Role of Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation

2016 ◽  
Vol 26 (4) ◽  
pp. 348-355 ◽  
Author(s):  
Nicola de’Angelis ◽  
Filippo Landi ◽  
Marco Nencioni ◽  
Anais Palen ◽  
Eylon Lahat ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Survival Rates ◽  
Early Recurrence ◽  
Best Supportive Care ◽  
Curative Intent ◽  
Sorafenib Group ◽  
Hepatocellular Carcinoma Recurrence ◽  
Retrospective Comparative Study ◽  
Hcc Recurrence

Context: The management of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is challenging, especially if it is not treatable by surgery or embolization. Objectives: The present study aims to compare the survival rates of liver transplanted patients receiving sorafenib or best supportive care (BSC) for HCC recurrence not amenable to curative intent treatments. Design: This is a retrospective comparative study on a prospectively maintained database. Participants: Liver transplanted patients with untreatable HCC recurrence receiving BSC (n = 18) until 2007 or sorafenib (n = 15) thereafter were compared. Results: No group difference was observed for demographic characteristics at the time of transplantation and at the time of HCC recurrence. On the explant pathology of the native liver, 81.2% patients were classified within the Milan criteria, and 53.1% presented with microvascular invasion. Hepatocellular carcinoma recurrence was diagnosed 17.8 months (standard deviation: 14.5) after LT, with 17 (53.1%) patients presenting with early recurrence (≤12 months). The 1-year survival from untreatable progression of HCC recurrence was 23.9% for the BSC and 60% for the sorafenib group ( P = .002). The type of treatment (sorafenib vs BSC) was the sole independent predictor of survival (hazard ratio: 2.98; 95% confidence interval: 1.09-8.1; P = .033). In the sorafenib group, 8 (53.3%) patients required dose reduction, and 2 (13.3%) patients discontinued the treatment due to intolerable side effects. Conclusion: Sorafenib improves survival and is superior to the BSC in cases of untreatable posttransplant hepatocellular carcinoma recurrence.

Left adrenal hepatocellular carcinoma recurrence in liver transplanted patient

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Alessandro Parente
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Cirrhosis ◽  
Adrenal Gland ◽  
Blood Test ◽  
Clinical Signs ◽  
Left Adrenal Gland ◽  
Hepatocellular Carcinoma Recurrence ◽  
Hcc Recurrence ◽  
Regional Treatment

Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been reported in less than 20% of patients fulfilling Milan Criteria. Mostly, it occurs within the liver, lungs, lymph nodes, bones and brain. A 45 years old Caucasian man affected by HCV-related liver cirrhosis with HCC, who underwent several multi-modal treatments, including hepatic resection, liver transplantation and loco regional treatment presented in our Department with an unusual mass within the left adrenal gland. No clinical signs were associated. However, considering his blood test and the high risk of HCC recurrence, a mini-invasive left surrenalectomy was performed showing HCC metastases in the left adrenal gland. This case shows that even extremely rare sites of HCC metastases have to be investigated, especially if, despite all available treatments, still persist a clinical or laboratory suspect.

Analysis of circulating tumor cells in patients with hepatocellular carcinoma recurrence following liver transplantation

2018 ◽  
Vol 66 (5) ◽  
pp. 1.6-6 ◽  
Author(s):  
Shaoping Wang ◽  
Yujian Zheng ◽  
Jun Liu ◽  
Feng Huo ◽  
Jie Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Diameter ◽  
Multicenter Studies ◽  
Patients With Cancer ◽  
T Stage ◽  
Hepatocellular Carcinoma Recurrence ◽  
Hcc Recurrence

Although studies have shown that detection of peripheral circulating tumor cells (CTCs) is an important tool for monitoring prognosis and therapeutic response in patients with cancer, few studies have analyzed their role in patients with hepatocellular carcinoma (HCC) following liver transplantation (LTx). The present study examined whether CTC levels were associated with HCC recurrence in patients with HCC after LTx. This prospective study included 47 patients who received LTx between October 2014 and May 2016 and who underwent analysis for peripheral CTCs at least twice using the CanPatrol system. Baseline Edmondson stage, T stage, accumulated tumor diameter, microvascular cancer embolus, and alpha-fetoprotein (AFP) levels were greater in patients with recurrence (all p<0.05). In addition, 70.2% of patients with HCC were CTC-positive. Although the proportion of CTC subtypes changes following LTx and over the follow-up period with increased epithelial and interstitial CTC levels, no significant associations were observed between change in total CTCs or CTC subtype and HCC recurrence (all p>0.05). In conclusion, baseline Edmondson stage, T stage, accumulated tumor diameter, microvascular cancer embolus, and AFP levels may be predictive of HCC recurrence following LTx; however, CTC levels and subtypes were not. Further large, multicenter studies are necessary to confirm these results.

scholarly journals Preferred Treatment with Curative Intent for Left Lateral Segment Early Hepatocellular Carcinoma under the Era of Minimal Invasive Surgery

2022 ◽  
Vol 12 (1) ◽  
pp. 79
Author(s):  
Tsung-Han Wu ◽  
Yu-Chao Wang ◽  
Hao-Chien Hung ◽  
Jin-Chiao Lee ◽  
Chia-Ying Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Invasive Surgery ◽  
Survival Rates ◽  
Curative Treatment ◽  
Treatment Modalities ◽  
Curative Intent ◽  
Lateral Segment ◽  
Left Lateral Segment ◽  
Early Hcc ◽  
Hcc Recurrence

Background: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. Methods: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. Results: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1–60.9 months) and 17.6 (range: 2.4–94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.

TLR9-1486C/T polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation

2019 ◽  
Vol 13 (12) ◽  
pp. 995-1004 ◽  
Author(s):  
Sara de la Fuente ◽  
María-Jesús Citores ◽  
José-Luis Lucena ◽  
Pablo Muñoz ◽  
Valentín Cuervas-Mons
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Real Time Pcr ◽  
Tumor Recurrence ◽  
Post Transplant ◽  
Explanted Liver ◽  
Increased Risk ◽  
Poorly Differentiated ◽  
Hepatocellular Carcinoma Recurrence ◽  
Hcc Recurrence

Aim: To determine whether TLR9 polymorphisms are associated with tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC). Patients & methods: All patients who underwent liver transplantation, and had viable HCC in the explanted liver were included. TLR9-1237C/T and -1486C/T polymorphisms were analyzed by real-time PCR and melting curves analysis. Results: 20 of 159 patients (12.6%) developed post-transplant HCC recurrence. Tumors exceeding Milan criteria, moderately-to-poorly differentiated tumors and microvascular invasion on explants, and pretransplant α-fetoprotein level (all p < 0.01) were associated with an increased risk, while TLR9-1486TT genotype was associated with a decreased risk of HCC recurrence (p = 0.03). Conclusion:  TLR9-1486C/T might help to preoperatively identify patients at low risk of post-transplant HCC recurrence.

scholarly journals Neither MICA Nor DEPDC5 Genetic Polymorphisms Correlate with Hepatocellular Carcinoma Recurrence following Hepatectomy

HPB Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Takashi Motomura ◽  
Yuki Ono ◽  
Ken Shirabe ◽  
Takasuke Fukuhara ◽  
Hideyuki Konishi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Genetic Polymorphisms ◽  
Survival Rates ◽  
Recurrence Free Survival ◽  
High Susceptibility ◽  
Free Survival ◽  
Hepatocellular Carcinoma Recurrence ◽  
Chronic Hepatitis C Patients ◽  
Hcc Recurrence

Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7% in MICA GG allele carriers, 38.7% in GA, and 20.8% in AA, respectively (P=0.72). The five-year RFS rate was 23.8% in DEPDC5 TT allele carriers and 31.8% in TG/GG, respectively (P=0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P<0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages.

scholarly journals Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2499
Author(s):  
Lisanne Noordam ◽  
Zhouhong Ge ◽  
Hadiye Özturk ◽  
Michail Doukas ◽  
Shanta Mancham ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Occult Metastasis ◽  
Recurrence Rates ◽  
Curative Intent ◽  
Cancer Testis Antigens ◽  
Negative Prognostic Factor ◽  
Increased Risk ◽  
Hcc Recurrence ◽  
Cancer Testis

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.

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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