Search

Purpose: Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs. Methods: Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival. Results: Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15–26%). Study quality (Odds ratio, OR 0.94, P = 0.016) and G3-PanNENs rate (OR 2.18, P = 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P < 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P < 0.001, G1 versus G3 HR 2.57, P < 0.001), microvascular (HR 1.25, P = 0.046) and perineural (HR 1.29, P = 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P = 0.253) and status of resection margins (R0 versus R1, P = 0.173) did not show any significant relationship with NF-PanNENs recurrence. Conclusion: Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.

Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Background The possible benefit of frozen section (FS) analysis during (PD) for pancreatic ductal adenocarcinoma (PDAC) and of additional resection up to total pancreatectomy (TP) is debated. Aim of this work is to evaluate the prognostic role of positive FS analysis after PD for PDAC. Methods Multicentric retrospective analysis on prospective databases of three institutions. Based on FS analysis patients were classified as FS negative/FS positive. All positive FS patients underwent extended PD (EPD) or TP. Postoperative outcomes, disease-free (DFS) and disease-specific survival (DSS) were evaluated. Results Of 371 patients, 58 (16%) had positive FS. This resulted in 313 (84%) SPD (standard pancreatoduodenectomy), 22 (6%) EPD and 36 (10%) TP. Postoperative mortality was higher in patients undergoing TP (11% compared to 4.5% in EPD and 1% in SPD; p = 0.01). 26% of patients underwent neoadjuvant therapy, and it did not decrease the rate of positive FS. Systemic/local relapse rates were 59% and 41% in negative FS group, and 78% and 22% in positive FS group (p = 0.031). Median DFS and DSS were 20 and 37 months in negative FS group, and 12 and 23 months in positive FS patients (p = 0.001). Independent predictors of recurrence were G3, N1/N2 status and positive FS. R1 resection, G3, N1/N2 status, perineural invasion and positive FS were independent predictors of DSS. Conclusions Positive FS analysis is a poor prognostic factor after PD for PDAC. It is significantly associated with a high rate of R1 resection at final histology, PDAC recurrence and poor survival.

BackgroundThe rate of patients with pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant chemotherapy is increasing, but upfront resection is still offered to most patients with resectable or borderline resectable disease. Encouraging data reported in adjuvant chemotherapy trials prompts surgeons towards upfront surgery, but such trials are subject to a significant selection bias. This systematic review aims to summarize available high-quality evidence regarding survival of patients treated with upfront surgery for PDAC.MethodsPubmed, Cochrane, and Web of Science Databases were interrogated for prospective studies published between 2000 and 2021 that included at least a cohort of patients treated with upfront surgery for resectable or borderline resectable PDAC. The Cochrane Collaboration’s risk-of-bias tool for randomized trials (RoB-2) was used to assess risk of bias in all randomized studies. Patient weighted median overall survival (OS) and disease-free survival (DFS) were calculated.ResultsOverall, 8,341 abstracts were screened, 17 reports were reviewed in full text, and finally 5 articles and 1 conference abstract underwent data extraction. Included studies were published between 2014 and 2021. All studies were RCTs comparing different neoadjuvant treatment strategies to upfront surgery. Three studies included only resectable PDAC patients, two studies recruited patients with resectable and borderline resectable disease, and one study selected only borderline resectable patients. A total of 439 patients were included in the upfront resection cohorts of the 6 studies, ranging between 20 to 180 patients per study. The weighted median OS after upfront surgery was 18.8 (95% CI 12.4 – 20.6) months. Median DFS was 9 (95% CI 1.6 – 12.5) months. Resection rate was 74.5% (range 65-90%). Adjuvant treatment was initiated in 68% (range 43-77%) of resected patients.ConclusionsHigh-quality data for PDAC patients undergoing upfront surgery is scarce. Meta-analysis from the included studies showed a significantly shorter OS and DFS compared to recently published studies focusing on adjuvant combination chemotherapy, suggesting that the latter may overestimate survival due to the exclusion of most patients scheduled for upfront surgery.

The oncological benefit of achieving a negative pancreatic neck margin through re-resection after a positive frozen section (FS) is debated. Aim of this network meta-analysis is to evaluate the survival benefit of re-resection after intraoperative FS neck margin examination following pancreatectomy for ductal adenocarcinoma.A systematic search of studies comparing different strategies for the management of positive FS was performed. Patients were classified in three groups based on FS and permanent section (PS): Group A (FS-, PS-R0), Group B (FSthorn, PS-R0), Group C (FS +/-, PS-R1). A frequent random-effects network-meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). Primary endpoint was overall survival (OS). Secondary endpoints were pathological outcomes.Seven retrospectives studies with 4205 patients were included and 99.1% of the pancreatic resections were pancreatoduodenectomies. Group A had the highest probability of better OS (SUCRA = 90%), compared to Group B (SUCRA = 48.7%) and Group C, which was the worst prognostic scenario (SUCRA = 11.3%). Group B had still a probability of longer OS compared to Group C (SUCRA 1/4 48.7% vs 11.3%). Pathological features were more favourable in Group A, with the highest SUCRA for T1-T2 tumors (92.6%), N0 status (89.4%), absence of perineural invasion (92.3%). Heterogeneity was low (tau-value

Background: In bowel surgery, adherence to enhanced recovery program (ERP) has been associated with improved recovery. The objective of this study was to evaluate the impact of adherence to ERP elements on outcomes, and identify factors associated with successful recovery following distal pancreatectomy (DP). Methods: Data for 376 patients who underwent DP managed within an ERP including 16 perioperative elements were reviewed. Primary endpoint was successful recovery, a composite outcome defined as length of hospital stay≤7 days, no severe complications nor readmissions. Results: Patients had a mean (SD) overall adherence of 76 (14)%. Overall, 166 (44%) patients had a successful recovery. There was a positive association between overall adherence and successful recovery (OR 1.19, 95%CI 1.08–1.31 for every additional element, p = 0.001), while an inverse relationship was found with comprehensive complication index (8% reduction, 95%CI -15 to −2%, p = 0.011). Adherence to postoperative phase interventions had the greatest impact on recovery (OR 1.29, 95%CI 1.13–1.47 for every additional postoperative element; p < 0.001). At multivariable regression, early termination of IV fluids was the only ERP element associated with successful recovery (OR 2.80, 95%CI 1.73–4.54; p < 0.001). Conclusion: Increased adherence to ERP elements was associated with successful early recovery and reduction of postoperative complication severity.

Background: A recent RCT showed similar postoperative outcomes and a reduced time to functional recovery in patients undergoing minimally invasive distal pancreatectomy (DP) compared to open approach. However, it reported very-high post-discharge readmission rates, calling for further investigation. The aim of our study was to evaluate the extent to which minimally invasive surgery impacts on postoperative readmissions following DP. Methods: Clinical data for patients undergoing DP between 2011 and 2018 were reviewed. Primary outcome was hospital readmission at 90 days after surgery. Secondary outcomes included post-discharge emergency department (ED) visits and time to functional recovery. Regression analyses were performed to evaluate the impact of the laparoscopic approach and other perioperative factors. Results: Overall, 376 consecutive patients underwent DP during the study period. Laparoscopy was successfully performed in 219 (58%) patients. Overall, 62 patients (16.5%) returned to the ED after discharge, 41 (18.7%) of laparoscopically operated patients, and21 (13.4%) of those undergoing open surgery (p = 0.162). Forty-six (12.2%) of them required readmission, 31 (14.2%) after laparoscopic, and 15 (9.6%) after open procedures (p = 0.179). At multivariate regression, a low preoperative physical status (OR 2.3, 95% CI 1.2–4.7; p = 0.017), occurrence of pancreatic fistula (OR 6.8, 95% CI 2.9–15.9; p < 0.001), and post-pancreatectomy hemorrhage (OR 3.9, 95% CI 1.2–13.1; p = 0.025) were significantly associated with 90-day readmission, while laparoscopy had no impact. Median time to reach functional recovery was 5 (IQR 4–6) days. At multivariate analysis, laparoscopy reduced time to functional recovery by 13% (95% CI −19 to −6%; p < 0.001), time to adequate oral intake by 19% (95% CI −27 to −10%; p < 0.001), and time to adequate pain control by 12% (95% CI −18 to −5%; p < 0.001). Conclusion: Hospital readmissions and ED visits following DP were not influenced by the surgical approach. A low preoperative physical status, occurrence of postoperative pancreatic fistula and hemorrhage were significantly associated with post-discharge readmission within 90days.Laparoscopy reducedtimetofunctional recovery.

Background: Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death in the USA. A wealth of evidence has demonstrated the chemopreventive activity of aspirin, statins, and metformin against PDAC. The aim of this study is to investigate the effect of aspirin, statins, and metformin on disease-free survival (DFS) and disease-specific survival (DSS) in a large population of PDAC patients undergoing pancreatic resection. Patients and Methods: All patients who underwent pancreatic resections between January 2015 and September 2018 were retrospectively reviewed. The potentially “chemopreventive agents” considered for the analysis were aspirin, statins, and metformin. Drug use was defined in case of regular assumption at least 6months before diagnosis and regularly after surgery along the follow-up period. Results: A total of 430 patients were enrolled in this study, with median DFS and DSS of 21months (IQR 13–30) months and 34 (IQR 26–52) months, respectively. On multivariable analysis, use of aspirin was associated with better DFS (HR: 0.62; p = 0.038). Metformin was associated with better DFS, without reaching statistical significance (p = 0.083). Use of statins did not influence DFS in the studied population. Aspirin, metformin, and statins were not associated with better DSS on multivariable analysis. Factors influencing DSS were pT3/pT4, N1, N2, no adjuvant treatment, G3, and ASA score > 3. Conclusions: The results suggest that chronic use of aspirin is associated with increased DFS but not with better DSS after surgical resection in patients with PDAC.

Background: Adequate criteria for pancreatic surgery centralization are debated. This retrospective study aimed to define a reproducible method for complex care centralization, accounting for hospital performance and access to care. Methods: The method consisted in: 1. Analysis of overall outcome and mortality-related factors. 2. Assessment of volume and adjusted mortality of each hospital. 3. Definition of different centralization models. 4. Final adjustments to guarantee access to care, evaluating travel times and waiting lists. This method was tested on Lombardy, the most populous Italian region (about 10 million inhabitants, 24 000 km2). Results: According to Ministry of Health data, 79 hospitals performed 3037 resections in 2014–2016. Mean overall mortality was 5.0%, increasing from 2.3%, of seven high-volume facilities (>30 resections/year) to 10.7% of 56 low-volume facilities (90% of the population), and limited impact on waiting list (1.1 extra-resection/hospital/week). Conclusion: The four-step method appears as a flexible tool to centralize pancreatic surgery, allowing regulatory institutions to estimate the effect of different models.

Background The benefits of centralization of pancreatic surgery have been documented, but policy differs between countries. This study aimed to model various centralization criteria for their effect on a nationwide cohort. Methods Data on all pancreatic resections performed between 2014 and 2016 were obtained from the Italian Ministry of Health. Mortality was assessed for different hospital volume categories and for each individual facility. Observed mortality and risk-standardized mortality rate (RSMR) were calculated. Various models of centralization were tested by applying volume criteria alone or in combination with mortality thresholds. Results A total of 395 hospitals performed 12 662 resections; 305 hospitals were in the very low-volume category (mean 2·6 resections per year). The nationwide mortality rate was 6·2 per cent, increasing progressively from 3·1 per cent in very high-volume to 10·6 per cent in very low-volume hospitals. For the purposes of centralization, applying a minimum volume threshold of at least ten resections per year would lead to selection of 92 facilities, with an overall mortality rate of 5·3 per cent. However, the mortality rate would exceed 5 per cent in 48 hospitals and be greater than 10 per cent in 17. If the minimum volume were 25 resections per year, the overall mortality rate would be 4·7 per cent in 38 facilities, but still over 5 per cent in 17 centres and more than 10 per cent in five. The combination of a volume requirement (at least 10 resections per year) with a mortality threshold (maximum RSMR 5 or 10 per cent) would allow exclusion of facilities with unacceptable results, yielding a lower overall mortality rate (2·7 per cent in 45 hospitals or 4·2 per cent in 76 respectively). Conclusion The best performance model for centralization involved a threshold for volume combined with a mortality threshold.

Pancreatic neuroendocrine neoplasms (PanNENs) are increasingly recognized entities, whose incidence has dramatically grown during the last two decades. Surgery plays a pivotal role in their management as it represents the only chance of cure. Since PanNENs display a wide range of aggressiveness, their surgical management needs to be tailored on tumor’s and patient’s characteristics. Currently, there are several open questions and burning issues in the field of PanNEN, such as the management of asymptomatic nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET) ≤ 2cm. An active surveillance of these small lesions has been demonstrated to be safe although the available evidences are only based on retrospective studies. On the other hand, formal pancreatic resection associated with lymphadenectomy represents the gold standard for patients with localized NF-PanNEN > 2cm or NF-PanNEN ≤ 2cm in the presence of symptoms, dilation of the main pancreatic duct or suspicion of nodal metastases. Surgery plays also an important role in the setting of metastatic disease. In particular, surgery is generally recommended in the presence of low-grade, resectable, metastatic disease, but several series have reported also a survival benefit of palliative primary tumor resection in patients with unresectable liver metastases. The role of surgery in PanNEN G3 is still controversial. Indeed, surgery is associated with an improved survival in patients with well-differentiated PanNET G3, whereas there is almost no survival benefit in case of poorly differentiated lesions.

Background: A fatty infiltration of the pancreas has been traditionally regarded as the main histological risk factor for postoperative pancreatic fistula, whereas the role of the secreting acinar compartment has been poorly investigated. The aim of this study was to evaluate the role of acinar content at pancreatic resection margin in the development of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis after pancreaticoduodenectomy. Methods: Data from 388 consecutive patients who underwent pancreaticoduodenectomy (2018–2019) were analyzed. Pancreatic section margins were histologically assessed for acinar, fibrosis, and fat content. Acinar content was categorized using median and third quartile as cut-offs. Univariate and multivariable analysis of possible predictors of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis were performed. Results: Acinar content was 80% in 66 patients (17.0%). The rate of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis was significantly higher in patients with acinar content >80% (39.4% and 33.3%, respectively) as well as in those with acinar content ≥60% and ≤80% (36.5% and 35.3%, respectively), compared with patients with acinar content 80%, odds ratio 2.93, P = .010) and clinically relevant postoperative acute pancreatitis (≥60% and ≤80%, odds ratio 9.42, P < .001; >80%, odds ratio 10.16, P < .001). Conclusion: An acinar content at pancreatic resection margin ≥60% is associated to an increased risk of clinically relevant postoperative pancreatic fistula and clinically relevant postoperative acute pancreatitis. Fat content was associated neither with clinically relevant postoperative pancreatic fistula nor with clinically relevant postoperative acute pancreatitis.

Letter to editor

During the last century, obesity has become a global epidemic. The effect of obesity on renal transplantation may occur in perioperative complications and impairment of organ function. Obese patients have metabolic derangements that can be exacerbated after transplantation and obesity directly impacts most transplantation outcomes. These recipients are more likely to develop adverse graft events, such as delayed graft function and early graft loss. Furthermore, obesity is synergic to some immunosuppressive agents in triggering diabetes and hypertension. As behavioral weight loss programs show disappointing results in these patients, bariatric surgery has been considered as a means to achieve rapid and long-term weight loss. Up-to-date literature shows laparoscopic bariatric surgery is feasible and safe in transplantation candidates and increases the rate of transplantation eligibility in obese patients with end-stage organ disease. There is no evidence that restrictive procedures modify the absorption of immunosuppressive medications. From 2013 to 2016 we performed six bariatric procedures (sleeve gastrectomy) on obese patients with renal transplantation; mean preoperative body mass index (BMI) was 39.8 kg/m2. No postoperative complication was observed and no change in the immunosuppressive medications regimen was needed. Mean observed estimated weight loss was 27.6%, 44.1%, 74.2%, and 75.9% at 1, 3, 6, and 12 months follow-up, respectively. Our recommendation is to consider patients with BMI >30 kg/m2 as temporarily ineligible for transplantation and as candidates to bariatric surgery if BMI >35 kg/m2. We consider laparoscopic sleeve gastrectomy as a feasible, first-choice procedure in this specific population.

Introduction The gap between the number of diabetic patients on the waiting list for transplantation and the number of pancreas donors is growing and it is mandatory to extend criteria for donor eligibility. Several reports showed the feasibility of pancreas transplantation from pediatric donors with comparable outcomes to adult donors in terms of long-term β-cell function. However, there is no consensus about donor age and weight limits. Case Report We present two cases of pancreas transplantation alone (PTA) from very small pediatric donors: a 2-year-old female (weight 13 kg, height 88 cm) and a 6-year-old male (weight 29 kg, height 122 cm). We used a novel “cephalic placement” technique. The pancreas was placed upon the aortic carrefour with cephalic pole upward with 3 anchorage points: the left common iliac vein (or the inferior cava vein), the right common iliac artery, and an ileal loop. Results No postoperative thrombosis occurred and the patients gained insulin independence instantaneously. CT scan performed on postoperative day 3 showed regular organ perfusion in both cases. Graft volume and surface calculated by CT reconstruction were, respectively, 25 cc and 89 cm 2 in the first case, and 46.5 cc and 123 cm 2 in the second case. Postoperative mixed meal tolerance tests showed normal glycemic profile. Patients are actually insulin independent at 4 years and 8 months. Conclusions Pancreases from very young pediatric donors are adequate to restore insulin independence after PTA in adult patients. The “cephalic placement” technique is feasible and effective using very small pancreases.

Pancreatic cystic neoplasms are one of the most frequent incidental findings in the field of pancreatic diseases, estimated to be present in up to 45% of the general population. They represent an heterogeneous group of tumors with different biological behavior and variable risk of progression to malignancy. While serous cystadenomas (SCAs) have no risk of malignant progression, mucinous cyst adenoma are malignant in 20% of cases and this risk is higher in intraductal papillary mucinous neoplasms (IPMN). Nonsurgical management could be applied in patients with a SCA and in low-risk IPMN and these patients could be managed with follow-up strategies. While follow-up could be interrupted in patients unfit for surgery due to comorbidities or age, and in SCA stable over time, recent evidences do not support surveillance discontinuation in patients with IPMNs fit for surgery.

Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose to familial breast and/or ovarian cancer. The lifetime risk of members of families with genetic predisposition depends on the mutations of susceptibility genes. BRCA1 mutations seem to confer the highest risk of developing neoplastic diseases. Apart from breast and ovarian cancer mutations in BRCA, related pathways are supposed to confer a smaller risk for additional cancers (colon, melanoma, pancreas, lymphoma, prostate, liver). All these tumors have an inherited component not necessarily associated with genetic susceptibility to BRCA genes. To date he main focus of this review has been argued still with difficulty. Just a deeper and complete evaluation of the topic will allow to establish how much is the contribution of BRCA mutations in different types of cancers other than breast and ovary.