ABSTRACT
OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.
ABSTRACT
BACKGROUND: Laparoscopic liver resection (LLR) has been associated with improved patient recovery as well as reduced postoperative adhesions compared to open LR (OLR) and could therefore facilitate redo liver surgery. LLR prior to liver transplantation (LT) is increasingly performed, LT being saved for HCC recurrence. LT is still performed by open surgery due to vascular reconstructions and underlying liver chronic disease. We evaluated the impact of laparoscopic approach for LR prior to LT in terms of intraoperative transfusions, adhesions severity and outcome. METHODS: Data from all patients who underwent a LT after LR in two French high-volume tertiary centers were retrospectively reviewed. The impact of LLR on per operative and postoperative outcome was assessed using logistic regression. RESULTS: 170 patients were included, 43 patients in the LLR group and 127 in the OLR group. Preoperative characteristics were comparable between both groups, except LLR group included more patients with "very early-stage" BCLC tumors than OLR group (51% vs. 33%, p = 0.02) and less anatomical resections (54% vs. 75%, p = 0.015). During LT, the transfusion rate was significantly higher in the OLR group (71.4% vs 44.2%, p = 0.002) as well as the proportion of type III adhesions according to OLSG classification (p < 0.001). Multivariate analysis found LLR to be an independent protective factor for adhesions and transfusion (p = 0.001 and p = 0.03 respectively). CONCLUSION: Laparoscopic liver resection was associated with reduced postoperative adhesions and transfusion requirements during subsequent liver transplantation.
Subject(s)
Colorectal Neoplasms , Hepatectomy , Liver Neoplasms , Neoadjuvant Therapy , Humans , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Prognosis , Survival Rate , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, AdjuvantABSTRACT
BACKGROUND: Appropriate risk stratification for the difficulty of liver transplantation (LT) is essential to guide the selection and acceptance of grafts and avoid morbidity and mortality. METHODS: Based on 987 LTs collected from 5 centers, perioperative outcomes were analyzed across the 3 difficulty levels. Each LT was retrospectively scored from 0 to 10. Scores of 0-2, 3-5 and 6-10 were then translated into respective difficulty levels: low, moderate and high. Complications were reported according to the comprehensive complication index (CCI). RESULTS: The difficulty level of LT in 524 (53%), 323 (32%), and 140 (14%) patients was classified as low, moderate and high, respectively. The values of major intraoperative outcomes, such as cold ischemia time (p = 0.04) and operative time (p < 0.0001) increased gradually with statistically significant values among difficulty levels. There was a corresponding increase in CCI (p = 0.04), severe complication rates (p = 0.05) and length of ICU (p = 0.01) and hospital (p = 0.004) stays across the different difficulty levels. CONCLUSION: The LT difficulty classification has been validated.
Subject(s)
Liver Transplantation , Postoperative Complications , Humans , Liver Transplantation/adverse effects , Retrospective Studies , Female , Middle Aged , Male , Risk Assessment , Postoperative Complications/classification , Postoperative Complications/etiology , Risk Factors , Treatment Outcome , Adult , Reproducibility of Results , Aged , Time Factors , Length of Stay , Europe , Operative Time , Cold Ischemia , Patient Selection , Predictive Value of TestsABSTRACT
CONTEXT: Clinical adoption of ex situ liver perfusion is growing. While hypothermic perfusion protects against ischemia-reperfusion injury in marginal grafts, normothermic perfusion enables organ viability assessment and therefore selection of borderline grafts. The combination of hypothermic and normothermic perfusion, known as "cold-to-warm," may be the optimal sequence for organ preservation, but is difficult to achieve with most commercial perfusion systems. We developed an adaptable customized circuit allowing uninterrupted "cold-to-warm" perfusion and conducted preclinical studies on healthy porcine livers and discarded human livers to demonstrate the circuit's efficacy. METHODS: In collaboration with bioengineers, we developed a customized circuit that adapts to extracorporeal circulation consoles used in cardiovascular surgery and includes a proprietary reservoir enabling easy perfusate change without interrupting perfusion. This preclinical study was conducted on porcine and human livers. Perfusion parameters (pressures, flows, oxygenation) and organ viability were monitored. RESULTS: The customized circuit was adapted to a LivaNova S5® console, and the perfusions were flow-driven with real-time pressure monitoring. Ten porcine liver and 12 discarded human liver perfusions were performed during 14 to 18 h and 7 to 25 h, respectively. No hyperpressure was observed (porcine and human portal pressure 2-6 and 2-8 mm Hg; arterial pressure 10-65 and 20-65 mm Hg, respectively). No severe histological tissue injury was observed (Suzuki score ≤ 3 at the end of perfusion). Seven (70%) porcine livers and five (42%) human livers met the UK viability criteria. CONCLUSION: The customized circuit and system design enables smooth uninterrupted "cold-to-warm" perfusion not present in current commercial perfusion systems.
Subject(s)
Liver , Organ Preservation , Perfusion , Animals , Liver/blood supply , Swine , Organ Preservation/methods , Organ Preservation/instrumentation , Humans , Perfusion/methods , Perfusion/instrumentation , Liver Transplantation/methods , Extracorporeal Circulation/instrumentation , Extracorporeal Circulation/methods , Equipment DesignABSTRACT
BACKGROUND: Optimal management of colorectal liver metastasis (CRLM) is based on a combination of chemotherapy and surgical resection. The tumor regression grade (TRG) score is a histological scoring system to evaluate response to chemotherapy. The prognosis of a heterogeneous response in cases of multiple metastases has not been evaluated according to the TRG score. PATIENTS AND METHODS: All patients who underwent liver resection for multiple CRLM after neoadjuvant chemotherapy in two tertiary centers from January 2015 to April 2019 were retrospectively included. Oncological characteristics and outcome between TRG 1-2-3 (good response group), TRG 4-5 (poor response group) and heterogeneous TRG (good and poor TRG among different lesions within the same patient) groups were compared. RESULTS: Among the 327 patients included, 134 (41.0%) had good response (TRG 1-2-3), 120 (36.7%) had poor response (TRG 4-5), and 73 (22.3%) had heterogeneous response. The type and number of cycles of chemotherapy, k-Ras mutational status, and tumor number or size did not differ between the three groups. Use of irinotecan-based and anti-VEGF neoadjuvant therapy was associated with better TRG response [irinotecan-based: hazard ratio (OR) = 1.744; p = 0.045; anti-VEGF neoadjuvant therapy: 2.054; p = 0.005). Overall survival (OS) was higher in the 1-2-3 TRG group than in the heterogeneous TRG group (2-year OS = 81.3% vs. 60.3%, respectively; p = 0.003) and the 4-5 TRG group (2-year OS = 81.3% vs. 55.0%, respectively; p = 0.012) and similar between the heterogeneous and 4-5 TRG groups. CONCLUSIONS: The proportion of heterogeneous pathological response according to TRG is 22.3%, and the prognosis is comparable to that of poor pathological response.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Hepatectomy , Liver Neoplasms , Neoadjuvant Therapy , Humans , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Male , Female , Retrospective Studies , Middle Aged , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate , Aged , Follow-Up Studies , Irinotecan/administration & dosage , Chemotherapy, AdjuvantABSTRACT
BACKGROUND: There are no data to evaluate the difference in populations and impact of centers with liver transplant programs in performing laparoscopic liver resection (LLR). METHODS: This was a multicenter study including patients undergoing LLR for benign and malignant tumors at 27 French centers from 1996 to 2018. The main outcomes were postoperative severe morbidity and mortality. RESULTS: A total of 3154 patients were included, and 14 centers were classified as transplant centers (N = 2167 patients, 68.7 %). The transplant centers performed more difficult LLRs and more resections for hepatocellular carcinoma (HCC) in patients who more frequently had cirrhosis. A higher rate of performing the Pringle maneuver, a lower rate of blood loss and a higher rate of open conversion (all p < 0.05) were observed in the transplant centers. There was no association between the presence of a liver transplant program and either postoperative severe morbidity (<10 % in each group; p = 0.228) or mortality (1 % in each group; p = 0.915). CONCLUSIONS: Most HCCs, difficult LLRs, and cirrhotic patients are treated in transplant centers. We show that all centers can achieve comparable safety and quality of care in LLR independent of the presence of a liver transplant program.
Subject(s)
Carcinoma, Hepatocellular , Laparoscopy , Liver Neoplasms , Liver Transplantation , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Liver Transplantation/adverse effects , Retrospective Studies , Hepatectomy/adverse effects , Laparoscopy/adverse effects , Length of Stay , Postoperative Complications/etiology , Postoperative Complications/surgeryABSTRACT
BACKGROUND: Integrating immunotherapy with locoregional therapies marks a significant milestone in the realm of hepatocellular carcinoma (HCC) treatment . This study aimed to assess the impact of addition of Atezolizumab-Bevacizumab (AtezoBev) on the outcome patients treated with SIRT. METHODS: We conducted a study that included all Child-Pugh A HCC treated with SIRT since 2017. We examined the effects of the addition of 3 infusions of AtezoBev before the SIRT procedure and after SIRT on patients outcome (AtezoBev-SIRT group). Time-to-event data were analyzed using Kaplan-Meier with the log-rank test. RESULTS: Thirty five HCC patients treated with SIRT were included, of whom 23 % also received AtezoBev infusions. The two groups were similar in terms of liver function and HCC parameters. The median OS was not reached for patients who received AtezoBev in combination with SIRT and 14 months for patients only treated by SIRT. The median PFS was higher in the group treated by SIRT and AtezoBev vs SIRT alone (11.3 months vs 5.8 months). In the global cohort, 8 patients presented a downstaging (23 %), 4 underwent liver surgery (1 in the AtezoBev-SIRT group) and 4 liver transplantation (1 in the AtezoBev-SIRT group) CONCLUSIONS: The administration of AtezoBev, both before and after SIRT, is associated with enhanced OS and PFS outcomes compared to SIRT alone for unresectable HCC.
Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Bevacizumab/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS: Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. RESULTS: During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. CONCLUSION: Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.
Subject(s)
Bile Duct Neoplasms , Carcinoma, Hepatocellular , Cholangiocarcinoma , Liver Neoplasms , Humans , Retrospective Studies , Cohort Studies , Propensity Score , Bile Ducts, Intrahepatic/pathologyABSTRACT
BACKGROUND AND AIMS: We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC). METHOD: All cirrhotic patients that received radiotherapy for HCC between 2012 and 2022 were included. Portal hypertension-Score was built using univariate analysis with the presence of esophageal varices (EV), platelet count, history of acute variceal bleeding (AVB) and spleen size. Time-to-events data were estimated using Kaplan-Meier method with log-rank and Cox-models. RESULTS: 60 patients were included (female 27%, age 67 years-old, Child-Pugh A 82%, alcoholic/non-alcoholic steatohepatitis/hepatitis C virus 55/40/32%). 38% and 15% presented history of ascites and AVB respectively, 25% had large EV, 53.5% presented PHT score ≥ 5. 92% were BCLC-0/A, median tumor size was 30 mm. At 6 months, ascites incidence was 19% and precluded access to further HCC treatment for all patients with HCC recurrence. All PHT parameters included in the score and PHT score ≥ 5 (hazard ratio (HR) = 14.07, p = 0.01) were associated with ascites occurrence. Transplantation free survival and recurrence free survival at 1 year were 56% and 47% respectively. Albi grade 3 (HR = 3.01; p = 0.04) was independently associated with Transplantation free survival. CONCLUSION: Radiotherapy should be cautiously performed in patients with PHT score ≥ 5 because of ascites occurrence risk precluding access to further HCC treatments.
Subject(s)
Carcinoma, Hepatocellular , Esophageal and Gastric Varices , Hypertension, Portal , Hypertension , Liver Neoplasms , Humans , Female , Aged , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/complications , Liver Neoplasms/epidemiology , Liver Neoplasms/radiotherapy , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/epidemiology , Esophageal and Gastric Varices/etiology , Ascites/etiology , Ascites/complications , Treatment Outcome , Gastrointestinal Hemorrhage/complications , Hypertension, Portal/etiology , Liver Cirrhosis/complications , Hypertension/complicationsABSTRACT
BACKGROUND: A textbook outcome (TO) describes the results of a successful liver transplantation (LT) in which all aspects of the LT and posttransplant courses were uneventful. We compared patient perceived experience of a TO with clinically defined TO. METHODS: This was a single-institution cohort study with retrospective chart review including patients who underwent LT from 2019 to 2021. Patients were asked to complete the survey at a scheduled posttransplant visit. The survey was designed to assess their viewpoints on the definition of a TO. A clinically defined TO was defined as no mortality, no severe complications, no need for reintervention, no prolonged hospital and intensive care unit stays, and no readmission. RESULTS: Of the 182 patients who were contacted, 132 (72.5%) completed the survey. Overall, 98 patients (74%) considered that they had experienced a TO. The clinically defined TO rate was 22.0%. Multivariate analysis showed that patients who did not experience severe complications were more likely to consider that they had a TO (P = 0.01; odds ratio: 3.2; 95% confidence interval: 1.3-7.9). CONCLUSIONS: From patients' perspectives, survival and avoidance of complications were the major characteristics of a TO.
Subject(s)
Liver Transplantation , Humans , Liver Transplantation/adverse effects , Cohort Studies , Retrospective Studies , Multivariate Analysis , Length of StayABSTRACT
BACKGROUND: Significant variations exist regarding the definition of difficult liver transplantation. The study goals were to investigate how liver transplant surgeons evaluate the surgical difficulty of liver transplantation and to use the identified factors to classify liver transplantation difficulty. METHODS: A Web-based online European survey was presented to liver transplant surgeons. The survey was divided into 3 parts: (1) participant demographics and practices; (2) various situations based on recipient, liver disease, tumor treatment, and technical factors; and (3) 8 real-life clinical vignettes with different levels of complexity. In part 3 of the survey, respondents were asked whether they would perform liver transplantation but were not aware that these patients eventually underwent liver transplantation. RESULTS: A total of 143 invites were sent out, and 97 (67.8%) participants completed the survey. Most participants considered previous spontaneous bacterial peritonitis, previous supra-mesocolic surgery, hypertrophy of segment I, and obesity to be recipient factors for high-difficulty liver transplantation. Most participants considered liver transplantation to be challenging in patients with Budd-Chiari syndrome, Kasai surgery, polycystic liver disease, diffuse portal vein thrombosis, and a history of open hepatectomy. The proportion of participants indicating that liver transplantation was warranted varied across the 8 cases, from 69% to 100%. Our classification of the surgical difficulty of liver transplantation employed these recipient-related, surgical history-related, and liver disease-related variables and 3 difficulty groups were identified: low, intermediate, and high difficulty groups. CONCLUSION: This survey provides an overview of the surgical difficulty of various situations in liver transplantation that could be useful for further benchmark and textbook outcome studies.
Subject(s)
Budd-Chiari Syndrome , Liver Transplantation , Venous Thrombosis , Humans , Budd-Chiari Syndrome/surgery , Venous Thrombosis/surgery , Hypertrophy , Surveys and QuestionnairesABSTRACT
BACKGROUND: Right hepatectomy (RH) for hepatocellular carcinoma (HCC) is ideally preceded by transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE). Laparoscopic approach improves short-term outcome and textbook outcome (TO), which reflects the "ideal" surgical outcome, after RH. However, laparoscopic RH on an underlying diseased liver and after TACE/PVE remains a challenging procedure. The aim of this study was to compare the outcomes in patients who underwent laparoscopic liver resection (LLR) or open liver resection (OLR) following TACE/PVE. PATIENTS AND METHODS: All patients with HCC who underwent RH after TACE/PVE in five French centers were retrospectively included. Outcomes were compared between the LLR group and the OLR group using propensity score matching (PSM). Quality of surgical care was defined by TO. RESULTS: Between 2005 and 2019, 117 patients were included (41 in LLR group, 76 in OLR group). Overall morbidity was comparable (51% versus 53%, p = 0.24). In LLR group, TO was completed in 66% versus 37% in OLR group (p = 0.02). LLR and absence of clamping were the only factors associated with TO completion [hazard ratio (HR) 4.27, [1.77-10.28], p = 0.001]. After PSM, 5-year overall survival (OS) and progression-free survival (PFS) were 55% in matched LLR versus 77% in matched OLR, p = 0.35, and 13% in matched LLR versus 17% in matched OLR, p = 0.97. TO completion was independently associated with a better 5-year OS (65.2% versus 42.5%, p = 0.007). CONCLUSION: Major LLR after TACE/PVE should be considered as a valuable option in expert centers to increase the chance of TO, the latter being associated with a better 5-year OS.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Laparoscopy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Retrospective Studies , Laparoscopy/methods , Propensity Score , Length of Stay , Treatment OutcomeABSTRACT
INTRODUCTION: After local or systemic treatment, a small number of patients with primarily unresectable intrahepatic cholangiocarcinoma (ICC) may benefit from secondary resection. This study aimed to analyze the oncological outcome of patients who underwent radical surgery after preoperative treatment. METHODS: From 2000 to 2021, all patients who underwent curative-intent liver resection for ICC in three tertiary centers were selected. Patients were divided into two groups: upfront surgery (US) and preoperative treatment (POT). Oncologic data (preoperative treatment, histologic data, adjuvant chemotherapy, overall survival, and recurrence-free survival) were compared between the two groups. RESULTS: Among 198 included patients, 31 (15.7%) received POT including chemotherapy (74.2%), radioembolization (12.9%), chemoembolization (9.7%), or combined radiotherapy and chemotherapy (3.2%). Major resection was performed in 156 (78.8%) patients, and 53 (26.8%) had vascular and/or biliary reconstruction. Histological findings were similar between US and POT group and were not affected by the type of POT. After a median follow-up of 23 months, recurrence rate (58.1% POT vs. 55.1% US, p = 0.760) and type were similar between groups. Recurrence-free survival at 1 and 3 years (41.9% and 22.6% vs. 46.7 and 21.6% in the POT and US, respectively, p = 0.989) and overall survival at 1 and 3 years (77.4% and 32.3% vs. 69.5% and 34.7% in the POT and US respectively, p = 0.323) were similar and independent of the POT type. CONCLUSION: After POT, downstaged patients who underwent curative-intent resection for initially unresectable ICC have similar long-term outcomes as those undergoing upfront surgery.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Induction Chemotherapy , Retrospective Studies , Cholangiocarcinoma/pathology , Hepatectomy , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Neoplasm Recurrence, Local/pathologyABSTRACT
BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, liver resection (LR) is recommended for early-stage (BCLC-A) hepatocellular carcinoma (HCC) but not for intermediate-stage (BCLC-B). This study aimed to assess the outcomes of LR in these patients using a subclassification tumour burden score (TBS). METHODS: All consecutive patients that underwent LR for BCLC-A and BCLC-B HCC between 01/2010 and 12/2020 in 4 tertiary referral centers were included. Clinical outcomes and overall survival (OS) were assessed in relation to TBS and BCLC stages. RESULTS: Among 612 patients included, 562 were classified as BCLC-A and 50 as BCLC-B. The incidence of overall postoperative complications (56.0 vs 41.5%, p = 0.053) and mortality (0 vs 1.6%, p = 1.000) were similar between BCLC-A and BCLC-B patients. OS was significantly higher for BCLC A/low TBS than BCLC B/low TBS (p = 0.009), while patients with medium and high TBS had similar OS, irrespective of BCLC stage (respectively p = 0.103 and p = 0.343). CONCLUSIONS: Patients with medium and high TBS had comparable OS and DFS, irrespective of BCLC A or B stage, and postoperative morbidity was comparable. These results highlight the need for refinement of the BCLC staging system, and LR could be considered for selected intermediate stage (BCLC-B) according to the tumour burden.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Tumor Burden , Neoplasm Staging , Retrospective Studies , Hepatectomy/adverse effectsABSTRACT
Liver failure includes distinct subgroups of diseases: Acute liver failure (ALF) without preexisting cirrhosis, acute-on-chronic liver failure (ACLF) (severe form of cirrhosis associated with organ failures and excess mortality), and liver fibrosis (LF). Inflammation plays a key role in ALF, LF, and more specifically in ACLF for which we have currently no treatment other than liver transplantation (LT). The increasing incidence of marginal liver grafts and the shortage of liver grafts require us to consider strategies to increase the quantity and quality of available liver grafts. Mesenchymal stromal cells (MSCs) have shown beneficial pleiotropic properties with limited translational potential due to the pitfalls associated with their cellular nature. MSC-derived extracellular vesicles (MSC-EVs) are innovative cell-free therapeutics for immunomodulation and regenerative purposes. MSC-EVs encompass further advantages: pleiotropic effects, low immunogenicity, storage stability, good safety profile, and possibility of bioengineering. Currently, no human studies explored the impact of MSC-EVs on liver disease, but several preclinical studies highlighted their beneficial effects. In ALF and ACLF, data showed that MSC-EVs attenuate hepatic stellate cells activation, exert antioxidant, anti-inflammatory, anti-apoptosis, anti-ferroptosis properties, and promote regeneration of the liver, autophagy, and improve metabolism through mitochondrial function recovery. In LF, MSC-EVs demonstrated anti-fibrotic properties associated with liver tissue regeneration. Normothermic-machine perfusion (NMP) combined with MSC-EVs represents an attractive therapy to improve liver regeneration before LT. Our review suggests a growing interest in MSC-EVs in liver failure and gives an appealing insight into their development to rehabilitate marginal liver grafts through NMP.
Subject(s)
Extracellular Vesicles , Liver Failure , Liver Transplantation , Mesenchymal Stem Cells , Humans , Liver Failure/metabolism , Liver Cirrhosis , Extracellular Vesicles/metabolism , Extracellular Vesicles/transplantation , Mesenchymal Stem Cells/metabolismSubject(s)
Laparoscopy , Liver Neoplasms , Liver Transplantation , Humans , Hepatectomy , Living Donors , Liver Neoplasms/surgeryABSTRACT
Background & Aims: Biliary complications (BC) following liver transplantation (LT) are responsible for significant morbidity. No technical procedure during reconstruction has been associated with a risk reduction of BC. The placement of an intraductal removable stent (IRS) during reconstruction followed by its endoscopic removal showed feasibility and safety in a preliminary study. This multicentric randomised controlled trial aimed at evaluating the impact of an IRS on BC following LT. Methods: This multicentric randomised controlled trial was conducted in 7 centres from April 2015 to February 2019. Randomisation was done during LT when a duct-to-duct anastomosis was confirmed with at least 1 of the stump diameters ≤7 mm. In the IRS group, a custom-made segment of a T-tube was placed into the bile duct to act as a stake during healing and was removed endoscopically 4 to 6 months post LT. The primary endpoint was the incidence of BC (fistulae and strictures) within 6 months post LT. The secondary criteria were complications related to the IRS placement or extraction, including endoscopic retrograde cholangio-pancreatography (ERCP)-related complications. Results: In total, 235 patients were randomised: 117 in the IRS group and 118 in the control group. BC occurred in 31 patients (26.5%) in the IRS group vs. 24 (20.3%) in the control group (p = 0.27), including 16 (13.8%) and 15 (12.8%) strictures, respectively. IRS migration occurred in 24 patients (20.5%), cholangitis in 1 (0.9%), acute pancreatitis in 2 (1.8%), and difficulty during endoscopic extraction in 19 (19.4%). No predictive factor for BC was identified. Conclusions: IRS does not prevent BC after LT and may require specific endoscopic expertise for removal. Trial registration number ClinicalTrialsgov: NCT02356939 (https://clinicaltrials.gov/ct2/show/NCT02356939?term=NCT02356939&draw=2&rank=1). Lay summary: Liver transplantation is a life-saving treatment for many patients with end-stage liver disease. However, it can be associated with complications involving the bile duct reconstruction. Herein, the placement of a specific stent called an intraductal removable stent was trialled as a way of reducing bile duct complications in patients undergoing liver transplantation. Unfortunately, it did not help preventing such complications.