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Pancreatic Neoplasms: HELP
Articles by Eugene P. Ceppa
Based on 30 articles published since 2010
(Why 30 articles?)
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Between 2010 and 2020, E. P. Ceppa wrote the following 30 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Clinical Trial Does PET with CT Have Clinical Utility in the Management of Patients with Intraductal Papillary Mucinous Neoplasm? 2015

Roch, Alexandra M / Barron, Morgan R / Tann, Mark / Sandrasegar, Kumar / Hannaford, Katheryn N / Ceppa, Eugene P / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Maximillian. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Radiology and Imaging Science, 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 #26095551.

ABSTRACT: BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are well-established pancreatic precancerous lesions. Indications for resection are outlined in the 2012 International Consensus Guidelines (ICG). Because of the low specificity of the ICG, many patients will undergo potentially unnecessary surgery for nonmalignant IPMNs. Several retrospective studies have reported that positron emission tomography (PET) with CT (PET/CT) is highly sensitive and specific in detecting malignant IPMNs. We hypothesized that PET/CT complements the ICG in identification of malignant IPMNs. STUDY DESIGN: From 2009 to 2013, patients with a suspected clinical or cytopathologic diagnosis of IPMN were prospectively enrolled in a clinical trial at a single center. Results of preoperative PET/CT on determination of IPMN malignancy (ie, high-grade dysplastic and invasive) was compared with surgical pathology. PET/CT uptake was considered increased if the standardized uptake value was ≥3. RESULTS: Of the 67 patients enrolled, 50 patients met all inclusion criteria. Increased PET/CT uptake was associated with significantly more malignant and invasive IPMNs (80% vs 13%; p < 0.0001 and 40% vs 3%; p = 0.004). When patients were divided into branch duct and main duct IPMNs, increased PET/CT uptake was also associated with more malignancy (60% vs 0%; p = 0.006 for branch duct IPMN and 100% vs 23%; p = 0.003 for main duct IPMN). Patients with ICG criteria (eg, worrisome features and high-risk stigmata) and increased PET/CT uptake had more malignant and invasive IPMNs than patients with ICG criteria, but no increased uptake (78% vs 17%; p = 0.001 and 33% vs 3%; p = 0.03). The sensitivity and specificity of the ICG criteria for detecting malignancy were 92% and 27%, respectively, and PET/CT was less sensitive (62%) but more specific (95%). When PET/CT was added to ICG criteria, the association resulted in 78% sensitivity and 100% specificity. CONCLUSIONS: The addition of PET/CT to preoperative workup improves the performance of the ICG for predicting malignant risk in patients with IPMN.

2 Article Pancreatic Adenocarcinoma Causing Necrotizing Pancreatitis: Not as Rare as You Think? 2020

Lewellen, Kyle A / Maatman, Thomas K / Heimberger, Mark A / Ceppa, Eugene P / House, Michael G / Nakeeb, Attila / Schmidt, C Max / Zyromski, Nicholas J. ·Indiana University School of Medicine, Indianapolis, Indiana. · Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. · Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: nzyromsk@iupui.edu. ·J Surg Res · Pubmed #32018143.

ABSTRACT: BACKGROUND: Necrotizing pancreatitis (NP) presents a unique clinical challenge because of its complex and lengthy disease course. Pancreatic necrosis occurs in 10%-20% of acute pancreatitis cases and may result from any etiology. Scattered reports describe pancreatic tumors causing NP; however, the relationship between these disease processes is not clear. We have treated patients whose NP was caused by pancreatic ductal adenocarcinoma (PDAC) and therefore sought to clarify the clinical outcomes of these patients. METHODS: Patients treated between 2005 and 2018 for NP caused by PDAC were identified. The relationship between NP and PDAC was examined, and the clinical courses of both disease processes were evaluated. RESULTS: Among 647 patients treated for NP, seven patients (1.1%) had PDAC and NP. The mean age at NP diagnosis was 60.6 y (range, 49-66). Two patients had postprocedural pancreatitis after cancer diagnosis, and the remaining five patients had NP caused by PDAC. Median duration between diagnoses of NP and PDAC was 5.6 mo (range, 3.5-21.8). For PDAC treatment, four patients received chemotherapy alone, one received palliative radiation therapy, and one died without oncologic management. One patient underwent operative resection of PDAC. Median survival was 12.7 mo (range, 0.4-49.9). CONCLUSIONS: PDAC may be a more common cause of NP than previously considered and should be considered in patients with NP of appropriate age in whom etiology is otherwise unclear. Prompt diagnosis facilitates optimal treatment in this challenging clinical situation.

3 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.

4 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.

5 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.

6 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.

7 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.

8 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.

9 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.

10 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.

11 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.

12 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.

13 Article Reduced morbidity with minimally invasive distal pancreatectomy for pancreatic adenocarcinoma. 2017

Plotkin, Anastasia / Ceppa, Eugene P / Zarzaur, Ben L / Kilbane, Elizabeth M / Riall, Taylor S / Pitt, Henry A. ·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. · Indiana University Health University Hospital, Indiana University Health, Indianapolis, IN, USA. · Department of Surgery, University of Arizona, Tucson, AZ, USA. · Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA. ·HPB (Oxford) · Pubmed #28161217.

ABSTRACT: BACKGROUND: Minimally invasive distal pancreatectomy (MISDP) has been shown to be safe relative to open distal pancreatectomy (ODP). However, MISDP has been slow to adopt for pancreatic adenocarcinoma (PDAC). This study sought to compare outcomes following MISDP vs. ODP for PDAC. METHODS: Data were prospectively collected from 2011 to 2014 for DP by the American College of Surgeons-National Surgical Quality Improvement Program. Patients without PDAC on surgical pathology were excluded. Impact of minimally invasive approach on morbidity and mortality was analyzed using two-way statistical analyses. RESULTS: Of 6198 patients undergoing DP, 501 (7.5%) had a pathologic diagnosis of PDAC. MISDP was undertaken in 166 (33.1%) patients, ODP was performed in 335 (66.9%). MISDP and ODP were not different in preoperative comorbidities or pathologic stage. Overall morbidity (MISDP 31%, ODP 42%; p = 0.024), transfusion (MISDP 6%, ODP 23%; p = 0.0001), pneumonia (MISDP 1%, ODP 7%; p = 0.004), surgical site infections (MISDP 8%, OPD 17%; p = 0.013), sepsis (MISDP 2%, ODP 8%; p = 0.007), and length of stay (MISDP 5.0 days, ODP 7.0 days; p = 0.009) were lower in the MIS group. Mortality (MISDP 0%, ODP 1%; p = 0.307), pancreatic fistula (MISDP 12%, ODP 19%; p = 0.073), and delayed gastric emptying (MISDP 3%, ODP 7%; p = 0.140) were similar. CONCLUSIONS: This analysis of a large multi-institution North American experience of DP for treatment of pancreatic adenocarcinoma suggests that short-term postoperative outcomes are improved with MISDP.

14 Article Smoking and IPMN malignant progression. 2017

Carr, R A / Roch, A M / Shaffer, K / Aboudi, S / Schmidt, C M / DeWitt, J / Ceppa, E P / House, M G / Zyromski, N J / Nakeeb, A / Schmidt, C M. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Medicine, Division of Gastroenterology, Indiana University Hospital, Indianapolis, IN, USA. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: maxschmi@iupui.edu. ·Am J Surg · Pubmed #28129918.

ABSTRACT: BACKGROUND: Patients with intraductal papillary mucinous neoplasm (IPMN) are at risk for invasive pancreatic cancer. We aim to characterize the impact of smoking on IPMN malignant progression. METHODS: Patients undergoing pancreatic resection for IPMN (1991-2015) were retrospectively reviewed using a prospectively collected database. RESULTS: Of 422 patients identified, 324 had complete data for analysis; 55% were smokers. Smoking status did not impact IPMN malignant progression (smokers/non-smokers: 22%/18% invasive grade; p = 0.5). Smokers were younger than non-smokers at the time of IPMN diagnosis (63 versus 68 years; p = 0.001). This association also held in the invasive IPMN subgroup (65 versus 72 years, p = 0.01). Despite this observation, rate of symptoms at diagnosis, cancer stage, and median survival were the same between smokers and non-smokers. CONCLUSION: Although smoking is not associated with IPMN malignant progression, invasive IPMN is diagnosed at a younger age in smokers. These data suggest tobacco exposure may accelerate IPMN malignant progression.

15 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.

16 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.

17 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.

18 Article Reducing Readmissions after Pancreatectomy: Limiting Complications and Coordinating the Care Continuum. 2015

Ceppa, Eugene P / Pitt, Henry A / Nakeeb, Attila / Schmidt, C Max / Zyromski, Nicholas J / House, Michael G / Kilbane, E Molly / George-Minkner, Alisha N / Brand, Beth / Lillemoe, Keith D. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Surgery, Temple University School of Medicine, Philadelphia, PA. Electronic address: Henry.pitt@tuhs.temple.edu. · Department of Nursing, Indiana University Health, Indianapolis, IN. · Clinical Decision Support, Indiana University Health, Indianapolis, IN. · Department of Surgery, Massachusetts General Hospital, Boston, MA. ·J Am Coll Surg · Pubmed #26228016.

ABSTRACT: BACKGROUND: Recent analyses of gastrointestinal operations document that complications are a key driver of readmissions. Pancreatectomy is a high outlier with respect to readmission. This analysis sought to determine if a multifactorial approach could reduce readmissions after pancreatectomy. STUDY DESIGN: From 2007 to 2012, the number of patients readmitted by 30 days after pancreaticoduodenectomy, and distal and total pancreatectomy was measured. Steps to decrease readmissions were implemented independently at 1-year intervals; these efforts included strategies to reduce complications, creation of a Readmissions Team with a "discharge coach," increased use of home health, preferred relationships with post-acute care facilities, and the adoption of "Project RED" (Re-Engineered Discharge). The ACS NSQIP was used to track 30-day outcomes for all pancreatic resections. The University HealthSystem Consortium was used to determine length of stay index. RESULTS: Over 5 years, 1,163 patients underwent proximal (66%), distal (32%), or total pancreatectomy (2%). The observed 30-day mortality was 2.9% for the study period, and the length of stay index (observed/expected days) was 1.10. Neither varied significantly over time. However, 30-day morbidity decreased from 57% to 46%, and proportion of patients with 30-day all-cause readmissions decreased from 23.0% to 11.5% (p = 0.001). CONCLUSIONS: All-cause 30-day readmissions after pancreatectomy decreased without increasing length of stay. Efforts by surgeons to decrease complications and an increased emphasis on coordination of care may be useful for reducing readmissions.

19 Article Invasive, mixed-type intraductal papillary mucinous neoplasm: superior prognosis compared to invasive main-duct intraductal papillary mucinous neoplasm. 2015

Ceppa, Eugene P / Roch, Alexandra M / Cioffi, Jessica L / Sharma, Neil / Easler, Jeffrey J / DeWitt, John M / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Electronic address: eceppa@iupui.edu. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Gastroenterology, Parkview Health System, Fort Wayne, IN. · Department of Medicine, Division of Gastroenterology, Indiana University Hospital, Indianapolis, IN. ·Surgery · Pubmed #26173683.

ABSTRACT: PURPOSE: It is unclear whether the duct involvement subtypes of intraductal papillary mucinous neoplasm (IPMN), ie, main (MD), mixed (MT), and branch (BD), confer any survival advantage when invasive IPMN occurs. We hypothesized that invasive MT-IPMN was associated with a better prognosis than invasive MD-IPMN. METHODS: A retrospective review of a prospectively maintained database was performed of patients who underwent resection for IPMN at a single academic institution from 1992 to 2014. Characterization of IPMN subtype was assessed on final operative pathology. Statistics included univariate analysis, Kaplan-Meier survival curves, and Cox regression for independent predictors of increased survival. RESULTS: Of 390 patients eligible for study, 74 had invasive IPMN (IPMC). Of these, 71 patients had complete data and were included in the analysis (17 MD-IPMC, 39 MT-IPMC, and 15 BD-IPMC). Median follow-up was 20 months (range, 2-174). MT-IPMC was associated with significantly greater overall survival (OS) (47 months) compared with MD-IPMC (12 months) (P = .049), but not with BD-IPMC (44 months) (P = .67). Multivariate Cox regression yielded a family history of pancreatic cancer, absence of jaundice, N0 status, negative margins, absence of lymphovascular invasion, and MT subtype as independent predictors of greater OS (P = .035, .015, .013, .036, .045, .043, respectively). No characteristic of IPMN (including MD diameter, solid component/mural nodule) was predictive of OS. CONCLUSION: MT-IPMC appeared to be associated with a greater OS compared with pure MD-IPMC. This begs the question of a different underlying biology of MT-IPMN and argues against classification of all main duct involved IPMN into a single category.

20 Article Does Pancreatic Stump Closure Method Influence Distal Pancreatectomy Outcomes? 2015

Ceppa, Eugene P / McCurdy, Robert M / Becerra, David C / Kilbane, E Molly / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max / Lillemoe, Keith D / Pitt, Henry A / House, Michael G. ·Department of Surgery, Indiana University School of Medicine, 545 Barnhill Dr, EH 541, Indianapolis, IN, 46202, USA, eceppa@iupui.edu. ·J Gastrointest Surg · Pubmed #25903852.

ABSTRACT: BACKGROUND: Pancreatic fistula remains the primary source of morbidity following distal pancreatectomy. Previous studies have reported specific methods of parenchymal transection/stump sealing in an effort to decrease the pancreatic fistula rate with highly variable results. The aim of this study was to determine postoperative outcomes following various pancreatic stump-sealing methods. STUDY DESIGN: All cases of distal pancreatectomy were reviewed at a single institution between January 2008 and June 2011 and were monitored with complete 30-day outcomes through ACS-NSQIP. Pancreatic stump-sealing method was used to create three operation groups (suture, staple, or saline-linked radiofrequency). Two- and three-way statistical analyses were performed among the operation groups. RESULTS: Two hundred three patients underwent distal pancreatectomy. The most common diagnoses included chronic pancreatitis, adenocarcinoma, and IPMN. The suture, staple, and SLRF groups included 90 (44%), 61 (30%), and 52 (26%) patients, respectively. Overall complications (range 31-38%) and pancreatic fistula (range 25-26%) were similar with each pancreatic closure technique. Operative technique was not associated with an increased need for postoperative interventions or hospital readmission. CONCLUSIONS: Postoperative outcomes after distal pancreatectomy are unaffected by the use of SLRF sealing of the pancreatic stump when compared to traditional suture or reinforced stapling techniques.

21 Article Extended distal pancreatectomy for pancreatic adenocarcinoma with splenic vein thrombosis and/or adjacent organ invasion. 2015

Roch, Alexandra M / Singh, Harjot / Turner, Alexandra P / Ceppa, Eugene P / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, Christian 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 #25547091.

ABSTRACT: BACKGROUND: Patients with adenocarcinoma of the pancreatic body/tail and associated vascular thrombosis or adjacent organ invasion are suboptimal candidates for resection. We hypothesized that extended distal pancreatectomy (EDP) for locally advanced adenocarcinoma is associated with a survival benefit. METHODS: We retrospectively reviewed a prospectively collected database of patients who underwent distal pancreatectomy (DP) for adenocarcinoma at a single academic institution (1996 to 2011) with greater than or equal to 2 years of follow-up. RESULTS: Among 680 DP patients, 93 were indicated for pancreatic adenocarcinoma. Splenic vein thrombosis (n = 26) did not significantly affect morbidity, mortality, or survival. Standard DP was performed in 70 patients and 23 underwent EDP with no difference in morbidity/mortality. Patients with EDP had a survival comparable with patients with standard DP (disease-free survival 18 vs 12 months = .8; overall survival 23 vs 17 months, P =.6). There was no difference in survival between EDP patients with versus without pathologic invasion of adjacent organs, but a trend favored those without. CONCLUSION: EDP is safe and should be considered in fit patients with locally advanced adenocarcinoma.

22 Article Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms. 2014

Roch, Alexandra M / Parikh, Janak A / Al-Haddad, Mohammad A / DeWitt, John M / Ceppa, Eugene P / House, Michael G / Nakeeb, Attila / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Medicine, Division of Gastroenterology, Indiana University Hospital, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Electronic address: maxschmi@iupui.edu. ·Surgery · Pubmed #25239347.

ABSTRACT: INTRODUCTION: Pancreatitis is associated with intraductal papillary mucinous neoplasm (IPMN). This association is in part due to inflammation from pancreatic ductal obstruction. Although the correlation between pancreatitis and the malignant potential of IPMN is unclear, the 2012 International Consensus Guidelines (ICG) consider pancreatitis a "worrisome feature." We hypothesized that serum pancreatic enzymes, markers of inflammation, are a better predictor of malignancy than pancreatitis in patients with IPMN. METHODS: Between 1992 and 2012, 364 patients underwent resection for IPMN at a single university hospital. In the past decade, serum amylase and lipase were collected prospectively as an inflammatory marker in 203 patients with IPMN at initial surveillance and "cyst clinic" visits. The latest serum pancreatic enzyme values within 3 months preoperatively were studied. Pancreatitis was defined according to the 2012 revision of the Atlanta Consensus. RESULTS: Of the 203 eligible patients, there were 76 with pancreatitis. Pancreatitis was not associated with an increased rate of malignancy (P = .51) or invasiveness (P = .08). Serum pancreatic enzymes categorically outside of normal range (high or low) were also not associated with malignancy or invasiveness. In contrast, as a continuous variable, the higher the serum pancreatic enzymes were, the greater the rate of invasive IPMN. Of the 127 remaining patients without pancreatitis, serum pancreatic enzymes outside of normal range (low and high) were each associated with a greater rate of malignancy (P < .0001 and P = .0009, respectively). Serum pancreatic enzyme levels above normal range (high) were associated with a greater rate of invasiveness (P = .02). CONCLUSION: In patients with IPMN without a history of pancreatitis, serum pancreatic enzymes outside of the normal range are associated with a greater risk of malignancy. In patients with a history of pancreatitis, there is a positive correlation between the levels of serum pancreatic enzymes and the presence of invasive IPMN. These data suggest serum pancreatic enzymes may be useful markers in stratification of pancreatic cancer risk in patients with IPMN.

23 Article The natural history of main duct-involved, mixed-type intraductal papillary mucinous neoplasm: parameters predictive of progression. 2014

Roch, Alexandra M / Ceppa, Eugene P / Al-Haddad, Mohammad A / DeWitt, John M / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Max. ·*Department of Surgery, Indiana University School of Medicine, Indianapolis; and †Department of Medicine, Division of Gastroenterology, Indiana University Hospital, Indianapolis. ·Ann Surg · Pubmed #25203885.

ABSTRACT: OBJECTIVE: As such, the natural history of MPD-involved IPMN is poorly understood. BACKGROUND: The high-risk of malignancy associated with main pancreatic duct (MPD)-involved intraductal papillary mucinous neoplasm (IPMN) has been established by surgical series. The International Consensus Guidelines recommend surgical resection of MPD-involved IPMN in fit patients. METHODS: A review of a prospectively collected database (1992-2012) of patients with IPMN undergoing primary surveillance was performed. Invasive progression was defined as invasive carcinoma on pathology and/or positive cytopathology. Analyses included univariate, logistic regression, and receiver operating characteristic curve analyses. RESULTS: A total of 503 patients with IPMN underwent primary surveillance, 70 for MPD-involved, mixed-type IPMN. Indications for intensive surveillance of these 70 high-risk patients were comorbidities, patient choice, and early/borderline MPD dilation (42%, 51%, and 7%, respectively). Mean follow-up was 4.7 years. Nine patients (13%) progressed at a mean of 3.5 (range, 1-9) years during follow-up. Univariate analyses yielded weight loss, interval (from isolated branch-duct IPMN) to MPD involvement, diffuse MPD dilation, increase of MPD diameter, absence of extra pancreatic cysts, elevated serum CA19-9 levels, and elevated serum alkaline phosphatase levels as significant. Maximum MPD and/or branch-duct diameter were not significant. In logistic regression, diffuse MPD dilation, serum CA19-9 and serum alkaline phosphatase levels, and absence of extra pancreatic cysts were predictors of invasiveness. The receiver operating characteristic curve indicated that the combination of these 4 factors achieved an accuracy of 98% in predicting progression. CONCLUSIONS: Primary surveillance of mixed-type IPMN may be a reasonable strategy in select patients. Diffuse MPD dilation, serum CA19-9, serum alkaline phosphatase, and absence of extrapancreatic cysts predict patients likely to progress during primary surveillance.

24 Article International Consensus Guidelines parameters for the prediction of malignancy in intraductal papillary mucinous neoplasm are not properly weighted and are not cumulative. 2014

Roch, Alexandra M / Ceppa, Eugene P / DeWitt, John M / Al-Haddad, Mohammad A / House, Michael G / Nakeeb, Atilla / Schmidt, C Max. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. ·HPB (Oxford) · Pubmed #25077378.

ABSTRACT: BACKGROUND: The International Consensus Guidelines (ICG) stratify risk for malignancy in patients with intraductal papillary mucinous neoplasm (IPMN) into three progressive categories according to whether patients show 'no criteria', 'worrisome features' (WFs) or 'high-risk stigmata' (HRS). OBJECTIVES: This study was conducted to test the hypothesis that type (clinical versus radiological) and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN. METHODS: A retrospective review of a prospectively maintained database of patients who underwent surgical resection for IPMN at a single, university-based medical centre during 1992-2012 was performed. Differences that achieved a P-value of <0.05 were considered significant. RESULTS: Of 362 patients, 340 were eligible for entry into the study and were categorized as demonstrating no criteria (n = 70), WFs (n = 185) or HRS (n = 85). Patients in the WFs group had higher rates of malignant and invasive IPMN than those in the no-criteria group [26.5% versus 4.3% (P < 0.0001) and 15.7% versus 4.3% (P = 0.02), respectively]. Patients in the HRS group had higher rates of malignant and invasive IPMN than those in the WFs group [56.5% versus 26.5% (P = 0.0001) and 42.4% versus 15.7% (P = 0.0001), respectively]. When radiological parameters only were considered for WFs versus HRS, no difference was found in rates of malignant or invasive IPMN. By contrast, when clinical parameters only were considered, patients in the HRS group had higher rates of malignant or invasive IPMN [66.7% versus 8.1% (P = 0.04) and 66.7% versus 2.7% (P = 0.01), respectively]. There was no stepwise increase in rates of malignant or invasive IPMN with the number of WFs. However, patients with only one WF had a lower risk for malignancy than patients with two or more WFs. CONCLUSIONS: The type and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN.

25 Article Nonoperative management of main pancreatic duct-involved intraductal papillary mucinous neoplasm might be indicated in select patients. 2014

Roch, Alexandra M / DeWitt, John M / Al-Haddad, Mohammad A / Schmidt, Christian M / Ceppa, Eugene P / House, Michael G / Zyromski, Nicholas J / Nakeeb, Attila / Schmidt, C Maximillian. ·Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Medicine, Division of Gastroenterology, Indiana University Hospital, Indianapolis, IN. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Electronic address: maxschmi@iupui.edu. ·J Am Coll Surg · Pubmed #24862887.

ABSTRACT: BACKGROUND: Although the natural history of intraductal papillary mucinous neoplasm (IPMN) remains unclear, large surgical series have reported malignancy in 40% to 90% of main pancreatic duct (MPD)-involved IPMN. Accordingly, the 2012 International Consensus Guidelines recommend surgical resection in patients with suspected MPD involvement. We hypothesized that nonoperative management of select patients with suspected MPD-involved IPMN might be indicated. STUDY DESIGN: From 1992 to 2012, 362 patients underwent surgical resection for pathologically confirmed IPMN at a single academic center. A retrospective review of prospectively collected data was performed. Main pancreatic duct involvement was suspected with an MPD diameter ≥5 mm on preoperative imaging. A multivariate analysis was conducted to assess predictors of malignancy. RESULTS: Of 362 patients, 334 had complete data for analysis. Main pancreatic duct involvement was suspected preoperatively in 171 patients. Final pathology revealed 20% high-grade dysplastic and 27% invasive IPMN (47% malignant). Preoperative cytopathology and serum carbohydrate antigen 19-9 independently predicted malignancy (p = 0.003 and p = 0.002, respectively) and invasiveness (p < 0.0001 and p = 0.001, respectively). Patients with both negative preoperative cytopathology and normal serum carbohydrate antigen 19-9 (ie, double negatives) had a lower rate of malignancy and invasiveness (28% and 8% vs 58% and 38%; p < 0.0001). The MPD diameter did not predict malignancy or invasiveness (p = 0.36 and p = 0.46, respectively). CONCLUSIONS: Patients with suspected MPD-involved IPMN have a highly variable rate of malignancy. Despite recent International Consensus Guidelines recommendations, these data suggest that MPD diameter is not an optimal gauge of malignant risk. Nonoperative management of suspected MPD-involved IPMN in select patients, particularly double negatives, might be indicated. Depending on age and comorbidity, operative risk might outweigh the risk of malignant progression in these patients.

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