Combination surgery for hepatocellular carcinoma: slashing and burning to improved survival.
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ABSTRACT:
SUBMITTER: McVey JC
PROVIDER: S-EPMC7475510 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Combination surgery for hepatocellular carcinoma: slashing and burning to improved survival.
McVey John C JC Sasaki Kazunari K
Annals of translational medicine 20200801 16
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Project description:BackgroundGiven the complexity of managing hepatocellular carcinoma (HCC), a multidisciplinary approach (MDT) is recommended to optimize management of HCC patients. However, evidence suggesting that MDT improves patient outcome is limited.MethodsWe performed a retrospective cohort study of all patients newly-diagnosed with HCC between 2005 and 2013 (n = 6,619). The overall survival (OS) rates between the patients who were and were not managed via MDT were compared in the entire cohort (n = 6,619), and in the exactly matched cohort (n = 1,396).ResultsIn the entire cohort, the 5-year survival rate was significantly higher in the patients who were managed via MDT compared to that of the patients who were not (71.2% vs. 49.4%, P < 0.001), with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval [CI]; 0.41-0.53). In the exactly matched cohort, the 5-year survival rate was higher in patients who were managed via MDT (71.4% vs. 58.7%, P < 0.001; HR [95% CI] = 0.67 [0.56-0.80]). The survival benefit of MDT management was observed in most pre-defined subgroups, and was especially significant in patients with poor liver function (ALBI grade 2 or 3), intermediate or advanced tumor stage (BCLC stage B or C), or high alphafetoprotein levels (≥200 ng/ml).ConclusionMDT management was associated with improved overall survival in HCC patients, indicating that MDT management can be a valuable option to improve outcome of HCC patients. This warrants prospective evaluations.
| S-EPMC6331107 | biostudies-literature
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| S-EPMC9577984 | biostudies-literature
Project description:BackgroundTransarterial Radioembolisation (TARE) requires multidisciplinary experience and skill to be effective. The aim of this study was to identify determinants of survival in patients with hepatocellular carcinoma (HCC), focusing on learning curves, technical advancements, patient selection and subsequent therapies.MethodsFrom 2005 to 2020, 253 patients were treated. TARE results achieved in an initial period (2005-2011) were compared to those obtained in a more recent period (2012-2020). To isolate the effect of the treatment period, differences between the two periods were balanced using "entropy balance".ResultsOf the 253 patients, 68 were treated before 2012 and 185 after 2012. In the second period, patients had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 1 (p = 0.025) less frequently, less liver involvement (p = 0.006) and a lesser degree of vascular invasion (p = 0.019). The median overall survival (OS) of patients treated before 2012 was 11.2 months and that of patients treated beginning in 2012 was 25.7 months. After reweighting to isolate the effect of the treatment period, the median OS of patients before 2012 increased to 16 months.ConclusionsBetter patient selection, refinement of technique and adoption of personalised dosimetry improved survival after TARE. Conversely, sorafenib after TARE did not impact life expectancy.
| S-EPMC9781303 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. In basic studies, the regulation of autophagy has offered promising results for HCC treatment. This study aimed to address the question of whether amiodarone can improve survival rates in HCC patients associated with autophagy. Using datasets from the National Health Insurance Research Database, we enrolled patients over 18 years of age that had been diagnosed with HCC between January 1997 and December 2010. Amiodarone and non-amiodarone users were matched at a 1:1 frequency, according to all variables. Additionally, HepG2 cells treated with amiodarone were evaluated by cell viability and autophagic change. Autophagic signaling was examined by immunoblotting and tissue array immunohistochemistry. Of the 10,946 patients diagnosed with HCC, each cohort included 221 patients after 1:1 propensity score matching. The median survival was 36.70 months for the amiodarone users, and 24.48 months for the non-amiodarone users. After adjusting for age, gender, comorbidities and treatment, amiodarone users had a significantly lower risk of mortality. Amiodarone users also demonstrated an improved 3-year survival rate. Furthermore, amiodarone treatment-induced autophagy in HepG2 cells was demonstrated by autophagosome formation associated with increasing LC3B-II, P62, and Beclin-1 expression. Autophagic flux also increased following amiodarone treatment with bafilomycin A1. SiRNA of LC3B knocked down endogenous LC3B formation and restored HepG2 cell viability. This study provides epidemiologic evidence that amiodarone via autophagic degradation machinery may offer survival benefits for HCC patients with a history of arrhythmia. Further randomized, blinded, and placebo-controlled trials are warranted for patients with HCC.
| S-EPMC6720201 | biostudies-literature
Project description:IntroductionWith technological advances, questions arise regarding how to best fit newer treatment modalities, such as transarterial therapies, into the treatment algorithm for patients with hepatocellular carcinoma (HCC).MethodsBetween 2005 and 2011, 128 patients initially treated with transarterial radioembolization or chemoembolization using drug-eluting beads were identified. The response was graded retrospectively. Toxicity was measured 1, 3, and 6 months after the first and last treatments.ResultsSixty-five patients (53%) were advanced stage. Twenty patients (16%) had an initial complete response, but with additional treatments, this was increased to 46 (36%). Patients with a complete response as their best response to treatment had a median survival [95% confidence interval (CI)] of 5.77 (2.58, upper limit not yet reached) years, significantly longer than those whose best response was a partial response, 1.22 (0.84, 2.06) years and those with stable disease as their best response, 0.34 (0.29, 0.67) years. Repeated treatments did not increase toxicity.DiscussionThis retrospective review of patients treated for intermediate and advanced stage HCC revealed a significant survival advantage in patients who achieved a complete response. These data support use of a multi-modality approach to intermediate and advanced stage HCC, combining liver-directed treatments as necessary to achieve a complete response.
| S-EPMC4402057 | biostudies-literature
Project description:Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15-0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17-0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59-58.82) and high BMI (OR = 1.19, 95% CI 1.07-1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p < 0.0001). After treatments, NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Non-Hispanic ethnicity and normal BMI differentiated non-cirrhosis versus cirrhosis NAFLD HCC. Further studies are warranted to identify additional biomarkers to stratify NAFLD patients without cirrhosis who are at risk for HCC.
| S-EPMC7303220 | biostudies-literature
Project description:Background & aimsThe deubiquitinase CYLD removes (K-63)-linked polyubiquitin chains from proteins involved in NF-κB, Wnt/ß-catenin and Bcl-3 signaling. Reduced CYLD expression has been reported in different tumor entities, including hepatocellular carcinoma (HCC). Furthermore, loss of CYLD has been shown to contribute to HCC development in knockout animal models. This study aimed to assess subcellular CYLD expression in tumor tissues and its prognostic significance in HCC patients undergoing liver resection or liver transplantation.MethodsSubcellular localization of CYLD was assessed by immunohistochemistry in tumor tissues of 95 HCC patients undergoing liver resection or transplantation. Positive nuclear CYLD staining was defined as an immunohistochemical (IHC) score ≥ 3. Positive cytoplasmic CYLD staining was defined as an IHC score ≥ 6. The relationship with clinicopathological parameters was investigated. Cell culture experiments were performed to analyze subcellular CYLD expression in vitro.ResultsCytoplasmic CYLD expression was observed in 57 out of 95 (60%) HCC specimens (cyt°CYLD+). Nuclear CYLD staining was positive in 52 out of 95 specimens (55%, nucCYLD+). 13 out of 52 nucCYLD+ patients (25%) showed a lack of cytoplasmic CYLD expression. nucCYLD+ was associated with prolonged overall survival in patients after resection or liver transplantation (P = 0.007). 5-year overall survival rates were 63% in nucCYLD+ vs. 26% in nucCYLD- patients. Nuclear CYLD staining strongly correlated with tumor grading (P<0.001) and Ki67 positivity (P = 0.005). nucCYLD+ did not prove to be an independent prognostic parameter. In vitro, Huh7, Hep3B and HepG2 showed reduced CYLD levels compared to the non-malignant liver cell line THLE-2. Induction of CYLD expression by doxorubicin treatment led to increased cytoplasmic and nuclear expression of CYLD.ConclusionsExpression of nuclear CYLD is a novel prognostic factor for improved survival in patients with HCC undergoing liver resection or transplantation.
| S-EPMC4199737 | biostudies-literature
Project description: Not available
| S-EPMC5892358 | biostudies-literature
Project description:Preoperative prediction of recurrence outcome in hepatocellular carcinoma (HCC) facilitates physicians' clinical decision-making. Preoperative imaging and related clinical baseline data of patients are valuable for evaluating prognosis. With the widespread application of machine learning techniques, the present study proposed the ensemble learning method based on efficient feature representations to predict recurrence outcomes within three years after surgery. Radiomics features during arterial phase (AP) and clinical data were selected for training the ensemble models. In order to improve the efficiency of the process, the lesion area was automatically segmented by 3D U-Net. It was found that the mIoU of the segmentation model was 0.8874, and the Light Gradient Boosting Machine (LightGBM) was the most superior, with an average accuracy of 0.7600, a recall of 0.7673, a F1 score of 0.7553, and an AUC of 0.8338 when inputting radiomics features during AP and clinical baseline indicators. Studies have shown that the proposed strategy can relatively accurately predict the recurrence outcome within three years, which is helpful for physicians to evaluate individual patients before surgery.
| S-EPMC9686395 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is an aggressive malignancy with high morbidity and mortality. Conversion therapy can improve surgical resection rate and prolong survival time for patients with advanced HCC. We show that combination therapy with lenvatinib and camrelizumab is a novel approach to downstage unresectable HCC.Case presentationA 49-year-old man was diagnosed with massive HCC with hilar lymph node and lung metastases. Since radical resection was not feasible, lenvatinib and camrelizumab were administered as first-line therapy. After 10 cycles of camrelizumab and continuous oral administration of lenvatinib, the tumor exhibited striking shrinkage in volume indicating a partial radiological response, accompanied by a reduction in the alpha-fetoprotein levels, followed by salvage resection. Intriguingly, an improvement in predictive biomarkers, like lactate dehydrogenase (LDH) and neutrophil-to-lymphocyte ratio (NLR), was observed. Notably, the pathological examination found high levels of necrosis in the resected tumor, and flow cytometry analysis indicated a significant increase in the ratio of CD5+ and CD5- B lymphocytes in the peripheral blood. After the treatment, the overall survival period was over 24 months, and no recurrence was observed 17-month post-surgery.ConclusionsA combination of lenvatinib and camrelizumab may be a new conversion therapy for initially unresectable HCC to resectable HCC, thus contributing to improve the disease prognosis. In addition, the combination regimen could cause an activated immune response, and LDH, NLR, and CD5+ B-cell levels might be predictors for immunotherapy efficacy.
| S-EPMC9887816 | biostudies-literature