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Background: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP)., Methods: Consecutive patients submitted to LDP or RDP from 2010 to 2020 in four high-volume Italian centers were included, with a minimum of 12 months of postoperative follow-up were included. QoL was evaluated using the EORTC QLQ-C30 and EQ-5D questionnaires, self-reported by patients. After a propensity score matching, which included BMI, gender, operation time, multiorgan and vascular resections, splenic preservation, and pancreatic stump management, the mean differential cost and Quality-Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane., Results: The study population consisted of 564 patients. Among these, 271 (49%) patients were submitted to LDP, while 293 (51%) patients to RDP. After propensity score matching, the study population was composed of 159 patients in each group, with a median follow-up of 59 months. As regards the QoL analysis, global health and emotional functioning domains showed better results in the RDP group (p = 0.037 and p = 0.026, respectively), whereas the other did not differ. As expected, the median crude costs analysis confirmed that RDP was more expensive than LDP (16,041 Euros vs. 10,335 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay more than 5697 Euros/QALY was accepted., Conclusion: RDP was associated with better QoL as explored by specific domains. Crude costs were higher for RDP, and the cost-effectiveness threshold was set at 5697 euros/QALY., (© 2024. The Author(s).)

The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry ( https://rediscover.unipi.it/ ) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC., (© 2024. The Author(s).)

Background: Robotic pancreatoduodenectomy is increasingly being implemented worldwide, with good results reported from individual expert centers. However, it is unclear to what extent outcomes will continue to improve during the learning curve, as large international studies are lacking., Methods: An international retrospective multicenter case series, including consecutive patients after robotic pancreatoduodenectomy from 18 centers in 8 countries in Europe, Asia, and South America until December 31, 2019, was conducted. A cumulative sum analysis was performed to determine the inflection points for the feasibility (operative time and blood loss) and proficiency (postoperative pancreatic fistula grade B/C and major morbidity) learning curves. Outcomes were compared in 3 groups on the basis of the learning curve inflection points., Results: Overall, 2,186 patients after robotic pancreatoduodenectomy were included. The feasibility learning curve was reached after 30-45 robotic pancreatoduodenectomy procedures and the proficiency learning curve after 90 robotic pancreatoduodenectomy procedures. These inflection points created 3 phases, which were associated with major morbidity (24.7%, 23.4%, and 12.3%, P < .001) but not 30-day mortality (2.1%, 2.0%, and 1.5%, P = .670). Other outcomes mostly continued to improve, including median operative time 432, 390, and 300 minutes (P < .0001), conversion 6.0%, 4.7%, and 2.7% (P = .002), bile leakage 7.2%, 4.1%, and 2.4% (P < .001), postpancreatectomy hemorrhage 6.5%, 6.1%, and 1.8% (n = 21) but not R0 resection (pancreatic ductal adenocarcinoma only) 78.5%, 73.9%, and 82.8% (P = .35), and 90-day mortality rate 3.1%, 3.5%, and 2.1% (P = .191). Centers performing >20 robotic pancreatoduodenectomies annually had lower rates of conversion, reoperation, and shorter median operative time as compared with centers performing 10-20 robotic pancreatoduodenectomies annually., Conclusion: This international multicenter study demonstrates that most outcomes of robotic pancreatoduodenectomy continued to improve during 3 learning curve phases without a negative effect on 90-day mortality. Randomized studies are needed in high-volume centers that have surpassed the first learning curves, to compare these outcomes with the open approach., (Copyright © 2024. Published by Elsevier Inc.)

Background: The use of robot-assisted and laparoscopic pancreatoduodenectomy is increasing, yet large adjusted analyses that can be generalized internationally are lacking. This study aimed to compare outcomes after robot-assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy in a pan-European cohort., Methods: An international multicenter retrospective study including patients after robot-assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy from 50 centers in 12 European countries (2009-2020). Propensity score matching was performed in a 1:1 ratio. The primary outcome was major morbidity (Clavien-Dindo ≥III)., Results: Among 2,082 patients undergoing minimally invasive pancreatoduodenectomy, 1,006 underwent robot-assisted pancreatoduodenectomy and 1,076 laparoscopic pancreatoduodenectomy. After matching 812 versus 812 patients, the rates of major morbidity (31.9% vs 29.6%; P = .347) and 30-day/in-hospital mortality (4.3% vs 4.6%; P = .904) did not differ significantly between robot-assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy, respectively. Robot-assisted pancreatoduodenectomy was associated with a lower conversion rate (6.7% vs 18.0%; P < .001) and higher lymph node retrieval (16 vs 14; P = .003). Laparoscopic pancreatoduodenectomy was associated with shorter operation time (446 minutes versus 400 minutes; P < .001), and lower rates of postoperative pancreatic fistula grade B/C (19.0% vs 11.7%; P < .001), delayed gastric emptying grade B/C (21.4% vs 7.4%; P < .001), and a higher R0-resection rate (73.2% vs 84.4%; P < .001)., Conclusion: This European multicenter study found no differences in overall major morbidity and 30-day/in-hospital mortality after robot-assisted pancreatoduodenectomy compared with laparoscopic pancreatoduodenectomy. Further, laparoscopic pancreatoduodenectomy was associated with a lower rate of postoperative pancreatic fistula, delayed gastric emptying, wound infection, shorter length of stay, and a higher R0 resection rate than robot-assisted pancreatoduodenectomy. In contrast, robot-assisted pancreatoduodenectomy was associated with a lower conversion rate and a higher number of retrieved lymph nodes as compared with laparoscopic pancreatoduodenectomy., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic., Methods: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020., Results: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001)., Conclusions: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 ten 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 (GWAS) 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: The authors have no interests to disclose.

Background: International multicenter audit-based studies focusing on the outcome of minimally invasive pancreatoduodenectomy (MIPD) are lacking. The European Registry for Minimally Invasive Pancreatic Surgery (E-MIPS) is the E-AHPBA endorsed registry aimed to monitor and safeguard the introduction of MIPD in Europe., Materials and Methods: A planned analysis of outcomes among consecutive patients after MIPD from 45 centers in 14 European countries in the E-MIPS registry (2019-2021). The main outcomes of interest were major morbidity (Clavien-Dindo grade ≥3) and 30-day/in-hospital mortality., Results: Overall, 1336 patients after MIPD were included [835 robot-assisted (R-MIPD) and 501 laparoscopic MIPD (L-MIPD)]. Overall, 20 centers performed R-MIPD, 15 centers L-MIPD, and 10 centers both. Between 2019 and 2021, the rate of centers performing L-MIPD decreased from 46.9 to 25%, whereas for R-MIPD this increased from 46.9 to 65.6%. Overall, the rate of major morbidity was 41.2%, 30-day/in-hospital mortality 4.5%, conversion rate 9.7%, postoperative pancreatic fistula grade B/C 22.7%, and postpancreatectomy hemorrhage grade B/C 10.8%. Median length of hospital stay was 12 days (IQR 8-21). A lower rate of major morbidity, postoperative pancreatic fistula grade B/C, postpancreatectomy hemorrhage grade B/C, delayed gastric emptying grade B/C, percutaneous drainage, and readmission was found after L-MIPD. The number of centers meeting the Miami Guidelines volume cut-off of ≥20 MIPDs annually increased from 9 (28.1%) in 2019 to 12 (37.5%) in 2021 ( P =0.424). Rates of conversion (7.4 vs. 14.8% P <0.001) and reoperation (8.9 vs. 15.1% P <0.001) were lower in centers, which fulfilled the Miami volume cut-off., Conclusion: During the first 3 years of the pan-European E-MIPS registry, morbidity and mortality rates after MIPD were acceptable. A shift is ongoing from L-MIPD to R-MIPD. Variations in outcomes between the two minimally invasive approaches and the impact of the volume cut-off should be further evaluated over a longer time period., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to compare robotic pancreatoduodenectomy with vein resection (PD-VR) based on the incidence of severe postoperative complications (SPC)., Background: Robotic pancreatoduodenectomy has been gaining momentum in recent years. Vein resection is frequently required in this operation, but no study has compared robotic and open PD-VR using a matched analysis., Methods: This was an intention-to-treat study designed to demonstrate the noninferiority of robotic to open PD-VR (2011-2021) based on SPC. To achieve a power of 80% (noninferiority margin:10%; α error: 0.05; ß error: 0.20), a 1:1 propensity score-matched analysis required 35 pairs., Results: Of the 151 patients with PD-VR (open = 115, robotic = 36), 35 procedures per group were compared. Elective conversion to open surgery was required in 1 patient with robotic PD-VR (2.9%). One patient in both groups experienced partial vein thrombosis. SPC occurred in 7 (20.0%) and 6 patients (17.1%) in the robotic and open PD-VR groups, respectively ( P = 0.759; OR: 1.21 [0.36-4.04]). Three patients died after robotic PD-VR (8.6%) and none died after open PD-VR ( P = 0.239). Robotic PD-VR was associated with longer operative time (611.1 ± 13.9 minutes vs 529.0 ± 13.0 minutes; P < 0.0001), more type 2 vein resection (28.6% vs 5.7%; P = 0.0234) and less type 3 vein resection (31.4% vs 71.4%; P = 0.0008), longer vein occlusion time (30 [25.3-78.3] minutes vs 15 [8-19.5] minutes; P = 0.0098), less blood loss (450 [200-750] mL vs 733 [500-1070.3] mL; P = 0.0075), and fewer blood transfusions (intraoperative: 14.3% vs 48.6%; P = 0.0041) (perioperative: 14.3% vs 60.0%; P = 0.0001)., Conclusions: In this study, robotic PD-VR was noninferior to open PD-VR for SPC. Robotic and open PD-VR need to be compared in randomized controlled trials., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The safety and efficacy of minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS) remain to be established in pancreatic cancer (PDAC) METHODS: Eighty-five open (O)-RAMPS were compared to 93 MI-RAMPS. The entropy balance matching approach was used to compare the two cohorts, eliminating the selection bias. Three models were created. Model 1 made O-RAMPS equal to the MI-RAMPS cohort (i.e., compared the two procedures for resectable PDAC); model 2 made MI-RAMPS equal to O-RAMPS (i.e., compared the two procedures for borderline-resectable PDAC); model 3, compared robotic and laparoscopic RAMPS., Results: O-RAMPS and MI-RAMPS showed "non-small" differences for BMI, comorbidity, back pain, tumor size, vascular resection, anterior or posterior RAMPS, multi-visceral resection, stump management, grading, and neoadjuvant therapy. Before reweighting, O-RAMPS had fewer clinically relevant postoperative pancreatic fistulae (CR-POPF) (20.0% vs. 40.9%; p = 0.003), while MI-RAMPS had a higher mean of lymph nodes (25.7 vs. 31.7; p = 0.011). In model 1, MI-RAMPS and O-RAMPS achieved similar results. In model 2, O-RAMPS was associated with lower comprehensive complication index scores (MD = 11.2; p = 0.038), and CR-POPF rates (OR = 0.2; p = 0.001). In model 3, robotic-RAMPS had a higher probability of negative resection margins., Conclusion: In patients with anatomically resectable PDAC, MI-RAMPS is feasible and as safe as O-RAMPS., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Living donor kidney transplantation (LDKTx) is recommended by all scientific societies. Living donor nephrectomy (LDN) is probably one of the safest surgical procedures, but it carries some risk for healthy donors. The aim of this study is to provide a snapshot of LDKTx activities in Italy and ask about safety measures implemented in LDN. Data on LDKTx were extracted from the national database. Safety measures were examined through a specific survey. Between 2001 and 2022 40,663 kidney transplants (31.4 per million population-pmp) were performed, including 4731 LDKTx (3.7 pmp). There was no postoperative death of the donor. After a median follow-up of 52.2 months [IQR:17.9-99.5], the 10-year donor survival rate was 93.38% (CI:97.52-98.94). There was evidence of renal disease in 65 donors (1.8%), including 42 (1.1%) with stage III end-stage renal disease. Twenty-nine out of 35 transplant centers (TC) involved in LDKTx responded to the survey (82.9%). Six TCs (21.4%) had a total experience of 20 or fewer LDN. Minimally invasive LDN was the first choice at 24 TC (82.8%). At 10 TC (37.0%) only one surgeon performed LDN. Nineteen TCs (65.5%) had a surgical safety checklist for LDN and 14 had a postoperative surveillance protocol. The renal artery was occluded in 3 TCs (10.3%) mainly by non-transfixion methods (including clips). Redundancy of key safety systems in the operating room was available in 22 of 29 centers (75.8%). In summary, LDKTx should be further implemented in Italy. Donor safety should be improved through the implementation of a national procedural protocol., (© 2023. The Author(s).)

Background: Newer chemotherapy regimens are reviving the role of pancreatectomy with arterial resection (PAR) in locally advanced pancreatic cancer. However, concerns about the early outcomes and learning curve of PAR remain. This study aimed to define the postoperative results and learning curve of PAR and provide preliminary data on oncologic outcomes., Materials and Methods: A single center's experiences (1993-2023) were retrospectively analyzed to define the postoperative outcomes and learning curve of PAR. Oncologic results were also reported., Results: During the study period 236 patients underwent PAR. Eighty PAR (33.9%) were performed until 2012, and 156 were performed thereafter (66.1%). Pancreatic cancer was diagnosed histologically in 183 patients (77.5%). Induction therapy was delivered to 18 of these patients (31.0%) in the early experience and to 101 patients (80.8%) in the last decade (P<0.0001). The superior mesenteric artery (PAR-SMA), celiac trunk/hepatic artery (PAR-CT/HA), superior mesenteric/portal vein, and inferior vena cava were resected in 95 (40.7%), 138 (59.2%), 189 (80.1%), and 9 (3.8%) patients, respectively. Total gastrectomy was performed in 35 (18.5%) patients. The thirty-day mortality rate was 7.2% and ninety-day mortality rate was 9.7%. The learning curve for mortality was 106 PAR (16.0% vs. 4.6%; odds ratio, OR=0.25 [0.10-0.67], P=0.0055). Comparison between the PAR-SMA and PAR-CT/HA groups showed no differences in severe postoperative complications (25.3% vs. 20.6%), 90-day mortality (12.6% vs. 7.8%), and median overall survival. Vascular invasion was confirmed in 123 patients (67.2%). The median number (interquartile range) of examined lymph nodes was 60.5 (41.3-83) and rate of R0 resection was 66.1% (121/183). Median overall survival for PAR was 20.9 (12.5-42.8) months, for PAR-SMA was 20.2 (14.4-44) months, and for PAR-CT/HA was 20.2 (11.4-42.7). Long-term prognosis improved by study decade (1993-2002: 12.0 [5.4-25.9] months, 2003-2012: 15.1 [9.8-23.4] months, and 2013-present: 26.2 [14.3-51.5] months; P<0.0001)., Conclusions: In recent times, PAR is associated with improved outcomes despite a steep learning curve. Pancreatic surgeons should be prepared to face the technical challenge posed by PAR., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities., Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures., Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient., Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months., Conclusion: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC)., Methods: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+., Results: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages., Conclusion: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data., Objective: To evaluate the length of pooled learning curves of MIDP in experienced centers., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included MIDP procedures performed from January 1, 2006, through June 30, 2019, in 26 European centers from 8 countries that each performed more than 15 distal pancreatectomies annually, with an overall experience exceeding 50 MIDP procedures. Consecutive patients who underwent elective laparoscopic or robotic distal pancreatectomy for all indications were included. Data were analyzed between September 1, 2021, and May 1, 2022., Exposures: The learning curve for MIDP was estimated by pooling data from all centers., Main Outcomes and Measures: The learning curve was assessed for the primary textbook outcome (TBO), which is a composite measure that reflects optimal outcome, and for surgical mastery. Generalized additive models and a 2-piece linear model with a break point were used to estimate the learning curve length of MIDP. Case mix-expected probabilities were plotted and compared with observed outcomes to assess the association of changing case mix with outcomes. The learning curve also was assessed for the secondary outcomes of operation time, intraoperative blood loss, conversion to open rate, and postoperative pancreatic fistula grade B/C., Results: From a total of 2610 MIDP procedures, the learning curve analysis was conducted on 2041 procedures (mean [SD] patient age, 58 [15.3] years; among 2040 with reported sex, 1249 were female [61.2%] and 791 male [38.8%]). The 2-piece model showed an increase and eventually a break point for TBO at 85 procedures (95% CI, 13-157 procedures), with a plateau TBO rate at 70%. The learning-associated loss of TBO rate was estimated at 3.3%. For conversion, a break point was estimated at 40 procedures (95% CI, 11-68 procedures); for operation time, at 56 procedures (95% CI, 35-77 procedures); and for intraoperative blood loss, at 71 procedures (95% CI, 28-114 procedures). For postoperative pancreatic fistula, no break point could be estimated., Conclusion and Relevance: In experienced international centers, the learning curve length of MIDP for TBO was considerable with 85 procedures. These findings suggest that although learning curves for conversion, operation time, and intraoperative blood loss are completed earlier, extensive experience may be needed to master the learning curve of MIDP.

Pancreas sparing total duodenectomy (PSTD) is an exceedingly rare procedure that is performed mostly for benign disease, widely involving the duodenum, that cannot be treated otherwise. PSTD requires meticulous dissection as well as reconstruction of both biliary and pancreatic drainage. Despite these technical aspects appear to be ideal for robotic assistance, robotic PSTD has not been described yet.Robotic PSTD was successfully performed in two patients. In both patients biliary and pancreatic drainage were reconstructed on the second jejunal loop, which was pulled in the duodenal bed. In the first patient, gastro-jejunostomy was performed on the blind end of the neo-duodenum (Billorth I type gastric reconstruction). In the second patient, gastro-jejunostomy was achieved in an antecolic position, 40 cm downstream the neo-ampulla in the second patient (Billorth II type gastric reconstruction). In both patients, indication to PSTD was duodenal polyps not amenable to endoscopic removal. The first patient suffered from prolonged delayed gastric emptying, but she is currently doing well 5 years and beyond after the procedure. The second patient complained of mild delayed gastric emptying that resolved spontaneously. He is now doing well 5 months after surgery.We have shown the feasibility of robotic PSTD in what we believe to be a world premiere. Further experience is required to refine the procedure and improve outcomes., (© 2023. Italian Society of Surgery (SIC).)

The prognostic value of carbohydrate antigen 125 (Ca 125) is emerging also in pancreatic cancer (PDAC). In this study, we aim to define the prognostic value of Ca 125 in resected PDAC of the head of the pancreas. This is a single-center, retrospective study. Data from patients with a pre-operative assay of Ca 125 who underwent a pancreatic resection for PDAC between 2010 and 2018 were analyzed. As per National Comprehensive Cancer Guidelines, tumors were classified in resectable (R-PDAC), borderline resectable (BR-PDAC), and locally advanced (LA-PDAC). The Kaplan-Meier method was used to evaluate the overall survival. Cox proportional hazard regression was used to evaluate the role of pre-operative Ca 125 in predicting survival (while adjusting for confounders). The maximally selected log-rank statistic was used to identify a Ca 125 cut-off defining two groups with different survival probability. Inclusion criteria were met by 207 patients (R-PDAC: 80, BR-PDAC: 91, and LA-PDAC: 36). Ca 125 predicted overall survival before and after adjusting for confounding factors in all categories of anatomic resectability (R-PDAC: HR = 4.3; p = 0.0249) (BR-PDAC: HR = 7.82; p = 0.0024) (LA-PDAC: HR = 11.4; p = 0.0043). In BR-PDAC and LA-PDAC (n = 127), the division in two groups (high vs. low Ca 125) correlated with T stage (p = 0.0317), N stage (p = 0.0083), mean LN ratio (p = 0.0292), and tumor grading (p = 0.0143). This study confirmed the prognostic value of Ca125 in resected pancreatic cancer and, therefore, the importance of biologic over anatomic resectability. Ca 125 should be routinely assayed in surgical candidates with PDAC., (© 2023. The Author(s).)

Careful preoperative planning is key in minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS). This retrospective study aims to show the practical implications of computed tomography distance between the right margin of the tumor and either the left margin of the spleno-mesenteric confluence (d-SMC) or the gastroduodenal artery (d-GDA). Between January 2011 and June 2022, 48 minimally invasive RAMPS were performed for either pancreatic cancer or malignant intraductal mucinous papillary neoplasms. Two procedures were converted to open surgery (4.3%). Mean tumor size was 31.1 ± 14.7 mm. Mean d-SMC was 21.5 ± 18.5 mm. Mean d-GDA was 41.2 ± 23.2 mm. A vein resection was performed in 10 patients (20.8%) and the pancreatic neck could not be divided by an endoscopic stapler in 19 operations (43.1%). In patients requiring a vein resection, mean d-SMC was 10 mm (1.5-15.5) compared to 18 mm (10-37) in those without vein resection (p = 0.01). The cut-off of d-SMC to perform a vein resection was 17 mm (AUC 0.75). Mean d-GDA was 26 mm (19-39) mm when an endoscopic stapler could not be used to divide the pancreas, and 46 mm (30-65) when the neck of the pancreas was stapled (p = 0.01). The cut-off of d-GDA to safely pass an endoscopic stapler behind the neck of the pancreas was 43 mm (AUC 0.75). Computed tomography d-SMC and d-GDA are key measurements when planning for MI-RAMPS., (© 2023. The Author(s).)

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 our study. We conducted a multiphase study analysing 7745 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 noncoding 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., (© 2022 UICC.)

Background: A preliminary analysis from the COVID-Advanced Gastrointestinal Cancer Surgical Treatment (AGICT) study showed that the rate of minimally invasive surgery (MIS) for elective and urgent procedures did not decrease during the pandemic year. In this article, we aimed to perform a subgroup analysis using data from the COVID-AGICT study to evaluate the trend of MIS during the COVID-19 pandemic period in Italy. Methods: This study was conducted collecting data of MIS patients from the COVID-AGICT database. The primary endpoint was to demonstrate whether the SARS-CoV-2 pandemic scenario reduced MIS for elective treatment of gastrointestinal cancer (GIC) in Italy in 2020. The secondary endpoint was to evaluate the impact of the pandemic period on perioperative outcomes in the MIS group. Results: In the pandemic year, 62% of patients underwent surgery with a minimally invasive approach, compared to 63% in 2019 ( P  = .23). In 2020, the proportion of patients undergoing elective MIS decreased compared to the previous year (80% versus 82%, P  = .04), and the rate of urgent MIS did not differ between the 2 years (31% and 33% in 2019 and 2020 - P  = .66). Colorectal cancer was less likely to be treated with MIS approach during 2020 (78% versus 75%, P  < .001). Conversely, the rate of MIS pancreatic resection was higher in 2020 (28% versus 22%, P  < .002). Conversion to an open approach was lower in 2020 (7.2% versus 9.2% - P  = .01). Major postoperative complications were similar in both years (11% versus 11%, P  = .9). Conclusion: In conclusion, although MIS for elective treatment of GIC in Italy was reduced during the COVID-19 pandemic period, our study revealed that the overall proportion of MIS (elective and urgent) and postoperative outcomes were comparable to the prepandemic period. ClinicalTrial.gov (NCT04686747).

Background: Difficulty scoring systems are important for the safe, stepwise implementation of new procedures. We designed a retrospective observational study for building a difficulty score for robotic pancreatoduodenectomy., Methods: The difficulty score (PD-ROBOSCORE) aims at predicting severe postoperative complications after robotic pancreatoduodenectomy. The PD-ROBOSCORE was developed in a training cohort of 198 robotic pancreatoduodenectomies and was validated in an international multicenter cohort of 686 robotic pancreatoduodenectomies. Finally, all centers tested the model during the early learning curve (n = 300). Growing difficulty levels (low, intermediate, high) were defined using cut-off values set at the 33rd and 66th percentile (NCT04662346)., Results: Factors included in the final multivariate model were a body mass index of ≥25 kg/m 2 for males and ≥30 kg/m 2 for females (odds ratio:2.39; P < .0001), borderline resectable tumor (odd ratio:1.98; P < .0001), uncinate process tumor (odds ratio:1.69; P < .0001), pancreatic duct size <4 mm (odds ratio:1.59; P < .0001), American Society of Anesthesiologists class ≥3 (odds ratio:1.59; P < .0001), and hepatic artery originating from the superior mesenteric artery (odds ratio:1.43; P < .0001). In the training cohort, the absolute score value (odds ratio = 1.13; P = .0089) and difficulty groups (odds ratio = 2.35; P = .041) predicted severe postoperative complications. In the multicenter validation cohort, the absolute score value predicted severe postoperative complications (odds ratio = 1.16, P < .001), whereas the difficulty groups did not (odds ratio = 1.94, P = .082). In the learning curve cohort, both absolute score value (odds ratio:1.078, P = .04) and difficulty groups (odds ratio: 2.25, P = .017) predicted severe postoperative complications. Across all cohorts, a PD-ROBOSCORE of ≥12.51 doubled the risk of severe postoperative complications. The PD-ROBOSCORE score also predicted operative time, estimated blood loss, and vein resection. The PD-ROBOSCORE predicted postoperative pancreatic fistula, delayed gastric emptying, postpancreatectomy hemorrhage, and postoperative mortality in the learning curve cohort., Conclusion: The PD-ROBOSCORE predicts severe postoperative complications after robotic pancreatoduodenectomy. The score is readily available via www.pancreascalculator.com., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Robot-assisted distal pancreatectomy (RDP) is increasingly used as an alternative to laparoscopic distal pancreatectomy (LDP) in patients with resectable pancreatic cancer but comparative multicenter studies confirming the safety and efficacy of RDP are lacking., Methods: An international, multicenter, retrospective, cohort study, including consecutive patients undergoing RDP and LDP for resectable pancreatic cancer in 33 experienced centers from 11 countries (2010-2019). The primary outcome was R0-resection. Secondary outcomes included lymph node yield, major complications, conversion rate, and overall survival., Results: In total, 542 patients after minimally invasive distal pancreatectomy were included: 103 RDP (19%) and 439 LDP (81%). The R0-resection rate was comparable (75.7% RDP vs. 69.3% LDP, p = 0.404). RDP was associated with longer operative time (290 vs. 240 min, p < 0.001), more vascular resections (7.6% vs. 2.7%, p = 0.030), lower conversion rate (4.9% vs. 17.3%, p = 0.001), more major complications (26.2% vs. 16.3%, p = 0.019), improved lymph node yield (18 vs. 16, p = 0.021), and longer hospital stay (10 vs. 8 days, p = 0.001). The 90-day mortality (1.9% vs. 0.7%, p = 0.268) and overall survival (median 28 vs. 31 months, p = 0.599) did not differ significantly between RDP and LDP, respectively., Conclusions: In selected patients with resectable pancreatic cancer, RDP and LDP provide a comparable R0-resection rate and overall survival in experienced centers. Although the lymph node yield and conversion rate appeared favorable after RDP, LDP was associated with shorter operating time, less major complications, and shorter hospital stay. The specific benefits associated with each approach should be confirmed by multicenter, randomized trials., (© 2023. The Author(s).)

Background: This Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic., Method: Our primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined., Results: Overall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year 'Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001)., Conclusions: Although the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Open pancreatoduodenectomy with vein resection (OPD-VR) is now standard of care in patients who responded to neoadjuvant therapies. Feasibility of robotic pancreatoduodenectomy (RPD) with vein resection (RPD-VR) was shown, but no study provided a detailed description of the technical challenges associated with this formidable operation. Herein, we describe the trips and tricks for technically successful RPD-VR., Methods: The vascular techniques used in RPD-VR were borrowed from OPD-VR, as well as from our experience with robotic transplantation of both kidney and pancreas. Vein resection was classified into 4 types according to the international study group of pancreatic surgery. Each type of vein resection was described in detail and shown in a video., Results: Between October 2008 and November 2021, a total of 783 pancreatoduodenectomies were performed, including 233 OPDs-VR (29.7%). RPD was performed in 256 patients (32.6%), and RPDs-VR in 36 patients (4.5% of all pancreatoduodenectomies; 15.4% of all pancreatoduodenectomies with vein resection; 14.0% of all RPDs). In RPD-VR vein resections were: 4 type 1 (11.1%), 10 type 2 (27.8%), 12 type 3 (33.3%) and 10 type 4 (27.8%). Vascular patches used in type 2 resections were made of peritoneum (n = 8), greater saphenous vein (n = 1), and deceased donor aorta (n = 1). Interposition grafts used in type 4 resections were internal left jugular vein (n = 8), venous graft from deceased donor (n = 1) and spiral saphenous vein graft (n = 1). There was one conversion to open surgery (2.8%). Ninety-day mortality was 8.3%. There was one (2.8%) partial vein thrombosis, treated with heparin infusion., Conclusions: We have reported 36 technically successful RPDs-VR. We hope that the tips and tricks provided herein can contribute to safer implementation of RPD-VR. Based on our experience, and according to data from the literature, we strongly advise that RPD-VR is performed by expert surgeons at high volume centers., (© 2023. The Author(s).)

Background: Triangle pancreatoduodenectomy adds to the conventional procedure the en bloc removal of the retroperitoneal lympho-neural tissue included in the triangular area bounded by the common hepatic artery (CHA), the superior mesenteric artery (SMA), and the superior mesenteric vein/portal vein. We herein aim to show the feasibility of "cold" triangle robotic pancreaticoduodenectomy (C-Tr-RPD) for pancreatic cancer (PDAC)., Methods: Cold dissection corresponds to sharp arterial divestment performed using only the tips of robotic scissors. After division of the gastroduodenal artery, triangle dissection begins by lateral-to-medial divestment of the CHA and anterior-to-posterior clearance of the right side of the celiac trunk. Next, after a wide Kocher maneuver, the origin of the SMA, and the celiac trunk are identified. After mobilization of the first jejunal loop and attached mesentery, the SMA is identified at the level of the first jejunal vein and is divested along the right margin working in a distal-to-proximal direction. Vein resection and reconstruction can be performed as required. C-Tr-RPD was considered feasible if triangle dissection was successfully completed without conversion to open surgery or need to use energy devices. Postoperative complications and pathology results are presented in detail., Results: One hundred twenty-seven consecutive C-Tr-RPDs were successfully performed. There were three conversions to open surgery (2.3%), because of pneumoperitoneum intolerance (n = 2) and difficult digestive reconstruction. Thirty-four patients (26.7%) required associated vascular procedures. No pseudoaneurysm of the gastroduodenal artery was observed. Twenty-eight patients (22.0%) developed severe postoperative complications (≥ grade III). Overall 90-day mortality was 7.1%, declining to 2.3% after completion of the learning curve. The median number of examined lymph nodes was 42 (33-51). The rate of R1 resection (7 margins < 1 mm) was 44.1%., Conclusion: C-Tr-RPD is feasible, carries a risk of surgical complications commensurate to the magnitude of the procedure, and improves staging of PDAC., (© 2022. The Author(s).)

Background: This study aims to describe the technique and the results of double-layer continuous suture hepaticojejunostomy (HJ) following pancreatoduodenectomy (PD) and total pancreatectomy (TP)., Methods: A prospectively maintained database was analyzed retrospectively to identify incidence and severity of biliary leaks (BL) (ISGLS definition), as well as of HJ stenosis (HJS), cholangitis, and need for redo-HJ (in patients with a follow-up ≥3 years) in a consecutive series of 800 procedures (PD = 603; TP = 197). Predictors of biliary complications were also identified., Results: BLs occurred in 5 patients (0.6%), including 2 (0.3%) combined pancreatic and biliary leaks. Rates of HJS, cholangitis, and need for redo-HJ were 6.1%, 5.4%, and 2.0%, respectively. Incidence of BL was 0.6% in open procedures (4/587) and 0.4% in robotic operations (1/213). Incidence of late biliary complications was also equivalent in open and robotic procedures. Occurrence of BL was predicted by ASA IV status and duodenal cancer, HJS by any associated vascular procedure and hepatic duct size < 8 mm, cholangitis by any associated vascular procedure and normal bilirubin/hepatic enzymes, and redo HJ by history of cholecystectomy and neuroendocrine tumor/cancer., Discussion: Double layer continuous suture HJ is associated with low BL rates, and an acceptable incidence of late complications., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective of this study is to determine the role of apparent diffusion coefficient (ADC) value at 3T magnetic resonance imaging (MRI) in the characterization of pancreatic cystic lesions., Methods: We retrospectively selected a total number of 223 patients with a conclusive diagnosis of pancreatic cystic lesion, previously undergoing MR examination on a 3 T system. The MRI protocol first included axial T1/T2-weighted sequences and magnetic resonance cholangiopancreatography. Diffusion-weighted MRI was performed using a spin-echo echo-planar sequence with multiple b values (0, 150, 500, 1000, and 1500 s/mm2) in all diffusion directions, obtaining an ADC map. Contrast-enhanced T1-weighted sequences were performed during the initial work-up of a pancreatic cystic lesion and when signs of malignancy were suspected during the MRI follow-up. The ADC value of each pancreatic lesion was measured using a monoexponential curve fitting with all the multiple b., Results: The final diagnosis of our study group included the following: serous cystadenomas (n = 42), mucinous cystadenomas (n = 14), intraductal papillary mucinous neoplasms (IPMNs) (n = 121), IPMNs with signs of malignancy at histopathologic examination (n = 24), pseudocysts (n = 9), other cystic lesions (n = 13). A statistically significant difference was observed between the ADC values of malignant IPMNs and those of each other group of pancreatic lesions (P < 0.001). The ADC value of benign IPMN was significantly higher than that of serous cystadenomas (P = 0.024). A statistically significant difference was observed between the ADCs of all mucinous cystic tumors (benign IPMNs together to mucinous cystadenomas) and the ADCs of serous cystadenomas (P = 0.014)., Conclusions: Fitted ADC value obtained at 3T MRI may be helpful in the characterization of pancreatic cystic lesions with particular regards of differential diagnosis between mucinous and serous cystic tumors and between malignant and benign IPMNs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers., Summary of Background Data: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients., Methods: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018., Results: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS., Conclusion: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Perivascular epithelioid cell tumors (PEComa)s are mesenchymal neoplasms located at various anatomic sites, which usually express both melanocytic and myogenic markers., Case Report: A 60-year-old woman underwent laparotomy for a huge, heterogeneous, right ovarian mass. The histological examination of the surgical specimen revealed a neoplasm consisting of both cells with clear or eosinophilic cytoplasm and spindle cells in a myxoid stroma. Immunostaining was positive for human melanoma black-45, h-caldesmon, desmin, actin, and transcription factor 3. Cell atypias were moderate, mitoses were 4/10 high power fields (HPF) and margins were focally infiltrative. These findings pointed to a diagnosis of ovarian PEComa. Twenty-five months later, two subcutaneous lesions were surgically removed on the left trapezius muscle and the median subumbilical area, respectively. The former was a desmoid fibromatosis, whereas the latter was a recurrence of PEComa with greater nuclear pleomorphism and higher number of mitoses (26/50 HPF) compared to the primary tumor. The patient was free of disease 11 months later., Conclusion: A long-term follow-up of gynecological PEComas is strongly recommended., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The 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., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, p = 3.03 × 10 -6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3 , a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Corradi, Gentiluomo, López de Maturana, Theodoropoulos, Roth, Maiello, Morelli, Archibugi, Izbicki, Sarlós, Kiudelis, Oliverius, Aoki, Vashist, van Eijck, Gazouli, Talar-Wojnarowska, Mambrini, Pezzilli, Bueno-de-Mesquita, Hegyi, Souček, Neoptolemos, Di Franco, Sperti, Kauffmann, Hlaváč, Uzunoğlu, Ermini, Małecka-Panas, Lucchesi, Vanella, Dijk, Mohelníková-Duchoňová, Bambi, Petrone, Jamroziak, Guo, Kolarova, Capretti, Milanetto, Ginocchi, Loveček, Puzzono, van Laarhoven, Carrara, Ivanauskas, Papiris, Basso, Arcidiacono, Izbéki, Chammas, Vodicka, Hackert, Pasquali, Piredda, Costello-Goldring, Cavestro, Szentesi, Tavano, Włodarczyk, Brenner, Kreivenaite, Gao, Bunduc, Vermeulen, Schneider, Latiano, Gioffreda, Testoni, Kupcinskas, Lawlor, Capurso, Malats, Campa and Canzian.)

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10-10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10-6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Creating fully implantable robots that replace or restore physiological processes is a great challenge in medical robotics. Restoring blood glucose homeostasis in patients with type 1 diabetes is particularly interesting in this sense. Intraperitoneal insulin delivery could revolutionize type 1 diabetes treatment. At present, the intraperitoneal route is little used because it relies on accessing ports connecting intraperitoneal catheters to external reservoirs. Drug-loaded pills transported across the digestive system to refill an implantable reservoir in a minimally invasive fashion could open new possibilities in intraperitoneal delivery. Here, we describe PILLSID (PILl-refiLled implanted System for Intraperitoneal Delivery), a fully implantable robotic device refillable through ingestible magnetic pills carrying drugs. Once refilled, the device acts as a programmable microinfusion system for precise intraperitoneal delivery. The robotic device is grounded on a combination of magnetic switchable components, miniaturized mechatronic elements, a wireless powering system, and a control unit to implement the refilling and control the infusion processes. In this study, we describe the PILLSID prototyping. The device key blocks are validated as single components and within the integrated device at the preclinical level. We demonstrate that the refilling mechanism works efficiently in vivo and that the blood glucose level can be safely regulated in diabetic swine. The device weights 165 grams and is 78 millimeters by 63 millimeters by 35 millimeters, comparable with commercial implantable devices yet overcoming the urgent critical issues related to reservoir refilling and powering., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Purpose of Review: To define recent changes and future directions in the practice of pancreas transplantation (PT). Two major events have occurred in the past 18 months: COVID-19 pandemic, and the first world consensus conference on PT. Several innovative studies were published after the consensus conference., Recent Findings: During COVID-19 pandemic PT activity decreased. COVID-19 in transplant recipients increases mortality rates, but data from kidney transplantation show that mortality might be higher in waitlisted patients.The world consensus conference provided 49 jury deliberations on the impact of PT on management of diabetic patients and 110 practice recommendations.Recent evidence demonstrates that PT alone is safe and effective, that results of simultaneous pancreas and kidney (SPK) remain excellent despite older recipient age and higher prevalence of type 2 diabetes, that use of hepatitis C virus (HCV)-positive donors into HCV-negative recipients is associated with good outcomes, and that use of sirolimus as primary immunosuppressant and costimulation blockade does not improve results of SPK., Summary: COVID-19 pandemic and the first world consensus conference on PT were major events. Although COVID-19 pandemic should not reduce PT activity in the future, a major positive impact on both volume and outcomes of PT is awaited from the proceedings of the world consensus conference., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study was designed to demonstrate non-inferiority of robot-assisted total pancreatectomy (RATP) to open total pancreatectomy (OPT) based on an intention-to-treat analysis, having occurrence of severe post-operative complications (SPC) as primary study endpoint. The two groups were matched (2:1) by propensity scores. Assuming a rate of SPC of 22.5% (non-inferiority margin: 15%; α: 0.05; β: 0.20; power: 80%), a total of 25 patients were required per group. During the study period (October 2008-December 2019), 209 patients received a total pancreatectomy. After application of exclusion and inclusion criteria, matched groups were extracted from an overall cohort of 132 patients (OPT: 107; RATP: 25). Before matching, the two groups were different with respect to prevalence of cardiac disease (24.3% versus 4.0%; p = 0.03), presence of jaundice (45.8% versus 12.0%; p = 0.002), presence of a biliary drainage (23.4% versus 0; p  = 0.004), history of weight loss (28.0% versus 8.0%; p = 0.04), and vein involvement (55.1% versus 28.0%) (p = 0.03). After matching, the two groups (OTP: 50; RATP: 25) were well balanced. Regarding primary study endpoint, SPC developed in 13 patients (26.0%) after OTP and in 6 patients (24.0%) after RATP (p = 0.85). Regarding secondary study endpoints, RATP was associated with longer median operating times [475 (408.8-582.5) versus 585 min (525-637.5) p = 0.003]. After a median follow-up time of 23.7 months (10.4-71), overall survival time [22.6 (11.2-81.2) versus NA (27.3-NA) p = 0.006] and cancer-specific survival [22.6 (11.2-NA) versus NA (27.3-NA) p = 0.02] were improved in patients undergoing RATP. In carefully selected patients, robot-assisted total pancreatectomy is non-inferior to open total pancreatectomy regarding occurrence of severe post-operative complications.

Current evidence shows that robotic pancreatoduodenectomy (RPD) is feasible with a safety profile equivalent to either open pancreatoduodenectomy (OPD) or laparoscopic pancreatoduodenectomy (LPD). However, major intraoperative bleeding can occur and emergency conversion to OPD may be required. RPD reduces the risk of emergency conversion when compared to LPD. The learning curve of RPD ranges from 20 to 40 procedures, but proficiency is reached only after 250 operations. Once proficiency is achieved, the results of RPD may be superior to those of OPD. As for now, RPD is at least equivalent to OPD and LPD with respect to incidence and severity of POPF, incidence and severity of post-operative complications, and post-operative mortality. A minimal annual number of 20 procedures per center is recommended. In pancreatic cancer (versus OPD), RPD is associated with similar rates of R0 resections, but higher number of examined lymph nodes, lower blood loss, and lower need of blood transfusions. Multivariable analysis shows that RPD could improve patient survival. Data from selected centers show that vein resection and reconstruction is feasible during RPD, but at the price of high conversion rates and frequent use of small tangential resections. The true Achilles heel of RPD is higher operative costs that limit wider implementation of the procedure and accumulation of a large experience at most single centers. In conclusion, when proficiency is achieved, RPD may be superior to OPD with respect to CR-POPF and oncologic outcomes. Achievement of proficiency requires commitment, dedication, and truly high volumes.

Background: Postoperative pancreatic fistula continues to occur frequently after pancreatoduodenectomy., Methods: We have described a modification of the Blumgart pancreaticojejunostomy. The modification of the Blumgart pancreaticojejunostomy was compared to the Cattel-Warren pancreaticojejunostomy in cohorts of patients matched by propensity scores based on factors predictive of clinically relevant postoperative pancreatic fistula, which was the primary endpoint of this study. Based on a noninferiority study design, 95 open pancreatoduodenectomies per group were needed. Feasibility of the modification of the Blumgart pancreaticojejunostomy in robotic pancreatoduodenectomy was also shown. All pancreaticojejunostomies were performed by a single surgeon., Results: Between October 2011 and May 2019, there were 415 pancreatoduodenectomies with either a Cattel-Warren pancreaticojejunostomy (n = 225) or a modification of the Blumgart pancreaticojejunostomy (n = 190). There was 1 grade C postoperative pancreatic fistula in 190 consecutive modification of the Blumgart pancreaticojejunostomies (0.5%). Logistic regression analysis showed that the rate of clinically relevant postoperative pancreatic fistula was not affected by consecutive case number. After exclusion of robotic pancreatoduodenectomies (the Cattel-Warren pancreaticojejunostomy: 82; modification of the Blumgart pancreaticojejunostomy: 66), 267 open pancreatoduodenectomies were left, among which the matching process identified 109 pairs. The modification of the Blumgart pancreaticojejunostomy was shown to be noninferior to the Cattel-Warren pancreaticojejunostomy with respect to clinically relevant postoperative pancreatic fistula (11.9% vs 22.9%; odds ratio: 0.46 [0.21-0.93]; P = .03), grade B postoperative pancreatic fistula (11.9% vs 18.3%; P = .18), and grade C postoperative pancreatic fistula (0 vs 4.6%; P = .05) as well as to all secondary study endpoints. The modification of the Blumgart pancreaticojejunostomy was feasible in 66 robotic pancreatoduodenectomies. In this subgroup with 1 conversion to open surgery (1.5%), a clinically relevant postoperative pancreatic fistula occurred after 9 procedures (13.6%) with no case of grade C postoperative pancreatic fistula and a 90-day mortality of 3%., Conclusion: The modification of the Blumgart pancreaticojejunostomy described herein is noninferior to the Cattel-Warren pancreaticojejunostomy in open pancreatoduodenectomy. This technique is also feasible in robotic pancreatoduodenectomy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)