scholarly journals Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 389 ◽  
Author(s):  
Markus Schoenberg ◽  
Jingcheng Hao ◽  
Julian Bucher ◽  
Rainer Miksch ◽  
Hubertus Anger ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cells ◽  
Independent Predictor ◽  
Disease Free Survival ◽  
Clinical Parameters ◽  
Free Survival ◽  
Cd8 Cells ◽  
Disease Free ◽  
Perivascular Infiltration ◽  
Hcc Recurrence

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3+ (p = 0.016) and CD8+ (p = 0.028) independently predicted better OS and DFS, respectively. CD20+ showed a trend towards better DFS (p = 0.076). Scoring of CD3+, CD8+, and CD20+ independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3+ cells is an independent predictor of better OS, and CD8+ cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients.

scholarly journals Potential Role of Adjuvant Lenvatinib in Improving Disease-Free Survival for Patients With High-Risk Hepatitis B Virus-Related Hepatocellular Carcinoma Following Liver Transplantation: A Retrospective, Case Control Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Bing Han ◽  
Han Ding ◽  
Shuai Zhao ◽  
Yichi Zhang ◽  
Jian Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
High Risk ◽  
Disease Free Survival ◽  
Control Group ◽  
Free Survival ◽  
Risk Patients ◽  
Disease Free ◽  
Hcc Recurrence

Background and AimAlthough liver transplantation (LT) is one of the most effective treatments for the patients with hepatocellular carcinoma (HCC), the high-risk patients suffer from a high ratio of tumor recurrence after LT. Lenvatinib, as a novel targeted drug, has shown an excellent effect in the treatment of advanced HCC, but there is no study on its effect in preventing HCC recurrence in the patients undergoing transplantation. Therefore, this study was designed to evaluate the role of adjuvant lenvatinib in preventing recurrence of high-risk LT recipients with HBV-related HCC.MethodsWe retrospectively analyzed 23 high-risk patients consisting of lenvatinib group (n=14) and control group (n=9) with HBV-related HCC who underwent LT in our center. Disease-free survival (DFS) and HCC recurrence of the two groups were compared. The adverse events (AEs) and drug tolerance of lenvatinib were evaluated.ResultsThe median DFS in lenvatinib group was 291 (95%CI 204–516) days, significantly longer than 182 (95%CI 56–537) days in control group (P=0.04). Three patients in lenvatinib group (21.4%) and five patients in control group (55.6%) had short-term HCC recurrence (P=0.11). All patients in lenvatinib group could tolerate oral lenvatinib for at least three cycles except six cases (42.9%) of dose reduction and 1 case of interruption (14.3%). Thirteen patients (92.9%) taking lenvatinib experienced AEs. The most common AEs were hypertension (64.3%) and proteinuria (42.9%), and the most serious AEs were Grade 3 for 4 cases (28.5%) according to common terminology criteria for adverse events (CTCAE) version 5.0. Additionally, no influence of lenvatinib on the dosage and blood concentration of FK506 was observed.ConclusionsAdjuvant lenvatinib had a potential benefit on prolonging the DFS and reducing the recurrence of high-risk HBV-related HCC patients following liver transplantation with an acceptable drug safety and patient tolerance.

Association of HERV-K and LINE-1 hypomethylation with reduced disease-free survival in melanoma patients

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1689-1706
Author(s):  
Maurizio Cardelli ◽  
Remco van Doorn ◽  
Lares Larcher ◽  
Michela Di Donato ◽  
Francesco Piacenza ◽  
...  
Keyword(s):  
Independent Predictor ◽  
Disease Free Survival ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Free Survival ◽  
Melanocytic Lesions ◽  
Long Interspersed Nuclear Elements ◽  
Melanoma Patients ◽  
And Gender ◽  
Disease Free

Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence.

scholarly journals Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chih-Wen Lin ◽  
Tsung-Chin Wu ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Free Survival ◽  
Before And After ◽  
Disease Free

Abstract Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

scholarly journals Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2810
Author(s):  
Muhammad Yogi Pratama ◽  
Alessia Visintin ◽  
Lory Saveria Crocè ◽  
Claudio Tiribelli ◽  
Devis Pascut
Keyword(s):  
Hepatocellular Carcinoma ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Therapy Response ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Free Survival ◽  
Microarray Profiling ◽  
Disease Free ◽  
Arterial Chemoembolization

The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD. The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC.

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