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.

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.

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.

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.

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.

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.

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.

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.

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.

Preoperative fecal elastase-1 (FE-1) adds value in predicting post-operative pancreatic fistula: not all soft pancreas share the same risk - A prospective analysis on 105 patients.

BACKGROUND: Scores predicting postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) mainly use intraoperative predictors. The aim of this study is to investigate the role of pancreatic exocrine function expressed by fecal elastase (FE-1) as preoperative predictor of POPF. METHODS: Patients scheduled for PD at the Department of General and Pancreatic Surgery, University of Verona Hospital, from April 2017 to July 2018 were prospectively enrolled. FE-1 was measured in a preoperative stool sample through an ELISA test. RESULTS: The study population consisted of 105 patients. The POPF rate was 17.1%. Patients developing POPF showed high values of FE-1 (454 vs 155 mcg/g; p < 0.01), and FE-1 was an independent predictor of POPF (OR 1.008, CI 95% 1.003-1.014; p < 0.01), even considering only patients with a "soft" texture. A cut-off value of 260 mcg/g presented 100% sensitivity and 64.3% specificity (AUC 0.83) in predicting POPF. Approximately 30% of patients with a "soft" pancreatic texture presented with FE-1 < 260 mcg/g and did not develop POPF. CONCLUSION: FE-1 is a promising tool to preoperatively assess the risk of POPF after PD. Further studies with larger populations are needed to potentially incorporate FE-1 into risk scores for PD with better stratification.

"Trivial" Cysts Redefine the Risk of Cancer in Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Potential Target for Follow-Up Discontinuation?

OBJECTIVES: The management of small and incidental branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) still is of concern. The aim is assessing the safety of a surveillance protocol through the evaluation of their progression to malignancy. METHODS: All presumed BD-IPMNs observed from 2000 to 2016 were included. Only patients presenting without worrisome features (WFs) and high-risk stigmata (HRS) at diagnosis were included. Development of WF, HRS, pancreatic cancer (PC), and survival were analyzed. BD-IPMNs were defined as trivial in the continuing absence of WF/HRS after 5 years of surveillance. The age-specific standardized incidence ratio of PC in the general population was used for comparison. RESULTS: A total of 1,036 BD-IPMNs without WF/HRS at diagnosis were included, 4.2% developed WF or HRS, and 1.1% developed PC after a median of 62 months. The median cyst growth rate was 0 mm/yr. A growth rate ≥2.5 mm/yr and the development of WF resulted independent predictors of PC. The standardized incidence ratio of PC for trivial BD-IPMN (n = 378) was 22.45 (95% confidence interval 8.19-48.86), but considering only patients aged >65 years (n = 198), it decreased to 3.84 (95% confidence interval 0.77-11.20). DISCUSSION: Surveillance of the vast majority of presumed BD-IPMNs is safe, as the risk of PC is comparable to postoperative mortality of pancreatic surgery. A growth rate ≥2.5 mm/yr is the main predictor of PC, reinforcing the role of repeated observations. A trivial BD-IPMN in patients aged >65 years might not increase the risk of developing PC compared with general population, identifying potential targets for follow-up discontinuation.

Residual pancreatic function after pancreaticoduodenectomy is better preserved with pancreaticojejunostomy than pancreaticogastrostomy: A long-term analysis.

BACKGROUND: Pancreatico-enteric anastomosis after pancreaticoduodenectomy can be performed using either a pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG). Differences in surgical outcomes are still a matter of debate, and less is known about long-term functional outcomes. METHODS: Twelve years after the conclusion of a comparative study evaluating the surgical outcomes of PJ and PG (Bassi et al., Ann Surg 2005), available patients underwent morphological and functional pancreatic assessment: pancreatic volume and duct diameter measured by MRI, impaired secretion after secretin, fecal fat, fecal elastase-1 (FE-1), serum vitamin D and endocrine function. Quality of life and symptom scores were evaluated with the EORTC QLQ-C30 questionnaire. RESULTS: Only 34 patients were available for assessment. No differences were found in terms of BMI variation, endocrine function, quality of life or symptoms. Exocrine function was more severely impaired after PG than after PJ (fecal fats 26.6 ±â€¯4.1 vs 18.2 ±â€¯3.6 g/day; FE-1 121.4 ±â€¯6.7 vs 170.2 ±â€¯25.5 µg/g, vitamin D 18.1 ±â€¯1.8 vs. 23.2 ±â€¯3.1 ng/mL). MRI assessment identified a lower pancreatic volume (26 ±â€¯3.1 vs. 36 ±â€¯4.1 cm3) and a more dilated pancreatic duct (4.6 ±â€¯0.92 vs. 2.4 ±â€¯0.18 mm) in patients with PG compared to those with PJ. CONCLUSION: Compared to PJ, PG is associated with a more severely impaired exocrine function long-term, but they result similar endocrine function and quality of life. In patients with a long life expectancy, this should be taken into account.

Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where?

BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up. METHODS: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods. RESULTS: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases. CONCLUSIONS: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.

The Actual Prevalence of Symptoms in Pancreatic Cystic Neoplasms: A Prospective Propensity Matched Cohort Analysis.

BACKGROUND: The prevalence of symptoms in pancreatic cystic neoplasms (PCNs) is mainly based on retrospective surgical series. The aim of this study is to describe the actual prevalence of symptoms in PCNs under surveillance. METHODS: Patients with PCNs under surveillance observed from 2015 to 2017 were submitted to magnetic resonance imaging (MRI) and a specific interview. An identical survey was carried out on a control population matched for age, sex, and comorbidities in which any pancreatic disease was excluded by MRI. RESULTS: Two groups of 184 individuals were compared. Patients with PCNs have a similar prevalence of abdominal pain when compared to controls (35.2 vs. 28.8, p = 0.2). PCNs in the distal pancreas experienced a significantly increased prevalence of abdominal pain (42.3 vs. 28.8%, p = 0.04), whereas size and presumed connection with the ductal system did not affect the prevalence of abdominal pain. PCNs associated with abdominal pain did not differ in terms of clinical and radiological features from asymptomatic ones. CONCLUSION: Patients with PCNs under surveillance have a similar prevalence of abdominal pain when compared to a matched population of controls. Abdominal pain might not correlate with radiological signs of malignancy.

Adjuvant chemotherapy is associated with improved postoperative survival in specific subtypes of invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas: it is time for randomized controlled data.

BACKGROUND: Very little is known about adjuvant chemotherapy for invasive Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas. The aim was to assess whether adjuvant chemotherapy affects survival. METHODS: Retrospective evaluation of invasive IPMNs. Patients treated with surgery alone or followed by adjuvant chemotherapy were compared in terms of survival. RESULTS: A total of 102 invasive IPMNs were analyzed. Median follow-up was 72 (5-318) months and 18.6% received adjuvant chemotherapy. Overall, recurrence rate was 40.2%, while 5-year overall survival and disease specific survival (DSS) were 65.3% and 69.4%, respectively. N1 disease (HR5.58, CI95% 2.49-12.51, p < 0.01), tubular type (HR2.35, CI95% 1.71-4.82, p = 0.05) and G3 tumors (HR4.54, CI95% 2.12-15.49, <0.01) were predictors of reduced DSS. Overall, there was no difference in the 5-year DSS comparing patients treated with adjuvant chemotherapy to surgery alone (61.8 vs. 69.4%, p = 0.8). Adjuvant chemotherapy significantly improved DSS only in N1 (5-years-DSS 76 vs. 35.8%, p = 0.01) and tubular carcinomas (5-years-DSS 88.9 vs. 53%, p = 0.03). CONCLUSIONS: Adjuvant therapy improves survival only in invasive IPMNs with nodal disease or tubular differentiation. Future trials are needed to improve the level of evidence about adjuvant chemotherapy.

Postoperative Acute Pancreatitis Following Pancreaticoduodenectomy: A Determinant of Fistula Potentially Driven by the Intraoperative Fluid Management.

OBJECTIVE: The aim of the study is to characterize postoperative acute pancreatitis (POAP). SUMMARY BACKGROUND DATA: A standardized definition of POAP after pancreaticoduodenectomy (PD) has been recently proposed, but specific studies are lacking. METHODS: The patients were extracted from the prospective database of The Pancreas Institute of Verona. POAP was defined as an elevation of the serum pancreatic amylase levels above the upper limit of normal (52 U/L) on postoperative day (POD) 0 or 1. The endpoints included defining the incidence and predictors of POAP and investigating the association of POAP with postoperative pancreatic fistula (POPF). RESULTS: The study population consisted of 292 patients who underwent PD. The POAP and POPF rates were 55.8% and 22.3%, respectively. POAP was an independent predictor of POPF (OR 3.8), with a 92% sensitivity and 53.7% specificity (AUC 0.79). Preoperative exocrine insufficiency (OR 0.39), neoadjuvant therapy (OR 0.29) additional resection of the pancreatic stump margin (OR 0.25), soft pancreatic texture (OR 4.38), and Main Pancreatic Duct (MPD) diameter ≤3 mm (OR 2.86) were independent predictors of POAP. In high-risk patients, an intraoperative fluid administration of ≤3 ml/kg/h was associated with an increased incidence of POAP (24.6 vs. 0%, P = 0.04) and POPF (27.6 vs. 11.4%, P = 0.05). CONCLUSION: This study represents the first clinical application of the only available definition of POAP as a specific complication of pancreatic surgery. POAP is associated with an increased occurrence of POPF and overall morbidity and could potentially be avoided through a specific intraoperative fluid regimen in high-risk pancreas.

Neoadjuvant Therapy Versus Upfront Resection for Pancreatic Cancer: The Actual Spectrum and Clinical Burden of Postoperative Complications.

BACKGROUND: Neoadjuvant therapy (NAT) is used for borderline-resectable or locally advanced pancreatic cancer (PDAC) and exhibits promising results in terms of pathological outcomes. However, little is known about its effect on surgical complications. METHODS: We analyzed 445 pancreatic resections for PDAC from 2014 to 2016 at The Pancreas Institute, Verona University Hospital. The Modified Accordion Severity Grading System and average complication burden (ACB) were used to compare patients treated with NAT with patients who underwent upfront surgery (UFS). RESULTS: Of 305 pancreaticoduodenectomies (PD), patients treated with NAT (n = 99) had less pancreatic fistula (POPF, 9.1% vs. 15.6%, p = 0.05) without grade C cases, but grade B ACB was increased (0.28 for NAT vs. 0.24 for UFS, p = 0.05). The postpancreatectomy hemorrhage (PPH) rate was lower in the NAT group (9.1% vs. 14.6%, p = 0.02), but ACB grades B (0.37 for NAT vs. 0.26 for UFS, p = 0.03) and C (0.43 for NAT vs. 0.29 for UFS, p = 0.05) were increased. Delayed gastric emptying (DGE) was increased in NAT cases (15.2% vs. 8.3%, p = 0.04), with higher grade C ACB (0.43 for NAT vs. 0.29 for UFS, p = 0.03). Of 94 distal pancreatectomies (DP), NAT patients (n = 26) developed more grade C POPF (11.5% vs. 1.5%, p = 0.04) and DGE (11.5% vs. 2.9%, p = 0.01) without differences in ACB. CONCLUSIONS: Patients undergoing PD for PDAC after NAT exhibited reduced incidence of POPF and PPH but increased incidence of DGE compared with patients treated with UFS. Among patients developing postoperative complications after PD, those receiving NAT were associated with increased clinical burden.

Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results.

BACKGROUND/OBJECTIVES: Screening/surveillance programs for pancreatic cancer (PC) in familial high-risk individuals (FPC-HRI) have been widely reported, but their merits remain unclear. The data reported so far are heterogeneous-especially in terms of screening yield. We performed a systematic review and meta-analysis of currently available data coming from screening/surveillance programs to evaluate the proportion of screening goal achievement (SGA), overall surgery and unnecessary surgery. METHODS: We searched MEDLINE, Embase, PubMed and the Cochrane Library database from January 2000 to December 2016to identify studies reporting results of screening/surveillance programs including cohorts of FPC-HRI. The main outcome measures were weighted proportion of SGA, overall surgery, and unnecessary surgery among the FPC-HRI cohort, using a random effects model. SGA was defined as any diagnosis of resectable PC, PanIN3, or high-grade dysplasia intraductal papillary mucinous neoplasm (HGD-IPMN). Unnecessary surgery was defined as any other final pathology. RESULTS: In a meta-analysis of 16 studies reporting on 1551 FPC-HRI cases, 30 subjects (1.82%), received a diagnosis of PC, PanIN3 or HGD-IPMNs. The pooled proportion of SGA was 1.4%(95% CI 0.8-2, p < 0.001, I2 = 0%). The pooled proportion of overall surgery was 6%(95% CI 4.1-7.9, p < 0.001, I2 = 60.91%). The pooled proportion of unnecessary surgery was 68.1%(95% CI 59.5-76.7, p < 0.001, I2 = 4.05%); 105 subjects (6.3%) received surgery, and the overall number of diagnoses from non-malignant specimens was 156 (1.5 lesion/subject). CONCLUSIONS: The weighted proportion of SGA of screening/surveillance programs published thus far is excellent. However, the probability of receiving surgery during the screening/surveillance program is non-negligible, and unnecessary surgery is a potential negative outcome.

Vanishing Pancreatic Cysts during Follow-Up: Another Step Towards De-Emphasizing Cyst Size as a Major Clinical Predictor of Malignancy.

INTRODUCTION: In the management of pancreatic cystic neoplasms (PCN), size plays a crucial role as the expression of disease progression. While many evidences regarding the natural history of growing pancreatic cysts exist, almost no data are available regarding cysts with a reduction in size. METHODS: Radiological and clinical data from patients of the dedicated pancreatic cysts outpatient clinic of the Department of General and Pancreatic Surgery, University of Verona Hospital were retrospectively reviewed. Patients diagnosed with PCNs reducing in size during follow-up were reviewed. RESULTS: From a total of 3,146 patients, we identified 12 (0.38%) vanishing/reducing cysts without a history of pancreatitis. Most of them were presumed IPMN (66.6%). The median follow-up was 69 months and the median cyst's size 30 mm (range 10-49). Most of the patients (75%) experienced a reduction in cyst size (median reduction of 8 mm, range 6-22) after a median time of 12 months (range 6-63), 3 patients experienced a complete disappearance of the cyst. CONCLUSION: Cyst size reduction during follow-up is a rare phenomenon of unknown explanation. It adds to the debate regarding the role of size as a clinical predictor whenever a definite diagnosis of a PCN cannot be reached.