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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 30-day mortality rate was 7.2% and 90-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.)

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 carbohydrate antigen 19.9 (CA 19.9) 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 analysed. A preoperative laboratory value of CA 19.9 greater than 37 U/l was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA 19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+., Results: A total of 2034 PDs from thirteen centres were included in the study. CA 19.9 greater than 37 U/l was significantly associated with higher N+ at univariate and multivariate analysis ( P <0.001). CA 19.9 levels greater than 37 U/l were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumours and with higher cut-off values for all cT stages., Conclusion: Lymph-nodal involvement is strongly related to preoperative CA 19.9 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 CA 19.9 values should be considered in a more biologically advanced stage., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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).)

Objective: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)., Background: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking., Methods: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines., Results: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ )., Conclusions: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population., Competing Interests: S.G.B.: support from Flinders Foundation grant: 49358025, NHMRC Ideas Grant: 2021009, Pankind 21.R7.INV.CB.UOSA.6.2. F.M.: Tsumura, Inc., Scientific Advisory Board. M.D.C. is a co-PI of a Boston Scientific–sponsored study and he has been awarded an industry grant by Haemonetics, Inc. M.H.: Intuitive Surgical—teaches courses and proctors. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)., Patients and Methods: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested., Results: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival., (© 2024. Society of Surgical Oncology.)

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).)

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien-Dindo ≥ 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of ≥ 20 MIPR and ≥ 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy., (© 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).)

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).)

Objective: To assess postoperative 90-day outcomes after minimally invasive (laparoscopic/robot-assisted) total pancreatectomy (MITP) in selected patients versus open total pancreatectomy (OTP) among European centers., Background: Minimally invasive pancreatic surgery is becoming increasingly popular but data on MITP are scarce and multicenter studies comparing outcomes versus OTP are lacking. It therefore remains unclear if MITP is a valid alternative., Methods: Multicenter retrospective propensity-score matched study including consecutive adult patients undergoing MITP or OTP for all indications at 16 European centers in 7 countries (2008-2017). Patients after MITP were matched (1:1, caliper 0.02) to OTP controls. Missing data were imputed. The primary outcome was 90-day major morbidity (Clavien-Dindo ≥3a). Secondary outcomes included 90-day mortality, length of hospital stay, and survival., Results: Of 361 patients (99MITP/262 OTP), 70 MITP procedures (50 laparoscopic, 15 robotic, 5 hybrid) could be matched to 70 OTP controls. After matching, MITP was associated with a lower rate of major morbidity (17% MITP vs. 31% OTP, P = 0.022). The 90-day mortality (1.4% MITP vs. 7.1% OTP, P = 0.209) and median hospital stay (17 [IQR 11-24] MITP vs. 12 [10-23] days OTP, P = 0.876) did not differ significantly. Among 81 patients with PDAC, overall survival was 3.7 (IQR 1.7-N/A) versus 0.9 (IQR 0.5-N/ A) years, for MITP versus OTP, which was nonsignificant after stratification by T-stage., Conclusion: This international propensity score matched study showed that MITP may be a valuable alternative to OTP in selected patients, given the associated lower rate of major morbidity., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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).)

Purpose: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort., Methods: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included., Results: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%., Conclusion: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pancreatic surgery is still a challenge even in high-volume centers. Clinically relevant postoperative pancreatic fistula (CR-POPF) represents the greatest contributor to major morbidity and mortality, especially following pancreatic distal resection. In this study, we compared robotic distal pancreatectomy (RDP) to open distal pancreatectomy (ODP) in terms of CR-POPF development and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: We collected data from five high-volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long-term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA (American Society of Anesthesiologists) score, body mass index (BMI), final pathology, and TNM (Tumour, Node, Metastasis) staging system VIII ed., Results: Two hundred and forty-six patients who underwent 82 RDPs and 164 ODPs were included. No differences were found in the incidence of CR-POPF. In the PDAC group, median DFS and OS were 10.8 months and 14.8 months in the ODP group and 10.4 months and 15 months in the RDP group, respectively., Conclusions: Robotic distal pancreatectomy is a safe surgical strategy for PDAC and incidence of CR-POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high-volume and proficient centers., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

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.)

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.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10 -9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism., (© 2021 UICC.)

Background: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking., Methods: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3., Results: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98)., Conclusion: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pancreatectomy with arterial resection is a treatment option in selected patients with locally advanced pancreatic cancer. This study aimed to identify factors predicting cancer-specific survival in this patient population. A single-Institution prospective database was used. Pre-operative prognostic factors were identified and used to develop a prognostic score. Matching with pathologic parameters was used for internal validation. In a patient population with a median Ca 19.9 level of 19.8 U/mL(IQR: 7.1-77), cancer-specific survival was predicted by: metabolic deterioration of diabetes (OR = 0.22, p = 0.0012), platelet count (OR = 1.00; p = 0.0013), serum level of Ca 15.3 (OR = 1.01, p = 0.0018) and Ca 125 (OR = 1.02, p = 0.00000137), neutrophils-to-lymphocytes ratio (OR = 1.16; p = 0.00015), lymphocytes-to-monocytes ratio (OR = 0.88; p = 0.00233), platelets-to-lymphocytes ratio (OR = 0.99; p = 0.00118), and FOLFIRINOX neoadjuvant chemotherapy (OR = 0.57; p = 0.00144). A prognostic score was developed and three risk groups were identified. Harrell's C-Index was 0.74. Median cancer-specific survival was 16.0 months (IQR: 12.3-28.2) for the high-risk group, 24.7 months (IQR: 17.6-33.4) for the intermediate-risk group, and 39.0 months (IQR: 22.7-NA) for the low-risk group (p = 0.0003). Matching the three risk groups against pathology parameters, N2 rate was 61.9, 42.1, and 23.8% (p = 0.04), median value of lymph-node ratio was 0.07 (IQR: 0.05-0.14), 0.04 (IQR:0.02-0.07), and 0.03 (IQR: 0.01-0.04) (p = 0.008), and mean value of logarithm odds of positive nodes was - 1.07 ± 0.5, - 1.3 ± 0.4, and - 1.4 ± 0.4 (p = 0.03), in the high-risk, intermediate-risk, and low-risk groups, respectively. An online calculator is available at www.survivalcalculator-lapdac-arterialresection.org . The prognostic factors identified in this study predict cancer-specific survival in patients with locally advanced pancreatic cancer and low Ca 19.9 levels undergoing pancreatectomy with arterial resection.

Minimally invasive pancreatic surgery is eventually gaining momentum, but concerns remain regarding the ability to manage challenging operative scenarios. A retrospective review of a prospectively maintained database was performed to identify patients who received arterial resection, or required arterial repair, during robot-assisted pancreatic resection (RA-PR). All procedures were video recorded. Between October 2008 and June 2019, a total of 361 RA-PR were performed. Associated vascular procedures were required in 31 patients (8.5%), including resection or repair of arterial segments in five cases (1.3%): celiac trunk (n = 1), hepatic artery (n = 2), splenic artery (n = 1), and superior mesenteric artery (n = 1). In three patients, an arterial resection was required to manage tumor infiltration. In the remaining two patients, an intraoperative injury demanded arterial repair. All procedures were completed without conversion to open surgery and no patient developed severe complications. At the longest follow-up, all vascular reconstructions are patent. Our results do not call for more liberal use of robotic assistance in borderline resectable or locally advanced pancreatic tumors, but rather emphasize the importance of proper preoperative planning and the need for advanced vascular skills for safe implementation of RA-PR.

Background: Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and treatment represents a still unresolved dilemma. Case Description: The patient was a 43-year-old Caucasian woman, with a 2-year history of repeated severe hypoglycemic events. The diagnostic work-up was strongly suggestive of insulinoma and the patient was submitted to surgical treatment carried out laparoscopically under robotic assistance. However, surgical exploration and intraoperative ultrasonography failed to detect a pancreatic tumor. Resection was therefore carried out based on the results of selective intra-arterial calcium stimulation test, following a step-up approach, eventually leading to a pancreatoduodenectomy at the splenic artery. The histopathology examination and the immunohistochemical staining were consistent with adult-onset nesidioblastosis. After surgery, the patient continued to experience hypoglycemia with futile response to medical treatments (octreotide, calcium antagonists, diazoxide, and prednisone). Following multidisciplinary evaluation and critical review of a repeat abdominal computed tomography scan, a small nodular lesion was identified in the tail of the pancreas. The nodule was enucleated laparoscopically and the pathological examination revealed an insulinoma. In spite of the insulinoma resection, glycemic values were only partially restored, with residual nocturnal hypoglycemia. Administration of uncooked cornstarch (1.25 g/kg body weight) at bedtime was associated with significant improvement of interstitial glucose levels ( p < 0.0001) and reduction of nocturnal hypoglycemia episodes ( p = 0.0002). Conclusions: This report describes a rare coexistence of adult-onset nesidioblastosis and insulinoma, suggesting the existence of a wide and continuous spectrum of proliferative β-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted., (Copyright © 2020 Dardano, Daniele, Lupi, Napoli, Campani, Boggi, Del Prato and Miccoli.)

Background: No study has shown the oncologic non-inferiority of robotic pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) for pancreatic cancer (PC)., Methods: This is a single institution propensity score matched study comparing RPD and ODP for resectable PC, based on factors predictive of R1 resection (≤ 1 mm). Only patients operated on after completion of the learning curve in both procedures and for whom circumferential margins were assessed according to the Leeds pathology protocol were included. The primary study endpoint was the rate of R1 resection. Secondary study endpoints were as follows: number of examined lymph nodes (N), rate of perioperative transfusions, percentage of patients receiving adjuvant therapies, occurrence of local recurrence, overall survival, disease-free survival, and sample size calculation for randomized controlled trials (RCT)., Results: Factors associated with R1 resection were tumor diameter, number of positive N, N ratio, logarithm odds of positive N, and duodenal infiltration. The matching process identified 20 RPDs and 24 OPDs. All RPDs were completed robotically. R1 resection was identified in 11 RPDs (55.0%) and in 10 OPDs (41.7%) (p = 0.38). There was no difference in the rate of R1 at each margin as well as in the proportion of patients with multiple R1 margins. RPD and OPD were also equivalent with respect to all secondary study endpoints, with a trend towards lower rate of blood transfusions in RPD. Based on the figures presented herein, a non-inferiority RCT comparing RPD and OPD having the rate of R1 resection as the primary study endpoint requires 3355 pairs., Conclusions: RPD and OPD achieved the same rate of R1 resections in resectable PC. RPD was also non-inferior to OPD with respect to all secondary study endpoints. Because of the high number of patients required to run a RCT, further assessment of RPD for PC would require the implementation of an international registry.

Introduction: The aim of this study is to analyze the evolution of pancreatectomy with venous resection in 10 referral Italian centers in the last 25 years., Methods: A multicenter database of 425 patients submitted to pancreatectomy with venous resection between 1991 and 2015 was retrospectively analyzed. Patients were classified in 5 periods: 1 (1991-1995); 2 (1996-2000); 3 (2001-2005); 4 (2006-2010); 5 (2011-2015). Indications and outcomes were compared according to the period of surgery., Results: Nineteen patients were operated in period 1, 28 in period 2, 91 in period 3, 140 in period 4, and 147 in period 5. Use of neoadjuvant therapy increased from 0% in period 1 and 2-12.1% in period 5. Postoperative complications ranged from 46.3% to 67.8%, and mortality from 5.3% to 9.2%. Median survival progressively increased, from 6 months in period 1-16 months in period 2, 24 months in period 3 and 4 and 35 months in period 5 (p = 0.004). Period, venous and nodal invasion were significant prognostic factors for survival., Conclusion: Management and outcomes of pancreatectomy with venous resection have evolved in the last 25 years in Italy. Improvement in patients' multidisciplinary management has lead to significant improvement of median survival., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The UICC/AJCC TNM staging system classifies lymph nodes as N0 and N1 in pancreatic cancer. Aim of the study is to determine whether the number of examine nodes, the nodal ratio (NR) and the logarithm odds of positive lymph nodes (LODDS) may better stratify the prognosis of patients undergoing pancreatectomy combined with venous resection for pancreatic cancer with venous involvement., Methods: A multicenter database of 303 patients undergoing pancreatectomy in 9 Italian referral centers was analyzed. The prognostic impact of number of retrieved and examined nodes, NR, LODDS was analyzed and compared with ROC curves analysis, Pearson test, univariate and multivariate analysis., Results: The number of metastatic nodes, pN, the NR and LODDS was significantly correlated with survival at multivariate analyses. The corresponding AUC for the number of metastatic nodes, pN, the NR and LODDS were 0.66, 0.69, 0.63 and 0.65, respectively. The Pearson test showed a significant correlation between the number of retrieved lymph nodes and number of metastatic nodes, pN and the NR. LODDS had the lower coefficient correlation. Concerning N1 patients, the NR, the LODDS and the number of metastatic nodes were able to significantly further stratify survival (p = 0.040; p = 0.046; p = 0.038, respectively)., Conclusions: The number of examined lymph nodes, the NR and LODDS are useful for further prognostic stratification of N1 patients in the setting of pancreatectomy combined with PV/SMV resection. No superiority of one over the others methods was detected.

Background: Robotic assistance enhances surgical dexterity and could facilitate wider adoption of laparoscopy for pancreatic resections (PR)., Methods: Data were prospectively entered into a database and analyzed retrospectively to assess feasibility and safety of robotic-assisted PR (RAPR). Additionally, robotic-assisted pancreaticoduodenectomy (RAPD) was compared to a contemporary group of open pancreaticoduodenectomies (OPD)., Results: Between October 2008 and October 2014, 200 consecutive patients underwent RAPR. Three procedures were converted to open surgery (1.5 %), despite 14 patients required associated vascular procedures. RAPD was performed in 83 patients (41.5 %), distal pancreatectomy in 83 (41.5 %), total pancreatectomy in 17 (8.5 %), tumor enucleation in 12 (6 %), and central pancreatectomy in 5 (2.5 %). Thirty-day and 90-day mortality rates were 0.5 and 1 %, respectively. Both deaths occurred after RAPD with vein resection. Complications occurred in 63.0 % of the patients (≥Clavien-Dindo grade IIIb in 4 %). Median comprehensive complication index was 20.9 (0-26.2). Incidence of grade B/C pancreatic fistula was 28.0 %. Reoperation was required in 14 patients (7.0 %). The risk of reoperation decreased after post-operative day 20 (OR 0.072) (p = 0.0015). When compared to OPD, RAPD was associated with longer mean operative time (527.2 ± 166.1 vs. 425.3 ± 92.7; <0.0001) but had an equivalent safety profile. The median number of examined lymph nodes (37; 28.8-45.3 vs. 36; 28-52.8) and the rate of margin positivity in patients diagnosed with pancreatic cancer were also similar (12.5 vs. 45.5 %)., Conclusions: RAPR, including RAPD, are safely feasible in selected patients. The results of RAPD in pancreatic cancer are encouraging but deserve further investigation.

Robotic assistance improves surgical dexterity in minimally invasive operations, especially when fine dissection and multiple sutures are required. As such, robotic assistance could be rewarding in the setting of robotic pancreatoduodenectomy (RPD). RPD was implemented at a high volume center with preemptive experience in advanced laparoscopy. Indications, surgical technique, and results of RPD are discussed against the background of current literature. RPD was performed in 112 consecutive patients. Conversion to open surgery was required in three patients, despite nine required segmental resection and reconstruction of the superior mesenteric/portal vein. No patient was converted to laparoscopy. A pancreato-jejunostomy was created in 106 patients (94.6 %), using either a duct-to-mucosa (n = 82; 73.2 %) or an invaginating (n = 24; 21.4 %) technique. Pancreato-gastrostomy was performed in one patient, the pancreatic duct was occluded in two patients, and a pancreatico-cutaneous fistula was created in three patients. Mean operative time was 526.3 ± 102.4 in the entire cohort and reduced significantly over the course of time. Experience was also associated with reduced rates of delayed gastric emptying and increased proportion of malignant tumor histology. Ninety day mortality was 3.6 %. Postoperative complications occurred in 83 patients (74.1 %) with a median comprehensive complication index of 20.9 (0-30.8). Clinically relevant pancreatic fistula occurred in 19.6 % of the patients. No grade C pancreatic fistula was noted in the last 72 consecutive patients. RPD is safely feasible in selected patients. Implementation of RPD requires sound experience with open pancreatoduodenectomy and advanced laparoscopic procedures, as well as specific training with the robotic platform.

Purpose: The role of pancreatectomy with en bloc venous resection and the prognostic impact of pathological venous invasion are still debated. The authors analyzed perioperative, survival results, and prognostic factors of pancreatectomy with en bloc portal (PV) or superior mesenteric vein (SMV) resection for borderline resectable pancreatic carcinoma, focusing on predictive factors of histological venous invasion and its prognostic role., Methods: A multicenter database of 406 patients submitted to pancreatectomy with en bloc SMV and/or PV resection for pancreatic adenocarcinoma was analyzed retrospectively. Univariate and multivariate analysis of factors related to histological venous invasion were performed using logistic regression model. Prognostic factors were analyzed with log-rank test and multivariate proportional hazard regression analysis., Results: Complications occurred in 51.9 % of patients and postoperative death in 7.1 %. Histological invasion of the resected vein was confirmed in 56.7 % of specimens. Five-year survival was 24.4 % with median survival of 24 months. Vein invasion at preoperative computed tomography (CT), N status, number of metastatic lymph nodes, preoperative serum albumin were related to pathological venous invasion at univariate analysis, and vein invasion at CT was independently related to venous invasion at multivariate analysis. Use of preoperative biliary drain was significantly associated with postoperative complications. Multivariate proportional hazard regression analysis demonstrated a significant correlation between overall survival and histological venous invasion and administration of adjuvant therapy., Conclusions: This study identifies predictive factors of pathological venous invasion and prognostic factors for overall survival, including pathological venous invasion, which may help with patients' selection for different treatment protocols.