scholarly journals Overview and Clinical Significance of Multiple Mutations in Individual Genes in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Taisuke Imamura ◽  
Yukiyasu Okamura ◽  
Keiichi Ohshima ◽  
Katsuhiko Uesaka ◽  
Teiichi Sugiura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Significance ◽  
Independent Predictor ◽  
Single Mutation ◽  
Recurrence Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Significant Difference ◽  
And Function ◽  
Worse Prognosis

Abstract BackgroundMultiple mutations (MMs) within individual oncogenes have been newly characterized as a mechanism for promotion of carcinogenesis. We investigated the spectra of the MMs and the clinical significance in hepatocellular carcinoma (HCC). MethodsWhole-exome sequencing and gene expression profiling were performed in 223 surgically resected HCCs. ResultsMMs within individual genes was identified in 178 samples (79.8%, MMs tumors). All the remaining samples carried single mutation (20.2%, SM tumors). Mutations identified as MMs show different mutational patterns with higher functional impact compared with mutations identified as SM. Recurrence-free survival was significantly worse in the group with MMs tumors than the group with SM tumors (P = 0.012). MMs tumor was identified as an independent predictor for worse prognosis (hazard ratio, 1.72; 95%, P = 0.045). MMs were observed particularly in MUC16 (15% of samples with at least one mutation in the gene) and CTNNB1 (14%). Although there was no significant difference in MUC16 mRNA expression between MUC16 wild-type and MUC16 SM tumors, the expression in MUC16 MMs tumors was significantly enhanced compared with MUC16 SM tumors (P < 0.001). MMs in MUC16 were associated with viral hepatitis, higher tumor markers and vascular invasion. Recurrence-free survival was significantly worse in the MUC16 MMs group than the MUC16 SM group (P = 0.022); no significant difference was observed between the MUC16 SM group and MUC16 wild-type group (P = 0.324).ConclusionsMMs are relatively common driver events that selectively occur in specific oncogenes and function in tumor-promoting activity.

scholarly journals Homeostatic Model Assessment of Insulin Resistance for Predicting the Recurrence of Hepatocellular Carcinoma after Curative Treatment

2019 ◽  
Vol 20 (3) ◽  
pp. 605 ◽  
Author(s):  
Kenji Imai ◽  
Koji Takai ◽  
Tatsunori Hanai ◽  
Atsushi Suetsugu ◽  
Makoto Shiraki ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Curative Treatment ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
The Impact ◽  
Hcc Recurrence

Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan–Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 μU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.

Evaluation of the neutrophil-lymphocyte ratio as a predictor of survival after liver transplantation for hepatocellular carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 170-170 ◽  
Author(s):  
A. R. Limaye ◽  
R. Cabrera
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Independent Predictor ◽  
Tumor Biology ◽  
Milan Criteria ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cumulative Survival ◽  
Neutrophil Lymphocyte Ratio

170 Background: The Milan criteria are utilized to predict outcomes in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT). Though the survival of these patients has significantly improved since the adoption of these criteria, the risk of recurrence after LT is as high as 20 percent. One limitation of the Milan criteria is the lack of any estimation of tumor biology. The neutrophil-lymphocyte ratio (NLR) has been proposed as a peripheral surrogate for tumor biology. The predictive power of the NLR has been demonstrated for several solid tumors, and early evidence points to a role in HCC. We hypothesize that the NLR is predictive of overall survival and recurrence-free survival in patients with HCC who undergo LT. Methods: This is a retrospective analysis of adult patients undergoing LT for HCC between 2000 and 2008 at our institution. We defined an elevated NLR as a ratio of five or greater. Results: We identified 160 patients who underwent LT for HCC, 28 of whom had an elevated NLR. Seventeen subjects experienced recurrent HCC during the study period. The cumulative survival for subjects with an elevated NLR (1-year cumulative survival 70% ± 0.08, 3-year cumulative survival 48% ± 0.09, 5-year cumulative survival 38% ± 0.11) was significantly lower than for subjects with a normal NLR (1-year survival 80% ± 0.04, 3-year survival 75% ± 0.04, 5-year survival 68% ± 0.06). On univariate analysis, seven factors (including an elevated NLR) predicted decreased overall and recurrence-free survival. However, after multivariate analysis, only three factors (including elevated NLR) remained significant as predictors of overall survival. Additionally, multivariate analysis revealed that an elevated NLR was the only significant independent predictor of recurrence-free survival. Conclusions: Preoperative NLR is a powerful independent predictor of overall survival and recurrence-free survival in patients undergoing LT for HCC. Measurement of NLR could serve as a useful and easily obtained adjunct to the MELD score and Milan criteria when evaluating this patient population and determining which patients will gain the most survival benefit from transplant. No significant financial relationships to disclose.

scholarly journals Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Hiraoka ◽  
Takashi Kumada ◽  
Toshifumi Tada ◽  
Joji Tani ◽  
Kazuya Kariyama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Hazard Analysis ◽  
Progression Free Survival ◽  
Significant Prognostic Factor ◽  
Disease Etiology ◽  
Alcoholic Fatty Liver ◽  
Free Survival ◽  
Significant Difference

AbstractIt was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

scholarly journals Inflammatory indexes in preoperative blood routine to predict early recurrence of hepatocellular carcinoma after curative hepatectomy

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
YiFeng Wu ◽  
ChaoYong Tu ◽  
ChuXiao Shao
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Tumour Size ◽  
Area Under The Curve ◽  
Early Recurrence ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Lymphocyte Ratio ◽  
Inflammatory Index ◽  
Curative Hepatectomy

Abstract Background The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. Methods The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. Results The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. Conclusion The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.

scholarly journals Cetuximab versus bevacizumab following prior FOLFOXIRI and bevacizumab in postmenopausal women with advanced KRAS and BRAF wild-type colorectal cancer: a retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunlong Huang ◽  
Xiaoyuan Gu ◽  
Xianshang Zeng ◽  
Baomin Chen ◽  
Weiguang Yu ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Primary Endpoints ◽  
Significant Difference ◽  
Inductive Treatment ◽  
Advanced Colorectal Carcinoma

Abstract Background An upgraded understanding of factors (sex/estrogen) associated with survival benefit in advanced colorectal carcinoma (CRC) could improve personalised management and provide innovative insights into anti-tumour mechanisms. The aim of this study was to assess the efficacy and safety of cetuximab (CET) versus bevacizumab (BEV) following prior 12 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus BEV in postmenopausal women with advanced KRAS and BRAF wild-type (wt) CRC. Methods Prospectively maintained databases were reviewed from 2013 to 2017 to assess postmenopausal women with advanced KRAS and BRAF wt CRC who received up to 12 cycles of FOLFOXIRI plus BEV inductive treatment, followed by CET or BEV maintenance treatment. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rate. The secondary endpoint was the rate of adverse events (AEs). Results At a median follow-up of 27.0 months (IQR 25.1–29.2), significant difference was detected in median OS (17.7 months [95% confidence interval [CI], 16.2–18.6] for CET vs. 11.7 months [95% CI, 10.4–12.8] for BEV; hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; p=0.007); Median PFS was 10.7 months (95% CI, 9.8–11.3) for CET vs. 8.4 months (95% CI, 7.2–9.6) for BEV (HR, 0.67; 95% CI 0.47–0.94; p=0.02). Dose reduction due to intolerable AEs occurred in 29 cases (24 [24.0%] for CET vs. 5 [4.8%] for BEV; p< 0.001). Conclusions CET tends to be superior survival benefit when compared with BEV, with tolerated AEs.

Radiofrequency Ablation With or Without Transcatheter Arterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial

2013 ◽  
Vol 31 (4) ◽  
pp. 426-432 ◽  
Author(s):  
Zhen-Wei Peng ◽  
Yao-Jun Zhang ◽  
Min-Shan Chen ◽  
Li Xu ◽  
Hui-Hong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Transcatheter Arterial Chemoembolization ◽  
Recurrence Free Survival ◽  
Treatment Allocation ◽  
Free Survival ◽  
End Point ◽  
Tumor Number ◽  
Arterial Chemoembolization

Purpose To compare radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). Patients and Methods A randomized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009. Patients were randomly asssigned to receive TACE combined with RFA (TACE-RFA; n = 94) or RFA alone (n = 95). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. Results At a follow-up of 7 to 62 months, 34 patients in the TACE-RFA group and 48 patients in the RFA group had died. Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group, respectively. The 1-, 3-, and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6%, 66.6%, and 61.8% and 85.3%, 59%, and 45.0%, respectively. The corresponding recurrence-free survivals were 79.4%, 60.6%, and 54.8% and 66.7%, 44.2%, and 38.9%, respectively. Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group (hazard ratio, 0.525; 95% CI, 0.335 to 0.822; P = .002; hazard ratio, 0.575; 95% CI, 0.374 to 0.897; P = .009, respectively). There were no treatment-related deaths. On logistic regression analyses, treatment allocation, tumor size, and tumor number were significant prognostic factors for overall survival, whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival. Conclusion TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm.

scholarly journals Impact of postoperative complications on long-term survival of hepatocellular carcinoma patients after liver resection

2021 ◽  
Author(s):  
Susumu Mochizuki ◽  
Hisashi Nakayama ◽  
Yutaka Midorikawa ◽  
Tokio Higaki ◽  
Masamichi Moriguchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Resection ◽  
Pleural Effusion ◽  
Postoperative Complications ◽  
Recurrence Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Survival

Objective The effect of postoperative complications including red blood transfusion (BT) on long-term survival for hepatocellular carcinoma (HCC) is unknown. The purpose of this study was to define the relationship between postoperative complications and long-term survival in patients with HCC. Methods Postoperative complications of 1251 patients who underwent curative liver resection for HCC were classified, and their recurrence-free survival (RFS) and cumulative overall survival (OS) were investigated. Results Any complications occurred in 503 patients (40%). Five-year RFS and 5-year OS in the complication group were 21% and 56%, respectively, significantly lower than the respective values of 32% ( p &lt; 0.001) and 68% ( p &lt; 0.001) in the no-complication group (n=748). Complications related to RFS were postoperative BT [Hazard ratio (HR): 1.726, 95% confidence interval (CI): 1.338–2.228, p &lt; 0.001], pleural effusion [HR: 1.434, 95% CI: 1.200–1.713, p &lt; 0.001] using Cox-proportional hazard model. Complications related to OS were postoperative BT [HR: 1.843, 95%CI: 1.380-2.462, p &lt; 0.001], ascites [HR: 1.562, 95% CI: 1.066–2.290 p = 0.022], and pleural effusion [HR: 1.421, 95% CI: 1.150–1.755, p = 0.001). Conclusions Postoperative complications were factors associated with poor long-term survival. Postoperative BT and pleural effusion, were noticeable complications that were prognostic factors for both recurrence-free survival and overall survival.

scholarly journals Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

2019 ◽  
Vol 25 (2) ◽  
pp. 220-232 ◽  
Author(s):  
Jing-Xian Gu ◽  
Xing Zhang ◽  
Run-Chen Miao ◽  
Xiao-Hong Xiang ◽  
Yu-Nong Fu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Rna Signature

scholarly journals Long Noncoding RNA PTTG3P Expression Is an Unfavorable Prognostic Marker for Patients With Hepatocellular Carcinoma

2019 ◽  
Vol 18 ◽  
pp. 153303381988798 ◽  
Author(s):  
Hansong Bai ◽  
Xing Luo ◽  
Dongxu Liao ◽  
Wei Xiong ◽  
Ming Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Confidence Interval ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Hazard Ratio ◽  
The Cancer Genome Atlas ◽  
Primary Hepatocellular Carcinoma ◽  
Recurrence Free Survival ◽  
Free Survival

Objective: PTTG3P, which maps to chromosome 8q13.1, is a novel long noncoding RNA with oncogenic properties in cancers. In this study, we aimed to investigate the prognostic value of PTTG3P in terms of overall survival and recurrence-free survival and its potential regulatory network and transcription pattern in patients with hepatocellular carcinoma. Patients and Methods: An in silico analysis was performed using data from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma. Results: Results showed that the high PTTG3P expression group was consistently associated with shorter overall survival and recurrence-free survival, regardless of pathological stages or tumor grade. High PTTG3P expression was an independent indicator of shorter overall survival (hazard ratio: 2.177, 95% confidence interval: 1.519-3.121, P < .001) and recurrence-free survival (hazard ratio: 2.222, 95% confidence interval: 1.503-3.283, P < .001). The genes strongly coexpressed with PTTG3P are enriched in several KEGG pathways that are closely associated with carcinogenesis and malignant transformation of hepatocellular carcinoma. Conclusion: Based on the findings, we infer that PTTG3P expression might serve as an independent prognostic biomarker in primary hepatocellular carcinoma.

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