Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

Full Robotic Whole Graft Liver Transplantation: A Step Into The Future.

OBJECTIVE: To report the first European series of full robotic whole liver transplantation (RLT) with technical details and future perspectives. SUMMARY BACKGROUND DATA: Few cases of liver transplantation with a minimally invasive approach using partial grafts have been reported so far, and no cases of robotic whole liver transplantation have been reported in the scientific literature. METHODS: The adopted technique was full robotic liver hepatectomy, followed by robotic implantation after graft introduction through a small midline incision. Patients presenting with Hepatocellular Carcinoma (HCC) in liver cirrhosis with a small caudate lobe, low degree of portal hypertension, no porto-mesenteric thrombosis, as well as low MELD patients have been considered ideal candidates. RESULTS: Six patients underwent RLT between February and March 2024 at Lisbon and Modena University Liver Transplant Centers. Warm ischemia time during RLT ranged between 55 and 90 min, with a total surgery duration between 440 and 710 min. The median total operative time was 595 (±111,3) minutes. Only one recipient had prolonged hyperbilirubinemia, which was safely treated. The median in-hospital stay was 7.5 days, (±4.8 days). CONCLUSIONS: RLT is a promising technique to further reduce the impact of liver transplantation thanks to smaller incision, gentle tissue manipulation, high magnification and precision for vascular and biliary anastomosis, and reduced postoperative pain. This is the first step toward the demonstration of the feasibility of minimally invasive surgery in liver transplantation, although further selection and technical refinements are needed to improve reproducibility.

Robotic Versus Laparoscopic Liver Resection in Various Settings: An International Multicenter Propensity Score Matched Study of 10.075 Patients.

OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

Clinical Outcomes of Robotic Resection for Perihilar Cholangiocarcinoma: A First, Multicenter, Trans-Atlantic, Expert-Center, Collaborative Study.

INTRODUCTION: Perihilar cholangiocarcinoma is a difficult cancer to treat with frequent vascular invasion, local recurrence, and poor survival. Due to the need for biliary anastomosis and potential vascular resection, the standard approach is an open operation. Suboptimal outcomes after laparoscopic resection had been sporadically reported by high-volume centers. In this first, Trans-Atlantic, multicenter study, we report our outcomes of robotic resection for perihilar cholangiocarcinoma. This is the largest study of its kind in the Western hemisphere. METHODS: Between 2016 and 2023, we prospectively followed patients undergoing robotic resection for perihilar cholangiocarcinoma at three, high-volume, robotic, liver-surgery centers. RESULTS: Thirty-eight patients underwent perihilar cholangiocarcinoma utilizing the robotic technique; Klatskin type-3 was the most common. The median age was 72 years, and 82% of the patients underwent preoperative biliary drainage. Median operative time was 481 minutes with a median estimated blood loss of 200 mL. The number of harvested lymph nodes was seven, and 11 (28%) patients yielded positive lymph nodes. Three patients required vascular reconstruction; 18% of patients had >1 biliary anastomosis. R0 resection margins were achieved in 82% of patients. Clavien-Dindo Grade ≥3 complications were seen in 16% of patients. The length of stay was 6 days. Five patients had an unplanned readmission within 30 days. One patient died within 30 days. With a median follow-up of 15 months, 68% of patients are alive without disease, 13% recurred, and 19% died. CONCLUSIONS: Application of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with acceptable short-term clinical and oncological outcomes.

Full robotic versus open ALPPS: a bi-institutional comparison of perioperative outcomes.

BACKGROUND: In primarily unresectable liver tumors, ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) may offer curative two-stage hepatectomy trough a fast and extensive hypertrophy. However, concerns have been raised about the invasiveness of the procedure. Full robotic ALPPS has the potential to reduce the postoperative morbidity trough a less invasive access. The aim of this study was to compare the perioperative outcomes of open and full robotic ALPPS. METHODS: The bicentric study included open ALPPS cases from the University Hospital Zurich, Switzerland and robotic ALPPS cases from the University of Modena and Reggio Emilia, Italy from 01/2015 to 07/2022. Main outcomes were intraoperative parameters and overall complications. RESULTS: Open and full robotic ALPPS were performed in 36 and 7 cases. Robotic ALPPS was associated with less blood loss after both stages (418 ± 237 ml vs. 319 ± 197 ml; P = 0.04 and 631 ± 354 ml vs. 258 ± 53 ml; P = 0.01) as well as a higher rate of interstage discharge (86% vs. 37%; P = 0.02). OT was longer with robotic ALPPS after both stages (371 ± 70 min vs. 449 ± 81 min; P = 0.01 and 282 ± 87 min vs. 373 ± 90 min; P = 0.02). After ALPPS stage 2, there was no difference for overall complications (86% vs. 86%; P = 1.00) and major complications (43% vs. 39%; P = 0.86). The total length of hospital stay was similar (23 ± 17 days vs. 26 ± 13; P = 0.56). CONCLUSION: Robotic ALPPS was safely implemented and showed potential for improved perioperative outcomes compared to open ALPPS in an experienced robotic center. The robotic approach might bring the perioperative risk profile of ALPPS closer to interventional techniques of portal vein embolization/liver venous deprivation.

Open, laparoscopic liver resection and percutaneous thermal ablation in elderly patients with hepatocellular carcinoma: outcomes and therapeutic strategy.

BACKGROUND: Liver resection and percutaneous thermal ablation (PTA) are considered curative option for hepatocellular carcinoma (HCC). This study aims to compare short- and long-term outcomes between open liver resection (OLR), laparoscopic liver resection (LLR), and PTA in elderly patients with single HCC and to define a liver map for therapeutic strategy according to HCC location and size. METHODS: A multicenter retrospective study was conducted in 10 European Hospital Center, including 239 consecutive liver resection (OLR and LLR) and PTA in elderly patients ≥ 70 years old with single HCC ≤ 30 mm. Perioperative data and long-term oncological outcomes were collected and compared between groups before and after propensity score matching. RESULTS: A total of 239 patients were enrolled, distributed as follows: 61 in the ORL group, 88 in the LLR group, and 90 in the PTA group. The hospital stay was longer in OLR and LLR groups compared to the PTA group (6, 5 and 3 days, respectively, p < 0.05). Morbidity was lower in the PTA group compared to the OLR group (11 vs. 26%, respectively, p < 0.05). Overall survival (OS) at 5 years was significantly higher in the OLR and LLR groups compared to the PTA group (82, 81, and 34%, respectively, p < 0.001). Disease-free survival (DFS) at 5 years was also significantly higher in the ORL and LLR groups compared to the PTA group (66, 50 and 20%, respectively, p < 0.001). These results were also confirmed after a propensity score matching analysis between surgery group (OLR and LLR) and the PTA group. PTA was the most used treatment for subcapsular and deep HCC not in contact with vascular structures compared to OLR and LLR. CONCLUSION: PTA in elderly patients ensures a shorter hospital stay and lower morbidity but worst survival compared to liver resection.

The role of resection in hepatocellular carcinoma BCLC stage B: A multi-institutional patient-level meta-analysis and systematic review.

PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. METHODS: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. RESULTS: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03-0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. CONCLUSION: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies.

Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis.

BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

Liver resection versus radiofrequency ablation in octogenarian patients for hepatocellular carcinoma: a propensity score multicenter analysis.

BACKGROUND: Liver resection (LR) and radiofrequency ablation (RFA) are considered curative options for hepatocellular carcinoma (HCC). The aim of this study was to compare outcomes after LR and RFA in octogenarian patients with HCC. MATERIALS AND METHODS: This multicenter retrospective study included 102 elderly patients (> 80 years old) treated between January 2009 and January 2019, who underwent LR or RFA for HCC (65 and 37 with, respectively). RESULTS: After Propensity Score Matching, the postoperative course of LR was burdened by a higher rate of complications than RFA group (64% vs 14%, respectively, p: 0.001). The LR group had also significantly longer operative time (207 ± 85 min vs 33 ± 49 min, p < 0.001) and postoperative hospital stays than the RFA group (7 d vs 2 d, p = 0.019). Overall survival at 1-, 2-, and 3-year were 86%, 86%, and 70% for the LR group and 82%, 64%, and 52% for the RFA group (p = 0.380). Disease-free survival at 1-, 2-, and 3-year were 89%, 74%, and 56% for the LR group, and 51%, 40%, and 40% for the RFA group (p = 0.037). CONCLUSION: Despite a higher rate of Dindo-Clavien I-II post-operative complications, a longer operative time and length of hospital stay, LR in octogenarian patients can provide comparable 90d mortality than RFA and better long-term outcomes.

Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation.

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p < 0.001). Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency.

Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study.

BACKGROUND: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. METHODS: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. RESULTS: We analysed data from 511 patients observing significant associations between quality of life's physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. CONCLUSIONS: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study.

INTRODUCTION AND OBJECTIVES: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases.

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a propensity score matching analysis.

BACKGROUND: Surgical resection is a first-line curative option for hepatocellular carcinoma, but its role is still unclear in elderly patients. The aim of our study was to compare short- and long-term outcomes of laparoscopic and open liver resection in elderly patients with hepatocellular carcinoma. METHODS: The study included 665 consecutive hepatocellular carcinoma liver resection cases in patients with ≥70 years of age treated in eight European hospital centres. Patients were divided into laparoscopic and open liver resection groups. Perioperative and long-term outcomes were compared between these groups. RESULTS: After a 1:1 propensity score matching, 219 patients were included in each group. Clavien-Dindo grades III/IV (6 vs. 20%, p = 0.04) were lower in the laparoscopic than in the open matched group. Hospital stay was shorter in the laparoscopic than in the open matched group (5 vs. 7 days, p < 0.001). There were no significant differences between laparoscopic and open groups regarding overall survival and disease-free survival at 1-, 3- and 5- year periods. CONCLUSION: Laparoscopic liver resection for hepatocellular carcinoma is associated with good short-term outcomes in patients with ≥70 years of age compared to open liver resection. Laparoscopic liver resection is safe and feasible in elderly patients with hepatocellular carcinoma.

Laparoscopic surgery versus radiofrequency ablation for the treatment of single hepatocellular carcinoma ≤3 cm in the elderly: a propensity score matching analysis.

BACKGROUND: Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) represented potential treatments for patients with a single hepatocellular carcinoma (HCC) smaller than 3 cm. As the aging population soared, our study aimed to examine the advantage/drawback balance for these treatments, which should be reassessed in elderly patients. METHODS: A multicentric retrospective study compared 184 elderly patients (aged >70 years) (86 patients underwent LLR and 98 had RFA) with single ≤3 cm HCC, observed from January 2009 to January 2019. RESULTS: After propensity score matching (PSM), the estimated 1- and 3-year overall survival rates were 96.5 and 87.9% for the LLR group, and 94.6 and 68.1% for the RFA group (p = 0.001) respectively. The estimated 1- and 3-year disease-free survival rates were 92.5 and 67.4% for the LLR group, and 68.5 and 36.9% for the RFA group (p = 0.001). Patients with HCC of anterolateral segments were more often treated with laparoscopic resection (47 vs. 36, p = 0.04). The median operative time in the resection group was 205 min and 25 min in the RFA group (p = 0.01). Length of hospital stay was 5 days in the resection group and 3 days in the RFA group (p = 0.03). CONCLUSION: Despite a longer length of hospital stay and operative time, LLR guarantees a comparable postoperative course and a better overall and disease-free survival in elderly patients with single HCC (≤3 cm), located in anterolateral segments.

Efficient T-Cell Compartment in HIV-Positive Patients Receiving Orthotopic Liver Transplant and Immunosuppressive Therapy.

BACKGROUND: In patients undergoing orthotopic liver transplant (OLT), immunosuppressive treatment is mandatory and infections are leading causes of morbidity/mortality. Thus, it is essential to understand the functionality of cell-mediated immunity after OLT. The aim of the study was to identify changes in T-cell phenotype and polyfunctionality in human immunodeficiency virus-positive (HIV+) and -negative (HIV-) patients undergoing immunosuppressive treatment after OLT. METHODS: We studied peripheral blood mononuclear cells from 108 subjects divided into 4 groups of 27: HIV+ transplanted patients, HIV- transplanted patients, HIV+ nontransplanted patients, and healthy subjects. T-cell activation, differentiation, and cytokine production were analyzed by flow cytometry. RESULTS: Median age was 55 years (interquartile range, 52-59 years); the median CD4 count in HIV+ patients was 567 cells/mL, and all had undetectable viral load. CD4+ and CD8+ T-cell subpopulations showed different distributions between HIV+ and HIV- OLT patients. A cluster representing effector cells expressing PD1 was abundant in HIV- transplanted patients and they were characterized by higher levels of CD4+ T cells able to produce interferon-γ and tumor necrosis factor-α. CONCLUSIONS: HIV- transplanted patients have more exhausted or inflammatory T cells compared to HIV+ transplanted patients, suggesting that patients who have already experienced a form of immunosuppression due to HIV infection respond differently to anti-rejection therapy.

First Case of Full Robotic ALPPS for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for intrahepatic cholangiocarcinoma (ICC) demonstrated good long-term outcomes1 and can increase the rate of resectability in locally advanced ICC;2 however, the rates of postoperative complications (Clavien-Dindo grade III) and mortality range between 13.6 and 44% and 0 and 29%, respectively.3 Minimally invasive strategies may reduce the risk of postoperative morbidity, with the same oncologic outcomes.4,5 We report the first case of full robotic ALPPS for advanced ICC. METHODS: The patient was a 61-year-old male diagnosed with a 6.5 cm ICC involving segments IV, V, and VIII. The total clean liver volume was 1553 cc3, with a future liver remnant (FLR) volume of 21.6% (segments I, II, and III: 337 cc3). The procedure was performed by a senior hepato-pancreato-biliary (HPB) surgeon at the robotic console and a junior HPB surgeon at the table side. RESULTS: Computed tomography scan on postoperative day (POD) 9 after stage 1 showed that FLR increased up to 38%. The indocyanine green clearance test showed a plasma disappearance rate of 19.8%/min and a retention rate at 15 min of 5.1%; complete blood tests are available at the end of the video. ALPPS was completed on POD 14, the postoperative course was uneventful, and the patient was discharged in good general condition on POD 5. Final pathology showed a 6 cm ICC, G3, R0 margin (10 mm), T2-N0-M0. The patient started adjuvant capecitabine, and after 6 months was in good general condition without signs of local or systemic recurrence. CONCLUSIONS: Robotic ALPPS combines the opportunity to perform a curative resection in patients presenting with insufficient FLR with the advantages of a minimally invasive approach. It is feasible and oncologically accurate for ICC when performed in fully trained HPB centers.

Sarco-Model: A score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation.

BACKGROUND & AIMS: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End-stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post-LT futility. METHODS: A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232). RESULTS: Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model2 . According to the model, one extra point of MELDNa was added for each 0.5 cm2 /m2 reduction of total psoas area (TPA) < 6.0 cm2 /m2 . At external validation, the Sarco-Model2 showed the best diagnostic ability for predicting the risk of 3-month dropout in patients with MELDNa < 20 (area under the curve [AUC] = 0.93; P = .003). Using the net reclassification improvement, 14.3% of dropped-out patients were correctly reclassified using the Sarco-Model2 . As for the futility threshold, transplanted patients with TPA < 6.0 cm2 /m2 and MELDNa 35-40 (n = 16/833, 1.9%) had the worse results (6-month graft loss = 25.5%). CONCLUSIONS: In sarcopenic patients with MELDNa < 20, the 'urgency' Sarco-Model2 should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥ 20. The Sarco-Model2 played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35-40, 'futile' transplantation should be considered.

Laparoscopic versus open right posterior sectionectomy: an international, multicenter, propensity score-matched evaluation.

BACKGROUND: Although laparoscopic liver resection has become the standard for minor resections, evidence is lacking for more complex resections such as the right posterior sectionectomy (RPS). We aimed to compare surgical outcomes between laparoscopic (LRPS) and open right posterior sectionectomy (ORPS). METHODS: An international multicenter retrospective study comparing patients undergoing LRPS or ORPS (January 2007-December 2018) was performed. Patients were matched based on propensity scores in a 1:1 ratio. Primary endpoint was major complication rate defined as Accordion ≥ 3 grade. Secondary endpoints included blood loss, length of hospital stay (LOS) and resection status. A sensitivity analysis was done excluding the first 10 LRPS patients of each center to correct for the learning curve. Additionally, possible risk factors were explored for operative time, blood loss and LOS. RESULTS: Overall, 399 patients were included from 9 centers from 6 European countries of which 150 LRPS could be matched to 150 ORPS. LRPS was associated with a shorter operative time [235 (195-285) vs. 247 min (195-315) p = 0.004], less blood loss [260 (188-400) vs. 400 mL (280-550) p = 0.009] and a shorter LOS [5 (4-7) vs. 8 days (6-10), p = 0.002]. Major complication rate [n = 8 (5.3%) vs. n = 9 (6.0%) p = 1.00] and R0 resection rate [144 (96.0%) vs. 141 (94.0%), p = 0.607] did not differ between LRPS and ORPS, respectively. The sensitivity analysis showed similar findings in the previous mentioned outcomes. In multivariable regression analysis blood loss was significantly associated with the open approach, higher ASA classification and malignancy as diagnosis. For LOS this was the open approach and a malignancy. CONCLUSION: This international multicenter propensity score-matched study showed an advantage in favor of LRPS in selected patients as compared to ORPS in terms of operative time, blood loss and LOS without differences in major complications and R0 resection rate.

Laparoscopic major hepatectomy for hepatocellular carcinoma in elderly patients: a multicentric propensity score­based analysis.

BACKGROUND: Considering the increase in overall life expectancy and the rising incidence of hepatocellular carcinoma (HCC), more elderly patients are considered for hepatic resection. Traditionally, major hepatectomy has not been proposed to the elderly due to severe comorbidities. Indeed, only a few case series are reported in the literature. The present study aimed to compare short-term and long-term outcomes between laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH) in elderly patients with HCC using propensity score matching (PSM). METHODS: We performed a multicentric retrospective study including 184 consecutive cases of HCC major liver resection in patients aged ≥ 70 years in _8 European Hospital Centers. Patients were divided into LMH and OMH groups, and perioperative and long-term outcomes were compared between the 2 groups. RESULTS: After propensity score matching, 122 patients were enrolled, 38 in the LMH group and 84 in the OMH group. Postoperative overall complications were lower in the LMH than in the OMH group (18 vs. 46%, p < 0.001). Hospital stay was shorter in the LMH group than in the OMH group (5 vs. 7 days, p = 0.01). Mortality at 90 days was comparable between the two groups. There were no significant differences between the two groups in terms of overall survival (OS) and disease-free survival (DFS) at 1, 3, and 5 years. CONCLUSION: LMH for HCC is associated with appropriate short-term outcomes in patients aged ≥ 70 years as compared to OMH. LMH is safe and feasible in elderly patients with HCC.