Pancreatic Adenocarcinoma. 2016

Roch, Alexandra M / House, Michael G / Cioffi, Jessica / Ceppa, Eugene P / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, 980 West Walnut Street C522, Indianapolis, IN, 46202, USA. · Department of Surgery, Indiana University School of Medicine, 980 West Walnut Street C522, Indianapolis, IN, 46202, USA. maxschmi@iupui.edu. ·J Gastrointest Surg · Pubmed #26768008.

ABSTRACT: INTRODUCTION: Several studies have confirmed the safety of pancreatoduodenectomy with portal/mesenteric vein resection and reconstruction in select patients. The effect of vein invasion and extent of invasion on survival is less clear. The purpose of this study was to examine the association between tumor invasion of the portal/mesenteric vein and long-term survival. METHODS: A retrospective review of a prospectively maintained database of patients who underwent pancreatoduodenectomy for pancreatic adenocarcinoma at a single academic medical center (2000-2014) was performed. Survival was compared using the Kaplan-Meier method and log-rank test. P < 0.05 was considered statistically significant. RESULTS: After non-pancreatic periampullary adenocarcinomas and patients with non-segmental (lateral wall only) resection of portal/mesenteric vein were excluded, there were 567 eligible patients. Of these, segmental vein resection was performed in 90 (16 %) with end-to-end primary anastomosis (67) or interposition graft reconstruction (23). Patients with vein resection more likely received neoadjuvant systemic therapy (59 vs. 4 %, p < 0.0001). Histopathology of patients undergoing vein resection revealed a distribution of T stage toward larger tumors and higher rates of perineural invasion. Portal/mesenteric vein resection, however, was not associated with differences in hospital stay, postoperative complications, or operative mortality. Patients with or without vein resection had comparable overall survival rates at 1-, 3-, and 5-years. On final surgical histopathology, only 52 of 90 (58 %) vein resections had adenocarcinoma involvement of the venous wall. Of these, depth of invasion was at the level of the adventitia (9), media/intima (34), and full thickness/intraluminal (9). Venous wall invasion (52) did not significantly influence overall survival (14 vs. 21 months, p = 0.08) but was associated with significantly shorter median disease-free survival (11.3 vs. 15.8 months, p = 0.03), predominantly due to local recurrence. The extent of invasion (adventitia, media/intima, full thickness/intraluminal) did not impact overall survival or disease-free survival (14.4 vs. 15.5 vs. 7.4 months, p = 0.08 and 11.2 vs. 12.2 vs. 5 months, 0.59, respectively). Portal/mesenteric vein resection, histopathologic invasion, or the extent of invasion were not independent predictors of overall survival in Cox regression analysis. CONCLUSION: Although Portal/mesenteric vein resection is associated with increased 90-day mortality, venous resection is not prognostic of overall survival. Although a subgroup analysis showed that a direct tumor invasion into the vein wall on final histopathology was associated with a higher rate of local recurrence but with no difference in overall survival (even when stratified according to extent of venous wall invasion), larger studies with an increased power will be needed to confirm these findings.

25 Article Factors influencing the cytotoxicity of α-methylene-γ-hydroxy esters against pancreatic cancer. 2015

Ramachandran, P Veeraraghavan / Helppi, Matthew A / Lehmkuhler, Arlie L / Marchi, Jennifer M / Schmidt, C Max / Yip-Schneider, Michele T. ·Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA. Electronic address: chandran@purdue.edu. · Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA. · Department of Surgery, Indiana University School of Medicine, 980 West Walnut Street, Indianapolis, IN 46202, USA; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 980 West Walnut Street, Indianapolis, IN 46202, USA. ·Bioorg Med Chem Lett · Pubmed #26264501.

ABSTRACT: A systematic study to identify the factors influencing the cytotoxicity of α-methylene-γ-hydroxy esters against three pancreatic cancer cell lines (Panc-1, MIA-PaCa-2, and BxPC-3) has established that, in addition to Michael acceptor abilities, the possibility to lactonize to α-methylene-γ-butyrolactones is as important. The substitution pattern and the number of carbons between the hydroxy and ester moieties also influence the bio-activity.

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