The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study.

BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

Is prolonged operative time associated with postoperative complications in liver surgery? An international multicentre cohort study of 5424 patients.

BACKGROUND: The relation between operative time and postoperative complications in liver surgery is unclear. The aim of this study is to assess the impact of operative time on the development of postoperative complications in patients who underwent minimally invasive or open liver resections of various anatomical extent and technical difficulty levels. METHODS: In this retrospective cohort study, patients that underwent a right hemihepatectomy (RH), technically major resection (anatomically minor resection in segment 1, 4a, 7 or 8; TMR) or left lateral sectionectomy (LLS) between 2000 and 2022 were extracted from a multicenter database comprising the prospectively maintained databases of 31 centers in 13 countries. Minimally invasive procedures performed during the learning curve were omitted. Logistic regression models, performed separately for 9 different groups based on stratification by procedure type and allocated surgical approach, were used to assess the association between the fourth quartile of operative time (25% of patients with the longest operative time) and postoperative complications. RESULTS: Overall, 5424 patients were included: 1351 underwent RH (865 open, 373 laparoscopic and 113 robotic), 2821 TMR (1398 open, 1225 laparoscopic and 198 robotic), and 1252 LLS (241 open, 822 laparoscopic and 189 robotic). After adjusting for potential confounders (age, BMI, gender, ASA grade, previous abdominal surgery, disease type and extent, blood loss, Pringle, intraoperative transfusions and incidents), the fourth quartile of operative time, compared to the first three quartiles, was associated with an increased risk of postoperative complications after open, laparoscopic and robotic TMR (aOR 1.35, p = 0.031; aOR 1.74, p = 0.001 and aOR 3.11, p = 0.014, respectively), laparoscopic and robotic RH (aOR 1.98, p = 0.018 and aOR 3.28, p = 0.055, respectively) and solely laparoscopic LLS (aOR 1.69, p = 0.019). CONCLUSIONS: A prolonged operative time is associated with an increased risk of postoperative complications, although it remains to be defined if this is a causal relationship.

Explainable artificial intelligence prediction-based model in laparoscopic liver surgery for segments 7 and 8: an international multicenter study.

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Outcomes After Minimally Invasive Versus Open Total Pancreatectomy: A Pan-European Propensity Score Matched Study.

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.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Development and external validation of a prediction model for overall survival after resection of distal cholangiocarcinoma.

BACKGROUND: Various prognostic factors are associated with overall survival (OS) after resection of distal cholangiocarcinoma (dCCA). The objective of this study was to develop and validate a prediction model for 3-year OS after pancreatoduodenectomy for dCCA. METHODS: The derivation cohort consisted of all patients who underwent pancreatoduodenectomy for dCCA in the Netherlands (2009-2016). Clinically relevant variables were selected based on the Akaike information criterion using a multivariate Cox proportional hazards regression model, with model performance being assessed by concordance index (C-index) and calibration plots. External validation was performed using patients from the Belgium Cancer Registry (2008-2016), and patients from two university hospitals of Southampton (U.K.) and Verona (Italy). RESULTS: Independent prognostic factors for OS in the derivation cohort of 454 patients after pancreatoduodenectomy for dCCA were age (HR 1.02, 95% CI 1.01-1.03), pT (HR 1.43, 95% CI 1.07-1.90) and pN category (pN1: HR 1.78, 95% CI 1.37-2.32; pN2: HR 2.21, 95% CI 1.63-3.01), resection margin status (HR 1.79, 95% CI 1.39-2.29) and tumour differentiation (HR 2.02, 95% CI 1.62-2.53). The prediction model was based on these prognostic factors. The optimism-adjusted C-indices were similar in the derivation cohort (0.69), and in the Belgian (0.66) and Southampton-Verona (0.68) validation cohorts. Calibration was accurate in the Belgian validation cohort (slope = 0.93, intercept = 0.12), but slightly less optimal in the Southampton-Verona validation cohort (slope = 0.88, intercept = 0.32). Based on this model, three risk groups with different prognoses were identified (3-year OS of 65.4%, 33.2% and 11.8%). CONCLUSIONS: The prediction model for 3-year OS after resection of dCCA had reasonable performance in both the derivation and geographically external validation cohort. Calibration slightly differed between validation cohorts. The model is readily available via www. pancreascalculator.com to inform patients from Western European countries on their prognosis, and may be used to stratify patients for clinical trials.

Outcomes of a Multicenter Training Program in Robotic Pancreatoduodenectomy (LAELAPS-3).

OBJECTIVE: To assess feasibility and safety of a multicenter training program in robotic pancreatoduodenectomy (RPD) adhering to the IDEAL framework for implementation of surgical innovation. BACKGROUND: Good results for RPD have been reported from single center studies. However, data on feasibility and safety of implementation through a multicenter training program in RPD are lacking. METHODS: A multicenter training program in RPD was designed together with the University of Pittsburgh Medical Center, including an online video bank, robot simulation exercises, biotissue drills, and on-site proctoring. Benchmark patients were based on the criteria of Clavien. Outcomes were collected prospectively (March 2016-October 2019). Cumulative sum analysis of operative time was performed to distinguish the first and second phase of the learning curve. Outcomes were compared between both phases of the learning curve. Trends in nationwide use of robotic and laparoscopic PD were assessed in the Dutch Pancreatic Cancer Audit. RESULTS: Overall, 275 RPD procedures were performed in seven centers by 15 trained surgeons. The recent benchmark criteria for low-risk PD were met by 125 (45.5%) patients. The conversion rate was 6.5% (n = 18) and median blood loss 250ml [interquartile range (IQR) 150-500]. The rate of Clavien-Dindo grade ≥III complications was 44.4% (n = 122), postoperative pancreatic fistula (grade B/C) rate 23.6% (n = 65), 90-day complication-related mortality 2.5% (n = 7) and 90-day cancer-related mortality 2.2.% (n = 6). Median postoperative hospital stay was 12 days (IQR 8-20). In the subgroup of patients with pancreatic cancer (n = 80), the major complication rate was 31.3% and POPF rate was 10%. Cumulative sum analysis for operative time found a learning curve inflection point at 22 RPDs (IQR 10-35) with similar rates of Clavien-Dindo grade ≥III complications in the first and second phase (43.4% vs 43.8%, P = 0.956, respectively). During the study period the nationwide use of laparoscopic PD reduced from 15% to 1%, whereas the use of RPD increased from 0% to 25%. CONCLUSIONS: This multicenter RPD training program in centers with sufficient surgical volume was found to be feasible without a negative impact of the learning curve on clinical outcomes.

The Impact of Neoadjuvant Treatment on Survival in Patients Undergoing Pancreatoduodenectomy With Concomitant Portomesenteric Venous Resection: An International Multicenter Analysis.

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.

EAES online educational resources: a survey of the membership of the European Association for Endoscopic Surgery (EAES).

BACKGROUND: The European Association for Endoscopic Surgery (EAES) strives to be a leader in promoting the development and expansion of minimally invasive surgery (MIS). Part of the association's mission statement is "to become an information hub for all practitioners of MIS". It is therefore important that the education segment of the association continues to be actively monitored and updated to ensure this mission statement is met. This project aimed to understand the trainees requirement in fulfilling this role, and to develop an practical action plan to ensure such requirements are adequately met. METHODS: Two sequential questionnaires were sent to all members of the EAES. The questionnaires sought to understand the demographics of the EAES membership, and their training requirements. This followed a Delphi methodology. The data collected included training status, level of competence in laparoscopic surgery and tools needed for improving laparoscopic skills. RESULTS: Four hundred and sixty-five responded to the first survey, and 209 responded to the second survey. There were 112 trainees (24.1%) in the first round. More than 50% of trainees were less than 8 years from graduation from medical school. Only 162 (34.8%) of respondents performed MIS in more than half their practice. Videos of common procedures were ranked the highest in terms of what trainees required to help improve their laparoscopic skills, followed by e-learning modules. CONCLUSION: There is a significant training gap identified amongst the trainee population of the EAES with regards to MIS training. Trainees were not performing MIS enough for them to feel confident with their skills. The EAES could fulfill this training requirement via expertly curated videos, and e-learning modules written by senior specialists.

A systematic review and meta-analysis comparing the short- and long-term outcomes for laparoscopic and open liver resections for liver metastases from colorectal cancer.

BACKGROUND: The laparoscopic approach to liver resection has experienced exponential growth in recent years. However, evidence-based guidelines are needed for its safe future progression. The main aim of our study was to perform a systematic review and meta-analysis comparing the short- and long-term outcomes of laparoscopic and open liver resections for colorectal liver metastases (CRLM). METHODS: To identify all the comparative manuscripts between laparoscopic and open liver resections for CRLM, all published English language studies with more than ten cases were screened. In addition to the primary meta-analysis, 3 specific subgroup analyses were performed on patients undergoing minor-only, major-only and synchronous resections. The quality of the studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology and Newcastle-Ottawa Score. RESULTS: From the initial 194 manuscripts identified, 21 were meta-analysed, including results from the first randomized trial comparing open and laparoscopic resections of CRLM. Five of these were specific to patients undergoing a synchronous resection (399 cases), while six focused on minor (3 series including 226 cases) and major (3 series including 135 cases) resections, respectively. Thirteen manuscripts compared 2543 cases but could not be assigned to any of the above sub-analyses, so were analysed independently. The majority of short-term outcomes were favourable to the laparoscopic approach with equivalent rates of negative resection margins. No differences were observed between the approaches in overall or disease-free survival at 1, 3 or 5 years. CONCLUSION: Laparoscopic liver resection for CRLM offers improved short-term outcomes with comparable long-term outcomes when compared to open approach.

Laparoscopic right posterior sectionectomy (LRPS): surgical techniques and clinical outcomes.

BACKGROUND: Right posterior sectionectomy is one of the most technically challenging laparoscopic liver resections. Currently, there is limited published data regarding the technique and results required to better understand its safety and feasibility. AIM: To report our experience, results and techniques, highlighting a variety of tips and tricks to facilitate this resection. A video is attached for technical demonstration. METHODS: Retrospective review of prospectively maintained databases from June 2006 to June 2016. Three different techniques were used: resection following hilar inflow control, inflow control at Rouviere's sulcus and resection with intra parenchymal control. RESULTS: 29 LRPS were performed over a 10-year period. Median operative time was 240 min (150-480). Pringle's manoeuvre was performed in 19 (65.5%) with a median total duration of 35 (20-75) min. Median perioperative blood loss was 600 (100-2500) ml. Additional liver resections were performed in 16 (55.1%). There were two(6.9%) laparoscopic to open conversions. Median postoperative hospital stay was 5 (2-30) days. The median size of the tumour resected was 25 (10-54) mm with median number of resected lesions were 2 (1-4), median free resection margin was 9.5 (1-45) mm, margins were infiltrated (R1) in two (6.7%) cases. There was one death within 30-days (3.4%). CONCLUSION: LRPS is feasible, efficient and safe. However, it is a technically challenging procedure and requires advance skills in liver and laparoscopic surgery. Surgeons should be familiar with a variety of approaches as each offers different advantages depending on the location and nature of the lesion, surgical preference and intraoperative findings.

Impact of a Nationwide Training Program in Minimally Invasive Distal Pancreatectomy (LAELAPS).

OBJECTIVE: To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP). SUMMARY OF BACKGROUND DATA: Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown. METHODS: From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005-2013) were compared with outcomes after training (2014-2015). RESULTS: In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score ≥III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7-12] vs 7 [5-8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12). CONCLUSION: A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.

Study International Multicentric Pancreatic Left Resections (SIMPLR): Does Surgical Approach Matter?

BACKGROUND: Minimally invasive surgery is increasingly preferred for left-sided pancreatic resections. The SIMPLR study aims to compare open, laparoscopic, and robotic approaches using propensity score matching analysis. METHODS: This study included 258 patients with tumors of the left side of the pancreas who underwent surgery between 2016 and 2020 at three high-volume centers. The patients were divided into three groups based on their surgical approach and matched in a 1:1 ratio. RESULTS: The open group had significantly higher estimated blood loss (620 mL vs. 320 mL, p < 0.001), longer operative time (273 vs. 216 min, p = 0.003), and longer hospital stays (16.9 vs. 6.81 days, p < 0.001) compared to the laparoscopic group. There was no difference in lymph node yield or resection status. When comparing open and robotic groups, the robotic procedures yielded a higher number of lymph nodes (24.9 vs. 15.2, p = 0.011) without being significantly longer. The laparoscopic group had a shorter operative time (210 vs. 340 min, p < 0.001), shorter ICU stays (0.63 vs. 1.64 days, p < 0.001), and shorter hospital stays (6.61 vs. 11.8 days, p < 0.001) when compared to the robotic group. There was no difference in morbidity or mortality between the three techniques. CONCLUSION: The laparoscopic approach exhibits short-term benefits. The three techniques are equivalent in terms of oncological safety, morbidity, and mortality.

Autogenic splenic implantation versus splenectomy in patients undergoing distal pancreatectomy for benign or low-grade malignant lesions of the distal pancreas: study protocol for a multicentre, open-label, randomized controlled trial (RESTORE).

BACKGROUND: The spleen plays a significant role in the clearance of circulating microorganisms. Sequelae of splenectomy, especially immunodeficiency, can have a deleterious effect on a patient's health and even lead to death. Hence, splenectomy should be avoided and spleen preservation during elective surgery has become a treatment goal. However, this cannot be achieved in every patient due to intraoperative technical difficulties or oncological reasons. Autogenic splenic implantation (ASI) is currently the only possible way to preserve splenic function when a splenectomy is necessary. Experience largely stems from trauma patients with a splenic rupture. Splenic immune function can be measured by the body's clearing capacity of encapsulated bacteria. The aim of this study is to assess the splenic immune function after ASI was performed during minimally invasive (laparoscopic or robotic) distal pancreatectomy with splenectomy. METHODS: This is the protocol for a multicentre, randomized, open-labelled trial. Thirty participants with benign or low-grade malignant lesions of the distal pancreas requiring minimally invasive distal pancreatectomy and splenectomy will be allocated to either additional intraoperative ASI (intervention) or no further intervention (control). An additional 15 patients who will undergo spleen-preserving distal pancreatectomy serve as the control group with normal splenic function. Six months postoperatively, after assumed restoration of splenic function, patients will be given a Salmonella typhi (Typhim Vi™) vaccine. The Salmonella typhi vaccine is a polysaccharide vaccine. The specific antibody titres immediately before and 4 to 6 weeks after vaccination will be measured. The ratio between pre- and post-vaccination antibody count is the primary outcome measure and secondary outcome measures include intraoperative details, length of hospital stay, 30-day mortality and morbidity. DISCUSSION: This study will investigate the splenic immune function of patients who undergo ASI during minimally invasive distal pancreatectomy with splenectomy. The splenic immune function will be measured using the surrogate outcome of specific antibody titre after vaccination with a Salmonella typhi vaccine. The results will reveal details about splenic function after ASI and guide further treatment options for patients when a splenectomy cannot be avoided. It might eventually lead to a new standard of care making sometimes more demanding and time-consuming spleen-preserving procedures redundant. TRIAL REGISTRATION: International Standard Randomized Controlled Trials Number (ISRCTN) ISRCTN10171587. Prospectively registered on 18 February 2019.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Neoadjuvant Chemotherapy for Intrahepatic, Perihilar, and Distal Cholangiocarcinoma: a National Population-Based Comparative Cohort Study.

INTRODUCTION: Data supporting the utilization of neoadjuvant chemotherapy (NAC) in patients receiving resection for cholangiocarcinoma (CCA) remains uncertain. We aimed to determine whether NAC followed by resection improves long-term survival in intrahepatic (iCCA), perihilar (hCCA), and distal (dCCA) cholangiocarcinoma, analyzed separately. METHODS: Patients undergoing surgery for iCCA, hCCA, and dCCA, receiving either none, NAC, or adjuvant chemotherapy (AC) from 2010 to 2016 were identified from the National Cancer Database (NCDB). Cox regression was performed to account for selection bias and to assess the impact of surgery alone (SA) versus either NAC or AC on overall survival (OS). RESULTS: There were 9411 patients undergoing surgery for iCCA (n = 3772, 39.5%), hCCA (n = 1879, 20%), and dCCA (n = 3760, 40%). Of these, 10.6% (n = 399), 6.5% (n = 123), and 7.2% (n = 271) with iCCA, hCCA, and dCCA received NAC, respectively. On adjusted analyses, patients receiving NAC followed by surgery had significantly improved OS, compared to SA for iCCA (HR 0.75, CI95% 0.64-0.88, p < 0.001), hCCA (HR 0.72, CI95% 0.54-0.97, p = 0.033), and for dCCA (HR 0.65, CI95% 0.53-0.78, p < 0.001). However, sensitivity analyses demonstrated no differences in OS between NACs, followed by surgery or AC after surgery in iCCA (HR 1.19, CI95% 0.99-1.45, p = 0.068), hCCA (HR 0.83 CI95% 0.59-1.19, p = 0.311), and dCCA (HR 1.13 CI95% 0.91-1.41, p = 0.264). CONCLUSIONS: This study associated NAC with increased OS for all CCA subtypes, even in patients with margin-negative and node-negative disease; however, no differences were found between NAC and AC. Our results highlight that a careful and interdisciplinary evaluation should be sought to consider NAC in CCA and warrant the need of larger studies to provide robust recommendation.

What Is the Current Role and What Are the Prospects of the Robotic Approach in Liver Surgery?

In parallel with the historical development of minimally invasive surgery, the laparoscopic and robotic approaches are now frequently utilized to perform major abdominal surgical procedures. Nevertheless, the role of the robotic approach in liver surgery is still controversial, and a standardized, safe technique has not been defined yet. This review aims to summarize the currently available evidence and prospects of robotic liver surgery. Minimally invasive liver surgery has been extensively associated with benefits, in terms of less blood loss, and lower complication rates, including liver-specific complications such as clinically relevant bile leakage and post hepatectomy liver failure, when compared to open liver surgery. Furthermore, comparable R0 resection rates to open liver surgery have been reported, thus, demonstrating the safety and oncological efficiency of the minimally invasive approach. However, whether robotic liver surgery has merits over laparoscopic liver surgery is still a matter of debate. In the current literature, robotic liver surgery has mainly been associated with non-inferior outcomes compared to laparoscopy, although it is suggested that the robotic approach has a shorter learning curve, lower conversion rates, and less intraoperative blood loss. Robotic surgical systems offer a more realistic image with integrated 3D systems. In addition, the improved dexterity offered by robotic surgical systems can lead to improved intra and postoperative outcomes. In the future, integrated and improved haptic feedback mechanisms, artificial intelligence, and the introduction of more liver-specific dissectors will likely be implemented, further enhancing the robots' abilities.