Background/Aim: We created a novel, preoperative wellness program (WP) that promotes recovery. This study assessed its impact on patient outcomes after pancreatectomy. Patients and Methods: Pancreatoduodenectomies (PD) and distal pancreatectomies (DP) performed from 2015 to 2018 were reviewed using our institutional NSQIP database. Patients in the WP had their medical conditions optimized and were provided with the following: chlorhexidine, topical mupirocin, incentive spirometer, and immune-nutrition supplements. Results: Out of a total of 669 pancreatectomy patients (411 PD, 258 DP), 308 were enrolled in the WP (188 PD, 120 DP). In the PD subgroup, on multivariable analysis (MVA), the WP patients had shorter lengths of hospital stay (LOS) (12 vs. 10 days, p<0.001). On MVA, WP patients had less post-op transfusion (20 vs. 10%, p=0.027). For the combined groups on MVA, LOS continued to be significant (OR=0.89, 95%CI=0.82-0.97, p<0.007). Conclusion: A preoperative patient centered WP may reduce the length of stay.

BACKGROUND:The decision to routinely leave a nasogastric tube after pancreatoduodenectomy remains controversial. We sought to determine the impact of immediate nasogastric tube removal versus early nasogastric tube removal (<24 h) on postoperative outcomes. METHODS:A retrospective review of our institution's prospective ACS-NSQIP database identified patients that underwent pancreatoduodenectomy from 2015 to 2018. Outcomes were compared among patients with immediate nasogastric tube removal versus early nasogastric tube removal. RESULTS:A total of 365 patients were included in primary analysis (no nasogastric tube, n = 99; nasogastric tube removed <24 h, n = 266). Thirty-day mortality and infectious, renal, cardiovascular, and pulmonary morbidity were similar in comparing those with no nasogastric tube versus early nasogastric tube removal on univariable and multivariable analyses (P > 0.05). Incidence of delayed gastric emptying (11.1 versus 13.2%) was similar between groups. Patients with no nasogastric tube less frequently required nasogastric tube reinsertion (n = 4, 4%) compared to patients with NGT <24 h (n = 39, 15%) (OR = 3.83, 95% CI [1.39-10.58]; P = 0.009). CONCLUSION:Routine gastric decompression can be safely avoided after uneventful pancreaticoduodenectomy.

Biliary fistula after pancreatoduodenectomy (PD) is associated with significant morbidity and mortality. The aim of this study was to determine the risk of early postoperative biliary fistula for developing biliary anastomotic stricture after PD. Retrospective review of all PD performed for various indications at a single institution between 2013 and 2018. Postoperative biliary fistulae were graded according to the International Study Group of Liver Surgery (ISGLS) as grade A–C. Multivariable analysis was performed for all comparative patient subgroups. A total of 843 patients underwent PD for malignant (68%) and benign (32%) indications. Postoperative biliary fistula developed in 66 (8%) patients; ISGLS grade A in 29 (3%), grade B in 32 (4%), and grade C in 5 (0.6%). Ninety-day mortality was 3% (25 patients). The remaining 818 patients were evaluated with a median follow-up of 16 months (IQR, 5–32 months). Biliary anastomotic stricture developed in 41 (5%) patients at a median of 10 months (IQR, 6–18 months) postoperatively. Strictures were managed with percutaneous (27 patients, 66%) or endoscopic (14 patients, 34%) stenting. No biliary stricture required operative anastomotic revision. Postoperative biliary fistula (HR, 4.4; 95% CI, 2.0–9.9; P = 0.0002) was associated with biliary anastomotic stricture; an increased risk for biliary anastomotic stricture was seen in patients with grade A (HR, 6.4; 95% CI, 2.4–16.9; P = 0.0002) and grade B (HR, 3.6; 95% CI, 1.2–10.9; P = 0.02) postoperative biliary fistula. Postoperative biliary fistula after pancreatoduodenectomy, including clinically insignificant, transient biliary fistula, is associated with an increased risk of a late biliary anastomotic stricture requiring stenting.

Objectives The yield of genetic testing of main pancreatic duct (MPD) fluid collected during endoscopic retrograde cholangiopancreatography (ERCP) versus endoscopic ultrasound-guided fine-needle aspiration is unclear. Methods Consecutive MPD fluid samples obtained by endoscopic ultrasound/ERCP with DNA profiling were reviewed, excluding specimens designated “no amplification.” Invasive disease included invasive cancer or malignant cytology. Results One hundred ten samples from 109 patients who underwent ERCP (n = 32) or endoscopic ultrasound-guided fine-needle aspiration (n = 78) were analyzed (2007–2018). Leading indications were dilated MPD and suspected intraductal papillary mucinous neoplasm. Elevated DNA quantity, KRAS, loss of heterozygosity (LOH), and GNAS mutations occurred in 61.5%, 25.5%, 16.4%, and 8.7% of samples, respectively. Elevated DNA quantity occurred more frequently in ERCP samples (84.4% vs 51.9%, P = 0.002); other mutation yields were similar (P > 0.05). Invasive pathology (P = 0.032) was associated with LOH in the subset of patients who underwent surgery (n = 44). Adverse events occurred more frequently after ERCP (28.1% vs 9.0%, P = 0.016). Conclusions Endoscopic MPD fluid sampling may yield genetic data to improve diagnosis and risk stratification. In our surgical cohort, LOH was the sole predictor of invasive pathology. Endoscopic ultrasound-guided fine-needle aspiration of MPD fluid, when possible, is preferred because of superior safety profile.

Background: Secretin-induced duodenal aspiration (SIDA) of pancreatic duct fluid has been proposed for pancreatic neoplasm screening in very high-risk patients. We sought to determine the clinical yield and safety of commercially-analyzed SIDA samples in patients at moderately elevated risk. Patients and Methods: A prospectively maintained institutional database of pancreatic fluid DNA profiles was retrospectively reviewed. Results: Fifty-seven patients underwent SIDA testing, most commonly for intraductal papillary mucinous neoplasms (n=43) and not otherwise specified solitary cysts (n=9). SIDA mutation yield was low compared to 37 concomitant endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples of pancreatic fluid: KRAS (2.5% vs. 40.0%), GNAS (2.6% vs. 11.1%) and allelic loss of heterozygosity (3.1% vs. 0%). Patients undergoing SIDA alone experienced no complications while 3 patients with concomitant EUS-FNA had post-procedural pancreatitis. Conclusion: The genetic yield of commercially-analyzed SIDA samples was relatively low in a moderately elevated risk cohort. SIDA testing may have a better safety profile than EUS-FNA.

Hepatectomy is a complex operative procedure frequently performed at academic institutions with trainee participation. The aim of this study was to determine the effect of assistant’s training level on outcomes following hepatectomy. A retrospective review of a prospective, single-institution ACS-NSQIP database was performed for patients that underwent hepatectomy (2013–2016). Patients were divided by trainee assistant level: hepatopancreatobiliary (HPB) fellow versus general surgery resident (PGY 4–5). Demographic, perioperative, and 30-day outcome variables were compared using Chi-Square/Fisher’s exact, Mann–Whitney U test, and multivariable regression. Cases involving a senior-level general surgery resident or HPB fellow as first assistant were included (n = 352). Those with a second attending, junior-level resident, or no documented assistant were excluded (n = 39). Patients undergoing hepatectomy with an HPB fellow as primary assistant had more frequent preoperative biliary stenting, longer operative time, and more concomitant procedures including biliary reconstruction, resulting in a higher rate of post-hepatectomy liver failure (PHLF) (15% vs. 8%, P = 0.044). However, trainee level did not impact PHLF on multivariable analysis (OR 0.60, 95% CI [0.29–1.25], P = 0.173). Fellows assisted with proportionally more major hepatectomies (45% vs. 31%; P = 0.010) and resections for hepatobiliary cancers (31% vs. 19%, P = 0.014). On stratified analysis of major and minor hepatectomies, outcomes were similar between trainee groups. Fellows performed higher complexity cases with longer operative time. Despite these differences, outcomes were similar regardless of assistant training level. Resident and HPB fellow participation in operations requiring liver resection provide comparable quality of care.

thiamin uptake and in the level of expression of THTR-1 and THTR-2 protein and mRNA.Similarly, exposure of mice to flagellin (5 c ˇg/ mice for 48 h) lead to a significant inhibition in thiamin uptake, as well as in the level of expression of THTR-1 and -2 protein and mRNA.Prolonged exposure of PAC 266-6 cells to flagellin also led to a significant inhibition in the activity of the SLC19A2 and SLC19A3 promoters and the effect appears to target the minimal promoter regions of these genes.Studies are in progress to delineate the exact molecular mechanism(s) involved in this inhibitory effect.This study for the first time provides clear evidence that exposure of PACs to flagellin negatively impacts the physiological and molecular parameters of thiamin uptake and that this effect is exerted, at least in part, at the level of transcription of the SLC19A2 and SLC19A3 genes [Supported by grants from the DVA and the NIH (DK-56061, DK58057, and AA 018071)].

Endoscopic ultrasound (EUS) is frequently conducted for the long term surveillance of pancreatic cystic neoplasm (PCNs). Repeat EUS-guided fine needle aspiration (EUS-FNA) can be combined with cytology, carcinoembryonic antigen (CEA), and more recently molecular analysis to assess for progression of DNA mutations over time. The natural history of KRAS mutations in PCNs over time is poorly described. The aim of this study was to assess the changes of KRAS mutations in PCNs over time and its impact on patient outcomes.

Background: Demand for pancreatic surgery is rising, occasionally necessitating consecutive PDs to be performed by a single surgeon in the same workday. The safety of this practice is unknown. Methods: Institutional prospective ACS-NSQIP data were reviewed for PDs (2013-2017). Instances where a single surgeon performed two PDs in the same day were a PD pair (PD1, PD2) and compared with univariable analysis. Paired vs. unpaired-PD matched analyses were performed. Results: 661 PDs (25-PD pairs) were performed. PD1 and PD2 revealed similar infectious (12% vs16%), pulmonary (8% vs8%), cardiovascular (12% vs4%), and aggregate (24% vs24%) morbidity (P>0.05). Pancreatic fistula (B + C 0%), delayed gastric emptying (4% vs12%), hospital stay (9.3 vs8.8 days), and 30day mortality (4% vs4%) were similar (P > 0.05). Matched outcomes were similar except higher cardiovascular morbidity for paired vs. unpaired PD (7% vso%; P=0.015). Conclusion: With proper patient selection, and in experienced hands at high-volume centers, two consecutive open PDs may be safely performed. (C) 2019 Elsevier Inc. All rights reserved.

Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.

Pancreatic cysts are extremely common and often pose a management dilemma. Some pancreatic cysts are pre-cancerous while others have little risk of developing into invasive cancers. Prior studies have evaluated the presence of KRASand GNASmutations in intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). However, the full spectrum of molecular alterations present in other types of pancreatic cysts, as well as how this information could impact clinical care, needs to be defined.

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. 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. 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. 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.

OBJECTIVES:We sought to determine if interleukin (IL)-1β and prostaglandin E2 (PGE2) (inflammatory mediators in pancreatic fluid) together with serum carbohydrate antigen (CA) 19-9 could better predict intraductal papillary mucinous neoplasm (IPMN) dysplasia than individual biomarkers alone. METHODS:Pancreatic cyst fluid (n = 92) collected via endoscopy or surgery (2003-2016) was analyzed for PGE2 and IL-1β (enzyme-linked immunosorbent assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1β [>20 pg/mL], and serum CA 19-9 [>36 U/mL]) were determined. RESULTS:Levels of IL-1β were higher in high-grade dysplasia (HGD)/invasive-IPMN (n = 42) compared with low/moderate IPMN (n = 37) (median [range], 54.6 [0-2671] vs 5.9 [0-797] pg/mL; P < 0.001; area under curve [AUC], 0.766). Similarly, PGE2 was higher in HGD/invasive IPMN (n = 45) compared with low/moderate IPMN (n = 47) (median [range], 1790 [20-15,180] vs. 140 [10-14,630] pg/mL; P < 0.001; AUC, 0.748). Presence of elevated PGE2 and IL-1β (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/invasive IPMN. Elevated levels of all 3 provided 100% specificity and PPV for HGD/invasive IPMN. CONCLUSIONS:Cyst fluid PGE2, IL-1β, and serum CA 19-9 in combination optimize specificity and PPV for HGD/invasive IPMN and may help build a panel of markers to predict IPMN dysplasia.

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. (C) 2018 Elsevier Inc. All rights reserved.