Background/Objectives: Heterogeneity in clinical scenarios of colorectal liver metastases (CRLM) leads to the possible application of different surgical strategies. Specifically, the possibility of performing combined colorectal and liver resections for synchronous CRLM has been proposed in specific settings but its feasibility, safety and impact in minimally invasive settings remain underexplored. This study examines a multicenter Italian experience, comparing perioperative outcomes of combined (CR) versus non-combined (NCR) minimally invasive liver resections (MILR) for CRLM. Methods: Patients from the prospective multicenter registry of the Italian Group of Minimally Invasive Liver Surgery (I Go MILS) who underwent MILR for CRLM between 2016 and 2024 were included. Perioperative outcomes were compared between CR and NCR using Nearest Neighbor Matching. Results: In total, 2286 patients were analyzed, including 1879 NCR and 407 CR. CR was associated with less challenging resections (technical difficulty Kawaguchi grade III: 7.13% vs. 14.53%, p < 0.001), longer operative time (385 vs. 270 min, p < 0.001) and higher major complication rate (11.55% vs. 5.11%, p < 0.001) compared to NCR. The conversion rate was similar between the two groups (9.09% vs. 7.91%, p = 0.479). Technical complexity, operative time, conversion, low-volume hospital, and CR was an independent predictor of major complications after matching. Conclusions: CR is associated with a higher risk of postoperative complications, despite being selected for minor liver resections, confirming the impact of associated colorectal surgery in determining the postoperative risk and hence highlighting the concept that accurate preoperative patient selection is a key step in guiding treatment allocation for CRLM. Therefore, MILR does not yet justify broadening indications for combined resection beyond carefully selected patients.

Background: Pancreatic ductal adenocarcinoma (PDAC) belongs to the group of killer human cancers. Its ferocity is sustained by an unusual mix of genetic changes—primarily in KRAS and TP53—a hypoxic as well as desmoplastic tumor microenvironment, plus metabolic and redox adaptations that allow tumor life amidst intense stress situations. Content: This paper will discuss the molecular networks of wild-type and mutant p53, wild-type and mutant KRAS, PUMA, TIGAR, PRMT5, NRF2, oxygen tension, reactive oxygen species (ROS), and oxidative stress pathways that contribute to pancreatic cancer. It will describe how these factors help set the tumor’s redox state and control apoptosis and therapeutic resistance. This shall therefore specifically discuss what role oxygen gradients play in pancreatic tissues, as well as retinoic acid, together with redox-targeted therapies that are specific to vulnerabilities within such types of networks. Summary and Outlook: An understanding of the crosstalk of these molecular pathways will be critical in designing rational therapeutic strategies. Genetics, metabolism, and microenvironmental integration may open a path toward combinatorial therapies that would resensitize PDAC to apoptosis and overcome resistance to current treatments.

Pancreatectomy with venous resection (PVR) for resectable pancreatic ductal adenocarcinoma (PDAC) may be preoperatively planned or intraoperatively required due to suspected vascular involvement. The prognostic impact of pathologically confirmed venous infiltration (PVI) in upfront PVR remains unclear. This study assesses such impact on overall survival (OS). Patients who underwent upfront PVR for PDAC were identified from a prospectively maintained database across three high-volume institutions. Clinical and pathological variables, including PVI status, were collected. Survival outcomes and predictors were analyzed using Cox regression models. A total of 295 patients underwent upfront PVR. Segmental end-to-end reconstruction (Type III) was the most common approach (69

Background: The adoption of robotic surgery in minimally invasive liver surgery has accelerated globally in the last decade, yet its impact on clinical outcomes and the associated benefits remain to be explored. Methods: The study analyzed 8928 minimally invasive liver resections recorded in the I Go MILS registry between 2015 and 2025. Temporal trends in surgical approach, Pringle maneuver utilization, conversion to open surgery, and postoperative morbidity were assessed using Cochran-Armitage and Spearman tests. Case-mix evolution was quantified by the Kawaguchi-Gayet difficulty score. Results: Robotic utilization increased monotonically from 10.4% to 42.2%, while fully laparoscopic procedures declined from 89.6% to 57.8%. Despite this transition, aggregate conversion and morbidity showed no significant temporal trends. Stratified analysis demonstrated lower observed conversion rates in the robotic group and a progressively narrowing difference in morbidity. Overall case-mix complexity increased significantly, driven exclusively by the laparoscopic arm, while the robotic case mix remained structurally stable. Conclusions: Aggregate outcome stability during the robotic transition suggests progressive case-mix complexification rather than technological stagnation. The robotic platform seems to be associated with an apparent conversion advantage; its higher observed morbidity may be attributable to structural differences in operative difficulty. Robotics act not as a substitute for laparoscopy but as a complementary approach applied to more complex resections.

BACKGROUND:Liver hypertrophy techniques have expanded resectability for major hepatectomy, yet real-world indication remains heterogeneous. We assessed agreement among hepatobiliary surgeons regarding indications and hypertrophy strategies choice across standardized clinical scenarios and explored discrepancies by tumor diagnosis and center experience. METHODS:We conducted a multicenter, cross-sectional, internet-based survey via the IGROWtoH network. The questionnaire included thirteen imaging-based cases with nine questions on multidisciplinary setting, indication, rescue strategies, and surgical approach. Modal response, pairwise agreement, and free-marginal multirater kappa (κ_free) were evaluated, with stratification by center volume (>50 vs ≤ 50 resections/year). RESULTS:Seventy-four surgeons participated, mostly working in high-volume centers. Agreement was near-unanimous for multidisciplinary discussion (>90%), but low for key domains as the choice of hypertrophy-inducing procedure (κ_free = 0.16) and the preferred surgical approach (open vs minimally invasive). Discrepancies varied by diagnosis: agreement on hypertrophy need and right hemiliver management was lowest in colorectal liver metastases (pairwise agreement ∼50%), whereas cholangiocarcinoma cases showed higher concordance (60-75%). High-volume centers demonstrated greater consistency, though procedure selection remained variable. CONCLUSIONS:Real-life decision-making on liver hypertrophy strategies is highly variable, influenced by diagnosis and partially mitigated by center volume. These findings support the need for standardized preoperative assessment, multidisciplinary-driven pathways, and prospective registry-based evidence.

BackgroundRobotic-assisted surgery requires training that integrates technical skills, visuospatial coordination, platform management, and anatomical understanding. Although synthetic and virtual-reality simulators are widely used, high-fidelity training on bodies donated to science remains comparatively underreported. This pilot study therefore aimed to evaluate participants’ perceived value of a robotic surgery training experience with the da Vinci Xi platform in a body donation setting, and to examine whether this perceived value was associated with participants’ views on the educational role of body donation.MethodsThis pilot post-course mixed-methods evaluation involved 41 residents and surgeons in general surgery and urology. The program combined dry-lab and wet-lab activities using the da Vinci Xi platform and three body donors. Participants completed a study-specific questionnaire including seven Likert-type items and two open-ended questions. Quantitative data were analyzed descriptively, through Spearman correlations and exploratory subgroup comparisons; qualitative responses underwent thematic analysis.ResultsCourse evaluations ratings were highly positive, with mean scores ranging from 4.59 to 4.88 on a 5-point scale. The mean Training Value Index was 4.70, and the five course evaluation items showed good internal consistency. All participants expressed high willingness to attend a similar course again, and 97.6% would recommend it to colleagues. Agreement that body donation represents a gold standard for medical and surgical education and training, and its perceived ethical importance, received high ratings from 95.1 and 97.6% of participants, respectively. Both were significantly associated with the Training Value Index. Qualitative feedback highlighted hands-on robotic practice, anatomical fidelity, operative-like workflow, and requests for longer or repeated training opportunities.ConclusionParticipants perceived robotic surgery training in a body donation setting as highly valuable, and this perception was closely linked to their broader recognition of the educational value of body donation. These preliminary findings suggest that combining technical training, anatomical complexity, team-based workflow, and ethical awareness may represent a promising complement to dry-lab and virtual-reality simulation, warranting further investigation to inform the development of more integrated robotic surgery curricula.

BACKGROUND:The optimal surgical technique for hepatocellular carcinoma (HCC) remains debated, particularly regarding the balance between perioperative morbidity and long-term oncological outcomes when comparing anatomical resection (AR) with non-anatomical resection (NAR). METHODS:This international, retrospective multicenter study included patients undergoing resection for solitary HCC ≤5 cm. Patients undergoing major hepatectomy (≥3 segments), two-stage hepatectomy, portal vein embolization, or non-curative procedures were excluded. After propensity score matching (PSM), perioperative outcomes, disease-free survival (DFS), and overall survival (OS) were analyzed, with subgroup analyses by surgical approach and tumour size. RESULTS:After propensity score matching, 442 patients were included in each group. NAR was associated with more favourable perioperative outcomes, including shorter operative time, lower blood loss, and lower rates of severe morbidity. DFS did not differ between groups. AR was associated with improved OS in the overall matched cohort (5-year OS: 77.2% vs. 67.2%; p = 0.041), in patients with larger tumours (≥3.6 cm; 81.3% vs. 61.3%; p = 0.022), and in those undergoing minimally invasive liver resection (74.5% vs. 63.2%; p = 0.001). No significant OS difference was observed in patients with smaller tumours (≤3.5 cm). CONCLUSION:NAR was associated with better perioperative outcomes, whereas AR was associated with improved OS in selected analyses. As DFS did not differ between groups and subgroup findings were exploratory, these results should be interpreted cautiously. Overall, the findings support an individualized, tumour-tailored surgical approach.

BACKGROUND:Robotic liver surgery (RLS) provides technical advantages over laparoscopic liver surgery, but no validated robotic-specific difficulty scoring system (DSS) exists. We evaluated the applicability of the Southampton DSS to RLS and developed a dedicated RLS difficulty model. STUDY DESIGN:This multicenter retrospective cohort study included adults undergoing planned RLS across 24 international hepatobiliary centers. The Southampton DSS was assessed for calibration and discrimination in predicting intraoperative complications. Given limited performance, a robotic-specific model (International RoboLiver DSS) was developed using multivariable logistic regression with prolonged operative time (more than 280 minutes; 75th percentile) as a surrogate of technical difficulty. Model discrimination, calibration, and bootstrap internal validation were performed. RESULTS:Among 1,497 RLS patients, higher Southampton DSS categories were associated with increased intraoperative complications (p = 0.003); however, discrimination was poor (area under the curve [AUC] 0.571, 95% CI 0.530 to 0.612) with miscalibration (slope 0.43; intercept 0.06). Independent predictors of prolonged operative time included neoadjuvant chemotherapy, earlier extrahepatic surgery, lesion greater than 50 mm, multiple lesions, bilobar disease, and technically or anatomically major resection. The International RoboLiver DSS demonstrated moderate discrimination (AUC 0.719, 95% CI 0.686 to 0.751) with excellent calibration (intercept 0.00; slope 1.14). Bootstrap validation confirmed model stability (corrected AUC 0.719). CONCLUSIONS:Difficulty factors in RLS partially overlap with laparoscopic liver surgery but are not directly transferable. The International RoboLiver DSS provides a calibrated, robot-specific tool for preoperative complexity stratification and operative planning in RLS. External validation is required.

Approximately 25% of patients with colorectal cancer (CRC) are diagnosed with distant metastases, with the liver being the most common site. A simultaneous approach to resections in these patients may lead to higher complication rates. Recent research suggests that minimally invasive surgical (MIS) techniques can help reduce this additional morbidity. This study examines a multicenter Italian experience, comparing perioperative outcomes of robotic (RS) and laparoscopic surgery (LS) in this setting. Patients from the prospective multicentre registry of the Italian Group of Minimally Invasive Liver Surgery (I Go MILS) who underwent MIS simultaneous resection for CRC with colorectal liver metastasis between 2015 and 2025 were included. Perioperative outcomes were compared between RS and LS using nearest neighbor matching with 2:1 ratio and caliper of 0.2 to mitigate the selection bias. A total of 505 patients were analyzed, including 415 undergoing LS and 90 undergoing RS. After matching, demographic characteristics were similar. Operative time, conversion rate (11.71% for LS vs 6.67% for RS, p = 0.224) and length of stay were comparable between the two groups. Robotic surgery enabled more challenging resections compared to laparoscopy and after matching for complexity was associated with lower major complications (21.62% vs 8.89%, p = 0.014). The robotic approach has demonstrated superior feasibility for technically challenging resections while maintaining similar length of stay, rate of conversion and postoperative complications, after matching for complexity RS was associated with a significantly lower rate of major complications. Robotic surgery can be an alternative to open surgery in complex cases in order to maximise the benefits of minimally invasive surgery and to have better short term postoperative outcomes.

Objective:The primary endpoint of this study was to compare liver transplantation (LT) with Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) in the treatment of colorectal liver metastases (CRLM).Background:ALPPS is usually performed for borderline CRLM cases and published oncological outcomes appear to be inferior to those obtained after LT.Methods:All consecutive patients undergoing ALPPS for CRLM across 14 centers between September 2012 and September 2022 were considered. The selected ALPPS patients were compared with patients receiving LT from November 2006 to June 2019 performed at a single institution. Entropy balancing was applied to eliminate all confounding bias simulating what would have happened if ALPPS patients had been transplanted.Results:During the study period, 121 consecutive patients were submitted to ALPPS and 46 were enrolled by fulfilling the inclusion criteria. These 46 cases were compared with 54 patients submitted to LT. Median OS after ALPPS was 76 months (95% CI: 28.9-123) compared with 72.7 months in patients who underwent LT (95% CI: 43.4-102 months). After reweighting, the risk of death related to ALPPS was higher when compared with LT (HR=1.40, 95% CI: 0.63-3.09) but no significant differences were found between the 2 groups (P=0.398). When splitting the ALPPS cohort into completed and failed procedures, the median OS in failed ALPPS (31.1 months, 95% CI: 0-73.3 months) was significantly lower than that of patients submitted to LT (P=0.043). When ALPPS patients were further selected based on SECA-II criteria, the median OS was significantly (P=0.022) higher in the LT group (not reached) compared with ALPPS (76 months, 95% CI: 21-130 months).Conclusions:LT without current stringent selection criteria did not provide a significant survival benefit compared with ALPPS. The final choice between these 2 strategies seems to depend on the possibility of completing stage 2 and whether the patient meets the most updated transplant criteria.

BACKGROUND:Conversion to open surgery forfeits any potential benefits of minimally invasive liver surgery (MILS), however, it remains uncertain whether the conversion itself introduces additional risk. The impact may differ depending on urgency (emergency or elective) and surgical approach (robotic or laparoscopic liver resection). This study aimed to evaluate outcomes of emergency and elective conversions in robotic liver resection (RLR) and laparoscopic liver resection (LLR). PATIENTS AND METHODS:Data from 34 international centers of patients undergoing converted MILS procedures (stratified for conversion urgency) were retrospectively compared with patients who underwent elective open liver surgery using propensity score matching. Additionally, RLR and LLR conversions were compared. Conversion risk factors were identified using multivariable logistic regression in RLR and LLR separately. RESULTS:Among 10,548 MILS procedures (n = 1626 RLR and n = 8922 LLR), 719 (6.8%) were converted. Both emergency (n = 226) and elective (n = 472) conversions were associated with longer operative time and more Pringle use compared with open surgery. Emergency conversions additionally showed higher blood loss, transfusion rates, severe morbidity, and even mortality. Matched analysis of 40 pairs of RLR and LLR conversions identified no significant differences in perioperative outcomes, although mortality following RLR conversion was remarkably high (7.7%). RLR conversion risk factors were bilobar disease and anatomically major resection; whereas LLR risk factors included cirrhosis, history of previous liver surgery, tumor size, technically complex, and anatomically major resection. CONCLUSIONS:Emergency conversions in MILS are associated with worse outcomes, whereas elective conversions appear safe, highlighting the importance of timely, controlled conversion. Further investigation into the safety of robotic conversions is warranted.

In candidates for hepatectomy, different techniques to induce liver hypertrophy and modulate the future liver remnant are available. However, their use in specific clinical scenarios is highly heterogeneous and there is no consensus about minimal safety standards needed to incorporate these strategies into routine clinical practice. The aim of this position paper was to summarize newly available evidence in the field and compare medical practice among different hepatobiliary surgical units to evaluate the transformative potential of liver hypertrophy techniques in surgical oncology. This paper sets the stage for a future structured consensus on the application of liver hypertrophy techniques before hepatectomy.

Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) has been linked to several advantages compared to open approach, but the actual benefit of robotic liver resection (RLR) over LLR in HCC needs further investigation. We performed a multicentric propensity-score matched (PSM) analysis comparing perioperative and oncologic outcomes of LLR vs. RLR for HCC. The PSM model was estimated using a multivariable logistic regression, with type of surgery as dependent variable and age, BMI, clinically-significant portal hypertension, αFP, size of principal lesion, number of nodules and Kawaguchi difficulty score as covariates. Overall (OS) and recurrence-free (RFS) survivals were estimated using the Kaplan–Meier method. Six-hundred-forty-seven HCC patients from 12 IGoMILS registry centers treated by LLR (553 patients) or RLR (94 patients) were included. After PSM, RLR resulted in wider surgical margins (median: 10 vs 5 mm; p = 0.002) with higher prevalence of R0 resection (98.9 vs 93.1

Background & Aims:For patients with single small (≤3 cm) hepatocellular carcinoma ablation is the first-line treatment, although a high rate of recurrence has been reported. The aim was to compare videolaparoscopic liver resection (laparoscopic resection group) vs. percutaneous thermoablation (ablation group) in terms of overall survival, recurrence-free survival and early recurrence in a real-life national scenario. Methods:The study is a retrospective collection with subsequent survival analysis. Data were collected from two Italian HCC registries, ITA.LI.CA and HE.RC.O.LE.S. An inverse probability of treatment weighting analysis was performed to balance baseline differences between groups. The Kaplan-Meier method and double-robust Cox multivariable regression were run to estimate the survival and the risk of mortality and recurrence. Results:Between 2008 and 2022, 1,465 patients were enrolled. The laparoscopic resection group and ablation group consisted of 496 and 969 patients, respectively. At baseline, the ablation group had more advanced liver disease, with higher rates of cirrhosis (90.7% vs. 77.3%, p <0.001) and Child-Pugh B status (18.4% vs. 8.8%, p <0.001). After a median follow-up of 59 months and after weighting median overall survival was 60 months (95% CI 52-66) for the ablation group and 93 months (95% CI 75-110) for the laparoscopic resection group (hazard ratio [HR] 0.607, 95% CI 0.533-0.691, p <0.001). Median recurrence-free survival was 26 months (95% CI 23-29) for the ablation group and 39 months (95% CI 30-55) for the laparoscopic resection group (HR 0.736, 95% CI 0.659-0.822, p = 0.0013). Laparoscopy was associated with a reduced risk of early recurrence (HR 0.747, 95% CI 0.655-0.853, p = 0.011). Conclusions:This study provides real-world evidence that for patients with single ≤3 cm HCC, videolaparoscopic liver resection offers superior long-term oncological outcomes compared with thermoablation. These findings support the preference for surgical treatment in this patient population. Impact and implications:Percutaneous thermoablation is considered an appropriate alternative to liver resection for small (≤3 cm) single hepatocellular carcinoma because of not-inferior overall survival, although several authors reported increased recurrence risk. Whether videolaparoscopic liver resection could guarantee comparable survival but superior oncologic control of the disease is a matter of debate. This study comparing videolaparoscopy vs. thermoablation in a large national cohort of 1,465 patients observed that the former guaranteed significant prolonged OS (93 months [95% CI 75-110] vs. 60 months [95% CI 52-66] for the ablation group) and recurrence-free survival (26 months [95% CI 23-29] for ablation patients and 39 months [95% CI 30-55] for laparoscopic resection patients) even after weighting all the preoperative and oncologic differences among the groups. Our results clearly address the need to rethink the role of thermoablation for single small HCC as a second-line treatment when laparoscopic liver resection is not feasible.

OBJECTIVE:The primary endpoint of this study was to compare liver transplantation (LT) with Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) in the treatment of colorectal liver metastases (CRLM). BACKGROUND:ALPPS is usually performed for borderline CRLM cases and published oncological outcomes appear to be inferior to those obtained after LT. METHODS:All consecutive patients undergoing ALPPS for CRLM across 14 centers between September 2012 and September 2022 were considered. The selected ALPPS patients were compared with patients receiving LT from November 2006 to June 2019 performed at a single institution. Entropy balancing was applied to eliminate all confounding bias simulating what would have happened if ALPPS patients had been transplanted. RESULTS:During the study period, 121 consecutive patients were submitted to ALPPS and 46 were enrolled by fulfilling the inclusion criteria. These 46 cases were compared with 54 patients submitted to LT. Median OS after ALPPS was 76 months (95% CI: 28.9-123) compared with 72.7 months in patients who underwent LT (95% CI: 43.4-102 months). After reweighting, the risk of death related to ALPPS was higher when compared with LT (HR=1.40, 95% CI: 0.63-3.09) but no significant differences were found between the 2 groups ( P =0.398). When splitting the ALPPS cohort into completed and failed procedures, the median OS in failed ALPPS (31.1 months, 95% CI: 0-73.3 months) was significantly lower than that of patients submitted to LT ( P =0.043). When ALPPS patients were further selected based on SECA-II criteria, the median OS was significantly ( P =0.022) higher in the LT group (not reached) compared with ALPPS (76 months, 95% CI: 21-130 months). CONCLUSIONS:LT without current stringent selection criteria did not provide a significant survival benefit compared with ALPPS. The final choice between these 2 strategies seems to depend on the possibility of completing stage 2 and whether the patient meets the most updated transplant criteria.

Acute Pancreatitis (AP) is a prevalent clinical pancreatic disorder characterized by acute inflammation of the pancreas, frequently associated with biliary or alcoholic events. If not treated with cholecystectomy after the first episode, patients may experience a recurrence of AP, with consequent need for emergency surgery and increased risk of death. Analyzing the risk factors that may contribute to the recurrence of Biliary and Alcoholic Pancreatitis (BAP and AAP), future research can be driven toward new solutions for preventing and treating this pancreatic disease. A systematic review was conducted selecting studies from BiomedCentral, PubMed, Scopus and Web of Science by two independent reviewers. Publications were considered only if written in English in the time interval between January 2000 and June 2024 and investigated the risk factors for the recurrence of BAP and AAP. At the end of the selection, a quality assessment phase was conducted using the PROBAST tool. In this systematic review, 8 articles were selected out of 6.945, involving a total sample of 11.271 patients of which 38.77

BACKGROUND:Liver resection classifications have traditionally been based on the number of segments resected. However, with advancements in techniques and the diffusion of minimally invasive surgery (MiLS), these classifications may no longer adequately represent the complexities of modern liver surgery. This study evaluates five liver resection classifications using a multicenter Italian database of hepatocellular carcinoma resections with the main focus of catching surgical outcomes, rather than technical complexity. METHODS:The study included 3280 resections (2436 open, 844 MiLS) from 25 Italian centers. Five classifications were assessed: Minor-Major, Segment-based, GK-LLR, S-L OLR, and CLISCO. Outcomes included morbidity, liver failure, and 90-day mortality. Chi-square or Fisher's exact tests were used for comparisons. RESULTS:All classifications showed increased morbidity and mortality with higher complexity. For open resections, Minor-Major and Segment-based classifications successfully stratified patients for all outcomes, outperforming other systems. However, all classifications performed poorly for MiLS patients. DISCUSSION:Minor-Major and Segment-based classifications remain the most accurate for predicting risks in open liver resections. The poor performance for MiLS patients highlights the need for a separate risk stratification tool for this approach. Current classifications do not always accurately represent the technical complexity and technological evolution in liver resection, particularly for MiLS procedures.