Search

The aim of the present study was to critically reappraise the experience at our high-volume institution to obtain new insights for future directions.The indications, surgical techniques, and perioperative management of pancreatoduodenectomy (PD) have profoundly evolved over the last 20 years.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.The study population consisted of 3000 patients. The median age, ASA ≥ 3 and number of nonbenchmark cases significantly increased over time ( P0.005). 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.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.

Objectives Medullary thyroid carcinoma (MTC) is caused by a malignant transformation in the parafollicular C-cells of the thyroid, where calcitonin (CT) is released. Nowadays, CT is the main tumor marker used in the diagnosis and follow-up of MTC patients. Nonetheless, procalcitonin (PCT) has recently been proposed as a useful complementary/alternative biomarker in MTC. Our aims were to investigate the diagnostic performance of CT and PCT and their combination in the differential diagnosis between active and inactive MTC and between MTC and non-MTC thyroid diseases, respectively. Methods Serum samples were collected from 16 patients with active (i.e. primary tumour before surgery or post-surgical recurrent disease) and 23 with inactive (i.e. complete remission) MTC, 125 patients with non-MTC benign thyroid disease and 62 patients with non-MTC thyroid cancers, respectively. Elecsys® CT and PCT measurements were simultaneously performed on the Cobas e601 platform (Roche Diagnostics, Rotkreutz, Switzerland). Results Both CT and PCT median values in active MTC (94 pmol/L and 1.17 ng/mL, respectively) were significantly higher compared with inactive MTC (0.28 and 0.06) and either benign (0.37 and 0.06) or malignant (0.28 and 0.06) non-MTC. Undetectable PCT was found in five non-MTC patients with false positive CT results. Conclusions Elecsys® PCT assay is a highly sensitive and specific alternative MTC marker. At the very least it appears useful in patients with positive CT results as negative PCT values securely exclude active MTC. The availability of both markers on the same automated platform facilitates reflex or reflective strategies to refine the laboratory diagnosis.

Objectives Serum calcitonin (CT) is pivotal in medullary thyroid cancer (MTC) management. Recently, progastrin releasing peptide (ProGRP) has been proposed as a candidate complementary tumor marker of MTC. As current data are sparse our study was undertaken to evaluate the distribution of ProGRP in patients with MTC and its relationship with the tumor burden. Additionally, serial measurement of CT, carcinoembryonic antigen (CEA) and ProGRP was evaluated in three patients undergoing tyrosine kinase inhibitors (TKI). Methods Seventy-eight, 125 and 62 sera from patients with MTC, non-medullary malignant and benign thyroid diseases were collected, respectively. ProGRP measurement was performed by Elecsys® assays on Cobas e601 platform (Roche Diagnostics). Results Significantly higher ProGRP levels were found in MTC compared to non-MTC patients. Among MTC patients ProGRP levels accurately discriminate patients with active from those with cured disease and, respectively, patients with loco-regional active disease from those with distant metastasis. Finally, ProGRP performed better than CT and CEA in monitoring the response to TKI therapy in three patients monitored serially. Conclusions Serum ProGRP is promising as a complementary tumor marker in MTC patients. Further studies will be required, mainly focused on monitoring ProGRP during TKI treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and carcinoembryonic antigen.

Background The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. Methods/design In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a “total neoadjuvant” therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. Trial registration NCT04090463 at clinicaltrials.gov.

Background Outcomes after surgery for sporadic pancreatic neuroendocrine neoplasms (Pan-NENs) were evaluated. Methods This multicentre study included patients who underwent radical pancreatic resection for sporadic non-functioning Pan-NENs. In survival analysis, the risk of mortality in this cohort was analysed in relation to that of the matched healthy Italian population. Relative survival (RS) was calculated as the rate between observed and expected survival. Factors related to RS were investigated using multivariable modelling. Results Among 964 patients who had pancreatic resection for sporadic non-functioning Pan-NENs, the overall RS rate was 91.8 (95 per cent c.i. 81.5 to 96.5) per cent. 2019 WHO grade (hazard ratio (HR) 5.75 (s.e. 4.63); P = 0.030) and European Neuroendocrine Tumour Society (ENETS) TNM stage (6.73 (3.61); P Conclusion A surgical approach seems without benefit for Pan-NECs, and unnecessary for small G1 sporadic Pan-NENs. Surgery alone may be insufficient for stage III–IV and G3 Pan-NENs.

Background Few studies have investigated inhibition in people with Down syndrome (DS), indicating contradictory results. Aim This meta-analysis investigated if people with DS show more severe difficulties on inhibition, compared to typically developing (TD) children matched on a measure of mental age (MA). Methods and procedures Literature search included studies conducted before March 2019, combining the following keywords: “Down syndrome” with “Inhibition”, “Interference control”, “Effortful control”, “Impulsivity”, “Self-regulation”, and “Executive functions”. Descriptive information was coded, according to inclusions criteria. Meta-analysis of standardized differences between DS and TD groups’ means was performed. Relevant moderators were also considered. Outcomes and results Eight studies were included in the meta-analysis, including 161 people with DS and 160 TD children. The results indicated that people with DS showed significantly lower inhibition abilities when they are matched on MA with TD children, instead no significant differences emerged when this matching was not provided. A high heterogeneity across studies was estimated. Conclusions and implications This meta-analysis indicates that people with DS show, on average, an inhibition deficit compared to TD matched children, albeit not a severe one. These results suggest the importance of investigating in depth inhibition processes in people with DS from childhood to young adulthood.

Introduction: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. Materials and methods: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006–2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. Results: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73–0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73–0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. Conclusion: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.

Ablation treatments have been increasingly applied as an alternative treatment for unresectable locally advanced pancreatic cancer (LAPC). The goal of LAPC therapy is surgical resection with negative margins (R0); however, that can be achieved only in a minority of patients and only following neoadjuvant treatment. Ablation might be useful for those patients with unresectable LAPC that do not progress towards metastatic stage and do not experience a true downstaging. Indeed, some LAPC that tend to grow locally, might be the subgroup of tumors that could benefit from ablation. Experience is necessary to select patients and the technique to adopt, since serious or fatal complications can occur. This review aims to discuss the role of ablation treatments in LAPC, with a unique focus on radiofrequency ablation and irreversible electroporation.

Introduction: Minimally invasive surgery (MIS) for pancreatic cancer has become very popular in modern pancreatic surgery. Evidence of the benefits of an MI approach are increasing thanks to prospe...

Background Postoperative pancreatic fistula is the primary contributor to morbidity after distal pancreatectomy. To date, no techniques used for the transection and closure of the pancreatic stump have shown clear superiority over the others. This study aimed to compare the rate of postoperative pancreatic fistula after pancreatic transection conducted with a reinforced stapler versus an ultrasonic dissector after a distal pancreatectomy. Method Prospectively collected data of consecutive patients who underwent distal pancreatectomy from 2014 to 2017 were reviewed retrospectively. We included distal pancreatectomies in which pancreatic transection was performed by reinforced stapler or ultrasonic dissector; we excluded extended distal pancreatectomies. To overcome the absence of randomization, we conducted a propensity matching analysis according to risk factors for postoperative pancreatic fistula. Results Overall, 200 patients met the inclusion criteria. The reinforced stapler was employed in 108 patients and the ultrasonic dissector in 92 cases. After one-to-one propensity matching, 92 patients were selected from each group. The matched reinforced stapler and ultrasonic dissector cohort had no differences in baselines characteristics except for the mini-invasive approach, which was more common in the ultrasonic dissector group (34% vs 51%, P = .025). Overall, 48 patients (26%) developed a postoperative pancreatic fistula, 46 (25%) a grade B postoperative pancreatic fistula, and 2 (1%) a grade C postoperative pancreatic fistula. In the reinforced stapler group, the rate of postoperative pancreatic fistula was 12% (n = 11) and in the ultrasonic dissector group 40% (n = 37) with a P Conclusion The results of this study suggest that the use of reinforced stapler for pancreatic transection decreases the risk of postoperative pancreatic fistula. A randomized trial is required to confirm these preliminary data.

Objective: The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent. Summary Background Data: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. Methods: A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in 9 European tertiary referral centers between February 2006 and December 2017 was performed. Collected data included demographics, histopathologic details, survival, and recurrence. OS and DFS analyses were performed using Kaplan–Meier curves and Cox proportional hazard models. Results: Overall, 887 patients were included, with a mean age of 66 ± 10 years. The median OS was 64 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 63%, 52%, and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin, and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09–5.21]), perineural invasion (HR = 1.50 [1.01–2.23]), and adjuvant chemotherapy (HR = 0.69 [0.48–0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65–4.27]). Conclusions: Independent predictors of OS in resected ampullary cancer were N-stage, perineural invasion, and adjuvant chemotherapy. N-stage was the only predictor of DFS. These findings improve predicting survival and recurrence after resection of ampullary adenocarcinoma.

Laparoscopic distal pancreatectomy (LDP) is becoming the standard treatment for left-sided pancreatic disease. Learning curve identification is essential to ensure a safe and steady expansion. However, large (n > 30) single-surgeon learning curve series are lacking. Data of all patients undergoing LDP between June 2007 and March 2016 by a single surgeon were collected prospectively. For learning curve analysis, the first 10, 20, 30, 40, and 50 LDPs were compared with LDPs performed thereafter. In total, 111 LDPs were performed, of which 2 (2%) were converted. Median operative time was 200 minutes (interquartile range [IQR] 150 to 245 minutes) and median blood loss was 200 mL (IQR 100 to 300 mL). Learning curve analysis did not show improvements in operative time or blood loss. However, the number of patients with pancreatic ductal adenocarcinoma increased after 30 cases and a significant reduction of Clavien-Dindo grade III or higher complications was seen; from 30% (n = 9) for cases 1 to 30 to 5% (n = 4) for cases 31 to 111 (p < 0.001). Similarly, the International Study Group on Pancreatic Fistula grade B/C fistulas (33% [n = 10] vs 9% [n = 7]; p = 0.001) and percutaneous drainage rate (23% [n = 7] vs 4% [n = 3]; p = 0.001) were lower. Hospital stay was 7 days (IQR 5 to 13 days) for cases 1 to 30 vs 5 days (IQR 4 to 6 days) for cases 31 to 111 (p < 0.001). Operative outcomes of LDP remained stable with increasing surgical complexity over time. Postoperative outcomes, such as complications and length of hospital stay, improved after the first 30 cases. When describing learning curves, short- and long-term outcomes should be considered

Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN9s related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. Trial registration number IRB 00006477.