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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).)

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).)

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).)

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).)

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.

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.

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6-10 cases in 38.9% of the centers, 11-20 cases in 16.7%, 21-30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.

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.

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.

No data are available on the learning curve in robotic distal pancreatectomy (RADP). The learning curve in RADP was assessed in 55 consecutive patients using the cumulative sum method, based on operative time. Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of surgery. No operation was converted to laparoscopic or open surgery and no patient died. Post-operative complications occurred in 34 patients (61.8%), being of Clavien-Dindo grade I-II in 32 patients (58.1%), including pancreatic fistula in 29 patients (52.7%). No grade C pancreatic fistula occurred. Four patients received blood transfusions (7.2%), three were readmitted (5.4%) and one required repeat surgery (1.8%). Based on the reduction of operative times (421.1 ± 20.5 vs 248.9 ± 9.3 min; p < 0.0001), completion of the learning curve was achieved after ten operations. Operative time of the first 10 operations was associated with a positive slope (0.47 + 1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45 procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p < 0.0001*). After completion of the learning curve, more patients had a malignant histology (0 vs 35.6%; p = 0.002), accounting for both higher lymph node yields (11.1 ± 12.2 vs 20.9 ± 18.5) (p = 0.04) and lower rate of spleen preservation (90 vs 55.6%) (p = 0.04). RADP was safely feasible in selected patients and the learning curve was completed after ten operations. Improvement in clinical outcome was not demonstrated, probably because of the limited occurrence of outcome comparators.