scholarly journals The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size

Liver Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Hiroji Shinkawa ◽  
Shogo Tanaka ◽  
Daijiro Kabata ◽  
Shigekazu Takemura ◽  
Ryosuke Amano ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Resection ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Treatment Strategies ◽  
Early Recurrence ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Tumor Differentiation ◽  
Negative Effects

<b><i>Introduction:</i></b> The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). <b><i>Methods:</i></b> A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. <b><i>Results:</i></b> In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (<i>p</i> = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring &#x3c;2, ≥2 and &#x3c;5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and &#x3c;5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. <b><i>Conclusions:</i></b> Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

scholarly journals Prognostic value of the ALBI grade among patients with single hepatocellular carcinoma without macrovascular invasion

2020 ◽  
Author(s):  
Heng Zou ◽  
Wenhao Chen ◽  
Huan Wang ◽  
Li Xiong ◽  
Yu Wen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Grading System ◽  
Term Survival ◽  
Proportional Hazards Regression ◽  
Disease Outcomes ◽  
Single Tumor

Abstract Overview and objective: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.

scholarly journals Prognostic value of the ALBI grade among patients with single hepatocellular carcinoma without macrovascular invasion

2020 ◽  
Author(s):  
Wenhao Chen ◽  
Zijian Zhang ◽  
Huan Wang ◽  
Li Xiong ◽  
Yu Wen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Grading System ◽  
Term Survival ◽  
Proportional Hazards Regression ◽  
Disease Outcomes ◽  
Single Tumor

Abstract Background: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.

scholarly journals Reclassification of tumor size for solitary HBV-related hepatocellular carcinoma by minimum p value method: a large retrospective study

2020 ◽  
Author(s):  
Hongzhi Liu ◽  
Yuan Yang ◽  
Chuanchun Chen ◽  
Lei Wang ◽  
Qizhen Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Clinicopathologic Characteristics ◽  
B Virus ◽  
The Difference

Abstract Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary hepatitis B virus (HBV) related HCC.Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm interval. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). If multiple cutoffs meet the above standard, univariate analysis will be performed by using the Cox proportional hazards regression model, and hazard ratio (HR) will be considered as a criterion to assess the difference in survival.Results There are 8 dichotomy, 8 trichotomy and no inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. The HR values of tumor size at these trichotomy cutoffs for OS were compared, the highest HR value is 2.79 when size cutoff is 3/9cm. Then, we reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.

Dynamic change of the systemic immune inflammation index predicts the prognosis of patients with hepatocellular carcinoma after curative resection

2016 ◽  
Vol 54 (12) ◽  
Author(s):  
Bei-li Wang ◽  
Lu Tian ◽  
Xing-Hui Gao ◽  
Xiao-Lu Ma ◽  
Jiong Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Curative Resection ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Dynamic Change ◽  
Early Recurrence ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Operating Characteristics ◽  
Immune Inflammation

AbstractBackground:The aim of the study was to determine the utility of the dynamic change and serial monitoring of the systemic immune inflammation index (SII), which was based on the numbers of patients’ lymphocytes (L), platelets (P), neutrophils (N) and defined as P*N/L, for predicting prognosis of patients with hepatocellular carcinoma (HCC) after curative resection.Methods:We conducted a prospective study of 163 patients with HCC who underwent curative resection at Zhongshan Hospital from January 2012 to May 2013. SII was calculated using data acquired before and approximately 1 month after surgery. An optimal cutoff value stratified patients into groups with high or low SII. Patients were classified into unfavorable and favorable groups using the dynamic change of the SII. Two groups that were further divided into four categories within the entire cohort and the low-risk subgroups were serially monitored for ≥6 months. Prognostic values of the SII and other factors were determined using the Kaplan-Meier method, the Cox proportional hazards model, and the receiver operating characteristics (ROC) curve.Results:The favorable group was likely to have cirrhosis, and the unfavorable group was likely to have larger tumors and a higher recurrence rate. Multivariate analysis revealed that tumor size and dynamic change of the SII were independent risk factors for early recurrence. Moreover, the predictive value of the SII was retained in α-fetoprotein (AFP)-negative and HBeAg-negative-HBV-DNA <2000 IU/mL subgroups. Further, the serial changes of the SII for recurrence and no recurrence groups were statistically significant.Conclusions:The dynamic change and serial monitoring of the SII represent new indicators for predicting the early recurrence of HCC determining advance optimal therapy in advance.

Ablation for hepatocellular carcinoma: Validating the 3-cm breakpoint.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 277-277
Author(s):  
Ryan Thomas Groeschl ◽  
T. Clark Gamblin ◽  
Kiran Turaga
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Study Groups ◽  
Cox Proportional Hazards ◽  
Rank Tests ◽  
Local Ablation ◽  
Cox Proportional Hazards Models ◽  
Confounding Variables

277 Background: Although many previous studies on ablation outcomes for hepatocellular carcinoma (HCC) have dichotomized tumor size around a 3cm cutoff to determine prognostic significance, a growing number of reports describe excellent outcomes for larger tumors. To address the sensibility of this somewhat arbitrary 3-cm cutoff, we stratified patients by 1cm tumor size intervals and hypothesized that disease-specific survival (DSS) would not vary significantly between adjacent groups. Methods: Patients treated with local ablation for T1 HCC (≤8cm) were identified from the Surveillance, Epidemiology, and End Results database (2004-2008). Log-rank tests were used to compare DSS curves of adjacent study groups, and multivariable Cox proportional hazards models were used adjust for confounding variables. Results: There were 1,093 patients included in the study (26% female, median age: 62 years). The 3-year DSS was significantly lower in patients with 3-4cm tumors compared to 2-3cm tumors (58% vs 72%, p=0.002, Table). In adjusted models, DSS did not vary significantly between any size intervals up to 3cm. Patients with 3-4cm tumors, however, had a poorer prognosis compared to patients with 2-3cm tumors (hazard ratio: 1.60, 95% confidence interval: 1.18-2.18, p=0.002). DSS also fell significantly when tumor size increased from 5-6cm to 6-7cm (53% vs 21%, 0.006). Age and alpha-fetoprotein levels were also independently predictive of DSS in most multivariable models; however, the presence or absence of cirrhosis was not predictive in any models (smallest p=0.382). Conclusions: This study defends the use of a 3cm breakpoint when studying outcomes after ablation for HCC. Although some have advocated that ablation is more successful in cirrhotics, we found no evidence for this in our study. [Table: see text]

scholarly journals Hepatic Resection Versus Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: A Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Linbin Lu ◽  
Peichan Zheng ◽  
Zhixian Wu ◽  
Xiong Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Resection ◽  
Transarterial Chemoembolization ◽  
Proportional Hazards ◽  
Intermediate Stage ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Real World Data ◽  
Risk Of Death ◽  
The Impact

BackgroundThe selection criteria for hepatic resection (HR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) are still controversial. We used real-world data to evaluate the overall survival (OS) in treatment with HR or transarterial chemoembolization (TACE).MethodsIn total, 942 patients with IM-HCC were categorized into the HR group and the TACE group. OS was analyzed using the Kaplan–Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analysis. Curve smoothing was performed through the generalized additive model. The interaction test was performed to evaluate the impact of HR on OS concerning risk factors. Also, we used multiple imputation to deal with missing data.ResultsIn total, 23.0% (n = 225) of patients received HR. At a median OS of 23.7 months, HR was associated with improved OS in the multivariate analysis [hazard ratio (HzR) = 0.45, 95%CI = 0.35–0.58; after PSM: HzR = 0.56, 95%CI = 0.41–0.77]. Landmark analyses limited to long-term survivors of ≥6 months, ≥1 year, and ≥2 years demonstrated better OS with HR in all subsets (all p &lt; 0.05). After PSM analysis, however, HR increased the risk of death by 20% (HzR = 1.20, 95%CI = 0.67–2.15) in the subgroup of patients with lactate dehydrogenase (LDH) ≤192 U/L (p for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and HR with respect to the 1-, 3-, and 5-year observed survival rates (all p &lt; 0.05).ConclusionHR was superior to TACE for intermediate-stage HCC in patients with LDH levels &gt;192 U/L. Moreover, TACE might be suitable for patients with LDH levels ≤192 U/L.

scholarly journals Hepatic resection versus transarterial chemoembolization for the intermediate stage hepatocellular carcinoma

2020 ◽  
Author(s):  
Linbin Lu ◽  
Peichan Zheng ◽  
Zhixian Wu ◽  
Xiong Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatic Resection ◽  
Proportional Hazards ◽  
Selection Criterion ◽  
Smooth Curve ◽  
Intermediate Stage ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Real World Data

AbstractBackgroundThe selection criterion for hepatic resection(HR) in intermediate-stage(IM) hepatocellular carcinoma(HCC) is still controversial. We used real-world data to evaluate the overall survival (OS) treated with HR or TACE.MethodsIn all, 946 patients with IM-HCC were categorized in HR and TACE group. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analyses. The smooth curve was performed through the generalized additive model. The interaction test was performed to evaluate the HR impact on OS concerning risk factors. Also, we used multiple imputation to deal with the missing data.ResultsTotally, 23.0% (n=225) of patients received HR. At a median overall survival of 23.7 months, HR was associated with the improved OS on multivariate analysis (hazard ratio, 0.45; 95%CI: 0.35, 0.58; after PSM: 0.56; 95%CI: 0.41, 0.77). Landmark analyses limited to long-term survivors of ≥ 6 months, ≥ 1, and ≥ 2 years demonstrated better OS with HR in all subsets (all P<0.05). After PSM analysis, however, HR increased 20% risk of survival (HR, 1.20; 95%CI: 0.67, 2.15) in the subgroup of LDH ≤192 U/L (P for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and the HR with respect to 1-, 3-, and 5-year observed survival rate (all P<0.05).ConclusionHepatic resection was superior to TACE for intermediate-stage HCC in the range of LDH level > 192 U/L. Moreover, TACE might be suitable for patients with LDH level ≤ 192 U/L.

scholarly journals Perioperative Geriatric Assessment as A Predictor of Long-Term Hepatectomy Outcomes in Elderly Patients with Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 842
Author(s):  
Masaki Kaibori ◽  
Hideyuki Matsushima ◽  
Morihiko Ishizaki ◽  
Hisashi Kosaka ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Geriatric Assessment ◽  
Proportional Hazards ◽  
Prognostic Indicator ◽  
Cox Proportional Hazards ◽  
Rate Of Change ◽  
Score Change ◽  
Comorbidity Burden ◽  
Reduction Group

This retrospective study recorded pertinent baseline geriatric assessment variables to identify risk factors for recurrence-free survival (RFS) and overall survival (OS) after hepatectomy in 100 consecutive patients aged ≥70 years with hepatocellular carcinoma. Patients had geriatric assessments of cognition, nutritional and functional statuses, and comorbidity burden, both preoperatively and at six months postoperatively. The rate of change in each score between preoperative and postoperative assessments was calculated by subtracting the preoperative score from the score at six months postoperatively, then dividing by the score at six months postoperatively. Patients with score change ≥0 comprised the maintenance group, while patients with score change <0 comprised the reduction group. The change in Geriatric 8 (G8) score at six months postoperatively was the most significant predictive factor for RFS and OS among the tested geriatric assessments. Five-year RFS rates were 43.4% vs. 6.7% (maintenance vs. reduction group; HR, 0.19; 95%CI, 0.11–0.31; p < 0.001). Five-year OS rates were 73.8% vs. 17.8% (HR, 0.12; 95%CI, 0.06–0.25; p < 0.001). Multivariate Cox proportional hazards analysis showed that perioperative maintenance of G8 score was an independent prognostic indicator for both RFS and OS. Perioperative changes in G8 scores can help forecast postoperative long-term outcomes in these patients.

scholarly journals Cyclin B1 acts as a tumor microenvironment-related cancer promoter and prognostic biomarker in hepatocellular carcinoma

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110162
Author(s):  
Yangming Hou ◽  
Xin Wang ◽  
Junwei Wang ◽  
Xuemei Sun ◽  
Xinbo Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Proportional Hazards ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Cyclin B1 ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Tumor Promoter ◽  
Protein Protein Interaction

Objectives The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. Methods The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein–protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. Results The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. Conclusions The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.

scholarly journals Tumor size may influence the prognosis of solitary hepatocellular carcinoma patients with cirrhosis and without macrovascular invasion after hepatectomy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bin-yong Liang ◽  
Jin Gu ◽  
Min Xiong ◽  
Er-lei Zhang ◽  
Zun-yi Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Staging System ◽  
Prognostic Impact ◽  
Term Survival ◽  
Long Term Survival ◽  
Before And After ◽  
Cirrhotic Patients ◽  
Curative Hepatectomy

AbstractHepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the  ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.

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