Long-term prognosis and management of hepatocellular carcinoma after curative treatment.
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ABSTRACT:
SUBMITTER: Nishida N
PROVIDER: S-EPMC7641545 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Long-term prognosis and management of hepatocellular carcinoma after curative treatment.
Clinical and molecular hepatology 20200921 4
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Project description:BackgroundCharacterized by spindle cell composition in hepatocellular carcinoma tumor, sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant with poor prognosis. In this study, we aimed to evaluate the clinical and pathological features of SHC and establish a nomogram that can predict long-term outcomes of the disease.MethodsWe retrospectively analyzed 63 patients who were diagnosed with SHC between October 2007 and November 2016 and used immunohistochemistry (IHC) to assessed various markers in liver samples. The clinical data and the histological and pathological findings were collected and used to build a nomogram to predict survival.ResultsThe median overall survival (OS) and the recurrence-free survival (RFS) in SHC were 23.2 and 8.4 months, respectively. High expression levels of tyrosine-protein kinase Met (17/63, 27.0%) were associated with poorer RFS (P=0.040). A panel of markers, consisting heat-shock protein 70 (HSP70), glutamine synthetase (GS), and glypican-3 (GPC3), merged as an independent risk factor for treatment outcomes. The nomogram, which including this panel of markers, predicted OS times with a concordance-index (C-index) score of 0.758 (95% CI: 0.672-0.843) in the training set and 0.832 (95% CI: 0.712-0.952) in the validation set. The use of the nomogram showed marked improvements in the prediction of patient outcomes compared with conventional staging systems (P<0.05).ConclusionsDiagnosis of SHC is rare and has a relatively poor prognosis. A panel of markers HSP70, GS and GPC3 served as an independent prognostic factor for SHC.
| S-EPMC9073769 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the most common malignancy in the elderly worldwide, but it is also common among younger individuals in areas with endemic hepatitis B virus infection. The differences in long-term oncological prognosis of young versus elderly patients after R0 liver resection for HCC were explored in this study. Using a Chinese multicentre database, consecutive patients who underwent R0 liver resection for HCC between 2007 and 2019 were analysed retrospectively. After excluding middle-aged (36-69 years old) patients, overall survival (OS), cancer-specific survival (CSS), and recurrence were compared between young (35 years or younger) and elderly (70 years or older) patients using propensity score matching (PSM). Among 531 enrolled patients, there were 192 (36.2 per cent) and 339 (63.8 per cent) patients categorized as young and elderly respectively. PSM created 140 pairs of matched patients. In the PSM cohort, 5-year OS was comparable for young versus elderly patients (51.7 versus 52.3 per cent, P = 0.533). Young patients, however, had a higher 5-year cumulative recurrence rate (62.1 versus 51.6 per cent, P = 0.011) and a worse 5-year CSS rate (54.0 versus 64.3 per cent, P = 0.034) than elderly patients. On multivariable Cox regression analyses, young patient age remained independently associated with an increased recurrence rate (hazard ratio 1.62, P = 0.016) and a decreased CSS rate (hazard ratio 1.69, P = 0.021) compared with older age. Following R0 liver resection for HCC, younger patients were at a higher risk of recurrence, and elderly patients had a better CSS rate. Thus, enhanced surveillance for HCC recurrence should be implemented for young patients.
| S-EPMC8794648 | biostudies-literature
Project description:BACKGROUND: Surgical resection is one important curative treatment for hepatocellular carcinoma (HCC), but the prognosis following surgery differs substantially and such large variation is mainly unexplained. A review of the literature yields a number of clinicopathologic parameters associated with HCC prognosis. However, the results are not consistent due to lack of systemic approach to establish a prediction model incorporating all these parameters. METHODS: We conducted a retrospective analysis on the common clinicopathologic parameters from a cohort of 572 ethnic Chinese HCC patients who received curative surgery. The cases were randomly divided into training (n = 272) and validation (n = 300) sets. Each parameter was individually tested and the significant parameters were entered into a linear classifier for model building, and the prediction accuracy was assessed in the validation set RESULTS: Our findings based on the training set data reveal 6 common clinicopathologic parameters (tumor size, number of tumor nodules, tumor stage, venous infiltration status, and serum alpha-fetoprotein and total albumin levels) that were significantly associated with the overall HCC survival and disease-free survival (time to recurrence). We next built a linear classifier model by multivariate Cox regression to predict prognostic outcomes of HCC patients after curative surgery This analysis detected a considerable fraction of variance in HCC prognosis and the area under the ROC curve was about 70%. We further evaluated the model using two other protocols; leave-one-out procedure (n = 264) and independent validation (n = 300). Both were found to have excellent prediction power. The predicted score could separate patients into distinct groups with respect to survival (p-value = 1.8e-12) and disease free survival (p-value = 3.2e-7). CONCLUSION: This described model will provide valuable guidance on prognosis after curative surgery for HCC in clinical practice. The adaptive nature allows easy accommodation for future new biomarker inputs, and it may serve as the foundation for future modeling and prediction for HCC prognosis after surgical treatment.
| S-EPMC2785835 | biostudies-other
Project description:BackgroundWe quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment.MethodsPatients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression.ResultsOne hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01-2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26-3.08), early recurrence (HR = 6.62, 95% CI:3.79-11.6) and late recurrence (HR = 3.75, 95% CI:1.99-7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE.ConclusionHost and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.
| S-EPMC7941925 | biostudies-literature
Project description:Age at diagnosis is a reported prognostic factor in a variety of solid cancers. In hepatocellular carcinomas (HCCs), several previous studies focused on patient age, but demonstrated inconclusive results on prognosis of young patients. Clinical outcome may differ according to the balance between tumor's own biologic behavior and underlying liver function thus explaining the inconclusive results in previous studies. In this study, we enrolled 282 patients who underwent curative hepatectomy for primary HCCs and had Child Pugh Class A, representing good liver function. Clinicopathologic features were compared between patients aged ≤40 years (young age group) and those aged >40 years (old age group). Thirty-five patients (12.4%) were classified as the young age group and showed larger tumor size (>5cm), higher Edmondson grade, more frequent intrahepatic metastasis and higher alpha-fetoprotein level (>200ng/mL) than old age group. Young age group showed shorter disease specific survival than the old age group. Symptomatic presentation without surveillance was more frequent in the young age group than old age group (45.7% vs. 23.9%). In gene expression profiling analysis, 69 differentially expressed genes between young and old age groups were generated and these genes were mostly associated with cell cycle or cell division. Mitotic rate was significantly higher in HCCs of young patients than those of old patients. In conclusion, HCCs in young patients have distinct clinicopathologic features. Poor prognosis in the young age group could be explained by late detection as well as their own aggressive tumor biology.
| S-EPMC4621918 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is on the rise because of the increase in lifestyle-related diseases.AimTo establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (EGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD.MethodsWe enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital. We categorized patients into two (RD, EGFR < 60 mL/min/1.73 m2; non-RD, EGFR ≥ 60 mL/min/1.73 m2) and three groups (severe CKD, EGFR < 30 mL/min/1.73 m2; mild CKD, 30 ≤ EGFR < 60 mL/min/1.73 m2; control, EGFR ≥ 60 mL/min/1.73 m2) according to renal function as defined by the EGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model to exclude the influence of patient characteristics. The mean postoperative observation period was 64.7 ± 53.0 mo.ResultsThe RD patients were significantly older and had lower serum total bilirubin, aspartate aminotransferase, and aspartate aminotransferase levels than the non-RD patients (P < 0.0001, P < 0.001, P < 0.05, and P < 0.01, respectively). No patient received maintenance hemodialysis after surgery. Although the overall postoperative complication rates were similar between the RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients (5.5% vs 1.8%; P < 0.05, 3.9% vs 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in the severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparable, even after PSM between the RD and non-RD groups to exclude the influence of patient characteristics, liver function, and other causes of death.ConclusionComorbid mild RD had a negligible impact on the prognosis of HCC patients who underwent curative hepatectomy with appropriate perioperative management, and close attention to severe CKD is necessary to prevent postoperative bleeding and surgical site infection.
| S-EPMC9353748 | biostudies-literature
Project description:BackgroundApplication of curative therapy for hepatocellular carcinoma is crucially dependent on underlying liver function. Using the recently described ALBI grade we examined the long-term impact of liver dysfunction on survival of early-stage hepatocellular carcinoma (HCC) patients.MethodsThis cohort study comprised 2559 HCC patients from different geographic regions, all treated with curative intent. We also examined the relation between indocyanine green (ICG) clearance and ALBI score. Survival was measured from the date of treatment to the date of death or last follow-up.ResultsThe ALBI score correlated well with ICG clearance. Among those undergoing surgical resection, patients with ALBI grade-1 (good liver function) survived approximately twice as long as those with ALBI grade-2 (less good liver function), although more than 90% of these patients were classified as Child-Pugh (C-P) grade A. In the cohort receiving ablative therapies, there was a similar difference in survival between ALBI grade-1 and grade-2. Cox regression analysis confirmed that the ALBI score along with age, gender, aetiology and tumour factors (AFP, tumour size/number and vascular invasion) independently influenced survival in HCC patients receiving curative treatments.ConclusionsThe ALBI score represents a simple approach to the assessment of liver function in patients with HCC. After potentially curative therapy, those with ALBI grade-1 survived approximately twice as long as those with ALBI grade-2. These data suggest that ALBI grade-1 patients are appropriately treated with surgical resection whereas ALBI grade-2 patients may, where the option exists, be more suitable for liver transplantation or the less invasive curative ablative therapies.
| S-EPMC4984858 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) frequently recurs even after curative hepatectomy. To develop an integrated multigene expression panel, 144 patients were randomly assigned to either discovery or validation set in a 1:2 ratio. Using surgically resected HCC specimens, expression levels of 12 candidate molecular markers were determined using quantitative reverse-transcriptase PCR. In the discovery set, an expression panel was developed according to the concordance index (C-index) values for overall survival from all 4095 combinations of the 12 candidate molecular markers. Expression scores was determined with weighting according to the coefficient in a Cox regression, and patients were classified into grade 1, 2 and 3. Reproducibility was then tested in the validation set. A panel consisting of four markers, PRMT5, MAGED4, DPYSL3 and AJAP1 was selected as the optimal and most well-balanced set with a C-index value of 0.707. Patient prognosis was clearly stratified by the expression grade using this panel. In the validation set, both overall and disease-free survival rates decreased incrementally with as the grade increased. Higher grades were significantly associated with tumor multiplicity and vessel invasion. The prevalence of extrahepatic recurrences was increased in grade 3 patients. The integrated multigene expression panel clearly stratified HCC patients into low, intermediate and high risk.
| S-EPMC5642618 | biostudies-literature
Project description:We developed a novel inflammation-nutrition scope (INS) based on systemic inflammatory response and nutritional status, and explored its prognostic value in hepatocellular carcinoma (HCC), especially for those with early-stage disease.The INS was developed based on a retrospective study of 185 patients with HCC undergoing hepatectomy between 2006 and 2007, and validated in a prospective study of 131 patients enrolled from 2009 to 2010. Prediction accuracy was evaluated with area under the receiver operating characteristic curve (AUCs).The INS was constructed as follows: patients with both an elevated red blood cell distribution width (RDW, ≥13.25%) and platelet-lymphocyte ratio (PLR, ≥1.1) were allocated a score of 2. Patients in whom only 1 or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. An elevated INS was associated with larger tumor size, tumor thrombus, and high tumor lymph nodes metastasis (TNM) stage. Univariate and multivariate analyses revealed the INS was an independent predictor for overall survival, and a prognostic factor for patients with TNM I stage. The AUCs of the INS for survival were higher than other conventional clinical indices.The INS is a promising predictor of poor outcome in patients with HCC, especially for those with early-stage disease, and is a promising tool for HCC treatment strategy decisions for future clinical trials targeting nutritional decline.
| S-EPMC5626267 | biostudies-literature
Project description:BackgroundRibosomal protein S11 (RPS11), a member of ribosomal protein family, is reported to overexpress in diverse malignancies and correlates with tumor recurrence. However, our current knowledge on RPS11 in hepatocellular carcinoma (HCC) remains limited. In this study, we are going to explore the potential prognostic value of RPS11 in HCC patients after curative resection.MethodsImmunohistochemistry (IHC) was performed to evaluate RPS11 expression on tissue microarrays in training cohort comprising 182 HCC patients and validation cohort enrolling 90 HCC patients in Zhongshan Hospital, Fudan University. Western blot and quantitative reverse transcription PCR (qRT-PCR) were also used to determine the expression level of RPS11 in liver cell lines. Two nomograms, calibration curves and decision curve analysis (DCA) were further performed to assess the performance of RPS11 level in predicting clinical outcomes of HCC patients. Additionally, single-sample gene-set enrichment analysis (ssGSEA) was conducted in TCGA liver cancer database to investigate the potential biological pathways involved in RPS11.ResultsBoth increased mRNA and protein levels of RPS11 were observed in most HCC cell lines when compared to the normal hepatocytes, and high tumor RPS11 level was associated with shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients after curative resection. Univariate and multivariate analysis indicated that RPS11 was an independent prognostic factor in HCC. Two nomograms, calibration and DCA curves were further established and displayed a superior prognostic accuracy of OS and RFS, and showed more clinical benefits than traditional staging systems in HCC. Furthermore, several pathways and molecules related to tumor resistance, survival and recurrence were enriched in high RPS11 expression by ssGSEA.ConclusionsTumorous RPS11 acts as a potential prognostic biomarker for HCC patients who received curative resection.
| S-EPMC7210141 | biostudies-literature