scholarly journals Morbidity, Prognostic Factors, and Competing Risk Nomogram for Combined Hepatocellular-Cholangiocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Xiaoyuan Chen ◽  
Yiwei Lu ◽  
Xiaoli Shi ◽  
Xuejiao Chen ◽  
Dawei Rong ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Primary Liver Cancer ◽  
Information Criterion ◽  
Competing Risk ◽  
Milan Criteria ◽  
Prognostic Indicators ◽  
Individual Treatment ◽  
Study Cohort ◽  
Survival Difference ◽  
Combined Hepatocellular Cholangiocarcinoma

Background. Combined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. This study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC. Methods. The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence was calculated using the joinpoint regression. The nomogram was developed based on multivariate competing risk survival analyses and validated by calibration curves. Akaike information criterion, Bayesian information criterion, Harrell’s C-index, and area under the receiver operating characteristic curves were obtained to compare prognostic performance. Decision curve analysis was introduced to examine the clinical value of the models. Results. The overall incidence of CHC was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an APC of 1.0% ( P > 0.05 ). CHC displayed intermediate clinicopathological features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Race, tumor size, vascular invasion, extrahepatic invasion, distant metastasis, grade, surgery, and Metavir stage were confirmed as the independent predictors of cancer-specific survival. The constructed nomogram was well calibrated, which showed better discrimination power and higher net benefits than the current American Joint Committee on Cancer staging system. Patients with liver transplantation had better survival than those with hepatectomy, especially patients within the Milan Criteria ( P = 0.022 and P = 0.015 ). There was no survival difference between liver transplantation and hepatectomy in patients beyond the Milan Criteria ( P = 0.340 ). Conclusion. The morbidity of CHC remained stable between 2004 and 2018. The constructed nomogram could predict the prognosis with good performance, which was meaningful to individual treatment strategies optimization. CHC patients should also be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed.

scholarly journals The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3730
Author(s):  
Berend R. Beumer ◽  
Roeland F. de Wilde ◽  
Herold J. Metselaar ◽  
Robert A. de Man ◽  
Wojciech G. Polak ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Resection ◽  
Early Stage ◽  
Disease Free Survival ◽  
Milan Criteria ◽  
Term Survival ◽  
Equal Distribution ◽  
Intention To Treat ◽  
Treat Analysis

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.

scholarly journals Prolonged Survival of a Patient with Advanced-Stage Combined Hepatocellular-Cholangiocarcinoma

2020 ◽  
Vol 14 (3) ◽  
pp. 658-667
Author(s):  
Sven H. Loosen ◽  
Nadine T. Gaisa ◽  
Maximilian Schmeding ◽  
Christoph Heining ◽  
Sebastian Uhrig ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Primary Liver Cancer ◽  
Advanced Stage ◽  
Rare Type ◽  
Treatment Protocols ◽  
Genetic Landscape ◽  
Standardized Treatment ◽  
Genomic Studies ◽  
Combined Hepatocellular Cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma (cHCC/CCA) represents a rare type of primary liver cancer with a very limited prognosis. Although just recently genomic studies have contributed to a better understanding of the disease’s genetic landscape, therapeutic options, especially for advanced-stage patients, are limited and often experimental, as no standardized treatment protocols have been established to date. Here, we report the case of a 38-year-old male patient who was diagnosed with extensive intrahepatic cHCC/CCA in an otherwise healthy liver without signs of chronic liver disease. An interdisciplinary stepwise therapeutic approach including locoregional liver-targeted therapy, systemic chemotherapy, liver transplantation, surgical pulmonary metastasis resection, and next-generation sequencing-based targeted therapy led to a prolonged overall survival beyond 5 years with an excellent quality of life. This case report comprises several provocative treatment decisions that are extensively discussed in light of the existing literature on this rare but highly aggressive malignancy.

scholarly journals Acute Liver Failure Caused byAmanita phalloidesPoisoning

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Luca Santi ◽  
Caterina Maggioli ◽  
Marianna Mastroroberto ◽  
Manuel Tufoni ◽  
Lucia Napoli ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Rna Polymerase Ii ◽  
Gastrointestinal Symptoms ◽  
Amanita Phalloides ◽  
Prognostic Indicators ◽  
Mushroom Poisoning ◽  
Lag Phase ◽  
Kidney Involvement

Mushroom poisoning is a relatively rare cause of acute liver failure (ALF). The present paper analyzes the pathogenesis, clinical features, prognostic indicators, and therapeutic strategies of ALF secondary to ingestion ofAmanita phalloides, which represents the most common and deadly cause of mushroom poisoning. Liver damage fromAmanita phalloidesis related to the amanitins, powerful toxins that inhibit RNA polymerase II resulting in a deficient protein synthesis and cell necrosis. After an asymptomatic lag phase, the clinical picture is characterized by gastrointestinal symptoms, followed by the liver and kidney involvement. Amatoxin poisoning may progress into ALF and eventually death if liver transplantation is not performed. The mortality rate afterAmanita phalloidespoisoning ranges from 10 to 20%. The management of amatoxin poisoning consists of preliminary medical care, supportive measures, detoxification therapies, and orthotopic liver transplantation. The clinical efficacy of any modality of treatment is difficult to demonstrate since randomized, controlled clinical trials have not been reported. The use of extracorporeal liver assist devices as well as auxiliary liver transplantation may represent additional therapeutic options.

scholarly journals Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma

HPB ◽  
2015 ◽  
Vol 17 (2) ◽  
pp. 168-175 ◽  
Author(s):  
Andreas Andreou ◽  
Safak Gül ◽  
Andreas Pascher ◽  
Wenzel Schöning ◽  
Hussein Al‐Abadi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Milan Criteria ◽  
Tumour Biology

Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the Milan Criteria: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 152 (5) ◽  
pp. S1124
Author(s):  
Thapanakul Emyoo ◽  
Piyapon Utako ◽  
Noriyo Yamashiki ◽  
Thunyarat Anothaisintawee ◽  
Ammarin Thakkinstian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Liver Transplantation ◽  
Meta Analysis ◽  
Milan Criteria

scholarly journals Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mamatha Bhat ◽  
Sergi Clotet-Freixas ◽  
Cristina Baciu ◽  
Elisa Pasini ◽  
Ahmed Hammad ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Protein Expression ◽  
Univariate Analysis ◽  
Milan Criteria ◽  
Post Transplant ◽  
Gene And Protein Expression ◽  
Galectin 3 ◽  
Transcriptomic Signature ◽  
Hcc Recurrence

Abstract Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Results Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01–0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16–0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20–432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1–6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01–8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2–5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples. Conclusions Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance.

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