Pancreatoduodenectomy in obese patients: surgery for nonmalignant tumors might be deferred.

BACKGROUND: Obesity has traditionally been considered a cause of increased surgical complexity and poor outcomes following pancreatoduodenectomy (PD). This study aimed at evaluating the role of obesity in terms of mortality and failure to rescue (FTR), with a particular focus on nonmalignant tumors. METHODS: All patients undergoing elective PD over 10 consecutive years were analyzed. Patients were stratified according to their BMI and categorized into two groups. Predictors of mortality and FTR were assessed through logistic regression. RESULTS: Out of 1865 patients included, 151 were obese (8.1%). Overall mortality and FTR were 3.1% and 14.1%, respectively. In obese patients, mortality was 6.0% and FTR 26.5%, significantly higher compared to nonobese (p < 0.05). In the multivariable analysis, obesity, age > 70 years, and ASA-PS score were independent predictors of mortality and FTR. Postoperative pancreatic fistula (35.8% vs. 25.8%), postpancreatectomy acute pancreatitis (24.5% vs. 12.5%), and chyle leak (6.0% vs. 3.2%) were more frequent among obese patients. In the subgroup of patients with nonmalignant tumors (n = 443), obesity was the only independent predictor of FTR. CONCLUSION: PD performed in obese patients was associated with higher surgical morbidity and mortality. When dealing with nonmalignant tumors, deferring surgery in obese patients should be strongly considered.

High-risk Pancreatic Anastomosis Versus Total Pancreatectomy After Pancreatoduodenectomy: Postoperative Outcomes and Quality of Life Analysis.

OBJECTIVE: To evaluate TP as an alternative to PD in patients at high-risk for popf. BACKGROUND: Outcomes of high-risk PD (HR-PD) and TP have never been compared. METHODS: All patients who underwent PD or TP between July 2017 and December 2019 were identified. HR-PD was defined according to the alternative fistula risk score. Postoperative outcomes (primary endpoint), pancreatic insufficiency, and quality of life after 12 months of follow-up (QoL) were compared between HR-PD or planned PD intraoperatively converted to TP (C-TP). RESULTS: A total of 566 patients underwent PD and 136 underwent TP during the study period. One hundred one (18%) PD patients underwent HR-PD, whereas 86 (63%) TP patients underwent C-TP. Postoperatively, the patients in the C-TP group exhibited lower rates of postpancreatectomy hemorrhage (15% vs 28%), delayed gastric emptying (16% vs 34%), sepsis (10% vs 31%), and Clavien-Dindo ≥3 morbidity (19% vs 31%) and had shorter median lengths of hospital stay (10 vs 21 days) (all P < 0.05). The rate of POPF in the HR-PD group was 39%. Mortality was comparable between the 2 groups (3% vs 4%). Although general, cancer- and pancreas-specific QoL were comparable between the HR-PD and C-TP groups, endocrine and exocrine insufficiency occurred in all the C-TP patients, compared to only 13% and 63% of the HR-PD patients, respectively, and C-TP patients had worse diabetesspecific QoL. CONCLUSIONS: C-TP may be considered rather than HR-PD only in few selected cases and after adequate counseling.

Pancreatoduodenectomy at the Verona Pancreas Institute: the Evolution of Indications, Surgical Techniques, and Outcomes: A Retrospective Analysis of 3000 Consecutive Cases.

OBJECTIVE: The aim of the present study was to critically reappraise the experience at our high-volume institution to obtain new insights for future directions. SUMMARY BACKGROUND DATA: The indications, surgical techniques, and perioperative management of pancreatoduodenectomy (PD) have profoundly evolved over the last 20 years. METHODS: All consecutive PDs performed during the last 20 years at the Verona Pancreas Institute were divided into four 5-year timeframes and retrospectively analyzed in terms of indications, intraoperative features, and surgical outcomes. Significant milestones were provided to understand practice changes using a before-after analysis method. RESULTS: The study population consisted of 3000 patients. The median age, ASA ≥ 3 and number of nonbenchmark cases significantly increased over time ( P < 0.005). Pancreatic cancer was the leading indication, representing 60% of patients/year in the last timeframe, 40% of whom received neoadjuvant treatment. Conversely, after the development of International Guidelines, the proportion of resected cystic neoplasms progressively and thoroughly decreased. Given the increased complexity of surgery for pancreatic cancer, the evolution of technologies, surgical techniques, and postoperative management allowed the maintenance of favorable surgical outcomes over time, with a stable 20.0% of patients with a Clavien-Dindo grade ≥ 3, an 11.7% failure to rescue and a 2.3% in-hospital mortality rate. The incidence of postoperative pancreatic fistula, hemorrhage, and delayed gastric emptying was 22.4%, 13.4%, and 12.4%, respectively. CONCLUSIONS: PD significantly evolved in Verona over the past 2 decades. Surgeries of greater complexity are currently performed on increasingly frailer patients, mostly for pancreatic cancer and often after neoadjuvant chemotherapy. However, the progression of all fields of pancreatic surgery, including the expanding use of postoperative pancreatic fistula mitigation strategies, has allowed satisfactory outcomes to be maintained.

Serous Cystic Neoplasms of the Pancreas Management in the Real-world: Still Operating on a Benign Entity.

OBJECTIVE: Our aim is to provide a real-life picture of serous cystic neoplasms (SCNs) management once a presumptive diagnosis is made. SUMMARY OF BACKGROUND DATA: SCNs of the pancreas are invariably benign entities. While consensus about their management is lacking, surgical resection still plays a role. METHODS: Presumed SCNs evaluated from 1990 to 2018 were included. Indications for surgery, predictors of resection, rate, and predictors of misdiagnosis in the surgical cohort and time trends of management strategies were the main outcomes. RESULTS: A total of 672 presumed SCNs were included. Presence of symptoms (37%) and large size (34.1%) were the most frequent indications for surgery. Symptoms (60.4% vs 19.0%, P < 0.001), size (45 vs 30 mm, P < 0.001), solid components (19.7% vs 6.2%, P < 0.001), thick walls (14.4 vs 5.6%, P = 0.001) and main pancreatic duct dilation (13.4% vs 5.6%, P = 0.004) were associated with upfront resection (n = 134, 19.9%). Upfront resection decreased over time and 15.4% of patients eventually crossed over to surgery. Increase in size (6.9 vs 1.3 mm/yr), development of symptoms (25.3% vs 3.4%, P < 0.001), solid component (6.0% vs 1.4%, P = 0.010) or jaundice (3.6% vs 0.7%, P = 0.028) were associated with crossing over to surgery. Major morbidity and mortality occurred in 17.1% and 1.7% of patients, respectively. Misdiagnosis occurred mostly in case of macrocystic/unilocular lesions of the body-tail. CONCLUSIONS: In the real-life scenario, SCNs still represent an indication for surgery particularly once large and symptomatic. During surveillance, resection occurs mostly in younger individuals for body/tail lesions. Evidence-based consensus on appropriate indications for surgery is urgently needed.

Open pancreaticoduodenectomy: setting the benchmark of time to functional recovery.

PURPOSE: No accepted benchmarks for open pancreaticoduodenectomy (PD) exist. The study assessed the time to functional recovery after open PD and how this could be affected by the magnitude of midline incision (MI). MATERIALS AND METHODS: Prospective snapshot study during 1 year. Time to functional recovery (TtFR) was assessed for the entire cohort. Further analyses were conducted after excluding patients developing a Clavien-Dindo ≥ 2 morbidity and after stratifying for the relative length of MI. RESULTS: The overall median TtFR was 7 days (n = 249), 6 days for uncomplicated patients (n = 124). A short MI (SMI, < 60% of xipho-pubic distance, n = 62) was compared to a long MI (LMI, n = 62) in uncomplicated patients. The choice of a SMI was not affected by technical issues and provided a significantly shorter TtFR (5 vs 6 days, p = 0.002) especially for pain control (4 vs. 5 days, p = 0.048) and oral food intake (5 vs. 6 days, p = 0.001). CONCLUSION: Functional recovery after open PD with MI is achieved within 1 week from surgery in half of the patients. This should be the appropriate benchmark for comparison with minimally invasive PD. Moreover, PD with a SMI is feasible, safe, and associated with a faster recovery.

The use of a mobile application to disseminate guidelines on cystic neoplasms of the pancreas - A snapshot study of 1000 case-simulations.

BACKGROUND: No data exist on the actual application of pancreatic cystic neoplasm (PCN) guidelines in clinical practice. AIM: Disseminate knowledge on existing PCN guidelines and determine which guidelines are prospectively chosen by iCyst app users for different case scenarios. METHODS: iCyst is a digital tool providing access to the three main existing guidelines (European, IAP, and AGA). Through a case simulation system, for one year, the app prospectively registered users' guideline choices. RESULTS: During the study period, 276 users downloaded iCyst and entered 1020 completed simulations. Most users were European (88%) and were either surgeons (69%) or gastroenterologists (29%). Six different representative scenarios were identified. Overall, the European guidelines were the most commonly preferred (52%). In 16% of cases, the users did not choose any of the available guidelines. CONCLUSION: Digital apps can be used to disseminate guidelines in clinical practice. Guideline dissemination might serve as the basis for future research lines on specific clinical scenarios that iCyst identifies as critical.

Progression vs Cyst Stability of Branch-Duct Intraductal Papillary Mucinous Neoplasms After Observation and Surgery.

Importance: The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information. Objective: To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations. Design, Setting, and Participants: The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months). Main Outcomes and Measures: Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination. Results: A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04 [95% CI, 2.94-87.40]; P = .001). Conclusions and Relevance: These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.

Pancreatoduodenectomy associated with colonic resections: indications, pitfalls, and outcomes.

Pancreatoduodenectomy (PD) associated with colonic resections (CR) (PD-CR) might be a viable option in case of locally advanced periampullary tumors or right colon cancer. The aim of this review was to reappraise the indications and outcomes of PD-CR focusing on the occurrence of postoperative pancreatic fistula (POPF) and colonic anastomotic leak (CAL). A systematic literature search was performed in Medline and Cochrane Central Register of Controlled Trials (CENTRAL) for studies published between 2000 and 2020 concerning PD-CR for periampullary or colonic neoplasms. Twenty-seven studies were selected. Morbidity after PD-CR ranged from 12 to 65% and surgery-related mortality was approximately 10%. When reported, the rates of POPF and AL were as high as 40% and 33%, respectively. The oncological results were strictly linked to the nature of the primary tumor and did not significantly differ from those achieved with standard resections. Surgical radicality and nodal status resulted the main determinants of outcome for pancreatic and colonic cancer, respectively. Solid evidence about the surgical outcomes of PD-CR is lacking, mainly due to the small proportion of patients undergoing such combined resection. Given the elevated surgical risk, a multidisciplinary evaluation is recommended for patient's selection. The increasing use of neoadjuvant therapies is expected to further change the indications and outcomes of PD-CR in the next future.

Negative pressure wound therapy for prevention of surgical site infection in patients at high risk after clean-contaminated major pancreatic resections: A single-center, phase 3, randomized clinical trial.

BACKGROUND: Surgical site infections are an important burden of pancreatic surgery, prolonging hospitalization and delaying adjuvant treatment. The aim of this study was to compare negative pressure wound therapy with standard sterile dressing in terms of the prevention of non-organ-space surgical site infection (superficial and deep surgical site infection) in the high-risk setting. METHODS: The trial was conducted at the University of Verona Hospital Trust, Verona, Italy, from July 25, 2018, through October 10, 2019, among adults undergoing surgery for periampullary neoplasms. Only patients at high-risk for surgical site infection based on body mass index, diabetes, steroids, neoadjuvant therapy, American Society of Anesthesiologists score, Charlson comorbidity index, duration of surgery, and blood loss were included and randomized. RESULTS: A total of 351 patients were screened, 100 met the inclusion criteria and were 1:1 allocated in the 2 arms. The difference in terms of non-organ-space surgical site infection comparing negative pressure wound therapy with standard sterile dressing was not significant (10.9 vs 12.2%, risk ratio [RR] 1.144, confidence interval [CI] 95% 0.324-4.040, P = 1.000). Hematomas (4.3 vs 2%, RR 1.565, CI 95% 0.312-7.848, P = .609) and organ-space infections (46.7 vs 43.8%, RR 1.059, CI 95% 0.711-1.576, P = .836) were similar. Negative pressure wound therapy prevented the development of seromas (0 vs 12.2%, RR 0.483, CI 95% 0.390-0.599, P = .027). The aesthetic result assessed on postoperative day 7 was better in the negative pressure wound therapy group (visual analogue scale, 8 vs 7, P = .029; Stony Brook Scar Evaluation Scale, 3.2 vs 2.5, P = .009), but it was no more evident on postoperative day 30 after a total number of 23 dropouts. CONCLUSION: Compared with standard sterile dressing, negative pressure wound therapy is not associated with an improved rate of non-organ-space surgical site infection after surgery for periampullary neoplasms in patients at high risk for surgical site infection. Additional studies will help identify the population that could benefit most from this intervention.

Predictors of pancreatic fistula healing time after distal pancreatectomy.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is common after distal pancreatectomy (DP). Whilst extensive investigation into potential predictors has been carried out, there is little evidence regarding POPF healing time. METHODS: This is a retrospective analysis of all consecutive DPs performed at the Department of General and Pancreatic Surgery, University of Verona Hospital Trust, from 2015 to 2019. Perioperative variables were analyzed identifying possible predictors of POPF healing time defined as days between surgery and last drain removal due to POPF. RESULTS: A total of 496 patients were included. POPF rate was 28.2% and median POPF healing time was 30 days (95% CI 28-31). Independent predictors of POPF were body mass index (BMI) (OR 1.073, 95% CI 1.010-1.147, p = 0.040), operative time (OR 95% CI 1.002-1.009, P = .003), and postoperative acute pancreatitis (OR 3.793, 95% CI, 1.852-7.767, P < .001). Independent predictors of POPF healing time were female sex (HR 1.323, 95% CI 1.093-1.998, P = .042), preoperative pancreatic enzyme replacement therapy (HR 2.319, 95% CI 1.195-4.498, P = .013), ASA score 3 (HR 0.278, 95% CI 0.119-0.646, P = .003), pancreatic transection with ultrasonic dissector (HR 0.605, 95% CI 0.404-0.907, P = .015), and positive drain cultures (HR 0.635, 95% CI 0.443-0.910, P = .013). CONCLUSION: POPF healing after DP is a slow process since only half of patients recover within 30 days of surgery. A longer healing time can be predicted early in the postoperative period with significant implications in therapeutic choices.

Postoperative hyperamylasemia (POH) and acute pancreatitis after pancreatoduodenectomy (POAP): State of the art and systematic review.

BACKGROUND: Postoperative hyperamylasemia is a frequent finding after pancreatoduodenectomy, but its incidence and clinical implications have not yet been analyzed systematically. The aim of this review is to reappraise the concept of postoperative hyperamylasemia with postoperative acute pancreatitis, including its definition, interpretation, and correlation. METHODS: Online databases were used to search all available relevant literature published through June 2019. The following search terms were used: "pancreaticoduodenectomy," "amylase," and "pancreatitis." Surgical series reporting data on postoperative hyperamylasemia or postoperative acute pancreatitis were selected and screened. RESULTS: Among 379 screened studies, 39 papers were included and comprised data from a total of 9,220 patients. Postoperative hyperamylasemia was rarely defined in most of these series, and serum amylase values were measured at different cutoff levels and reported on different postoperative days. The actual levels of serum amylase activity and the representative cutoff levels required to reach a diagnosis of postoperative acute pancreatitis were markedly greater on the first postoperative days and tended to decrease over time. Most studies analyzing postoperative hyperamylasemia focused on its correlation with postoperative pancreatic fistula and other postoperative morbidities. The incidence of postoperative acute pancreatitis varied markedly between studies, with its definition completely lacking in 40% of the analyzed papers. A soft pancreatic parenchyma, a small pancreatic duct, and pathology differing from cancer or chronic pancreatitis were all predisposing factors to the development of postoperative hyperamylasemia. CONCLUSION: Postoperative hyperamylasemia has been proposed as the biochemical expression of pancreatic parenchymal injury related to localized ischemia and inflammation of the pancreatic stump. Such phenomena, analogous to those associated with acute pancreatitis, could perhaps be renamed as postoperative acute pancreatitis from a clinical standpoint. Patients with postoperative acute pancreatitis experienced an increased rate of all postoperative complications, particularly postoperative pancreatic fistula. Taken together, the discrepancies among previous studies of postoperative hyperamylasemia and postoperative acute pancreatitis outlined in the present review may provide a basis for stronger evidence necessary for the development of universally accepted definitions for postoperative hyperamylasemia and postoperative acute pancreatitis.

Redefining the Role of Drain Amylase Value for a Risk-Based Drain Management after Pancreaticoduodenectomy: Early Drain Removal Still Is Beneficial.

BACKGROUND: The application of postoperative pancreatic fistula (POPF) risk stratification and mitigation strategies requires an update of the protocol for an early drain removal after pancreaticoduodenectomy (PD). The aim of the study is to highlight the unreliability of a single drain fluid amylase (DFA) cutoff-based protocol in the setting of a risk-based drain management. METHODS: The role of postoperative day one (POD1) DFA in predicting POPF was explored in the setting of both selective drain placement and early drain removal protocols. Receiver operating characteristics (ROC) curves were used to assess the POPF diagnostic performance in terms of negative predictive value (NPV) of several POD1 DFA cutoffs in different clinical scenarios according to POPF risk and mitigation strategies. RESULTS: The areas under the curve (AUCs) for POD1-DFA were 0.815 for intermediate risk and pancreaticojejunostomy (PJ) (best cutoff 1000 IU/L, NPV 92.9%), 0.712 for intermediate risk and PJ with external stent (best cutoff 1000 IU/L, NPV 88.8%), and 0.574 for high risk and external stent (best cutoff 250 IU/L, NPV 93.7%). Independent predictors of POPF were body mass index, pancreatic texture, and early drain removal, whereas POD1 DFA was not. CONCLUSION: In the era of risk stratification and mitigation strategies, selective early drain removal still is associated with a reduced rate of POPF. However, a single protocol based on POD1-DFA is not suitable for all clinical scenarios after PD.

Pancreatic surgery is a safe teaching model for tutoring residents in the setting of a high-volume academic hospital: a retrospective analysis of surgical and pathological outcomes.

BACKGROUND: Academic hospitals must train future surgeons, but whether residents could negatively affect the outcomes of major procedures is a matter of concern. The aim of this study is to assess if pancreatic surgery is a safe teaching model. METHODS: Outcomes of 1230 major pancreatic resections performed at a high-volume pancreatic teaching hospital between 2015 and 2018 were compared according to the first surgeon type, attending vs resident. RESULTS: Residents performed a selection of 132 (16%) pancreaticoduodenectomies (PD) and 46 (11%) distal pancreatectomies (DP). For PD, pancreatic fistula (25% vs 0, p < 0.001), biliary fistula (7.1% vs 3.5%, p = 0.04) and operative time (400 vs 390 min, p < 0.001) were lower for residents but post-pancreatectomy hemorrhage was higher (20.5% vs 13% p = 0.024). For DP, pancreatic fistula rate was lower for residents (31.7% vs 17.5% p = 0.046). There was no difference in terms of lymph nodes retrieval both for PDs and DPs, while the R1 resections were more frequent among PDs performed by attending surgeons (31.5% vs 15.7%, p = 0.023). CONCLUSION: The active participation of residents does not negatively affect outcomes of major pancreatic resections in a high-volume center. By means of case selection and continuous tutoring, pancreatic surgery represents a safe and valid teaching model.

Characterization of postoperative acute pancreatitis (POAP) after distal pancreatectomy.

BACKGROUND: Postoperative acute pancreatitis has recently been reported as a specific complication after pancreatoduodenectomy. The aim of this study was to characterize postoperative acute pancreatitis after distal pancreatectomy. METHODS: We analyzed the outcomes retrospectively of 368 patients who underwent distal pancreatectomies during the period January 2016 to December 2019. Postoperative acute pancreatitis was defined as an increase of serum amylase activity greater than our laboratory normal upper limit on postoperative days 0 to 2. We assessed the incidence of postoperative acute pancreatitis after distal pancreatectomy and examined possible predictors of postoperative acute pancreatitis and relationships of postoperative acute pancreatitis with postoperative pancreatic fistula. RESULTS: The rates of postoperative acute pancreatitis and postoperative pancreatic fistula after distal pancreatectomy were 67.9% and 28.8%, respectively. Patients who developed postoperative acute pancreatitis experienced an increased rate of severe morbidity (18.4 vs 9.3%; P = .030). Neoadjuvant therapy (odds ratio 0.28, 0.09-0.85; P = .025), age ≥ 65 y (odds ratio 0.34, 0.13-0.85; P = .020), duct size (odds ratio 0.02, 0.002-0.47; P = .013), pancreatic thickness (odds ratio 3.4, 1.29-8.9; P = .013), resection at the body-tail level (odds ratio 4.3, 1.15-23.19; P = .041), and neuroendocrine histology (odds ratio 1.14, 1.06-3.90; P = .013) were independent predictors of postoperative acute pancreatitis. Furthermore, postoperative acute pancreatitis was an independent predictor of postoperative pancreatic fistula (odds ratio 5.8, 2.27-15.20; P < .001). Postoperative pancreatic fistula occurred in 37% of patients who developed postoperative acute pancreatitis. Patients developing postoperative acute pancreatitis alone demonstrated a statistically significantly increased rate of biochemical leakage and bacterial contamination in the peripancreatic drainage fluid. CONCLUSION: Postoperative acute pancreatitis is a frequent event after distal pancreatectomy and, despite its close association with postoperative pancreatic fistula, evidently represents a separate phenomenon. A universally accepted definition of postoperative acute pancreatitis that applies to all types of pancreatic resections is needed, because it may identify patients at greater risk for additional morbidity immediately after pancreatic resections.

Pros and pitfalls of externalized trans-anastomotic stent as a mitigation strategy of POPF: a prospective risk-stratified observational series.

BACKGROUND: Several advantages and pitfalls have been related to externalized trans-anastomotic stents (ETS) after pancreaticoduodenectomy. The purpose of this study was to investigate the effect of an ETS effect in a risk-stratified setting. METHODS: Data from patients at either intermediate- or high-risk for postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy were prospectively analyzed from January 2016 to December 2019. Outcomes included POPF rate, mean complication burden (ACB), and complications related to ETS malfunction. RESULTS: A total of 540 patients met the inclusion criteria. Following an intention-to-treat analysis, there was no difference in terms of POPF and the ACB in the intermediate (22 vs.29%, p = 0.148; 0.38 vs.0.24, p = 0.082) and high-risk categories (58 vs.37%, p = 0.103; 0.33 vs.0.33, p = 0.478) comparing PJ to PJ-ETS. Excluding patients experiencing ETS malfunction (n = 45, 22%), ETS was associated with a significantly reduced ACB in the intermediate-risk (0.38 vs.0.26, p = 0.009) and POPF rate in the high-risk category (58 vs.32%, p = 0.033). In patients with ETS malfunction an increased rate of severe morbidity (Clavien-Dindo ≥ III, 33 vs.19%, p = 0.044) was observed as compared to patients with functioning ETS. CONCLUSION: ETS provides crucial advantages for prevention and mitigation of POPF depending on risk setting and its correct functioning. ETS malfunction is not uncommon and increases morbidity. Improving ETS design and fixing technique might lead to better outcomes.

Seasonal variations in pancreatic surgery outcome A retrospective time-trend analysis of 2748 Whipple procedures.

BACKGROUND: Observing cyclic patterns in surgical outcome is a common experience. We aimed to measure this phenomenon and to hypothesize possible causes using the experience of a high-volume pancreatic surgery department. METHODS: Outcomes of 2748 patients who underwent a Whipple procedure at a single high-volume center from January 2000 to December 2018 were retrospectively analyzed. Three different hypotheses were tested: the effect of climate changes, the "July effect" and the effect of vacations. RESULTS: Clavien-Dindo ≥ 3 morbidity was similar during warm vs. cold months (22.5% vs. 19.8%, p = 0.104) and at the beginning of activity of new trainees vs. the rest of the year (23.5 vs. 22.5%, p = 0.757). Patients operated when a high percentage of staff is on vacation showed an increased Clavien-Dindo ≥ 3 morbidity (22.3 vs. 18.5%, p = 0.022), but similar mortality (2.3 vs. 1.8%, p = 0.553). The surgical waiting list was also significantly longer during these periods (37 vs. 27 days, p = 0.037). Being operated in such a period of the year was an independent predictor of severe morbidity (OR 1.271, CI 95% 1.086-1.638, p = 0.031). CONCLUSION: Being operated when more staff is on vacation significantly affects severe morbidity rate. Future healthcare system policies should prevent the relative shortage of resources during these periods.

CD117 Is a Specific Marker of Intraductal Papillary Mucinous Neoplasms (IPMN) of the Pancreas, Oncocytic Subtype.

The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN) category. IOPN is composed of oxyphil cells, usually expressing MUC5AC, MUC6, and Hep Par-1, and harboring PRKACA/B fusion genes as their genetic hallmark. Although IOPNs are associated with an infiltrative adenocarcinoma in up to 30% of cases, the survival rate after surgical resection approaches 100%. This highlights the importance of the correct IOPN diagnosis, above all in cases with an associated invasive component. In this study, the immunohistochemical expression of CD117 was investigated in 111 IPMNs, including 17 oncocytic, 45 gastric, 20 pancreatico-biliary, and 29 intestinal IPMNs. We also tested the expression of MUC5AC, MUC6, and Hep Par-1 in the IOPN cohort. CD117 positivity was significantly more frequent in IOPNs compared to the other IPMN subtypes (p < 0.0001). Furthermore, within IOPN, a lower or absent CD117, MUC5AC, MUC6, and Hep Par-1 expression tended to be associated with the presence of an infiltrative component. Our findings shed light into the biology of these complex lesions, which are confirmed to be a distinctive IPMN subtype; notably, CD117 emerged as a potential, additional tool in the differential diagnosis of IPMNs.

Pancreaticojejunostomy With Externalized Stent vs Pancreaticogastrostomy With Externalized Stent for Patients With High-Risk Pancreatic Anastomosis: A Single-Center, Phase 3, Randomized Clinical Trial.

Importance: The operative scenarios with the highest postoperative pancreatic fistula (POPF) risk represent situations in which fistula prevention and mitigation strategies have the strongest potential to affect surgical outcomes after pancreaticoduodenectomy. Evidence from studies providing risk stratification is lacking. Objective: To investigate whether pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG), both with externalized transanastomotic stent, is the best reconstruction method for patients at high risk of POPF after pancreaticoduodenectomy. Design, Setting, and Participants: A single-center, phase 3, randomized clinical trial was conducted at the Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy, from July 12, 2017, through March 15, 2019, among adults undergoing elective pancreaticoduodenectomy and considered at high risk for pancreatic fistula after intraoperative assessment of the fistula risk score, some of whom were randomized to undergo PG or PJ. All analyses were performed on an intention-to-treat basis. Interventions: Intervention consisted of PJ or PG, both with externalized transanastomotic stent and octreotide omission. Main Outcomes and Measures: The primary end point was POPF. The secondary end points were Clavien-Dindo grade 3 or higher morbidity, postpancreatectomy hemorrhage, delayed gastric emptying, and average complication burden. Results: A total of 604 patients were screened for eligibility; 82 were at high risk for POPF (fistula risk score, 7-10), and 72 were randomized undergo PG (n = 36; 20 men and 16 women; median age, 65 years [interquartile range, 23-82]) or PJ (n = 36; 26 men and 10 women; median age, 63 years [interquartile range, 35-79]). There was no significant difference in the incidence of POPF between patients who underwent PG and patients who underwent PJ (18 [50.0%] vs 14 [38.9%]; P = .48), but for patients who developed a POPF, the mean (SD) average complication burden was lower for those who underwent PJ than for those who underwent PG (0.25 [0.13] vs 0.39 [0.17]; P = .04). The rates of postpancreatectomy hemorrhage (14 [38.9%] in the PG group vs 9 [25.0%] in the PJ group; P = .31) and delayed gastric emptying (16 [44.4%] in the PG group vs 18 [50.0%] in the PJ group; P = .81) were similar, but patients who underwent PG presented with a significantly higher incidence of Clavien-Dindo grade 3 or higher morbidity than those who underwent PJ (17 [47.2%] vs 8 [22.2%]; P = .047). Conclusions and Relevance: Among patients at the highest risk for POPF, those who underwent PG or PJ experienced similar rates of POPF. However, PG was associated with an increased incidence of Clavien-Dindo grade 3 or higher morbidity and with an increased average complication burden for the patients who developed a POPF. For patients at high risk for pancreatic fistula, PJ with the use of externalized stent and octreotide omission should be considered the most appropriate technical strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT03212196.

Psychological distress in patients under surveillance for intraductal papillary mucinous neoplasms of the pancreas: The "Sword of Damocles" effect calls for an integrated medical and psychological approach a prospective analysis.

INTRODUCTION: Most intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can be safely surveilled. Their psychological impact is not known. The aim of this study is to obtain a psychological profile of patients under surveillance and compare the results to patients undergoing surgery. METHODS: Patients under surveillance for IPMNs evaluated between 2017 and 2019 at the pancreatic cysts clinic of The Pancreas Institute of Verona were compared to patients undergoing surgery for the same disease. Patients with high-risk stigmata were excluded in both groups. Patients were profiled with the Barratt Simplified Measure of Socio-Economic Status (BSMSS), the Brief Coping Orientation to Problems Experienced (Brief-COPE), the Perceived Stress Scale (PSS), the Symptom Checklist-90 and the Short Form Health Survey (SF-36). Age, sex, BSMSS and Brief-COPE were used to match patients with the propensity score as potential sources of bias. RESULTS: Two hundred patients were profiled. After the matching, 74 patients under surveillance were compared to 74 patients who underwent surgery. Patients under surveillance reported significantly increased scores for symptoms such as somatization (0.71 vs. 0.54, p = 0.032), depression (0.45 vs 0.31, p = 0.047) and anxiety (0.45 vs. 0.27, p = 0.002). They also reported a reduced health perception in the domain of physical role functioning (54 vs. 68, p = 0.046). CONCLUSION: Patients under surveillance for a presumed IPMN experience anxiety and stress and feel less healthy than do patients undergoing surgery. This reduction in quality of life should always be taken into account and warrants an integrated medical-psychological approach in selected cases.

Drain fluid's pH predicts anastomotic leak in colorectal surgery: results of a prospective analysis of 173 patients.

BACKGROUND: The early risk assessment of anastomotic leak (AL) after colorectal surgery is crucial. Several markers have been proposed, including peritoneal fluid's pH. Aim of the present study is to evaluate the role of drain fluid pH as predictor of AL. METHODS: All patients undergoing colorectal surgery from January 2015 to December 2017 were considered eligible. Hartmann procedures, procedures including temporary ileostomy and emergency surgery were excluded. Drain fluid was submitted for pH and chemical-physical assessment on postoperative day 1 (POD1) and postoperative day 3 (POD3). RESULTS: Out of 173 patients, those who developed AL showed a lower drain fluid's pH on POD1 and on POD3 compared to patients who did not (P<0.05). The plotted ROC curves identified 7.53 as pH cut-off on POD1 (AUC 0.80) and 7.21 on POD3 (AUC 0.86). With both the cut-offs, pH was an independent predictor of AL at multivariable analysis (P<0.001). pH<7.53 on POD1 and pH<7.21 on POD3 showed 93.75% sensitivity and 97% specificity respectively. CONCLUSIONS: Drain fluid's pH on POD1 is useful to select patients who will not develop AL while on POD3 it might identify those requiring a more careful management.