Case Of Advanced Hepatocellular Carcinoma Research Articles

Regorafenib combined with a PD-1 inhibitor in the second-line setting for unresectable hepatocellular carcinoma in real-world practice.

Most advanced hepatocellular carcinoma (HCC) cases administered molecular targeted agents and/or anti-programmed cell death-1 (PD-1) inhibitors have no response or develop resistance. Moreover, second-line therapies still cannot provide beneficial clinical outcomes. A pilot study assessing combined regorafenib and PD-1 inhibitor as second-line treatment of advanced HCC reported promising effectiveness. The current single-center, retrospective, real-world study was carried out between January 2019 and July 2021. Advanced HCC cases were administered second-line regorafenib combined with a PD-1 inhibitor or regorafenib alone were assessed. Progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were determined. Totally 46 HCC cases were analyzed, most of whom underwent previous systemic treatment comprising targeted therapy and immunotherapy. Tumor response was evaluated in 25 and 21 individuals in the regorafenib + PD-1 inhibitor and regorafenib monotherapy groups, respectively: ORRs were 21.7% and 8.7%, and DCRs were 47.8% and 32.6%, respectively. Median PFS was markedly longer in the regorafenib plus PD-1 inhibitor group (11.5 months) compared with the regorafenib monotherapy group (5.1 months, P=0.049). This study suggested regorafenib and a PD-1 inhibitor in combination may provide significant clinical benefits in HCC cases showing progression following first-line treatment. Further analysis in real-world studies with large cohorts is warranted to confirm these findings.

Transarterial Chemoembolization Plus Sorafenib versus Transarterial Chemoembolization Alone for Advanced Hepatocellular Carcinoma: An Umbrella Review of Meta-Analyses and Systematic Reviews.

Sorafenib is the standard treatment for most cases of advanced hepatocellular carcinoma (HCC), based on Western and Eastern clinical guidelines. Thus, an increasing number of transarterial chemoembolization (TACE) plus sorafenib combination therapies have been used in clinical practice. In addition, several systematic reviews and meta-analyses have explored the efficacy and safety of the combination of TACE and sorafenib. Therefore, we performed an umbrella review to summarize and evaluate these evidence-based studies. PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to June 1, 2023. All meta-analyses that evaluated the effect of TACE plus sorafenib on HCC were considered eligible. The quality of the included meta-analyses was evaluated by AMSTAR2 (A Measurement Tool to Assess Systematic Reviews). The quality of evidence per association provided in the meta-analyses was rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). This study was registered with PROSPERO (Registration ID: CRD42023420417). We included 12 meta-analyses, including randomized clinical trials, cohort studies, and observational studies. A total of 44 associations with overall survival, survival rate, time to disease progression, overall response rate, disease control rate, and adverse events were evaluated in this umbrella review. The quality of most associations ranged from low to very low, indicating that flaws were significant in the current meta-analyses. This umbrella review identified beneficial associations between TACE and sorafenib combination therapy in advanced HCC. However, owing to the low certainty of the evidence, clinicians should interpret our results with caution when applying them in clinical practice, and high-quality studies are required in the future to confirm our results.

A Case of Advanced Hepatocellular Carcinoma with Bone Metastases Managed with Tyrosine Kinase Inhibitors and Aggressive Palliative Radiation Therapy: Role of Combination Therapy for Extending Survival

We report the case of a 68-year-old man with advanced hepatocellular carcinoma (HCC) with multiple bone metastases (BM) treated with tyrosine kinase inhibitors. Despite an insufficient disease control on BM with a progression free survival (PFS) of 6 months, sorafenib was not discontinued and multiple radiation therapy (RT) sessions with a palliative purpose were performed. Thanks to this aggressive radiotherapy approach in order to control the bone tumor burden, the patient has continued sorafenib for 34.6 months achieving an overall survival (OS) of 41.3 months. This result highlights the importance of a tailored management of patients with advanced HCC and the role of the RT for BM control, even if at lower cumulative radiation dose, for extending patient survival.

Bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced hepatocellular carcinoma: A retrospective study.

544 Background: The combination of bevacizumab and immune checkpoint inhibitors (ICI) has demonstrated promising efficacy and safety in the first-line treatment of advanced hepatocellular carcinoma (HCC). However, this combination has not been examined in patients with previous first-line treatment of ICI and tyrosine kinase inhibitor. This study aimed to investigate the effectiveness and safety of bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced HCC. Methods: The retrospective study included patients with advanced HCC who received combined therapy of bevacizumab and atezolizumab or sintilimab after failure of lenvatinib plus ICI between July 28, 2020 and March 7, 2022. Baseline patient characteristics were collected. Treatment response, overall response rate (ORR) and disease control rate (DCR) were evaluated according to response evaluation criteria in solid tumors (RECIST) version 1.1. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Treatment-related adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: A total of 20 patients with advanced HCC were included, with a median follow-up time of 11.05 (5.03-20.63) months. Eleven patients died by the last follow-up on August 12, 2022. There were 18 males (90%) and two females (10%). The average age was 59.9±12.08 years. Seven patients (35%) had distant metastasis, and nine (45%) had vascular invasion. Liver function was classified as Child-Pugh grade A in 17 patients (85%) and grade B in three (15%). Patients with Barcelona Clinic Liver Cancer (BCLC) stages B, C and D were 1 (5%), 16 (80%) and 3 (15%), respectively. Eighteen patients (90%) had previous topical therapy. Of all patients previously administered lenvatinib plus ICI as first-line treatment, 14 (70%) had PFS longer than three months. ORR and DCR were 15% (95% confidence interval [CI], 3.2-37.9) and 55% (95% CI, 31.5-76.9), respectively. Median OS was 8.00 months (95% CI, 0.00-16.66), while median PFS was 3.80 months (95% CI, 2.41-5.19). Adverse events were observed in 14 patients (70%). Adverse events of grade 3 or worse occurred in six patients (30%). Conclusions: The combination of bevacizumab with atezolizumab or sintilimab had tolerable safety profile but poor response in the second-line treatment of HCC. Despite the satisfying efficacy as first-line therapy, this combination is not a cost-effective recommendation for advanced HCC cases who failed the first-line treatment of lenvatinib plus ICI. [Table: see text]

Rare case of hepatocellular carcinoma metastasis to urinary bladder: A case report

BACKGROUNDHepatocellular carcinoma (HCC) is a primary liver cancer with high prevalence and mortality. There are many cases of advanced HCC at the time of diagnosis. Treatment methods and prognosis are different depends on whether metastasis is present. Thus, it is necessary to make an accurate evaluation at the time of diagnosis. Extrahepatic metastases of HCC usually occur through hematogenous spread or through adjacent organs such as the peritoneum. Metastasis to the urinary bladder alone is rare. Here, we report a rare case of biopsy-proven solitary metastasis of HCC to the bladder in a 60-year-old woman. CASE SUMMARYA 60-year-old female patient was found to be positive for hepatitis B surface antigen by chance after abdominal ultrasonography showed abnormal findings. Thus, liver dynamic computed tomography (CT) was performed. The patient visited the hospital for further examination. Ultrasound and CT showed 3.6 cm sized arterial enhancing mass in segment 5 and an infiltrative mass in segment 8. The patient was diagnosed with HCC through liver dynamic magnetic resonance imaging and liver biopsy. Afterwards, she underwent two transcatheter arterial chemoembolizations within five months for HCC. During follow-up, a newly appeared bladder tumor was found on liver dynamic CT. She underwent transurethral resection of the bladder tumor for diagnosis and treatment. The tissue was confirmed as metastatic HCC. CONCLUSIONAlthough rare, metastasis to urinary bladder from HCC can occur without evidence of other distant metastases. Thus, regular follow-up imaging examination and clinical attention are required.

Outcomes of reduction hepatectomy combined with postoperative multidisciplinary therapy for advanced hepatocellular carcinoma.

BACKGROUNDThe prognosis of advanced hepatocellular carcinoma (HCC) that is not indicated for curative hepatectomy remains poor, despite advances in the treatment of HCC, including the development of tyrosine kinase inhibitors (TKIs). The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy, including those of recently treated cases, should be investigated.AIMTo examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy.METHODSThirty cases of advanced HCC that were not indicated for curative hepatectomy, in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, were divided into postoperative complete remission (POCR) (+) and POCR (-) groups, depending on whether POCR of all evaluable lesions was achieved through postoperative treatment. The cases in the POCR (-) group were subdivided into POCR (-) TKI (+) and POCR (-) TKI (-) groups, depending on whether TKIs were administered postoperatively.RESULTSThe 5-year overall survival rate and mean survival time (MST) after reduction hepatectomy were 15.7% and 28.40 mo, respectively, for all cases; 37.5% and 56.55 mo, respectively, in the POCR (+) group; and 6.3% and 14.84 mo, respectively, in the POCR (-) group (P = 0.0041). Tumor size, major vascular invasion, and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival outcomes. The number of tumors in the remnant liver was the only factor that differed significantly between the POCR (+) and POCR (-) groups, and POCR was achieved significantly more frequently when ≤ 3 tumors remained in the remnant liver (P = 0.0025). The MST was 33.52 mo in the POCR (-) TKI (+) group, which was superior to the MST of 10.74 mo seen in the POCR (-) TKI (-) group (P = 0.0473).CONCLUSIONReduction hepatectomy combined with multidisciplinary postoperative treatment for unresectable advanced HCC that was not indicated for curative hepatectomy was effective when POCR was achieved via multidisciplinary postoperative therapy. To achieve POCR, reduction hepatectomy should aim to ensure that ≤ 3 tumors remain in the remnant liver. Even in cases in which POCR is not achieved, combined treatment with reduction hepatectomy and multidisciplinary therapy can improve survival outcomes when TKIs are administered.

Efficacy and tolerability of Sorafenib plus metronomic chemotherapy S-1 for advanced hepatocellular carcinoma in preclinical and clinical assessments

ObjectiveAlthough sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus sorafenib. MethodsAntitumor effects and toxicity of this combination were tested with HAK-1B xenograft and spontaneous HCC mouse models, and a prospective pilot study was performed to compare therapeutic effects and safety between sorafenib plus MC S-1 for 12 advanced HCC cases and the historical control of 363 sorafenib-treated advanced HCC patients at our hospital from July 2011 to June 2015. ResultsIn mice, the combination chemotherapy enhanced anti-angiogenic effects, resulting in a stronger tumor hypoxic environment and increased tumor cell apoptosis. Clinically, the objective response rate of the combination chemotherapy was higher than that of sorafenib mono therapy (16.7%; 2/12 vs 5.2%; 19/363, p < 0.05); however, there were no significant differences in overall survival and time to progression. Adverse events including alopecia, thrombocytopenia, and pancreatic enzymes elevation in the combination chemotherapy were higher than those of sorafenib. No patient treated with the combination chemotherapy discontinued treatment due to severe adverse events. ConclusionsSorafenib plus MC S-1 seems to be effective and tolerable for patients with advanced HCC and could be considered a treatment option for these patients.

A long-term survival case of advanced hepatocellular carcinoma treated with multidisciplinary therapies with progression to hepatic arterial infusion chemotherapy and hepatectomy

A long-term survival case of advanced hepatocellular carcinoma treated with multidisciplinary therapies with progression to hepatic arterial infusion chemotherapy and hepatectomy

Serum betatrophin and irisin levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) development is a complex process with well-known risk factors, however the role of betatrophin/angiopoietin-like protein 8 and irisin has been poorly investigated thus far. The aim of this study is to measure betatrophin and irisin serum levels in HCC, cirrhotic patients and controls, assess their relationship with cancer etiology and grade, metabolic abnormalities and liver dysfunction severity. Serum betatrophin and irisin concentrations were measured with commercially available ELISA kits in 69 cirrhotic patients with HCC, 24 patients with non-viral cirrhosis and 20 healthy volunteers. The severity of liver disfunction was assessed according to Child-Pugh (C-P) score, while HCC grade according to the Barcelona clinic liver cancer (BCLC) staging system. Serum betatrophin concentration was significantly higher (33.7 ± 13.4 versus 12.3 ± 2.0 ng/ml; P < 0.001), while serum irisin level significantly lower in HCC patients compared to controls (2.52 ± 1.14 versus 4.46 ± 1.34 μg/ml; P = 0.02). Betatrophin level was also significantly elevated among cirrhotic patients compared to healthy volunteers. More evident serum betatrophin increase was found in patients with viral disease (34.8 ± 12.9 versus 26.1 ± 13.8 ng/ml; P < 0.001). Serum irisin concentration was significantly decreased in more advanced HCC cases (stage A versus C according to BCLC: 3.4 ± 1.3 versus 1.89 ± 1.1 μg/ml; P = 0.02). Decline of serum irisin (A: 3.4 ± 1.2; B: 2.42 ± 0.8; C: 1.91 ± 1.19 μg/ml; P = 0.03) and up-regulation of serum betatrophin levels (A: 24.1 ± 13.8; B: 39.3 ± 11.4; C: 46.2 ± 9.4 ng/ml; P = 0.03) were observed in patients with more advanced cirrhosis according to C-P score. We concluded that betatrophin serum level increased in cirrhotic patients, compared to controls. Since there was no difference between cirrhotic patients with and without intercurrent HCC, we suppose it may have an influence on fibrosis development, however not hepatocarcinogensis. Irisin serum level decreased in HCC patients, especially with more advanced disease grade, and was inversely related to the severity of liver disfunction.

A case of advanced hepatocellular carcinoma with gallbladder invasion.

A case of advanced hepatocellular carcinoma with gallbladder invasion.

Inactivation of Transcriptional Repressor Capicua Confers Sorafenib Resistance in Human Hepatocellular Carcinoma.

Background & AimsSorafenib is a multireceptor tyrosine kinase inhibitor that can prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Although most HCC patients who receive sorafenib ultimately show disease progression, it still is unclear whether and how HCC cells acquire chemoresistance during sorafenib treatment in human beings.MethodsWe analyzed surgically resected HCC tissues from a patient who received sorafenib for prevention of HCC recurrence after surgery (Adjuvant Sorafenib for Hepatocellular Carcinoma after Resection or Ablation trial) and established patient-derived HCC cells. Whole-exome sequence analysis was performed to detect mutations in sorafenib-resistant clones. We examined 30 advanced HCC cases immunohistochemically and 140 HCC cases enrolled in the Adjuvant Sorafenib for Hepatocellular Carcinoma after Resection or Ablation trial using microarray analysis to evaluate the association of Capicua Transcriptional Repressor (CIC) status with sorafenib treatment response.ResultsWe found a CIC mutation in recurrent HCC specimens after sorafenib. CIC encodes Capicua, a general sensor of receptor tyrosine kinase signaling. HCC cells established from the recurrent tumor specimen showed chemoresistance to sorafenib in vitro and in vivo. Established sorafenib-resistant Huh1 and Huh7 cell lines showed reduced expression of Capicua without mutations. Immunohistochemical analysis showed that HCC patients with low Capicua expression showed poor overall survival. Microarray analysis showed that the CIC gene signature could predict the preventive effect of adjuvant sorafenib treatment on HCC recurrence. Intriguingly, although CIC knockdown induced sorafenib resistance in HCC cell lines, regorafenib suppressed growth of sorafenib-resistant, Capicua-inactivated HCC cells and inhibited extracellular signal-regulated kinase phosphorylation.ConclusionsEvaluation of Capicua status may be pivotal to predict response to sorafenib, and regorafenib treatment could be effective to treat HCC with functional Capicua impairment.

Liver Transplantation after Successful Downstaging with Hepatic Arterial Infusion Chemotherapy in a Patient with Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The majority of patients with HCC are diagnosed at advanced disease stages with vascular invasion, where curative approaches are often not feasible. Currently, sorafenib is the only available standard therapy for HCC with portal vein tumor thrombosis (PVTT). However, in many cases, sorafenib therapy fails to achieve satisfactory results in clinical practice. We present a case of advanced HCC with PVTT that was treated with hepatic arterial infusion chemotherapy (HAIC) followed by liver transplantation. Three cycles of HAIC treatment resulted in necrotic changes in most of the tumors, and PVTT was reduced to an extent at which liver transplantation was possible. Further studies are required to determine the treatment strategies for advanced HCC with PVTT that can improve prognosis. (J Liver Cancer 2019;19:64-68)

A case of advanced hepatocellular carcinoma treated successfully with Juzentaihoto

A case of advanced hepatocellular carcinoma treated successfully with Juzentaihoto

Potential Efficacy of Allergen Removed Rhus Verniciflua Stokes Extract to Maintain Progression-Free Survival of Patients With Advanced Hepatobiliary Cancer

Hepatobiliary cancers are among the leading causes of cancer-related deaths worldwide. Most of the early-stage, surgically resectable cases show recurrence, and when they do, the prognosis is dismal with limited available treatment options. Here, we report three patients with relapsed hepatobiliary cancers who presented relatively long progression-free survival with the administration of a natural product, allergen removed Rhus verniciflua Stokes (RVS) extract. After commencement of RVS extract, they were progression-free for over 56 months in one case of recurred cholangiocarcinoma, and for over 16 and 114 months respectively, in two cases of advanced hepatocellular carcinoma. These cases suggest that the RVS extract could be a potential alternative for advanced hepatobiliary cancer that has no other available treatment.

Clinical analysis of electroacupuncture and multiple acupoint stimulation in relieving cancer pain in patients with advanced hepatocellular carcinoma.

The objective of this study is to investigate the clinical efficacy and safety of electroacupuncture and multiple acupoint stimulation in relieving cancer pain in patients with advanced hepatocellular carcinoma. Sixty-five cases of advanced hepatocellular carcinoma with cancer pain were selected in our hospital and were divided into electroacupuncture multiple acupoint stimulation group (electroacupuncture group) (n = 32) and fentanyl transdermal patch analgesia group (control group) (n = 33) according to analgesic methods and intentions. In the electroacupuncture group, electric acupuncture treatment was administered at different acupoints, including Baihui, Quchi, Neiguan, Xuehai, Zusanli, and Sanyinjiao acupoint, once a day for 7 days. In the control group, a fentanyl transdermal patch was placed on the upper left arm every 3 days and replaced with a continuous external paste once for 7 days. Pain scores in the two groups before and during the treatment were evaluated with a visual analog scale (VAS), and adverse reactions during the treatment were recorded. The VAS pain score of the electroacupuncture group was significantly decreased on day 3 (P < 0.05), but the pain scores were not significantly different (P > 0.05) between the two groups 4 days after treatment. For treatment-related side effects, there were 3 cases of subcutaneous hemorrhage in the electroacupuncture group; 1 case of skin rashes and 3 cases of nausea and vomiting in the control group. The incidences of adverse reactions in the two groups were 9.4% and 12.1%, respectively, without significant difference (P > 0.05). Cancer pain in patients with advanced hepatocellular carcinoma can be alleviated with electroacupuncture and multiple acupoint stimulation, but the onset pain relief was slow. To improve the analgesic effects of this technique, the combination of various analgesic methods should be necessary in early stage of the treatment.

The value of 64-slice spiral CT perfusion imaging in the treatment of liver cancer with argon-helium cryoablation.

We analyzed the effectiveness of using 64-slice spiral computed tomography (CT) and perfusion imaging to guide argon-helium cryoablation treatment of liver cancer. In total, 60 cases of advanced hepatocellular carcinoma before surgery treated with argon-helium cryoablation were inlcuded in the present study. Retrospective summary of the 60 cases of metaphase and advanced liver cancer were used as the control group. The control group were treated using cryoablation with argon-helium knife. We used enhanced scanning with 64-slice spiral CT to define the extent of their lesions and prepared a plan of percutaneous cryoablation for the treatment. Intraoperatively, we used the dynamics of CT perfusion imaging to observe the frozen ablation range and decreased the rate of complications. After surgery, the patients were followed-up regularly by 64-slice CT. We used conventional X-ray, CT and magnetic resonance imaging (MRI) for pre-operative lateralization. Intraoperative X-ray or ultrasound guidance and follow-up with CT or MTI were added to determine the clinical effectiveness and prognosis. The results showed that the total effective rate was improved significantly and incidence rate of overall complications decreased markedly in the observation group. Following treatment, AFP decreased significantly while the total freezing area and time were reduced significantly. The median survival time was increased significantly in the observation group. The numeric values of hepatic arterial perfusion, portal vein perfusion and hepatic arterial perfusion index were all markedly lowered after treatment. Differences were statistically significant (P<0.05). In conclusion, the use of 64-slice spiral CT perfusion imaging may considerably improve the effects of liver cancer treatment using the argon-helium cryoablation. It extended the survival time and reduced complications.

Polymyositis Associated with Advanced Hepatocellular Carcinoma

Background: Polymyositis associated with alcoholic cirrhosis and hepatocellular carcinoma (HCC) is very rare. We report a case of advanced HCC in alcoholic cirrhosis that presented with proximal muscle weakness. Methods: A 57 year old male had a 8 week history of gradually progressive proximal muscle weakness, manifesting as I nability to stand, gradual hoarseness of voice and difficulty in swallowing. He lost 15 kgs of weight. On examination, there was bilateral symmetrical weakness in both proximal muscles of upper and lower limbs - grade 2 / 5 strength. There was involvement of neck extensors and flexors. Deep Tendon reflexes were absent and peripheral sensation was normal. He had firm hepatomegaly. Subsequently, the patient was put on non invasive ventilatory support for respiratory muscle weakness. His aspartate aminotransferase was 1218 (0 to 40) IU/L, alanine aminotransferase 776 (30 to 129) IU/L, total bilirubin 3.42 (0.0 to 1.2) mg/dL, alkaline phosphatase 300 (30-129) U/L, prothrombin international normalized ratio 1.48. His creatine phosphokinase was 6,963 (0 to 190) IU/L. His viral profiles were negative for HBV, HIV and HCV. Autoantibodies - anti-dsDNA, anti-Jo-1, anti-neutrophilic cytoplasmic antibody, anti-RNP, anti-SSA, and anti-SSB were negative. Abdominal triphasic computed tomography showed irregular liver and nodular outline, with heterogeneous arterial-enhancing, washout in venous phase, in segment VII and VIII ( Figure 1). A non enhancing hypodense lesion was seen in caudate lobe (Figure 2). AFP levels were markedly raised to the level 7511 (0 to 9.0 ) IU/ml. EMG revealed increased insertional activity, frequent fibrillations, myotonic discharges and reduced recruitment.Figure 1Figure 2Figure 3Discussion: Diagnosis of Polymyositis as a paraneoplastic manifestation of HCC BCLC stage C was made. Only 4 cases of Polymyositis associated with HCC are reported. A possible pathogenetic mechanism is that an autoimmune process triggered by the tumor leads to clonally expanded CD8 cytotoxic T-cells. These invade muscle fibers and express major histocompatibility complex class 1 antigen and release cytokines, causing muscle inflammation. Figure Legends Figure A: Liver shows heterogenous attenuation with arterial enhancement of the space occupying lesion in segment VII and VIII. Figure B: Liver shows contrast washout in the venous phase, of the space occupying lesion in segment VII and VIII.

소라페닙 및 방사선 병합 치료 후 좋은 반응을 보인 간문맥 침윤을 동반한 진행성 간세포암종 1예

소라페닙 및 방사선 병합 치료 후 좋은 반응을 보인 간문맥 침윤을 동반한 진행성 간세포암종 1예

Emerging roles of FGF signaling in hepatocellular carcinoma.

Liver cancer is the fifth most common malignance in the world. It has been known that 90% of liver cancers are hepatocellular carcinoma (HCC). It is estimated that more than 740,000 new cases of HCC were diagnosed and approximately 700,000 deaths were occurred worldwide. In the USA, 35,660 people will be diagnosed with HCC and 24,550 patients will die from HCC in year 2015. In China, more than 400,000 new cases will be developed and 370,000 patients will die due to this deadly disease. Although surgical resection and liver transplantation have been improved, the 5-year survival rate has no significant decrease in part due to the fact that most patients are in the late stage at diagnosis. Additionally, many HCC patients exhibit low sensitivity to standard radiotherapy and chemotherapy. For example, sorafenib is the standard drug for the treatment of advanced HCC cases; however, the median overall survival of these HCC patients is still less than 1 year partly due to drug resistance. Therefore, it is pivotal to discover the new therapeutic drugs for the treatment of HCC patients. Emerging evidence has suggested that hepatitis C virus (HCV) and hepatitis B virus (HBV) infection are important risk factors for the incidence of HCC. In addition, obesity, diabetes and nonalcoholic steatohepatitis have been found to contribute to HCC incidence. Without a doubt, the presence of cirrhosis is the overriding risk factor for HCC. In recent years, several lines of evidence has defined that some genes and cellular signaling pathways play a key role in the development and progression of HCC, including Notch, PI3K (phosphatidylinositol 3-Kinase)/Akt, extracellularregulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), Hedeghog, and Wnt pathways. Moreover, some growth factor signaling pathways such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) have also been emerged as critical players in tumorigenesis including liver carcinogenesis. Among some of these pathways, FGF has recently gained high attention in HCC development and progression. Therefore, in this article, we will briefly describe recent advances in the physiological function and molecular mechanism of FGF in HCC. We also present the current chemical inhibitors of FGF/FGFR and natural agents that inactivate FGF signaling pathway. Lastly, we will discuss whether FGF/FGFR could be the prognostic markers and/ or potential targets for the treatment of HCC patients.

A case of advanced hepatocellular carcinoma cured with antiviral therapy and sorafenib

A case of advanced hepatocellular carcinoma cured with antiviral therapy and sorafenib