Indocyanine green (ICG)-guided robotic resection for liver adenoma: combined technologies for precision surgery.

HCA resection is crucial to prevent bleeding and malignant transformation. The aim of this study was to enhance the precision of tumor resection in hepatocellular adenoma (HCA) through the combination of intraoperative ultrasound (IOUS) and indocyanine green (ICG) fluorescence imaging. ICG was intravenously injected 24 h before surgery, enabling positive staining of HCA nodules. IOUS guided the parenchymal transection performed using the RoboLap approach. IOUS combined with ICG effectively demarcated lesions, allowing precision surgery while sparing healthy liver tissue. Intraoperative frozen examination further validated the potential of ICG to identify previously undetected lesions. The study showed promising advantages of ICG in HCA resections, potentially reducing the risk of recurrence and malignant transformation. The combined robotic and laparoscopic approach improved the feasibility of parenchymal-sparing surgery, offering a cautious assessment of HCA lesions.

Evaluation of the economic impact of the robotic approach in major and postero-superior segment liver resections: a multicenter retrospective analysis.

Background: Economic impact of robotic liver surgery (RLS) is still a debated issue due to the heterogeneity of liver resections considered and the lack of a rigorous methodology. Therefore, the aim of this study is to perform a time-driven activity-based costing (TD-ABC) comparing the costs of RLS, laparoscopic liver surgery (LLS) and open liver surgery (OLS) in the context of complex liver resections and to compare short term perioperative outcomes. Methods: The institutional databases of two Italian high volume hepatobiliary centres were retrospectively reviewed from February 2021 to April 2022. Patients submitted to major hepatectomies or postero-superior liver resections were selected and divided into three groups according to the approach scheduled (RLS, LLS and OLS) and compared. Major contributors of perioperative expenses were calculated using the TD-ABC model and accurately quantifying each unit resource consumed per patient and the time spent performing each activity. A primary intention-to-treat analysis (ITT-A) including conversions in the RLS and LLS groups was performed. Results: Forty-seven RLS, 101 LLS and 124 OLS were collected. LLS and RLS showed reduced blood loss, morbidity, mortality and hospital stay compared with open. A trend towards reduced conversion rate in RLS compared to LLS was registered. Total costs associated with RLS were estimated at €10,637 vs. €9,543 for LLS and vs. €13,960 for OLS. The higher intraoperative costs associated with RLS (+153.3% vs. OLS and +148.2% vs. LLS, P<0.001), primarily related to surgical equipment expenses, were slightly offset by the postoperative savings (-56.0% vs. OLS and -29.4% vs. LLS, P<0.001) resulting from significantly reduced hospital stays. Conclusions: RLS offers economic advantages over OLS, as initial higher costs are offset by better perioperative outcomes. The evolving robotic marketplace is expected to drive down RLS costs, promoting widespread adoption in minimally invasive procedures. Despite its higher costs than LLS, RLS's ability to enhance minimally invasive feasibility makes it a preferred choice for complex cases, reducing the need for conversions.

Achievement of textbook outcome after hepatectomy combined with thermal ablation for colorectal liver metastases.

BACKGROUND: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach. METHODS: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks. RESULTS: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99-7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11-0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82-0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03-0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not. CONCLUSIONS: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease.

Minimally Invasive Approach Provides Oncological Benefit in Patients with High Risk of Very Early Recurrence (VER) After Surgery for Intrahepatic Cholangiocarcinoma (iCCA).

BACKGROUND: Surgery for intrahepatic cholangiocarcinoma (iCCA) is jeopardized by significant risk of early recurrence (≤ 6 months). The aim of the present study is to analyze the oncological benefit provided by laparoscopic over open approach for iCCA in patients with high risk of very early recurrence (VER). MATERIALS AND METHODS: A total of 532 liver resections (LR) were performed for iCCA [265 by minimally invasive surgery (MIS) and 267 with open approach, matched through a 1:1 propensity score] and stratified using the postoperative prediction model of VER. Outcomes were compared between open and laparoscopic approaches, specifically evaluating oncological benefit. RESULTS: The percentage of patients with high risk of VER was similar (32.7% in the laparoscopic group and 35.3% in the open group, pNS). The number of retrieved nodes as well as the rate and depth of negative resection margins were comparable between laparoscopic and open. The surgery-adjuvant treatment interval was shorter in laparoscopic patients in the overall series, as well in the subgroup of high risk of VER. The rate of patients starting adjuvant treatments within 2 months from surgery was higher in laparoscopic group compared with open group. In VER high-risk group both disease-free survival (DFS) and overall survival (OS) were significantly improved in MIS compared with open group (p = 0.032 and p = 0.026, respectively). CONCLUSIONS: In patients with high risk of VER, laparoscopy translates into an advantage in terms of recurrence-free survival, likely related to lower biological impact of surgery, together with a shorter interval between surgery and start of adjuvant treatments, even allowing for a higher number of patients to start adjuvant therapies within 2 months from resection.

Immunotherapy for transplantation of hepatocellular carcinoma: the next frontier in adjunctive therapy.

PURPOSE OF REVIEW: The increasing success of liver transplantation in hepatocellular carcinoma (HCC) drives an ever-evolving search for innovative strategies to broaden eligible patients' pools. Recent advances in immuno-oncology have turned the spotlight on immune checkpoint inhibitors (ICIs). This review offers an updated overview of ICIs in liver transplantation for HCC, exploring neoadjuvant and adjuvant approaches and addressing unanswered questions on safety, patients' selection, and response predictors. RECENT FINDINGS: ICIs have transitioned from being a last-chance therapeutic hope to becoming an integral cornerstone in the treatment of advanced HCC, holding great promise as a compelling option not only to downstage patients for transplantation but also as an alternative strategy in addressing posttransplantation disease recurrence. Despite ongoing refinements in immunotherapeutic agents, the complex molecular pathways involved emphasize the need for a comprehensive approach to integrate immunotherapy in liver transplantation. SUMMARY: Initial concerns about graft rejection, with ICIs as a bridging therapy to liver transplantation, were successfully addressed using adequate immunosuppressants strategies and minimized with a sufficient washout period. Post-liver transplantation disease recurrence remains challenging, requiring a balance between effective therapy and preserving graft function. Emphasis should be placed on clinical trials validating the risk-benefit ratio of ICIs for liver transplantation, guiding appropriate patients' selection, and establishing clear management pathways.

The P2X7 receptor in mucosal adaptive immunity.

The P2X7 receptor (P2X7R) is a widely distributed cation channel activated by extracellular ATP (eATP) with exclusive peculiarities with respect to other P2XRs. In recent years, P2X7R has been shown to regulate the adaptive immune response by conditioning T cell signaling and activation as well as polarization, lineage stability, cell death, and function in tissues. Here we revise experimental observations in this field, with a focus on adaptive immunity at mucosal sites, particularly in the gut, where eATP is hypothesized to act in the reciprocal conditioning of the host immune system and commensal microbiota to promote mutualism. The importance of P2X7R activity in the intestine is consistent with the transcriptional upregulation of P2xr7 gene by retinoic acid, a metabolite playing a key role in mucosal immunity. We emphasize the function of the eATP/P2X7R axis in controlling T follicular helper (Tfh) cell in the gut-associated lymphoid tissue (GALT) and, consequently, T-dependent secretory IgA (SIgA), with a focus on high-affinity SIgA-mediated protection from enteropathogens and shaping of a beneficial microbiota for the host.

Mechanism and Effect of HNF4α Decrease in a Rat Model of Cirrhosis and Liver Failure.

BACKGROUND & AIMS: HNF4α, a master regulator of liver development and the mature hepatocyte phenotype, is down-regulated in chronic and inflammatory liver disease. We used contemporary transcriptomics and epigenomics to study the cause and effects of this down-regulation and characterized a multicellular etiology. METHODS: Progressive changes in the rat carbon tetrachloride model were studied by deep RNA sequencing and genome-wide chromatin immunoprecipitation sequencing analysis of transcription factor (TF) binding and chromatin modification. Studies compared decompensated cirrhosis with liver failure after 26 weeks of treatment with earlier compensated cirrhosis and with additional rat models of chronic fibrosis. Finally, to resolve cell-specific responses and intercellular signaling, we compared transcriptomes of liver, nonparenchymal, and inflammatory cells. RESULTS: HNF4α was significantly lower in 26-week cirrhosis, part of a general reduction of TFs that regulate metabolism. Nevertheless, increased binding of HNF4α contributed to strong activation of major phenotypic genes, whereas reduced binding to other genes had a moderate phenotypic effect. Decreased Hnf4a expression was the combined effect of STAT3 and nuclear factor kappa B (NFκB) activation, which similarly reduced expression of other metabolic TFs. STAT/NFκB also induced de novo expression of Osmr by hepatocytes to complement induced expression of Osm by nonparenchymal cells. CONCLUSIONS: Liver decompensation by inflammatory STAT3 and NFκB signaling was not a direct consequence of progressive cirrhosis. Despite significant reduction of Hnf4a expression, residual levels of this abundant TF still stimulated strong new gene expression. Reduction of HNF4α was part of a broad hepatocyte transcriptional response to inflammation.

Predicting futility of upfront surgery in perihilar cholangiocarcinoma: Machine learning analytics model to optimize treatment allocation.

BACKGROUND: While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. METHODS: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome. RESULTS: A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. CONCLUSIONS: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features.

Defining and predicting textbook outcomes for perihilar cholangiocarcinoma: analysis of factors improving achievement of desired postoperative outcomes.

BACKGROUND: Definition of textbook outcome (TO), defined as a single indicator combining the most advantageous short-term outcomes, is still lacking for perihilar cholangiocarcinoma (PHC). The primary endpoint of the present study is to analyze the rate of achievement of a disease-specific TO for PHC within a high volume tertiary referral centre. Secondary endpoints are to identify predictive factors of TO-achievement and to analyze the impact of achieving TO on long-term results. METHODS: Between 2010 and 2022, a total of 237 patients undergoing combined liver and biliary resection for PHC at tertiary referral centre were included. Disease-specific TO were defined as: no 90-day mortality, no postoperative complications, no readmission, no intraoperative transfusions and resection margins. A logistic regression model was developed to identify predictors associated with TO-achievement. Kaplan-Meier curves were designed to determine TO's impact on survival. RESULTS: TO was achieved in 60 (25.3%) patients. At multivariate logistic regression, preoperative biliary drainage [odds ratio (OR) 2.90 (1.13-3.40), P =0.026], high prognostic nutritional index [OR 7.11 (6.71-9.43), P =0.007[ and minimally invasive approach [OR 3.57 (2.31-3.62), P =0.013] were identified as independent predictors of TO. High ASA score [OR 0.38 (0.17-0.82), P =0.013] decreased the odds of TO. A significant improvement in both overall survival and disease-free survival was associated to TO fulfilment. CONCLUSION: Since the achievement of TO correlates with better disease-free and overall survival, every effort should be made to ameliorate modifiable aspects prior to surery: management within referral centres with dedicated experience in biliary tract cancer and preoperative optimization protocol may positively contribute to improve postoperative outcomes, increasing the chance to obtain TO. Moreover, the implementation of advanced minimally invasive programs plays as well.

Robo-Lap Approach Optimizes Intraoperative Outcomes in Robotic Left and Right Hepatectomy.

Background: The aim of the present study is to evaluate the possible advantages of the Robo-Lap (parenchymal transection by laparoscopic ultrasonic dissector and robotic bipolar forceps and scissors) compared with pure robotic technique (parenchymal transection by use of robotic bipolar forceps and scissors) in major anatomical liver resections with specific focus on intraoperative outcomes. Methods: Major liver resections performed by robotic approach between February 1, 2021 and March 31, 2023 were stratified into two groups according to the approach used to address the phase of liver transection; Pure Robotic Group (n = 21) versus Robo-Lap Group (n = 48). The two groups were compared in terms of intra- and postoperative outcomes and in terms of rate of achievement of intraoperative textbook outcomes. Results: Conversion rate was similar between the two groups while incidence of adverse intraoperative events (according to Satava classification) was higher in the Pure Robotic compared with the Robo-Lap group (85.7% vs 39.6%, p < 0.001). Time to perform parenchymal transection was significantly shorter in the Robo-Lap group (180 min) compared with the Pure Robotic Group (240 min), p = 0.003. Intraoperative textbook outcomes were achieved in a lower proportion of patients in the Pure Robotic compared with the Robo-Lap group. Conclusion: Outcomes of the present study suggest a favorable role of the Robo-Lap approach in robotic major resections as it allows an improvement of the intraoperative results, a greater probability of an uneventful conduction of the procedure, and therefore, better management of the operating room time.

Comparing Liver Venous Deprivation and Portal Vein Embolization for Perihilar Cholangiocarcinoma: Is It Time to Shift the Focus to Hepatic Functional Reserve Rather than Hypertrophy?

Purpose: Among liver hypertrophy technics, liver venous deprivation (LVD) has been recently introduced as an effective procedure to combine simultaneous portal inflow and hepatic outflow abrogation, raising growing clinical interest. The aim of this study is to investigate the role of LVD for preoperative optimization of future liver remnant (FLR) in perihilar cholangiocarcinoma (PHC), especially when compared with portal vein embolization (PVE). Methods: Between January 2013 and July 2022, all patients diagnosed with PHC and scheduled for preoperative optimization of FTR, through radiological hypertrophy techniques, prior to liver resection, were included. FTR volumetric assessment was evaluated at two distinct timepoints to track the progression of both early (T1, 10 days post-procedural) and late (T2, 21 days post-procedural) efficacy indicators. Post-procedural outcomes, including functional and volumetric analyses, were compared between the LVD and the PVE cohorts. Results: A total of 12 patients underwent LVD while 19 underwent PVE. No significant differences in either post-procedural or post-operative complications were found. Post-procedural FLR function, calculated with (99m) Tc-Mebrofenin hepatobiliary scintigraphy, and kinetic growth rate, at both timepoints, were greater in the LVD cohort (3.12 ± 0.55%/min/m2 vs. 2.46 ± 0.64%/min/m2, p = 0.041; 27.32 ± 16.86%/week (T1) vs. 15.71 ± 9.82%/week (T1) p < 0.001; 17.19 ± 9.88%/week (T2) vs. 9.89 ± 14.62%/week (T2) p = 0.034) when compared with the PVE cohort. Post-procedural FTR volumes were similar for both hypertrophy techniques. Conclusions: LVD is an effective procedure to effectively optimize FLR before liver resection for PHC. The faster growth rate combined with the improved FLR function, when compared to PVE alone, could maximize surgical outcomes by lowering post-hepatectomy liver failure rates.

Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.

BACKGROUND: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. METHODS: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. RESULTS: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. CONCLUSION: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.

A "cui prodest" evaluation on the development of a minimally invasive liver surgery program: a differential benefit analysis of open and laparoscopic approach for left and right hemihepatectomies.

BACKGROUND: The correlation between technical feasibility and short-term clinical advantage provided by laparoscopic over open technique for major hepatectomies is unclear. This monocentric retrospective study investigates the possible differences in the benefit provided by minimally invasive approach between left and right hepatectomy, deepening the concept of differential benefit in the setting of anatomical major resections. METHODS: All hemihepatectomies performed from January 2004 to December 2021 were identified in the institutional database. A propensity score method was used to match minimal invasive (MILS) and open pairs in the left hemihepatectomies (LH) and right hemihepatectomies (RH) groups with a 1:1 ratio to adjust any potential selection bias. The differential benefit for left and right hepatectomy provided by laparoscopic over open technique was evaluated in a pure analysis (i.e., including cases converted to open) and a risk-adjusted analysis (i.e., after excluding open conversion from the laparoscopic series). RESULTS: The analysis of the risk-adjusted differential benefit demonstrated better result of the MILS in the RH group than in the LH group, in terms of blood loss (∆ blood loss - 150 and - 350, respectively; differential benefit: 200 mL, p < 0.05), morbidity (∆ rate of morbidity - 11.3% and - 18.1%, respectively; differential benefit: 6.8%, p < 0.05) and length of stay, LOS (∆ LOS - 1 day and - 3 days, respectively; differential benefit: 2 days, p < 0.05). CONCLUSION: While MILS is associated with improved clinical outcomes both in left and right hepatectomy procedures, the greater advantage provided by laparoscopy was documented in patients undergoing right hepatectomy, i.e. for more technically demanding procedures. A MILS program should include the broadest range of liver resections to ensure the full benefits of the laparoscopic technique.

The failure to rescue factor: aftermath analyses on 224 cases of perihilar cholangiocarcinoma.

The term "failure to rescue" (FTR) has been recently introduced in the field of hepato-biliary surgery to label cases in which major postoperative complications lead to postoperative fatality. Perihilar cholangiocarcinoma (PHC) surgery has consistently high postoperative morbidity and mortality rates in which factors associated with FTR are yet to be discovered. The primary endpoint of this study is to compare the Rescue with the FTR cohort referencing patients' characteristics and management protocols applied. A cohort of 224 consecutive patients undergoing surgery for PHC, between 2010 and 2021, was enrolled. Perioperative variables were analyzed according to the severity of major postoperative complications (Clavien ≥ 3a). Kaplan-Meier survival analyses were performed to determine complications' impact on survival. Major complications were reported in 86 cases (38%). Among the major complications' cohort, 72 cases (84%) were graded Clavien 3a-4 (Rescue group), while 14 (16%) cases were graded Clavien 5 (FTR group). Number of lymph-node metastases (OR = 1.33 (1.08-1.63) p = 0.006), poorly differentiated (G3) adenocarcinoma (OR = 7.55 (1.24-45.8) p = 0.028, reintervention (OR = 16.47 (2.76-98.08) p = 0.002), and prognostic nutritional index < 40 (OR = 3.01 (2.265-3.654) p < 0.001) rates were independent predictors of FTR. Right resection side (OR 2.4 (1.33-4.34) p = 0.004) increased the odds of major complications but not of FTR. No difference in overall survival was identified. A distinction of perioperative factors associated with postoperative complications' severity is crucial. Patients developing severe outcomes seem to have different biological and nutritional profiles, showing that efficient preoperative protocols are strategic to identify and avert the risk of FTR.

Radial and longitudinal margins in surgery of perihilar cholangiocarcinoma: When R1 definition is associated with different prognosis.

BACKGROUND: Infiltrated margins of resection (R1) and lymph node invasion are dominant negative predictors of survival in patients with a resectable perihilar cholangiocarcinoma. Less clear is whether survival predictors stratify differently between R0 (tumor-free margins) and R1 patients and whether the prognosis of the latter patients is influenced by the pattern of neoplastic infiltration (ie, radial versus longitudinal infiltration). We retrospectively evaluated a series of reported resected perihilar cholangiocarcinoma to obtain insights on the predictive power of these histologic features. METHODS: The study includes 264 patients with perihilar cholangiocarcinoma treated between 2004 and 2019 in our center and followed up for >18 months. There were 176 patients with R0 (66.6%) and 88 patients with R1 (33.3%), 31 with radial infiltration only, 30 with longitudinal infiltration only, and 27 with both infiltration patterns. In all patients, the criteria for resection was the absence of metastatic involvement (ie, distant organ metastases, liver metastases, and lymph node metastases beyond the hepatoduodenal ligament). Histopathologic specimens of the resected tumors were centrally reviewed by a pathologist unaware of the clinical outcomes. RESULTS: Three- and 5-year long-term survival were significantly better in R0 (respectively) compared to R1 patients (55% and 42% vs 42% and 18%, respectively, P < .05). In R1 patients with radial infiltration only and those with radial + longitudinal infiltration, both disease-free and overall survival were worse than those with longitudinal infiltration only (median disease-free survival of 18 and 23 months, respectively, P < .05, median overall survival of 33 and 39 months, respectively, P < .05). At multivariable analysis, nodal status, side of hepatectomy, grading, and presence of radial margin infiltration were associated with long-term outcome. CONCLUSION: Radial infiltration of resection margins enhances the negative prognostic value of R1 margins in perihilar cholangiocarcinoma patients and should specifically be accounted for in the prediction of the outcome of adjuvant therapy.

Conversion of Minimally Invasive Liver Resection for HCC in Advanced Cirrhosis: Clinical Impact and Role of Difficulty Scoring Systems.

BACKGROUND: Minimally invasive liver resections (MILRs) in cirrhosis are at risk of conversion since cirrhosis and complexity, which can be estimated by scoring systems, are both independent factors for. We aimed to investigate the consequence of conversion of MILR for hepatocellular carcinoma in advanced cirrhosis. METHODS: After retrospective review, MILRs for HCC were divided into preserved liver function (Cohort-A) and advanced cirrhosis cohorts (Cohort-B). Completed and converted MILRs were compared (Compl-A vs. Conv-A and Compl-B vs. Conv-B); then, converted patients were compared (Conv-A vs. Conv-B) as whole cohorts and after stratification for MILR difficulty using Iwate criteria. RESULTS: 637 MILRs were studied (474 Cohort-A, 163 Cohort-B). Conv-A MILRs had worse outcomes than Compl-A: more blood loss; higher incidence of transfusions, morbidity, grade 2 complications, ascites, liver failure and longer hospitalization. Conv-B MILRs exhibited the same worse perioperative outcomes than Compl-B and also higher incidence of grade 1 complications. Conv-A and Conv-B outcomes of low difficulty MILRs resulted in similar perioperative outcomes, whereas the comparison of more difficult converted MILRs (intermediate/advanced/expert) resulted in several worse perioperative outcomes for patients with advanced cirrhosis. However, Conv-A and Conv-B outcomes were not significantly different in the whole cohort where "advanced/expert" MILRs were 33.1% and 5.5% in Cohort A and B. CONCLUSIONS: Conversion in the setting of advanced cirrhosis can be associated with non-inferior outcomes compared to compensated cirrhosis, provided careful patient selection is applied (patients elected to low difficulty MILRs). Difficulty scoring systems may help in identifying the most appropriate candidates.

Total portal vein replacement with peritoneal interposition graft during Whipple's procedure for extrahepatic cholangiocarcinoma: a technical report.

BACKGROUND: Aggressive surgical resection in locally advanced hepatopancreatobiliary (HPB) malignancies is frequently advocated as the only potentially curative treatment. In recent years, advances in chemotherapy regimens and surgical techniques have led to improved oncologic outcomes and overall survival, by increasing the rates of radical (R0) resections. Vascular resections are increasingly reported to further increase disease clearance rates. Within this perspective, the issue of vascular reconstruction has raised growing interest, drawing particular attention to vascular substitutes and surgical techniques for reconstruction. CASE PRESENTATION: A case of extrahepatic cholangiocarcinoma with high clinical suspicion of vascular infiltration of the portal trunk at preoperative assessment is reported. An autologous interposition graft, harvested from diaphragmatic peritoneum, was chosen as a vascular substitute leading to successful portal trunk reconstruction and overcoming all possible drawbacks associated with cadaveric and artificial grafts reconstructions. CONCLUSION: This solution was strategic to ensure complete oncologic clearance averting the risk of positive margins (R1) at final pathology.

Belimumab use during pregnancy: Interim results of the belimumab pregnancy registry.

BACKGROUND: Belimumab is approved for active, autoantibody-positive systemic lupus erythematosus (SLE) and lupus nephritis, but limited data exist regarding its use in pregnancy. The Belimumab Pregnancy Registry (BPR, GSK Study BEL114256; NCT01532310) was created to evaluate pregnancy and infant outcomes following belimumab exposure. METHODS: Individuals with SLE exposed to belimumab from 4 months before and/or during pregnancy can enroll into the BPR. The primary outcome is major birth defects; secondary outcomes include miscarriages, stillbirths, elective termination, pre-term birth, neonatal death, small for gestational age, and adverse infant outcomes during the first year of life. Belimumab exposure timing, concomitant medications, and other potential confounding factors are also collected. Data up to March 8, 2021, are reported descriptively. RESULTS: From an expected sample size target of 500 prospective pregnancies with a known outcome, only 55 were enrolled in the study. Among these, two pregnancy losses and 53 pregnancies with a live birth outcome were reported. Ten of the 53 live birth pregnancies resulted in a major birth defect. Ten pregnancies were enrolled after the pregnancy outcome occurred and were examined retrospectively (four live births with no defects, four miscarriages, and two elective terminations). There was no indication or pattern of birth defects associated with belimumab. CONCLUSIONS: Low recruitment numbers for the BPR and incomplete information limit the conclusions regarding belimumab exposure during pregnancy. There was no pattern or common mechanism of birth defects associated with belimumab within the BPR data.