Robot-assisted pancreaticoduodenectomy with vascular resection: technical details and results from a high-volume center

Background: Pancreaticoduodenectomy with vein resection (PD-VR) is widely accepted as a standard procedure to achieve a higher rate of R0 resections in borderline resectable pancreatic tumors. Thanks to the availability of newer technologies, such as the da Vinci Surgical System, several high-volume centers are reporting small series of minimally invasive PD-VR. Methods: A retrospective review of a prospectively maintained database was performed to identify patients who underwent robot-assisted PD-VR (RAPD-VR) between May 2011 and December 2019. The following factors were specifically analyzed: intraoperative results, post-operative complications, mortality at 90 days, patency of vascular reconstructions, overall survival (OS) and disease-free survival (DFS). Results: During the study period 184 patients underwent RAPD, including 22 who received a RAPDVR (12.0%). The superior mesenteric vein was resected in 9 patients (40.9%), the portal vein in 3 patients (13.6%) and the spleno-mesenteric junction in 10 patients (45.5%). Based on the classification provided by the International Study Group on Pancreatic Surgery these procedures were classified as follows: 1 type I (4.5%), 3 type II (13.6%), 10 type III (45.5%) and 8 type IV (36.4%). In no patient the splenic vein was ligated and left behind. The splenic vein was always reimplanted either on the porto-mesenteric axis or in the inferior vena cava. All but one procedure, were completed under robotic assistance (conversion rate 1/22; 4.5%) after a mean operative time of 610.0±83.5 minutes. Median estimated blood loss was 899.7 mL (719.4–1,430.2 mL), with 2 patients (9.1%) receiving intraoperative blood transfusions. Sixteen patients developed post-operative complications (72.7%), graded ≥III (according to Clavien-Dindo) in 5 patients (22.7%). Two patients died within 90 days, accounting for a postoperative mortality of 9.1%. Interestingly, post-operative pancreatic fistula (grade B) occurred in only 1 patient (4.5%). Repeat surgery was required in 4 patients (18.2%) and hospital readmission in 1 patient (4.5%). At the longest available follow-up, vein reconstruction was patent in 19 patients (86.4%). Eighteen patients had a final diagnosis of pancreatic ductal adenocarcinoma (81.8%). After circumferential study of resection margins, microscopic tumor residual ≤1 mm was found in 11 patients (50.0%). The mean number of examined lymph nodes was 42.2 (±16.3), and vascular infiltration was confirmed in 13 patients (59.1%). Median OS was 39.7 (27.5–not available) and DFS 32.9 (11.5–45.8). Tumor recurrence was identified in 6 patients (27.3%). One patient (4.5%) developed isolated local recurrence. Conclusions: We have shown the feasibility of RAPD-VR. The results reported herein need to be confirmed in larger series and their generalizability remains to be established

Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in this study. We conducted a multi-phase study analysing 7,745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14,666 PDAC cases and 221,897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR=1.11, 95%CI=1.07-1.15, P=5.25×10-9 ). CDKN2B-AS1/ANRIL is a long non-coding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. This article is protected by copyright. All rights reserved

A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma

Pleiotropic variants (i.e. genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted 10 years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61 052 variants reported to be associated by at least one genome-wide association study with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16 055 pancreatic ductal adenocarcinoma (PDAC) cases and 212 149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P = 6.52 × 10-5) and 7q36.3-rs288762 (P = 3.03 × 10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell-differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.</p

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888Funder: Pisa University Hospital, Pisa, ItalyFunder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246

Duodenocefalopancreasectomia robotica versus open per adenocarcinoma duttale del pancreas: analisi del residuo tumorale microscopico (R) e della sopravvivenza.

La sopravvivenza globale dell’adenocarcinoma duttale del pancreas (ACDP) risultano ancora oggi modeste e dal punto di vista chirurgico, secondo alcuni autori, sembrerebbero essere influenzate dal residuo microscopico sui margini di resezione. L’intervento ad intento curativo R0 ad oggi risulta essere l’unica possibilità di guarigione dalla malattia. Con l’avvento della chirurgia robotica, alcuni autori nel mondo hanno iniziato ad adottare questo approccio anche nella duodenocefalopancreasectomia (DCP) e, dimostrata la sua fattibilità, si è aperto così il dibattito sull’appropriatezza oncologica. In questo lavoro vengono analizzati il residuo microscopico (R0/R1) e la sopravvivenza confrontando la DCP robotica (DCP-R) e quella open (DCP-O) eseguite per ACDP

The transplant of the uterus

Objective: to estimate the number of potential donors and potential recipients per year for uterus transplantation in the Italian setting. Setting: referral center for transplant and reproductive medicine. Design: survey, retrospective analysis. Patient(s): Patients affected by Mayer-Rokitansky-Küster-Hauser syndrome and deceased donors from 2001 to 2018. Intervention(s): analysis in detail of the deceased donors used in Tuscany from 2001 to 2018 accordingly with a uterus transplant protocol elaborated in our hospital, survey among patients affected by Mayer-Rokitansky-Küster-Hauser syndrome Main Outcome measure(s): estimated number of donors and recipients for uterus transplant per year. Result(s): the number of potential usable donors is estimated in 97 per year in Italy and the number of potential candidates to uterus transplant resulted at least 1,400.We report a pilot survey between women affected by Mayer-Rokitansky-Küster-Hauser syndrome. Thirteen out of 54 (24%) patients responded to a specific questionnaire, 92% have a strong will of motherhood and think UTx an effective solution; 70% are interested in UTx but do not fully understand if the benefits exceed the risks. Conclusion(s): in Italy the need of Utx is real and the number of donors is reasonable to start a pilot clinical trial. Information is mandatory, as it is necessary to create a dedicated multispeciality team to follow candidates before, during and after the path to transplantatio