Extrahepatic Portal Hypertension following Liver Transplantation: a Rare but Challenging Problem

This study reports our experience of 8 cases of extrahepatic portal hypertension after 273 orthotopic liver transplantations in 244 adult patients over a 10- year period. The main clinical feature was ascites, and the life-threatening complication was variceal bleeding. Extrahepatic portal hypertension was caused by portal vein stenosis in 6 patients, and left-sided portal hypertension in 2 patients after inadventent ligation of portal venous tributaries or portasystemic shunts. All patients with portal vein stenosis had complete relief of portal hypertension after percutaneous transhepatic venoplasty (n=4) or surgical reconstruction (n=2), after a median follow-up of 33 (range: 6–62) months. Of the 2 patients with left-sided portal hypertension, one died after splenectomy and one rebled 6 months after left colectomy. This study suggests that extrahepatic portal hypertension is a series complication after liver transplantation that could be prevented by meticulous portal anastomosis and closure of portal tributaries or portasystemic shunts to improve the portal venous flow. However, any ligation has to be performed under ultrasound guidance to avoid inadventent venous ligations

Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

INTRODUCTION: King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation. METHODS: We analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility. RESULTS: 152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%). CONCLUSION: ALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation

Use of Artificial Intelligence as an Innovative Method for Liver Graft Macrosteatosis Assessment

The worldwide implementation of a liver graft pool using marginal livers (ie, grafts with a high risk of technical complications and impaired function or with a risk of transmitting infection or malignancy to the recipient) has led to a growing interest in developing methods for accurate evaluation of graft quality. Liver steatosis is associated with a higher risk of primary nonfunction, early graft dysfunction, and poor graft survival rate. The present study aimed to analyze the value of artificial intelligence (AI) in the assessment of liver steatosis during procurement compared with liver biopsy evaluation. A total of 117 consecutive liver grafts from brain-dead donors were included and classified into 2 cohorts: ≥30 versus <30% hepatic steatosis. AI analysis required the presence of an intraoperative smartphone liver picture as well as a graft biopsy and donor data. First, a new algorithm arising from current visual recognition methods was developed, trained, and validated to obtain automatic liver graft segmentation from smartphone images. Second, a fully automated texture analysis and classification of the liver graft was performed by machine-learning algorithms. Automatic liver graft segmentation from smartphone images achieved an accuracy (Acc) of 98%, whereas the analysis of the liver graft features (cropped picture and donor data) showed an Acc of 89% in graft classification (≥30 versus <30%). This study demonstrates that AI has the potential to assess steatosis in a handy and noninvasive way to reliably identify potential nontransplantable liver grafts and to avoid improper graft utilization

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery

Background: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. Patients and methods: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. Results: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. Conclusion: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcom

Computer-assisted liver graft steatosis assessment via learning-based texture analysis

Purpose: Fast and accurate graft hepatic steatosis (HS) assessment is of primary importance for lowering liver dysfunction risks after transplantation. Histopathological analysis of biopsied liver is the gold standard for assessing HS, despite being invasive and time consuming. Due to the short time availability between liver procurement and transplantation, surgeons perform HS assessment through clinical evaluation (medical history, blood tests) and liver texture visual analysis. Despite visual analysis being recognized as challenging in the clinical literature, few efforts have been invested to develop computer-assisted solutions for HS assessment. The objective of this paper is to investigate the automatic analysis of liver texture with machine learning algorithms to automate the HS assessment process and offer support for the surgeon decision process. Methods: Forty RGB images of forty different donors were analyzed. The images were captured with an RGB smartphone camera in the operating room (OR). Twenty images refer to livers that were accepted and 20 to discarded livers. Fifteen randomly selected liver patches were extracted from each image. Patch size was 100 × 100. This way, a balanced dataset of 600 patches was obtained. Intensity-based features (INT), histogram of local binary pattern (HLBPriu2), and gray-level co-occurrence matrix (FGLCM) were investigated. Blood-sample features (Blo) were included in the analysis, too. Supervised and semisupervised learning approaches were investigated for feature classification. The leave-one-patient-out cross-validation was performed to estimate the classification performance. Results: With the best-performing feature set (HLBPriu2+INT+Blo) and semisupervised learning, the achieved classification sensitivity, specificity, and accuracy were 95, 81, and 88%, respectively. Conclusions: This research represents the first attempt to use machine learning and automatic texture analysis of RGB images from ubiquitous smartphone cameras for the task of graft HS assessment. The results suggest that is a promising strategy to develop a fully automatic solution to assist surgeons in HS assessment inside the OR

Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer

Background: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. Patients and methods: A large series of surgically resected liver metastases (n = 153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (α-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. Results: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. Conclusions: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplati

Impact of Microvascular Invasion on Clinical Outcomes After Curative-Intent Resection for Intrahepatic Cholangiocarcinoma

Background: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC. Methods: A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI). Results: A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P 18 months) prognosis. Conclusions: Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence.info:eu-repo/semantics/publishedVersio

Vascular invasion and survival after liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry

Background: Studies suggest that vascular invasion may be a superior prognostic marker compared with traditional selection criteria, e.g. Milan criteria. This study aimed to investigate the prognostic value of micro and macrovascular invasion in a large database material. Methods: Patients liver transplanted for HCC and cirrhosis registered in the European Liver Transplant Registry (ELTR) database were included. The association between the Milan criteria, Up-to-seven criteria and vascular invasion with overall survival and HCC specific survival was investigated with univariate and multivariate Cox regression analyses. Results: Of 23,124 patients transplanted for HCC, 9324 had cirrhosis and data on explant pathology. Patients without microvascular invasion, regardless of number and size of HCC nodules, had a five-year overall survival of 73.2%, which was comparable with patients inside both Milan and Up-to-seven criteria. Patients without macrovascular invasion had an only marginally reduced survival of 70.7% after five years. Patients outside both Milan and Up-to-seven criteria without micro or macrovascular invasion still had a five-year overall survival of 65.8%. Conclusion: Vascular invasion as a prognostic indicator remains superior to criteria based on size and number of nodules. With continuously improving imaging studies, microvascular invasion may be used for selecting patients for transplantation in the future

Defining Long-Term Survivors Following Resection of Intrahepatic Cholangiocarcinoma

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. METHODS: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5). RESULTS: Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived  5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT. CONCLUSION: While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.info:eu-repo/semantics/publishedVersio

Long-Term Outcomes After Curative Resection of HCV-Positive Versus Non-Hepatitis Related Hepatocellular Carcinoma: an International Multi-Institutional Analysis

Background: To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades. Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias. Results: Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000-2009 55% vs. 2010-2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000-2009 53% vs. 2010-2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients. Conclusion: While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable.info:eu-repo/semantics/publishedVersio