The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

Correction to: Single-centre comparison of robotic and open pancreatoduodenectomy: a propensity score-matched study.

In the Abstract, in the Methods section the sentence "Of the 121 included patients, 78 underwent RAPD and 43 underwent OPD." Should read: Of the 121 included patients, 77 underwent OPD and 44 underwent RAPD."

Single-centre comparison of robotic and open pancreatoduodenectomy: a propensity score-matched study.

BACKGROUND: Pancreatoduodenectomy for pancreatic head and periampullary cancers is still associated with high perioperative morbidity and mortality. The aim of this study was to compare the short-term outcomes of robot-assisted pancreatoduodenectomy (RAPD) and open pancreatoduodenectomy (OPD) performed in a high-volume centre. METHODS: A single-centre, prospective database was used to retrospectively compare the early outcomes of RAPD procedures to standard OPD procedures completed between January 2014 and December 2018. Of the 121 included patients, 78 underwent RAPD and 43 underwent OPD. After propensity score matching (PSM), 35 RAPD patients were matched with 35 OPD patients with similar preoperative characteristics. RESULTS: There were no statistically significant differences in most of the baseline demographics and perioperative outcomes in the two groups after PSM optimization with the exception of the operative time (530 min (RAPD) versus 335 min (OPD) post-match, p < 0.000). No differences were found between the two groups in terms of complications (including pancreatic leaks, 11.4% in both OPD and RAPD), perioperative mortality, reoperations or readmissions. Earlier refeeding was obtained in the RAPD group vs. the OPD group (3 vs. 4 days, p = 0.002). Although the differences in the length of the hospital stay and blood transfusions were not statistically significant, both parameters showed a positive trend in favour of RAPD. The number of harvested lymph nodes was similar and oncologically adequate. CONCLUSIONS: RAPD is a safe and oncologically adequate technique to treat malignancies arising from the pancreatic head and periampullary region. Several perioperative parameters resulted in trends favouring RAPD over OPD, at the price of longer operating time. Data should be reinforced with a larger sample to guarantee statistical significance.

The Cholegas trial: long-term results of prophylactic cholecystectomy during gastrectomy for cancer-a randomized-controlled trial.

BACKGROUND: The incidence of cholelithiasis has been shown to be higher for patients after gastrectomy than for the general population, due to vagal branch damage and gastrointestinal reconstruction. The aim of this trial was to evaluate the need for routine concomitant prophylactic cholecystectomy (PC) during gastrectomy for cancer. METHODS: A multicenter, randomized, controlled trial was conducted between November 2008 and March 2017. Of the total 130 included patients, 65 underwent PC and 65 underwent standard gastric surgery only for curable cancers. The primary endpoint was cholelithiasis-free survival after gastrectomy for gastric adenocarcinoma. Cholelithiasis was detected by ultrasound exam. RESULTS: After a median follow-up of 62 months, eight patients (12.3%) in the control group developed biliary abnormalities (four cases of gallbladder calculi and four cases of biliary sludge), with only three (4.6%) being clinically relevant (two cholecystectomies needed, one acute pancreatitis). One patient in the PC group had asymptomatic biliary dilatation during sonography after surgery. The cholelithiasis-free survival did not show statistical significance between the two groups (P = 0.267). The number needed to treat with PC to avoid reoperation for cholelithiasis was 1:32.5. CONCLUSIONS: Concomitant PC during gastric surgery for malignancies, although reducing the absolute number of biliary abnormalities, has no significant impact on the natural course of patients.

Robotic enucleations of pancreatic benign or low-grade malignant tumors: preliminary results and comparison with robotic demolitive resections.

BACKGROUND: The incidental detection of benign to low-grade malignant small pancreatic neoplasms increased in the last decades. The surgical management of these patients is still under debate. The aim of this paper is to evaluate the safety and feasibility of robotic enucleations and to compare the outcomes with non-parenchymal sparing robotic resections. METHODS: The study included a total of 25 patients. Nine of them underwent a robotic enucleation (EN Group) and 16 patients received a robotic demolitive resection (DR Group). Perioperative and medium-term outcomes were compared between the two groups. RESULTS: Patients' baseline characteristics were similar in the two groups except for presence of symptoms and tumor size, due to the inclusion criteria. Operative time was significantly shorter and postoperative results were better for EN group, including a significant shorter hospitalization (5 vs. 8 days, p = 0.027), reduced pancreatic leaks (22% vs. 50%, p = 0.287) and a better preservation of glandular function (100% vs. 62.5%, p = 0.066). Mortality rate was zero in both groups, with all patients free from disease at a median follow-up of 18 months. CONCLUSIONS: The risks of under/overtreatment remain still unavoidable for benign to low-grade malignant small pancreatic neoplasms. Simple enucleation should be performed whenever oncological appropriate, to achieve the best postoperative outcomes. The adoption of robotic technique might widen the indications for parenchymal sparing, minimally invasive surgery.

Association Between Compliance to an Enhanced Recovery Protocol and Outcome After Elective Surgery for Gastric Cancer. Results from a Western Population-Based Prospective Multicenter Study.

BACKGROUND: The association between compliance to an enhanced recovery protocol (ERAS) and outcome after surgery for gastric cancer has been poorly investigated, particularly in Western patients. The aim of the study was to evaluate whether the rate of adherence to the ERAS program was correlated with outcome and time of discharge. METHODS: A prospective, observational, multicenter study was designed to be performed at Italian referral centers for gastric surgery. The protocol was discussed and approved by the Italian Research Group on Gastric Cancer. Twenty-three ERAS domains were applied. A multivariate logistic regression was used to assess the association between ERAS compliance and overall and major complication rates. The Poisson regression model (measured as mean ratios) was used to assess the association of ERAS compliance rate and length of stay (LOS). RESULTS: Eight centers participated and 290 subjects with a median age of 73 years were enrolled. The overall rates of adherence to pre-, intra-, and postoperative ERAS items were 69.8%, 60.3%, and 82.5%, respectively. At the multivariate model, there was an association between overall rate of morbidity and an overall ERAS compliance rate greater than 70% (OR 0.413; 95% CI 0.235-0.7240; P 0.002). A similar association was found for major complications (OR 0.328; 95% CI 0.151-0.709; P 0.005). The Poisson regression showed that in patients with ERAS compliance rate >70%, LOS was reduced of approximately 20% (mean ratio 0.812; 95% CI 0.694-0.950; P 0.009). CONCLUSIONS: These results suggest a moderate compliance to an ERAS program and a significant association between adherence and outcomes.

Ultrasound-Guided Robotic Enucleation of Pancreatic Neuroendocrine Tumors.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are relatively rare neoplasms with a low to mild malignant potential. They can be further divided into functioning and nonfunctioning, according to their secretive activity. Surgery is an optimal approach, but the classic open approach is challenging, with some patients having long hospitalization and potentially life-threatening complications. The robotic approach for PanNETs may represent an option to optimize their management. METHODS: We retrospectively reviewed our prospectively maintained databases from 2 high-volume Italian centers for pancreatic surgery. Demographics, pathological characteristics, perioperative outcome, and medium-term follow-up of patients who underwent robotic pancreatic enucleations were collected. RESULTS: Twelve patients with final diagnosis of PanNET were included. The mean age of the patients was 53.8 years (25-77). The median body mass index was 26 (24-29). Three lesions were functioning insulinomas, while the others were nonfunctioning tumors. No deaths occurred. Mild postoperative complications occurred, except for 1 grade B pancreatic fistula. The mean postoperative stay was 3.9 days (2-5). CONCLUSIONS: Our results confirm that robotic enucleation is a feasible and safe approach for the treatment of PanNETs, with short hospital stay and low incidence of morbidity.

Minimally invasive versus open pancreatic enucleation. Systematic review and meta-analysis of surgical outcomes.

Parenchymal sparing procedures are gaining interest in pancreatic surgery and recent studies have reported that minimally invasive pancreatic enucleation may be associated with enhanced outcomes when compared with traditional surgery. By meta-analyzing the available data from the literature, minimally invasive surgery is not at higher risk of pancreatic fistula and offers a number of advantages over conventional surgery for pancreatic enucleation.

Intra-tumoral IFN-γ-producing Th22 cells correlate with TNM staging and the worst outcomes in pancreatic cancer.

PDAC (pancreatic ductal adenocarcinoma) is the fifth leading cause of cancer-related death. The causes of this cancer remain unknown, but increasing evidence indicates a key role of the host immune response and cytokines in human carcinogenesis. Intra-tumoral IL (interleukin)-22 levels have been shown to be elevated in PDAC patients. However, little is known regarding the expression and clinical relevance of Th22 cells in human PDAC and, furthermore, which TILs (tumour-infiltrating lymphocytes) are the main producers of IL-22 is unknown. In the present study, we characterized the functional proprieties of the different subsets of IL-22-producing TILs and analysed their relationship with the TNM staging system and patient survival. We have demonstrated for the first time that, in PDAC patients, the T-cells co-producing IFN-γ (interferon γ) and exerting perforin-mediated cytotoxicity are the major intra-tumoral source of IL-22. In addition, isolated Th22 cells were able to induce apoptosis, which was antagonized by IL-22. Finally, we observed that the IL-22-producing T-cells were significantly increased in tumour tissue and that this increase was positively correlated with TNM staging of PDAC and poorer patient survival. These novel findings support the dual role of the anti-tumour immune system and that IL-22-producing cells may participate in PDAC pathogenesis. Therefore monitoring Th22 levels could be a good diagnostic parameter, and blocking IL-22 signalling may represent a viable method for anti-PDAC therapies.

Novel prognostic factors after radical resection of hepatocellular carcinoma: Updating an old issue.

In this editorial, I comment on the article by Li et al published in the recent issue of the World Journal of Gastrointestinal Surgery in 2023, investigating the role of some novel prognostic factors for early survival after radical resection of liver cancer. Liver cancer is an important burden among Asian and Western populations, despite recent advances in both medicine (from virus eradication to systemic target therapies) and surgery. However, survival after proven radical surgery remains poor, with recurrences being the rule. Many prognostic scores have been developed and validated to select those patients who will best benefit from radical liver surgery, although the final general and oncological outcomes continue to be highly jeopardized. Unfortunately, no single biomarker can resolve all these issues for hepatocellular carcinoma, and it remains to be proven whether some of them maintain predictive power in the long-term follow-up. In the ongoing era of "precision" medicine, the novel prognostic markers, including immune inflammatory and nutritional indexes could be of great help in better stratify surgical candidates.

Ex vivo analysis of pancreatic cancer-infiltrating T lymphocytes reveals that ENO-specific Tregs accumulate in tumor tissue and inhibit Th1/Th17 effector cell functions.

Pancreatic cancer (PC) is an aggressive disease with dismal prognosis. Surgical resection is the recommended treatment for long-term survival, but patients with resectable PC are in the minority (with a 5-year survival rate of 20 %). Therefore, development of novel therapeutic strategies, such as anti-PC immunotherapy, is crucial. α-Enolase (ENO1) is an enzyme expressed on the surface of pancreatic cancer cells and is able to promote cell migration and cancer metastasis. The capacity of ENO1 to induce an immune response in PC patients renders it a true tumor-associated antigen. In this study, we characterized the effector functions of ENO1-specific T cells isolated from PC patients, and we specifically evaluated the successful role of intra-tumoral T helper 17 (Th17) cells and the inhibitory role of regulatory T (Tregs) cells in respectively promoting or reducing the cancer-specific immune response. In this ex vivo study, we have demonstrated, for the first time, that ENO1-specific Th17 cells have a specific anti-cancer effector function in PC patients, and that there are decreased levels of these cells in cancer compared to healthy mucosa. Conversely, there are elevated levels of ENO1-specific Tregs in PC patients which lead to inhibition of the antigen-specific effector T cells, thus highlighting a possible role in promoting PC progression. These results may be relevant for the design of novel immunotherapeutic strategies in pancreatic cancer.

The Cholegas Study: safety of prophylactic cholecystectomy during gastrectomy for cancer: preliminary results of a multicentric randomized clinical trial.

BACKGROUND: Cholelithiasis is more frequent in patients after gastrectomy, due to dissection of vagal branches and gastrointestinal reconstruction. METHODS: A randomized controlled trial was conducted from November 2008 to March 2012. Patients were randomized into two groups: prophylactic cholecystectomy (PC) and standard gastric surgery only (SS) for curable cancers. We planned three end points: evaluation of the number of patients who developed symptoms and needed further surgery for cholelithiasis after standard gastric cancer surgery, evaluation of the incidence of cholelithiasis overall after standard gastric cancer surgery and perioperative complications or costs of prophylactic cholecystectomy. The present study answers to the last end point only. RESULTS: After 40 months from the beginning of study, 172 patients were eligible from 9 Centers. Ten patients refused consent and 32 were excluded due to flawing of inclusion criteria (not confirmed adenocarcinomas and no R0 surgery). Therefore, final analysis included 130 patients: 65 in PC group and 65 in SS. Among PC group, 12 patients had surgical complications during the perioperative period; only 1 biliary leakage, conservatively treated, might have been caused by prophylactic cholecystectomy. 6 patients had surgical complications in SS group. One postoperative death occurred in PC group due to pulmonary embolism. Differences were not statistically significant. Similarly, no differences were significant in duration of surgery, blood loss, hospital stay. CONCLUSIONS: Concomitant cholecystectomy during standard surgery for gastric malignancies seemed to add no extra perioperative morbidity, mortality and costs to the sample included in the study.

Routine use of simultaneous laparoendoscopic approach in patients with confirmed gallbladder and bile duct stones: fit for laparoscopy fit for "rendezvous".

BACKGROUND: The aim of the present work was to determine the feasibility and efficacy, in terms of equipment coordination and timing, of the laparoendoscopic intraoperative rendezvous technique (RVT) for the treatment of gallbladder and common bile duct stones (CBDS). METHODS: The procedure was considered in 269 unselected patients with a suspicion or preoperative imaging demonstration of CBDS who were fit for laparoscopic cholecystectomy (LC). Common bile duct stones were confirmed by intraoperative laparoscopic cholangiography (IOC) in only 113 of these patients (42 %). In 17 (15 %) patients the planned procedure was aborted because of organizational problems, mainly the unavailability of endoscopists in the urgent setting. The remaining 96 patients (84 %) underwent a formal attempt at RVT. Intraoperative endoscopic retrograde cholangiography (ERC) was performed, during LC, by means of a guidewire that reached the duodenum through the cystic duct. RESULTS: In 18 patients (19 %) the complete procedure failed, either because of difficulty in passing the guidewire through the papilla or because of other technical difficulties that required conversion to laparotomy. An intraoperative ERC was completed in six patients in the classical way (no guidewire) without conversion. No mortality and few complications were recorded (3 % overall: 1 perforation and 2 cholangitis). Retained stones were successively detected in 6 patients (6 %) and successfully retreated by a further ERC. Globally, the one-stage procedure (with and without the guidewire) was possible in 84 of 96 patients (87 %). CONCLUSIONS: The RVT appears to be effective and safe as it was performed at our institution, with an overall percentage of definitive success (passed guide wire and no further ERC) of 81 %. The RVT should be considered as a good option for the treatment of simultaneous gallstones and CBDS.

Distal pancreatectomy with or without radical approach, vascular resections and splenectomy: Easier does not always mean easy.

Because distal pancreatectomy (DP) has no reconstructive steps and less frequent vascular involvement, it is thought to be the easier counterpart of pancreaticoduodenectomy. This procedure has a high surgical risk and the overall incidences of perioperative morbidity (mainly pancreatic fistula), and mortality are still high, in addition to the challenges that accompany delayed access to adjuvant therapies (if any) and prolonged impairment of daily activities. Moreover, surgery to remove malignancy of the body or tail of the pancreas is associated with poor long-term oncological outcomes. From this perspective, new surgical approaches, and aggressive techniques, such as radical antegrade modular pancreato-splenectomy and DP with celiac axis resection, could lead to improved survival in those affected by more locally advanced tumors. Conversely, minimally invasive approaches such as laparoscopic and robotic surgeries and the avoidance of routine concomitant splenectomy have been developed to reduce the burden of surgical stress. The purpose of ongoing surgical research has been to achieve significant reductions in perioperative complications, length of hospital stays and the time between surgery and the beginning of adjuvant chemotherapy. Because a dedicated multidisciplinary team is crucial to pancreatic surgery, hospital and surgeon volumes have been confirmed to be associated with better outcomes in patients affected by benign, borderline, and malignant diseases of the pancreas. The purpose of this review is to examine the state of the art in distal pancreatectomies, with a special focus on minimally invasive approaches and oncological-directed techniques. The widespread reproducibility, cost-effectiveness and long-term results of each oncological procedure are also taken into deep consideration.

A national survey on the current status of minimally invasive gastric practice on behalf of GIRCG.

Italian Research Group for Gastric Cancer (GIRCG), during the 2013 annual Consensus Conference to gastric cancer, stated that laparoscopic or robotic approach should be limited only to early gastric cancer (EGC) and no further guidelines were currently available. However, accumulated evidences, mainly from eastern experiences, have supported the application of minimally invasive surgery also for locally advanced gastric cancer (AGC). The aim of our study is to give a snapshot of current surgical propensity of expert Italian upper gastrointestinal surgeons in performing minimally invasive techniques for the treatment of gastric cancer in order to answer to the question if clinical practice overcome the recommendation. Experts in the field among the Italian Research Group for Gastric Cancer (GIRCG) were invited to join a web 30-item survey through a formal e-mail from January 1st, 2020, to June 31st, 2020. Responses were collected from 46 participants out of 100 upper gastrointestinal surgeons. Percentage of surgeons choosing a minimally invasive approach to treat early and advanced gastric cancer was similar. Additionally analyzing data from the centers involved, we obtained that the percentage of minimally invasive total and partial gastrectomies in advanced cases augmented with the increase of surgical procedures performed per year (p = 0.02 and p = 0.04 respectively). It is reasonable to assume that there is a widening of indications given by the current national guideline into clinical practice. Propensity of expert Italian upper gastrointestinal surgeons was to perform minimally invasive surgery not only for early but also for advanced gastric cancer. Of interest volume activity correlated with the propensity of surgeons to select a minimally invasive approach.

Isoforms of the orphan nuclear receptor COUP­TFII differentially modulate pancreatic cancer progression.

The expression of the nuclear receptor transcription factor (TF) COUP­TFII is broadly associated with cell differentiation and cancer development, including of pancreatic ductal adenocarcinoma (PDAC), a devastating disease with one of the poorest prognoses among cancers worldwide. Recent studies have started to investigate the pathological and physiological roles of a novel COUP­TFII isoform (COUP­TFII_V2) that lacks the DNA­binding domain. As the role of the canonical COUP­TFII in PDAC was previously demonstrated, the present study evaluated whether COUP­TFII_V2 may have a functional role in PDAC. It was demonstrated that COUP­TFII_V2 naturally occurs in PDAC cells and in primary samples, where its expression is consistent with shorter overall survival and peripheral invasion. Of note, COUP­TFII_V2, exhibiting nuclear and cytosolic expression, is linked to epithelial to mesenchymal transition (EMT) and cancer progression, as confirmed by nude mouse experiments. The present results demonstrated that COUP­TFII_V2 distinctively regulates the EMT of PDAC and, similarly to its sibling, it is associated with tumor aggressiveness. The two isoforms have both overlapping and exclusive functions that cooperate with cancer growth and dissemination. By studying how PDAC cells switch from one isoform to the other, novel insight into cancer biology was gained, indicating that this receptor may serve as a novel possible target for PDAC management.

Robotic enucleation for oesophageal benign and borderline tumours: Less is more?

BACKGROUND: Oesophageal benign to borderline tumours are rare entities, and their optimal treatment strategy remains controversial. Surgical robotic enucleation is an option to optimize their management. METHODS: We prospectively collected data on seven consecutive oesophageal benign to borderline tumours operated robotically over a 4-year period. Patient baseline characteristics, perioperative outcomes and medium-term follow-ups were reviewed and analysed retrospectively. RESULTS: Two patients underwent a robotic oesophagectomy and five underwent a simple enucleation. These last were the objective of the final analysis. Median operative time was 150 min. Neither deaths nor postoperative complications occurred. Median oral feeding started on postoperative day 3.5. The median postoperative stay was 5 days. Final histopathology confirmed two gastrointestinal stromal tumours, two leiomyomas and one simple cyst. CONCLUSIONS: Robotic enucleation of oesophageal benign to borderline tumours is a feasible procedure in a dedicated oesophageal unit, with optimal perioperative outcomes in a small series of cases with limited follow-up.

Robotic Versus Open Liver Resection in Hepatocarcinoma: Surgical and Oncological Outcomes.

BACKGROUND: Minimally invasive approaches are spreading in every field of surgery, including liver surgery. However, studies comparing robotic hepatectomy with the conventional open approach regarding oncologic outcomes for hepatocellular carcinoma are limited. MATERIALS AND METHODS: We retrospectively reviewed demographics characteristics, pathologic features, surgical, and oncological outcomes of patients who underwent robotic and conventional open liver resection for hepatocellular carcinoma. RESULTS: No significant differences in demographics features, tumor size, tumor location, and type of liver resection were found. The morbidity rate was similar, 23% for the open group versus 17% of the robotic group (P=0.605). Perioperative data analysis showed a greater estimated blood loss in patients who underwent open resection, if compared with robotic group (P=0.003). R0 resection and disease-free resection margins showed no statistically significant differences. The 3-year disease-free survival of the robotic group was comparable with that of the open group (54% vs. 37%; P=0.592), as was the 3-year overall survival (87% vs. 78%; P=0.203). CONCLUSIONS: The surgical and the oncological outcomes seem to be comparable between minimally invasive and open hepatectomy. Robotic liver resections are effective, and do not compromise the oncological outcome, representing a reasonable alternative to the open approach.

Robotic versus open pancreaticoduodenectomy: Is there any difference for frail patients?

BACKGROUND: Old age and frailty are predictors of early postoperative results after pancreatic surgery. We analysed the results of robotic and open pancreatoduodenectomy in elderly and frail patients. METHODS: Data from the local robotic pancreatoduodenectomy database were reviewed and matched with those from open operations during the same period (2014-2020). Both old age and frailty were used to determine any correlation with postoperative outcomes. Elderly patients were defined as patients aged 70 years or more, while frailty was classified according to the validated modified Frailty Index. RESULTS: A total of 118 pancreatoduodenectomies were included in the analysis: 65 (55.1%) robotic and 53 (44.9%) open. More than 50% of patients were frail. Overall, 7.6% of patients experienced grade IV Clavien-Dindo complications, and 3.4% died within 90 days after surgery. Frail patients experienced a similar rate of severe complications after robotic vs. open operations (5.3 vs. 11.6; p = 0.439) but earlier refeeding (3 days vs. 4 days; p = 0.006) and earlier drain removal (6 days vs. 7 days; p = 0.046) when operated on by a robotic approach. The oncological outcomes, including limphnodes retrieval, residual disease, recurrences, and survival, were not influenced by the surgical approach. Non-elderly patients also showed more benefits with the robotic approach (lower complication index, earlier refeeding, and drain removal). CONCLUSIONS: Robotic pancreatoduodenectomy is associated with risks of major complications that are comparable to those of open operation in frail patients. Some perioperative parameters (refeeding, drain removal) seem to favour robotics in frail patients and younger patients, although at the price of longer operating times.