The impact of advanced patient age in liver transplantation: a European Liver Transplant Registry propensity-score matching study.

BACKGROUND: The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era. METHODS: The aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method. RESULTS: A total of 10,172 cases were analysed. Recipient age >65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23-1.65,p < 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p < 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p < 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p > 0.05) between groups. CONCLUSION: Liver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.

XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions that underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single-cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NAFLD/NASH spectrum showed that type 1 cDCs (cDC1) were more abundant and activated in disease. Sequencing of physically interacting cDC-T cell pairs from liver-draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1DTA mice or using anti-XCL1-blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1+ cDC1 as an important driver of liver pathology.

The Impact of Establishing a Dedicated Liver Surgery Program at a University-affiliated Hospital on Workforce, Workload, Surgical Outcomes, and Trainee Surgical Autonomy and Academic Output.

Objective: To detail the implementation of a dedicated liver surgery program at a university-affiliated hospital and to analyze its impact on the community, workforce, workload, complexity of cases, the short-term outcomes, and residents and young faculties progression toward technical autonomy and academic production. Background: Due to the increased burden of liver tumors worldwide, there is an increased need for liver centers to better serve the community and facilitate the education of trainees in this field. Methods: The implementation of the program is described. The 3 domains of workload, research, and teaching were compared between 2-year periods before and after the implementation of the new program. The severity of disease, complexity of procedures, and subsequent morbidity and mortality were compared. Results: Compared with the 2-year period before the implementation of the new program, the number of liver resections increased by 36% within 2 years. The number of highly complex resections, the number of liver resections performed by residents and young faculties, and the number of publications increased 5.5-, 40-, and 6-fold, respectively. This was achieved by operating on more severe patients and performing more complex procedures, at the cost of a significant increase in morbidity but not mortality. Nevertheless, operations during the second period did not emerge as an independent predictor of severe morbidity. Conclusions: A new liver surgery program can fill the gap between the demand for and supply of liver surgeries, benefiting the community and the development of the next generation of liver surgeons.

Novel classification of non-malignant portal vein thrombosis: A guide to surgical decision-making during liver transplantation.

Non-tumoral portal vein thrombosis (PVT) is present at liver transplantation in 5% to 26% of cirrhotic patients, and the prevalence of complex PVT as defined here (grade 4 Yerdel, and grade 3,4 Jamieson and Charco) has been reported in 0% to 2.2%. Adequate portal inflow is mandatory to ensure graft and patient survival after liver transplantation. With time, the proposed classifications of non-tumoral chronic PVT have evolved from being anatomy-based, to also incorporating functional parameters. However, none of the currently proposed classifications are directed towards decision-making, regarding the choice of inflow to the graft during transplantation and the outcomes thereof. The present scoping review i) addresses the limits of the currently available classifications in terms of surgical decisiveness, ii) clarifies the concept of physiological or non-physiological portal inflow reconstruction, and subsequently, iii) proposes a new classification of non-tumoral PVT in candidates for liver transplantation; to help tailor the surgical strategy to an individual patient, in order to provide portal inflow to the graft together with control of prehepatic portal hypertension whenever feasible.

Local Ablation Does Not Worsen Perioperative Outcomes After Liver Transplant for Hepatocellular Carcinoma.

OBJECTIVE. Local ablation of hepatocellular carcinoma (HCC) before liver transplant has important advantages, such as preventing disease progression, tumor downstaging, and offering a test of time. However, it might render liver transplant more technically demanding. Thus far, its potential effect on liver transplant outcomes is still unknown, and, therefore, the current study was performed. MATERIALS AND METHODS. Patients who underwent liver transplant for HCC at a single tertiary referral center between 2008 and 2016 were included and retrospectively analyzed. Patients who underwent liver resection and local ablation before liver transplant were excluded. Patients treated with local ablation before liver transplant were compared with those not treated with local ablation, both before and after propensity score matching. In addition, the local ablation group was compared with patients who underwent primary resection before liver transplant. Posttreatment mortality and morbidity were determined, and overall and disease-free survival rates were calculated. RESULTS. In total, 182 patients were included. Twenty-six patients underwent resection but not local ablation before liver transplant. Of the remaining 156 patients, 66 (42%) underwent local ablation before liver transplant and 90 (58%) did not. Perioperative mortality and morbidity were similar in both groups before and after propensity score matching (8% and 74% in the local ablation group vs 10% and 83% in the non-local ablation group, p = 0.60 and 0.17, respectively). In addition, no significant differences in long-term outcomes were observed between the groups before and after propensity score matching. Also, no differences were observed in outcomes in the local ablation group versus the liver resection group. CONCLUSION. Local ablation before liver transplant does not have a negative effect on outcomes after liver transplant for HCC.

Combined hepatic and portal vein embolization as preparation for major hepatectomy: a systematic review.

BACKGROUND: Some patients remain deemed unsuitable for resection after portal vein embolization (PVE) because of insufficient hypertrophy of the future remnant liver (FRL). Hepatic and portal vein embolization (HPVE) has been shown to induce hypertrophy of the FRL. The aim of this study was to provide a systematic review of the available literature on HPVE as preparation for major hepatectomy. METHODS: The literature search was performed on online databases. Studies including patients who underwent preoperative HPVE were retrieved for evaluation. RESULTS: Six articles including 68 patients were published between 2003 and 2017. HPVE was performed successfully in all patients with no mortality and morbidity-related procedures. The degree of hypertrophy of the FRL after HPVE ranged from 33% to 63.3%. Surgical resection after preoperative HPVE could be performed in 85.3% of patients, but 14.7% remained unsuitable for resection because of insufficient hypertrophy of the FRL or tumor progression. Posthepatectomy morbidity and mortality rates were 10.3% and 5.1%, respectively. The postoperative liver failure rate was nil. CONCLUSION: HPVE as a preparation for major hepatectomy appears to be feasible and safe and could increase the resectability of patients initially deemed unsuitable for resection because of absent or insufficient hypertrophy of the FRL after PVE alone.

Impact of narrow margin and R1 resection for hepatocellular carcinoma on the salvage liver transplantation strategy. An intention-to-treat analysis.

BACKGROUND: No studies have investigated whether narrow margin is a risk factor for hepatocellular carcinoma recurrence outside transplantability criteria. The objective was to assess on an intent-to-treat (ITT) basis whether hepatectomy with narrow margin affects the outcomes in patients enrolled in the salvage liver transplantation (LT) strategy. METHODS: From 2007 to 2016, patients enrolled in the salvage LT strategy were divided into 2 groups: narrow (<10 mm) vs. wide (≥10 mm) margin groups. R1 resection was defined as positive histologic margin involvement. Recurrence rate, transplantability rate of recurrence and ITT overall survival (ITT-OS) were evaluated. RESULTS: A total of 81 patients were studied: 43 patients with narrow margin and 38 with wide margin. The recurrence rates, pattern and delay of recurrence, transplantability following recurrence, and ITT-OS were similar between the two groups. These results were maintained when comparing patients with R1 resection to those with R0 resection. CONCLUSION: On an ITT basis, hepatectomy with narrow margin or R1 resection did not impair the transplantability of recurrence and survival of patients enrolled in the salvage LT strategy. Narrow margin and even R1 resection following hepatectomy in the setting of salvage LT strategy should not be the basis for altering the strategy.

Short- and Long-term Outcomes after Robotic and Laparoscopic Liver Resection for Malignancies: A Propensity Score-Matched Study.

OBJECTIVES: A laparoscopic approach improves short-term outcomes and maintains long-term outcomes compared to an open approach. In turn, the recent development of robotic surgery raises the question whether it performs as well as laparoscopic surgery. The aim of this study was to compare the short- and long-term outcomes of laparoscopic liver resection (LLR) and robotic liver resection (RLR) for malignancies. METHOD: From 2011 to 2017, the study population included 111 patients in the LLR group and 61 in the RLR group. Short- and long-term outcomes were compared before and after propensity score matching (PSM). RESULTS: Operative mortality rate was nil. The intraoperative blood transfusion rate was higher during RLR (15% vs. 2%, p = 0.0009). Major morbidity and hospital stay were not different between the two groups. The resection margin width (LLR 7 mm vs. RLR 10 mm, p = 0.13) and R1 resection rates (resection margin width < 1 mm; LLR 15% vs. RLR 11%, p = 0.49) were similar. After PSM (55 patients in each group), the blood transfusion, major morbidity, hospital stay and R1 resection were similar between the two groups. When considering the largest subset of patients with hepatocellular carcinoma including 114 patients (66%), the 3-year overall survival rate was 80% in the LLR group and 97% in the RLR group (p = 0.10) and remained similar after PSM (p = 0.27). The 3-year recurrence-free survival rate was 50% in the LLR group and 64% in the RLR group (p = 0.30) and remained similar after PSM (p = 0.26). CONCLUSIONS: No differences were found in blood transfusion, incidence of positive resection margins and long-term outcomes between the two techniques. RLR does not compromise short-term and oncologic outcomes in patients with liver cancers.

Porto-Rex Shunt for Left Portal Vein Reconstruction During Right Extended Hepatectomy for Advanced Extrahepatic Biliary Cancer.

Resection offers the only chance of long-term survival or cure for perihilar cancer, provided R0 resection is achieved with margin-negative status of the remnant liver, bile duct, proximal hepatic artery, and portal vein. End-to-end anastomosis of the portal trunk to the left portal branch is the conventional portal reconstruction in cases of right extended hepatectomy requiring resection of the portal vein bifurcation. This mandatory reconstruction may be challenging due to (1) vessel incongruence, (2) fragility of the left portal branch wall, and more importantly, and (3) the divergent orientation of the two vessels exposing to vascular twisting/kinking. We report here the first two cases of porto-Rex shunt, between the portal vein trunk and the left portal vein in the umbilical fissure during right extended hepatectomy for advanced extrahepatic biliary cancer: one following failed conventional portal reconstruction and one to achieve macroscopically complete resection.

Safety of laparoscopic hepatectomy in patients with hepatocellular carcinoma and portal hypertension: interim analysis of an open prospective study.

BACKGROUND: The laparoscopic approach might increase the number of cirrhotic patients with hepatocellular carcinoma (HCC) indicated for liver resection, otherwise contraindicated due to portal hypertension. The goal of this study was to confirm the safety of laparoscopic liver resection (LLR) in patients with portal hypertension. METHODS: This prospective, single-center, open study (ClinicalTrials.gov ID: NCT02145013) included all consecutive cirrhotic patients who underwent LLR for HCC from 2014 to 2017. Short-term outcomes were compared between patients with and without clinically significant portal hypertension (CSPH, defined by hepatic venous pressure gradient ≥ 10 mmHg). RESULTS: The study population included 45 patients, comprising 27 patients (60%) in the no CSPH group and 18 patients (40%) in the CSPH group. All planned procedures could be performed. The two groups did not differ in the extent of resection, transfusion, duration of clamping, and need for conversion. Overall, the 90-day mortality and severe morbidity rates were nil. Moderate morbidity was significantly higher in the CSPH group (39 vs. 4%, p = 0.01); however, the two groups did not differ in the rate of unresolved liver decompensation. Intensive care unit and hospital stays were significantly longer in the CSPH group. At 2 years, overall survival was 77% in the no CSPH group and 100% in the CSPH group (p = 0.17), and recurrence-free survival was 55% in the no CSPH group and 79% in the CSPH group (p = 0.10). CONCLUSION: LLR is safe in BCLC 0-A patients with CSPH, with no mortality and good short-term outcomes. Re-evaluation of the BCLC guidelines is needed.

Liver transplantation in elderly patients: a systematic review and first meta-analysis.

BACKGROUND: Elderly recipients are frequently discussed by the scientific community but objective indication for this parameter has been provided. The aim of this study was to synthesize the available evidence on liver transplantation for elderly patients to assess graft and patient survival. METHODS: A literature search of the Medline, EMBASE, and Scopus databases was carried out from January 2000 to August 2018. Clinical studies comparing the outcomes of liver transplantation in adult younger (<65 years) and elderly (>65 years) populations were analyzed. The primary outcomes were patient mortality and graft loss rates. This review was registered (Number CRD42017058261) as required in the international prospective register for systematic review protocols (PROSPERO). RESULTS: Twenty-two studies were included involving a total of 242,487 patients (elderly: 23,660 and young: 218,827) were included in this study. In the meta-analysis, the elderly group had patient mortality (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 0.97-1.63; P = 0.09; I2 = 48%) and graft (HR: 1.09; 95% CI: 0.81-1.47; P = 0.59; I2 = 12%) loss rates comparable to those in the young group. CONCLUSIONS: Elderly patients have similar long-term survival and graft loss rates as young patients. Liver transplantation is an acceptable and safe curative option for elderly transplant candidates.

18F-FDG PET/CT predicts microvascular invasion and early recurrence after liver resection for hepatocellular carcinoma: A prospective observational study.

BACKGROUND: This study assessed the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in the prediction of MVI and early recurrence following resection. METHOD: This prospective study (ClinicalTrials.gov ID: NCT02145013) included 78 consecutive HCC patients who underwent 18F-FDG PET/CT before curative-intent resection from 2014 to 2017. Prognostic factors available before surgery for predicting MVI and early recurrence (≤2 years) were identified by univariate and multivariate analyses. RESULTS: The 18F-FDG PET/CT result was positive in 30 (38%) patients. MVI was present in 33% (26/78) of specimens. Early recurrence occurred in 19% (14/74) of surviving patients. PET/CT positivity was the sole independent predictor of MVI (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1-11.2; p = 0.03), with a specificity and sensitivity for predicting MVI of 73% and 62%, respectively. Analysis of variables available before surgery showed that PET/CT positivity (hazard ratio [HR] = 5.8, 95% CI = 1.6-20.4; p = 0.006) and the male sex (HR = 6.6; 95% CI = 1.8-24.2; p = 0.005) were independent predictors of early recurrence. CONCLUSION: 18F-FDG PET/CT predicts MVI and early recurrence after surgery for HCC and could be used to select patients for neoadjuvant treatment.

Hepatic venous outflow obstruction after whole liver transplantation of large-for-size graft: versatile intra-operative management.

BACKGROUNDS/AIMS: Preservation of the native inferior vena cava using a large graft during adult whole liver transplantation is associated with a potential risk of hepatic venous outflow compression/obstruction, which may adversely affect both graft and short-term patient outcomes. Intraoperative placement of materials to restore adequate hepatic venous outflow can overcome this complication. METHODS: Data of patients who underwent liver transplantation between 2011 and 2016 were retrospectively reviewed. All cases of hepatic venous outflow obstruction due to large graft size managed via intraoperative intervention were analyzed. The literature was searched for studies reporting adult cases of hepatic venous outflow obstruction following whole liver transplantation managed extrahepatically. RESULTS: Three patients diagnosed with intraoperative hepatic venous outflow obstruction due to large graft size were managed via retro-hepatic placement of breast implants (2 cases) or abdominal pads (1 case). It was successfully carried out in all cases. Four studies including 15 patients were identified in the literature search. Different types of materials such as inflatable materials (Foley catheter, Blakemore balloon), surgical gloves or breast implants, were used. CONCLUSIONS: Placement of inflatable materials leads to gradual deflation in the postoperative period, which might obviate the need for reoperation. Breast implants could be left in place indefinitely due to their bio-inert nature.

Impact of postoperative complications on long-term survival following surgery for T4 colorectal cancer.

BACKGROUND: Postoperative complications (POCs) after the resection of locally advanced colorectal cancer (CRC) may influence adjuvant treatment timing, outcomes, and survival. This study aimed to evaluate the impact of POCs on long-term outcomes in patients surgically treated for T4 CRC. METHODS: All consecutive patients who underwent the resection of T4 CRC at a single centre from 2004 to 2013 were retrospectively analysed from a prospectively maintained database. POCs were assessed using the Clavien-Dindo classification. Patients who developed POCs were compared with those who did not in terms of recurrence-free survival (RFS) and overall survival (OS). RESULTS: The study population comprised 106 patients, including 79 (74.5%) with synchronous distant metastases. Overall, 46 patients (43%) developed at least one POC during the hospital stay, and of those patients, 9 (20%) had severe complications (Clavien-Dindo ≥ grade III). POCs were not associated with OS (65% with POCs vs. 69% without POCs; p = 0.72) or RFS (58% with POCs vs. 70% without POCs; p = 0.37). Similarly, POCs did not affect OS or RFS in patients who had synchronous metastases at diagnosis compared with those who did not. CONCLUSIONS: POCs do not affect the oncological course of patients subjected to the resection of T4 CRC, even in cases of synchronous metastases.

Liver Transplantation for Neuroendocrine Tumors: What Have We Learned?

Neuroendocrine tumors are slow-growing tumors and associated with prolonged overall survival even in the presence of untreated liver metastases. The presence of liver metastases may be responsible for severe symptoms with impairment of quality of life. Liver resection has been proposed to achieve better symptom control and/or improve overall survival, but this concerns less than 20% of patients with liver metastases. In addition, the chance to be really cured after liver resection is around 40%, which prompts consideration of liver transplantation as the only potential curative treatment. Time has come to move beyond the traditional debate around the best candidates and prognostic factors for liver transplantation. This review gives the opportunity to discuss new insights: (1) outcome of liver transplantation for neuroendocrine liver metastases as compared with hepatocellular carcinoma, (2) outcome of salvage liver transplantation as a secondary procedure after surgical resection of neuroendocrine liver metastases, (3) outcome of palliative liver transplantation for neuroendocrine liver metastases, and (4) the chance to be cured after liver transplantation for neuroendocrine liver metastases.

Safety and feasibility of elective liver resection in adult Jehovah's Witnesses: the Henri Mondor Hospital experience.

BACKGROUND: Elective liver resection (LR) in Jehovah's Witness (JW) patients, for whom transfusion is not an option, involves complex ethical and medical issues and surgical difficulties. METHODS: Consecutive data from a LR program for liver tumors in JWs performed between 2014 and 2017 were retrospectively reviewed. A systematic review of the literature with a pooled analysis was performed. RESULTS: Ten patients were included (median age = 61 years). None needed preoperative erythropoietin. Tumor biopsy was not performed. Major hepatectomy was performed in 4 patients. The median estimated blood loss was 200 mL. A cell-saver was installed in 2 patients, none received saved blood. The median hemoglobin values before and at the end of surgery were 13.4 g/dL and 12.6 g/dL, respectively (p = 0.04). Nine complications occurred in 4 patients, but no postoperative hemorrhage occurred. In-hospital mortality was nil. Nine studies including 35 patients were identified in the literature; there was reported no mortality and low morbidity. None of the patients were transfused. CONCLUSIONS: By using a variety of blood conservation techniques, the risk/benefit ratio of elective liver resection for liver was maintained in selected adult JW patients. JW faith should not constitute an absolute exclusion from hepatectomy.