Treatment Outcome Of Hepatocellular Carcinoma Research Articles

The Negative Impact of Sarcopenia on Hepatocellular Carcinoma Treatment Outcomes.

Hepatocellular carcinoma (HCC) represents a major global health concern, characterized by evolving etiological patterns and a range of treatment options. Among various prognostic factors, sarcopenia, characterized by loss of skeletal muscle mass, strength, and function, has emerged as a pivotal contributor to HCC outcomes. Focusing on liver transplantation, surgical resection, locoregional treatments, and systemic therapies, this review aims to analyze the impact of sarcopenia on HCC treatment outcomes, shedding light on an underexplored subject in the pursuit of more personalized management. A comprehensive literature review was conducted by searching peer-reviewed articles on sarcopenia and treatment outcomes in patients with HCC from inception up to October 2023. Sarcopenia was found to be prevalent among HCC patients, exhibiting different occurrence, possibly attributable to diverse diagnostic criteria. Notably, despite variations in studies utilizing skeletal muscle indices, sarcopenia independently correlated with lower overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) across surgical (both transplantation and resection), locoregional, and systemic therapies, including tyrosine-kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs). Moreover, a link between sarcopenia and increased rate and severity of adverse events, particularly in surgery and TKIs recipients, and larger tumor size at diagnosis was observed. While baseline sarcopenia negatively influenced treatment outcomes, alterations in muscle mass post-treatment emerged as primary determinants of reduced OS. Sarcopenia, either present before or after HCC treatment, negatively correlates with response to it, across all etiologies and therapeutic strategies. Although only a few studies have evaluated the impact of supervised physical activity training on muscle mass and OS after HCC treatment, it is crucial to evaluate the presence of sarcopenia before treatment initiation, to better stratify patients' prognosis, thus performing a more tailored approach, and identify therapies able to restore muscle mass in HCC patients. Conversely, the impact of sarcopenia on HCC recurrence and extrahepatic spread remains inadequately explored.

Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma

T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.

LI-RADS category is associated with treatment outcomes of small single HCC: surgical resection vs. radiofrequency ablation.

To assess whether the Liver Imaging Reporting and Data System (LI-RADS) category is associated with the treatment outcomes of small single hepatocellular carcinoma (HCC) after surgical resection (SR) and radiofrequency ablation (RFA). This retrospective study included 357 patients who underwent SR (n =209) or RFA (n =148) for a single HCC of ≤ 3 cm between 2014 and 2016. LI-RADS categories were assigned. Overall survival (OS), recurrence-free survival (RFS), and local tumor progression (LTP) rates after treatment were compared according to the LI-RADS category (LR-4/5 vs. LR-M) before and after propensity score matching (PSM). Prognostic factors for treatment outcomes were assessed. In total, 357 patients (mean age, 59 years; men, 272) with 357 HCCs (294 LR-4/5 and 63 LR-M) were included. After PSM (n =78 in each treatment group), there were 10 and 11 LR-M HCCs in the SR and RFA group, respectively. There were no significant differences in OS or RFS. However, SR provided a lower 5-year LTP rate than RFA (1.4% vs. 14.9%, p = 0.001). SR provided a lower 5-year LTP rate than RFA for LR-M HCCs (0% vs. 34.4%, p = 0.062) and LR-4/5 HCCs (1.5% vs. 12.0%, p = 0.008). The LI-RADS category was the sole risk factor associated with poor OS (hazard ratio [HR] 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032). LI-RADS classification is associated with the treatment outcome of HCC, supporting favorable outcomes of SR over RFA for LTP, especially for HCCs categorized as LR-M. Liver Imaging Reporting and Data System category has a potential prognostic role, supporting favorable outcomes of surgical resection over radiofrequency ablation for local tumor progression, especially for hepatocellular carcinoma categorized as LR-M. • SR provided a lower 5-year LTP rate than RFA for HCCs categorized as LR-M (0% vs. 34.4%, p = 0.062) and HCCs categorized as LR-4/5 (1.5% vs. 12.0%, p = 0.008). • There is a steeply increased risk of LTP within 1 year after RFA for LR-M HCCs, compared to SR. • The LI-RADS category was the sole risk factor associated with poor OS (HR 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032) in patients with HCC of ≤ 3 cm treated with SR or RFA.

Predictive Power of the Albumin-Bilirubin Score for Hepatotoxicity in Stereotactic Ablative Radiation Therapy for Hepatocellular Carcinoma.

Assessment of liver function is crucial in predicting treatment outcomes for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score for predicting hepatotoxicity following stereotactic body radiation therapy (SBRT) in HCC patients. A retrospective analysis was conducted on 123 HCC cases treated between 2018 and 2020. ALBI and Child-Turcotte-Pugh (CTP) scores were calculated, and hepatotoxicity was defined as a post-SBRT CTP score increase ≥2. Receiver operating characteristic (ROC) curves were used for comparison. The optimal cutoff value of the ALBI score was determined. Among the 121 patients analyzed, hepatotoxicity occurred in 5%. The ALBI score showed better predictive accuracy (area under the ROC curve: 0.77) than the CTP score. The optimal cutoff value of the ALBI score was -2.47, with a sensitivity of 85.7% and a specificity of 71.1%. Multivariable analysis revealed that ALBI score and PTV were significant factors for hepatotoxicity. In conclusion, the ALBI score demonstrated prognostic value for hepatotoxicity prediction after SBRT in HCC patients. Considering the ALBI score and PTV provides valuable insights for assessing hepatotoxicity risk during SBRT treatment for HCC.

Targeting liver cancer stem cell through EpCAM therapy targeted with chemotherapy endorse enhanced progression in hepatocellular carcinoma

BackgroundTwo chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors such as hypoxia, cancer stem cells, and drug efflux mechanism cancer stem cells (CSC) which are significant factors involved in chemoresistance. It has been exposed that targeting liver cancer stem cells and chemotherapeutic drugs have a better selected, overall survival rate for hepatocellular carcinoma patients.AimThis study aims to investigate the effectiveness of targeting stem cells for liver cancer using a therapy that targets EpCAM in combination with chemotherapy and how this approach can enhance the treatment outcomes in hepatocellular carcinoma, the most prevalent kind of liver cancer.ResultsThe outcome was studied by flow cytometry, Western blot, RT-PCR, and cytotoxicity assays. EpCAM gene silenced and XAV939-treated cells showed decreased expression of CD133, a liver cancer stem cell (LCSC) marker in flow cytometry analysis, and reduced expression of ABCG2 gene, which is a reliable marker for chemoresistance in RT-PCR and western blot analysis; it was also unable to form colonies in colony forming assay. Similarly, in the spheroid formation assay, EpCAM gene silenced cells and XAV939-treated cells in combinations with cisplatin treatment were powerless to appear spheroid, whereas cisplatin alone-treated cells showed spheroids. In the cytotoxicity assay, cisplatin alone and combined with EpCAM silenced and XAV939-treated cells showed more lactate dehydrogenase (LDH) release than EpCAM silenced arm XAV939 treated components.ConclusionThese findings confirm our hypothesis that conventional chemotherapy kills cancer cells but not cancer stem cells. We believe EpCAM-targeted therapy enhances chemosensitivity and decreases relapsed chances. This approach might be the best option for a better prognosis for hepatocellular carcinoma patients.

Voxel-Based Dosimetry Predicts Hepatotoxicity in Hepatocellular Carcinoma Patients Undergoing Radioembolization with 90Y Glass Microspheres.

Personalized dosimetry holds promise to improve radioembolization treatment outcomes in hepatocellular carcinoma (HCC) patients. To this end, tolerance absorbed doses for nontumor liver tissue are assessed by calculating the mean absorbed dose to the whole nontumor liver tissue (AD-WNTLT), which may be limited by its neglect of nonuniform dose distribution. Thus, we analyzed whether voxel-based dosimetry could be more accurate in predicting hepatotoxicity in HCC patients undergoing radioembolization. Methods: In total, 176 HCC patients were available for this retrospective analysis; of these, 78 underwent partial- and 98 whole-liver treatment. Posttherapeutic changes in bilirubin were graded using the Common Terminology Criteria for Adverse Events. We performed voxel-based and multicompartment dosimetry using pretherapeutic 99mTc-labeled human serum albumin SPECT and contrast-enhanced CT/MRI and defined the following dosimetry parameters: AD-WNTLT; the nontumor liver tissue volume exposed to at least 20 Gy (V20), at least 30 Gy (V30), and at least 40 Gy (V40); and the threshold absorbed dose to the 20% (AD-20) and 30% (AD-30) of nontumor liver tissue with the lowest absorbed dose. Their impact on hepatotoxicity after 6 mo was analyzed using the area under the receiver-operating-characteristic curve; thresholds were identified using the Youden index. Results: The area under the curve for prediction of posttherapeutic grade 3+ increases in bilirubin was acceptable for V20 (0.77), V30 (0.78), and V40 (0.79), whereas it was low for AD-WNTLT (0.67). The predictive value could further be increased in the subanalysis of patients with whole-liver treatment, where a good discriminatory power was found for V20 (0.80), V30 (0.82), V40 (0.84), AD-20 (0.80), and AD-30 (0.82) and an acceptable discriminatory power was found for AD-WNTLT (0.63). The accuracies of V20 (P = 0.03), V30 (P = 0.009), V40 (P = 0.004), AD-20 (P = 0.04), and AD-30 (P = 0.02) were superior to that of AD-WNTLT but did not differ significantly from each other. The respective thresholds were 78% (V30), 72% (V40), and 43 Gy (AD-30). Statistical significance was not reached for partial-liver treatment. Conclusion: Voxel-based dosimetry may more accurately predict hepatotoxicity than multicompartment dosimetry in HCC patients undergoing radioembolization, which could enable dose escalation or deescalation with the intent to optimize treatment response. Our results indicate that a V40 of 72% may be particularly useful in whole-liver treatment. However, further research is warranted to validate these results.

Risk factors, clinical characteristics, and treatment outcomes for hepatocellular carcinoma in Rwanda.

e16339 Background: Hepatocellular carcinoma (HCC) is increasing worldwide with limited treatment options, a poor prognosis, and survival rates of less than 5 years. In Sub-Saharan Africa, over 46,000 new cases are reported every year, and HCC is commonly associated with alcohol consumption, viral hepatitis, especially Hepatitis B (HBV) and C (HCV), aflatoxin exposure, obesity, type II diabetes, and HIV infection. In Rwanda, often young people are diagnosed with HCC in the late stages of the disease, and treatment options are limited. Rwanda has made great achievements in the prevention and treatment of HBV and HCV. However, there is a lack of data on HCC in Rwanda and its associated risk factors. In this study, we report the prevalence of common risk factors, available treatment options, and treatment outcomes among patients with HCC in Rwanda. Methods: This was a retrospective study of patients aged 18 years of age and above diagnosed with HCC from 2016 to 2021 in three tertiary hospitals: University Teaching Hospital of Kigali, King Faisal Hospital, and Rwanda Military Hospitals. Data were abstracted from patients’ paper charts and electronic medical records and recorded in REDCap and analyzed in STATA. Results: Overall, 219 individuals were included in the study. 32.9% were female, the median age was 32 (26–54) years, and 48.4% came from the capital city of Kigali. Only 13.3% of patients had histo-pathological confirmation of HCC, while 86.7 % were diagnosed clinically with radiological images, alpha-fetoprotein, and other clinical findings. The most common risk factors were HCV and HBV infection with a prevalence of 27.4% and 20.1%, respectively. HIV infection and diabetes mellitus were present in 6.9% and 6.2% of patients, respectively. More than 80% of patients had had clinical or ultrasound evidence of cirrhosis, including ascites or hepatic encephalopathy and only 8.9% of patients received Sorafenib, and no patient had surgical resection, ablation, or liver transplant. Only 15.1% of patients received palliative care with opiate therapy. Among all patient diagnosed with HCC, 36% died within 3 months of diagnosis. Conclusions: In this retrospective study of the three largest treatment centers in Rwanda, the majority of HCC cases occurred at a young age with a high rate of mortality. HBV and HCV were the most frequent risk factors, and the majority of patients had clinical characteristics of decompensated liver failure. There is a clear lack of diagnostic tools, most glaringly pathologic diagnosis, and an extreme lack of treatment options. Increased awareness for HBV and HCV prevention and screening as well as further studies on etiology of HCC cases and management are needed.

Is There Really a Difference in Outcomes between Men and Women with Hepatocellular Cancer?

Hepatocellular carcinoma (HCC) is a male-dominated disease. Currently, gender differences remain incompletely defined. Data from the state tumor registry were used to investigate differences in demographics, comorbidities, treatment patterns, and cancer-specific survival (HSS) among HCC patients according to gender. Additional analyses were performed to evaluate racial differences among women with HCC. 2627 patients with HCC were included; 498 (19%) were women. Women were mostly white (58%) or African American (39%)-only 3.8% were of another or unknown race. Women were older (65.1 vs. 61.3 years), more obese (33.7% vs. 24.2%), and diagnosed at an earlier stage (31.7% vs. 28.4%) than men. Women had a lower incidence of liver associated comorbidities (36.1% vs. 43%), and more often underwent liver-directed surgery (LDS; 27.5% vs. 22%). When controlling for LDS, no survival differences were observed between genders. African American women had similar HSS rates compared to white women (HR 1.14 (0.91,1.41), p = 0.239) despite having different residential and treatment geographical distributions. African American race and age >65 were predictive for worse HSS in men, but not in women. Overall, women with HCC undergo more treatment options-likely because of the earlier stage of the cancer and/or less severe underlying liver disease. However, when controlling for similar stages and treatments, HCC treatment outcomes were similar between men and women. African American race did not appear to influence outcomes among women with HCC as it did in men.

Dual role of PID1 in regulating apoptosis induced by distinct anticancer-agents through AKT/Raf-1-dependent pathway in hepatocellular carcinoma

The treatment outcome of hepatocellular carcinoma (HCC) is severely hampered due to its etiology, and thus in depth understanding of the genetic mechanisms underlying response of HCC to various anticancer agents is needed. Here, we have identified Phosphotyrosine interaction domain-containing protein 1 (PID1) as a novel regulator involved in modulation of apoptosis induced by anticancer agents in a context-dependent manner. PID1 relieved chemotherapy-induced ROS production, mitochondrial outer membrane permeability and mitochondrial respiratory depression. In addition, PID1 restricted AKT-mediated inhibition on Raf-1 through interacting with PDPK1 at phosphorylated tyrosine sites, thus enhancing Raf-1-mediated BAD inhibition. Interestingly, AKT, Bcl2 inhibition or Raf-1 silencing abolished PID1-mediated anti-apoptotic effects. However, PID1 altered the rhythmicity of pharmacological activity of Sorafenib on various survival-related kinases, thus resulting in AKT blockade via Raf-1/BRAF/ERK/MEK pathway. BRAF inhibition or Raf-1 depletion disrupted PID1-mediated barrier in AKT activation in response to Sorafenib. Moreover, in vivo study indicated that PID1 deficiency led to increased survival rate upon Doxorubicin treatment but reduced efficacy of Sorafenib. Overall, we propose that PID1 can function as an underlying biomarker of resistance to conventional chemotherapeutic agents but sensitivity towards Sorafenib.

Prevalence and Effect of Low Skeletal Muscle Mass among Hepatocellular Carcinoma Patients Undergoing Systemic Therapy: A Systematic Review and Meta-Analysis.

Low skeletal muscle mass (LSMM) is associated with poor outcomes in hepatocellular carcinoma (HCC) patients. With the emergence of new systemic therapeutics, understanding the effect of LSMM on HCC treatment outcomes is critically important. This systematic review and meta-analysis investigates the prevalence and effect of LSMM among HCC patients undergoing systemic therapy as reported in studies identified in searches of the PubMed and Embase databases published through 5 April 2023. The included studies (n = 20; 2377 HCC patients undergoing systemic therapy) reported the prevalence of LSMM assessed by computer tomography (CT) and compared the survival outcomes [overall survival (OS) or progression-free survival (PFS)] between HCC patients with and without LSMM. The pooled prevalence of LSMM was 43.4% (95% CI, 37.0-50.0%). A random-effects meta-analysis showed that HCC patients receiving systemic therapy with comorbid LSMM had a lower OS (HR, 1.70; 95% CI, 1.46-1.97) and PFS (HR, 1.32; 95% CI, 1.16-1.51) than did those without. Subgroup analysis according to systemic therapy type (sorafenib, lenvatinib, or immunotherapy) yielded similar results. In conclusion, LSMM is prevalent among HCC patients undergoing systemic therapy and is associated with poorer survival. Early intervention or prevention strategies to improve muscle mass may be necessary for this patient population.

Combined detection of circulating tumor cells, \u03b1-fetoprotein heterogene-3 and \u03b1-fetoprotein in the early diagnosis of HCC for the prediction of efficacy, prognosis, recurrence after microwave ablation

BackgroundEarly diagnosis can significantly improve treatment outcomes for hepatocellular carcinoma (HCC) patients. Currently, the dosage of serum alpha fetoprotein (AFP) is widely used in the diagnosis of HCC, but this biomarker has low specificity and may cause false positive or false negative results. Thus, it’s necessary to find and validate other serum tumor markers that in association for AFP would increase the sensitivity and the specificity in the HCC diagnosis. This study investigated the predictive value of combined of AFP, AFP-L3, and Circulating tumor cells (CTCs).MethodsA total of 105 patients with HCC after microwave ablation (MWA) were divided into non recurrence group, recurrence group, good prognosis (CR + PR group, CR: Complete remission, PR: Partial remission) and poor prognosis (SD + PD group, SD: Stable, PD: Progression). ROC curve was used to analyze the short-term efficacy, prognosis and clinical value of combined detection of the three indicators in predicting postoperative recurrence of HCC patients with MWA.ResultsThe positive rate of serum CTCs, AFP-L3 and AFP combined detection in the diagnosis of HCC is higher than that of single index and two index detection. The AUC, sensitivity and specificity of serum CTCs, AFP-L3 and AFP combined detection was better than that of single index and two indexes in patients with HCC after MWA.ConclusionsCombined detection of AFP, AFP-L3, and CTCs can effectively make up for the shortcomings of the detection with single and pairwise indicators. It can’t only diagnose HCC in early, but also has a high clinical value of predicting the short-term efficacy, prognosis and recurrence of HCC patients after MWA treatment.

SAT488 - Effectiveness of sorafenib dose modifications on treatment outcome of hepatocellular carcinoma: analysis in real-life settings

SAT488 - Effectiveness of sorafenib dose modifications on treatment outcome of hepatocellular carcinoma: analysis in real-life settings

Dual effects of gossypol on human hepatocellular carcinoma via endoplasmic reticulum stress and autophagy.

Treatment outcomes for hepatocellular carcinoma (HCC) remain unsatisfactory, and effective new therapeutic methods are urgently needed. Gossypol has been shown to have an anti-HCC effect, but the underlying mechanism requires further study. In this study, we found gossypol inhibited HCC cells in vitro and in vivo. Typical apoptosis was induced in HCC cells. Dilated ER and autophagosomes were observed by electron microscopy, and the activation of the unfolded protein response and autophagy markers suggested that gossypol induced both ER stress and autophagy. C/EBP homologous protein was the key factor that led to apoptotic cell death, whereas inositol-requiring enzyme 1α and eukaryotic initiation factor 2α played a protective role. Autophagy protected the cells from ER stress-related apoptosis. Both in vitro and in vivo studies indicated that inhibition of autophagy enhanced the anti-HCC effect of gossypol. Taken together, ER stress is the molecular mechanism underlying gossypol-induced apoptosis and autophagy. Gossypol exhibits anti-HCC activity primarily through the activation of apoptosis. However, gossypol-induced autophagy protects HCC cells from ER stress. Therefore, a combination therapy of gossypol and autophagy inhibitors may lead to an enhanced anti-HCC effect.

Resolvin D1 prevents epithelial-mesenchymal transition and reduces the stemness features of hepatocellular carcinoma by inhibiting paracrine of cancer-associated fibroblast-derived COMP

BackgroundCancer stem cells (CSCs) require stromal signals for maintaining pluripotency and self-renewal capacities to confer tumor metastasis. Resolvin D1 (RvD1), an endogenous anti-inflammatory lipid mediator, has recently been identified to display anti-cancer effects by acting on stroma cells. Our previous study reveals that hepatic stellate cells (HSCs)-derived cartilage oligomeric matrix protein (COMP) contributes to hepatocellular carcinoma (HCC) progression. However, whether RvD1 inhibits paracrine of cancer-associated fibroblasts (CAFs)-derived COMP to prevent epithelial-mesenchymal transition (EMT) and cancer stemness in HCC remains to be elucidated.MethodsCAFs were isolated from HCC tissues. Direct and indirect co-culture models were established to analyze the interactions between HCC cells and CAFs in the presence of RvD1 in vitro. The transwell and tumor sphere formation assays were used to determine invasion and stemness of HCC cells. The subcutaneous tumor formation and orthotopic liver tumor models were established by co-implantation of CAFs and HCC cells to evaluate the role of RvD1 in vivo. To characterize the mechanism of RvD1 inhibited paracrine of COMP in CAFs, various signaling molecules were analyzed by ELISA, western blotting, reactive oxygen species (ROS) detection, immunofluorescence staining, dual luciferase reporter assay and chromatin immunoprecipitation assay.ResultsOur data revealed that RvD1 treatment can impede the CAFs-induced cancer stem-like properties and the EMT of HCC cells under co-culture conditions. In vivo studies indicated that RvD1 intervention repressed the promoting effects of CAFs on tumor growth and metastasis of HCC. Furthermore, RvD1 inhibited CAF-induced EMT and stemness features of HCC cells by suppressing the secretion of COMP. Mechanistically, formyl peptide receptor 2 (FPR2) receptor mediated the suppressive effects of RvD1 on COMP and forkhead box M1 (FOXM1) expression in CAFs. Notably, RvD1 impaired CAF-derived COMP in a paracrine manner by targeting FPR2/ROS/FOXM1 signaling to ultimately abrogate FOXM1 recruitment to the COMP promoter.ConclusionOur results indicated that RvD1 impaired paracrine of CAFs-derived COMP by targeting FPR2/ROS/FOXM1 signaling to repress EMT and cancer stemness in HCC. Thus, RvD1 may be a potential agent to promote treatment outcomes in HCC.

Lipiodol deposition in portal vein tumour thrombus predicts treatment outcome in HCC patients after transarterial chemoembolisation.

To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE). We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT. The overall survival (OS) and progression-free survival (PFS) were compared between negative and positive lipiodol deposition groups; furthermore, the value of the combinatorial evaluation of tumour responses and lipiodol deposition in PVTT in predicting prognosis was analysed in subgroup patients with stable disease (SD) after TACE. Of the 379 patients, 264 (69.7%) had negative and 115 (30.3%) had positive lipiodol deposition in PVTT after TACE. Multivariate analysis identified positive lipiodol deposition in PVTT as an independent prognostic factor for favourable OS (p = 0.001). The median OS and PFS of negative and positive lipiodol deposition groups were 4.70 vs. 8.97months (p = 0.001) and 3.1months vs. 5.8months (p < 0.001). In subgroup patients, the median OS and PFS of negative and positive lipiodol deposition groups were 4.7months vs. 10.5months (p < 0.001) and 3.5months vs. 7.0months (p < 0.001), respectively. The patients with positive lipiodol deposition in PVTT had a longer OS than those with negative lipiodol deposition. Furthermore, the positive lipiodol deposition in PVTT can further differentiate HCC patients with favourable prognosis from SD patients. • Lipiodol deposition in PVTT is a prognostic indicator for HCC patients after TACE treatment. • Positive lipiodol deposition in PVTT is associated with a better prognosis.

Hepatocellular Carcinoma in β-Thalassemia Patients: Review of the Literature with Molecular Insight into Liver Carcinogenesis.

With the continuing progress in managing patients with thalassemia, especially in the setting of iron overload and iron chelation, the life span of these patients is increasing, while concomitantly increasing incidences of many diseases that were less likely to show when survival was rather limited. Hepatocellular carcinoma (HCC) is a major life-threatening cancer that is becoming more frequently identified in this population of patients. The two established risk factors for the development of HCC in thalassemia include iron overload and viral hepatitis with or without cirrhosis. Increased iron burden is becoming a major HCC risk factor in this patient population, especially in those in the older age group. As such, screening thalassemia patients using liver iron concentration (LIC) measurement by means of magnetic resonance imaging (MRI) and liver ultrasound is strongly recommended for the early detection of iron overload and for implementation of early iron chelation in an attempt to prevent organ-damaging iron overload and possibly HCC. There remain lacking data on HCC treatment outcomes in patients who have thalassemia. However, a personalized approach tailored to each patient’s comorbidities is essential to treatment success. Multicenter studies investigating the long-term outcomes of currently available therapeutic options in the thalassemia realm, in addition to novel HCC therapeutic targets, are needed to further improve the prognosis of these patients.

Nanomedicines reveal how PBOV1 promotes hepatocellular carcinoma for effective gene therapy

There exists an urgent medical demand at present to develop therapeutic strategies which can improve the treatment outcome of hepatocellular carcinoma (HCC). Here, we explore the biological functions and clinical significance of PBOV1 in HCC in order to push forward the diagnosis and treatment of HCC. Using theranostical nanomedicines, PBOV1 is verified to be a key oncogene which greatly promotes HCC proliferation, epithelial-to-mesenchymal transition, and stemness by activating the Wnt/β-catenin signaling pathway. Therefore, single-chain antibody for epidermal growth factor receptor (scAb-EGFR)-targeted nanomedicine effectively silencing the PBOV1 gene exhibits potent anticancer effects. In vivo HCC-targeting siRNA delivery mediated by the theranostical nanomedicine remarkably inhibits the tumor growth and metastasis. In addition, the superparamagnetic iron oxide nanocrystals (SPION)-encapsulated nanomedicines possess high MRI detection sensitivity, which endows them with the potential for MRI diagnosis of HCC. This study shows that PBOV1 represents a prognostic biomarker and therapeutic target for HCC.

Hepatocellular Carcinoma in a β-Thalassemia Intermedia Patient: Yet Another Case in the Expanding Epidemic

The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is increasing, the two well recognized HCC risk factors in thalassemia being iron overload and chronic hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, whereas chronic hepatitis leads to necroinflammation that can accelerate progression to HCC. We hereby report the case of a non transfused, hepatitis C-negative, β-thalassemia intermedia (β-TI) patient from our practice who had evidence of significant iron overload, suggesting the importance of increased iron burden as a HCC risk factor in this patient population. As such, screening thalassemia patients using magnetic resonance imaging (MRI)-based liver iron concentration (LIC) measurement and liver ultrasound is strongly recommended for early detection of iron overload and HCC, respectively. Data appears to be lacking on HCC treatment outcomes in patients who have thalassemia, but an approach tailored to each patient’s comorbidities is key to treatment success. The prognosis of these patients can be improved by multicenter studies investigating novel HCC therapeutic targets in the thalassemia realm.

Conformal external beam radiation or selective internal radiation therapy-a comparison of treatment outcomes for hepatocellular carcinoma.

Non-operative treatment for hepatocellular carcinoma (HCC) has expanded significantly with the use of selective internal radiotherapy (SIRT) mostly with yttrium 90 ((90)Y) tagged microspheres and highly conformal external beam radiation therapy such as stereotactic body radiotherapy (SBRT) to treat unresectable liver tumors for local tumor control. SBRT is a noninvasive procedure using external radiation source under image guidance, while SIRT delivers radioactive particles by transarterial radioembolization (TARE). However, the survival benefits of SBRT versus SIRT have never been compared. The aim of the present study is to compare the outcomes of overall and disease specific survival (DSS) using SIRT versus SBRT to treat HCC. The Surveillance, Epidemiology, and End Results (SEER) registry database [2004-2011] was queried for cases of unresectable HCC. Patients with missing data and those who received surgery were excluded from the study. A total of 189 patients with unresectable HCC were identified and used for statistical analysis, with 112 receiving SBRT and 77 receiving SIRT. Overall and disease-specific survival was compared using multivariable cox proportional hazard models. After adjusting for confounding factors (age at diagnosis, gender, race, grade, stage, AFP level and type of surgery), there were no significant difference in overall survival (OS) [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.49-1.07; P=0.1077] and DSS (HR, 0.70; 95% CI, 0.46-1.05; P=0.0880) for SIRT compared to SBRT. However, patients with elevated AFP level were associated with higher death risk (P=0.0459) and disease specific death risk (P=0.0233) than those with AFP within normal limits in both treatment groups. The retrospective analysis serves as the first comparison of SIRT to SBRT in treatment of unresectable HCC. Our findings suggest both treatment approaches result in similar outcomes in overall and disease-specific survival benefit. Future prospective randomized trials are needed to better evaluate and compare the two radiation modalities, as well as other non-operative therapies used in the treatment of HCC.

Intention-to-treat analysis of various treatment outcomes for hepatocellular carcinoma defined BCLC stage a with portal hypertension

Object: To compare the long-term outcomes of various treatment for HCC defined BCLC stage A with portal hypertension. Method: Between 2006 and 2014, 197 HCC patients defined BCLC stage A with portal hypertension were evaluated. For these patients, BCLC staging system recommended liver transplantation. But, actually performed treatment was various. In this study, for their first HCC treatment, liver transplantation (LT) was selected in 4 patients, surgical resection (SR) in 20 patients, RFA in 105 patients, and TACE in 68 patients. The primary end point of this study was recurrence-free survival (RFS) and the secondary end points were overall survival (OS). Result: The 5-year RFS rates for LT, SR, RFA, and TACE were 100%, 58.5%, 30.9%, and 31.1% (Fig 1). The 5-year OS rates for the 4 groups were 100%, 74.3%, 50.2%, and 53% (Fig 2). But, there was no statistical difference. However, there were statistical differences for RFS and OS between surgical treatment group (ST group, n = 24; LT and SR) and non-surgical treatment group (NST group, n = 173; RFA and TACE). The 5-year RFS rates for ST and NST groups were 65.1% and 31% (p = 0.048; fig 3). The 5-year OS rates for the 2 groups were 77.5% and 51.9% (p = 0.021; fig 4). Conclusion: Such as liver transplantation and surgical resection, surgical treatment may provide better survival and lower recurrence rates than non-surgical treatment for patients with HCC defined BCLC stage A with portal hypertension.