Dataset Information

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

ABSTRACT:

Background

Patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) are not traditionally considered eligible for liver transplantation (LT) due to poor outcomes.

Aim

To compare outcomes between living donor LT (LDLT) patients with hepatocellular carcinoma (HCC) and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients.

Methods

Data for pathologically diagnosed cHCC-CC patients (n = 111) who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review. Patients (n = 141) who received LDLT for HCC at Samsung Medical Center from January 2013 to March 2017 were selected as the control group. Seventy patients in two groups, respectively, were selected by 1:1 matching.

Results

Cumulative disease-free survival (DFS) and overall survival (OS) in the cHCC-CC group were significantly worse than in the HCC group both before and after matching. Extrahepatic recurrence incidence in the cHCC-CC group was higher than that in the HCC group (75.5% vs 33.3%, P < 0.001). Multivariate analysis demonstrated that the cHCC-CC group had significantly higher rates of tumor recurrence and death compared to the HCC group. In cHCC-CC subgroup analysis, frequency of locoregional therapies > 3, tumor size > 3 cm, and lymph node metastasis were predisposing factors for tumor recurrence in multivariate analysis. Only a maximum tumor size > 3 cm was a predisposing factor for death.

Conclusion

The poor prognosis of patients diagnosed with cHCC-CC after LT can be predicted based on the explanted liver. Frequent regular surveillance for cHCC-CC patients should be required for early detection of tumor recurrence.

SUBMITTER: Kim J

PROVIDER: S-EPMC10405106 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

Kim Jongman J Joo Dong-Jin DJ Hwang Shin S Lee Jeong-Moo JM Ryu Je-Ho JH Nah Yang-Won YW Kim Dong-Sik DS Kim Doo-Jin DJ You Young-Kyoung YK Yu Hee-Chul HC

World journal of gastrointestinal surgery 20230701 7

<h4>Background</h4>Patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) are not traditionally considered eligible for liver transplantation (LT) due to poor outcomes.<h4>Aim</h4>To compare outcomes between living donor LT (LDLT) patients with hepatocellular carcinoma (HCC) and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients.<h4>Methods</h4>Data for pathologically diagnosed cHCC-CC patients (<i>n</i> = 1 ...[more]

PMID: 37555110

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Project description:BackgroundCombined hepatocellular-cholangiocarcinoma (CHC) is a rare but vital heterogeneous histological subtype of primary liver cancer (PLC) with no standardized treatment strategy. This study aimed to preliminarily investigate the role of liver transplantation (LT) in CHC and develop a novel risk scoring model (RSM) to evaluate the benefits of transplantation.MethodsThe study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence or ratio was calculated utilizing the Joinpoint regression. Propensity score matching (PSM) was introduced to reduce the selection bias between groups. A novel RSM was developed based on the independent prognostic factors identified by the Cox regression model. The predictive performance of the RSM was compared with the Milan Criteria and the University of California, San Francisco (UCSF) Criteria, respectively.ResultsA total of 223 CHC patients were enrolled, and 60 (26.9%) of them received LT. The incidence-based mortality did not decrease between 2004 and 2015 (APC =1.7%, P=0.195). Although LT was considered an independent protective predictor for CHC, it showed a declining ratio from 33.3% in 2004 to 15.4% in 2015 (APC =-8.9%, P=0.012). The LT recipients had better outcomes than others who underwent hepatectomy or local destruction (P<0.05). Compared with other subtypes of PLC, the post-transplantation prognoses of CHC patients were similar to those with hepatocellular carcinoma (P>0.05) but significantly better than those with intrahepatic cholangiocarcinoma (ICC) (P<0.05). Based on the RSM (vascular invasion: 1 point; tumor size >2 cm: 1 point; multiple tumors: 2 points), patients were stratified into two prognostic subgroups: the low-risk (scoring ≤2) and the high-risk (scoring >2 or extrahepatic metastasis) groups. Patients in the low-risk group were more likely to benefit from LT. The predictive performance of the RSM outperformed the Milan and UCSF Criteria in both the training and validation sets.ConclusionsTherapeutic strategies for CHC should be further improved. Patients with CHC should also be considered potential LT candidates. The novel RSM could be helpful to stratify patients and assist clinical decision-making.

Project description:Background and aimsLiver 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.MethodsPatients 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.ResultsSeventy-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.ConclusionsSignificantly 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.

Project description:BackgroundCardiac liver cirrhosis secondary to Fontan procedure has been associated with hepatocellular carcinoma at a younger age. However, Fontan associated liver disease and combined hepatocellular-cholangiocarcinoma has not been previously reported. Combined hepatocellular-cholangiocarcinoma is a rare cancer that accounts for 2-5% of primary liver tumors and poses significant diagnostic and treatment challenges. This case highlights these needs and potential screening and treatment considerations. Herein we describe a case of combined hepatocellular-cholangiocarcinoma in a patient with autism, congenital heart disease, and Fontan procedure.Case descriptionThe patient is a 27-year-old male who presented with a liver mass detected on MRI performed in the context of a rising alpha-fetoprotein during a screening visit. Biopsy of the mass revealed a combined hepatocellular-cholangiocarcinoma which was staged as localized. Due to the COVID-19 pandemic and subsequent halt of all elective surgeries, the patient received local therapy with chemoembolization followed by pembrolizumab. The disease progressed though, and therapy was changed to gemcitabine plus cisplatin. Patient received 2 cycles of therapy, after which he and his family decided to transfer medical care to Memorial Sloan Kettering. Next generation sequencing of the tumor revealed TP53 and FGFR2 mutations. By then patient was also found to have lung metastasis. To help address the hepatocellular carcinoma, lenvatinib was added. Patient had sustainable disease control for about a year, yet eventually developed thrombocytopenia complicated by an episode of gastrointestinal bleeding. With a worsening performance status, adverse events of the treatment, and recurrent hospitalizations, a goals of care discussion with his family led to the discontinuation of active cancer therapy and patient was started on best supportive care. Patient remained in active follow-up until the time of this report and passed away less than a year from initiating best supportive care alone.ConclusionsThis challenging case raises awareness towards screening and monitoring all patients with Fontan procedure for Fontan associated liver disease and liver cancers, including combined hepatocellular-cholangiocarcinoma. To the best of our knowledge, this is the first description of combined hepatocellular-cholangiocarcinoma occurring in the context of cardiac cirrhosis. The management difficulties that led to altering the goals of care, is another reminder of the dynamic nature of the care oncologists would provide.

Dataset Information

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

Background

Aim

Methods

Results

Conclusion

Publications

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

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