Hepatocellular carcinoma (HCC) is a global health problem, although developing countries are disproportionally affected: over 80% of HCCs occur in such regions. About three-quarters of HCCs are attributed to chronic HBV and HCV infections. In areas endemic for HCV and HBV, viral transmission occurs at an early age, and infected individuals develop HCC in mid-adulthood. As these are their most productive years of life, HCC accounts for a substantial burden on the health-care system and drain of productive capacity in the low-income and middle-income countries most affected by HCV and HBV infections. Environments with disparate resource levels require different strategies for the optimal management of HCC. In high-resource environments, guidelines from the American Association for the Study of Liver Diseases or European Association for the Study of the Liver should be applied. In intermediate-resource or low-resource environments, the fundamental focus should be on primary prevention of HCC, through universal HBV vaccination, taking appropriate precautions and antiviral treatments. In intermediate-resource and low-resource environments, the infrastructure and capacity for abdominal ultrasonography, percutaneous ethanol injection, radiofrequency ablation and surgical resection should be established. Programs to provide targeted therapy at low cost, similar to the approach used for HIV therapy in the developing world, should be pursued.

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Hepatocellular carcinoma: A global view.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.21933

Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?

Radiofrequency Ablation for Hepatocellular Carcinoma: 10-Year Outcome and Prognostic Factors

Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis.

Objective: To review the literature on current management of hepatocellular carcinoma (HCC). Background: Hepatocellular carcinoma represents one of the most common malignancies worldwide with a rising incidence in western countries. There have been substantial advances in the surgical and medical treatment of HCC within the past 2 decades. Methods: A literature review was performed in the MEDLINE database to identify studies on the management of HCC. On the basis of the available evidence recommendations for practice were graded using the Oxford Centre for Evidence-based Medicine classification. Results: Advances in surgical technique and perioperative care have established surgical resection and orthotopic liver transplantation (OLT) as primary curative therapy for HCC in noncirrhotic and cirrhotic patients, respectively. Primary resection and salvage OLT may be indicated in cirrhotics with preserved liver function. Selection criteria for OLT remain debated, as slight expansion of the Milan criteria may not worsen prognosis but is limited by organ shortage and prolonged waiting time with less favorable outcome on intention-to-treat analyses. Strategies of neoadjuvant treatment before OLT require evaluation within prospective trials. Transarterial chemoembolization is the primary therapy in patients with inoperable HCC and compensated liver function. Although systemic chemotherapy is not effective in patients with advanced HCC, there is recent evidence that these patients benefit from new molecular targeted therapies. If these agents are also effective in the neoadjuvant and adjuvant setting is currently being investigated. Furthermore, selective intra-arterial radiation therapy represents a promising new approach for treatment of unresectable HCC. Conclusions: Recent developments in the surgical and medical therapy have significantly improved outcome of patients with operable and advanced HCC. A multidisciplinary approach seems essential to further improve patients' prognosis.

Hepatocellular carcinoma: current management and perspectives for the future.

OBJECTIVE To compare the clinical results of surgical resection (SR) and percutaneous thermal ablation (PTA) for early-stage hepatocellular carcinoma (HCC) (single tumor nodule <or= 5 cm in diameter, or <or= 3 nodules with <or= 3 cm in diameter) METHODS One hundred and five patients with 114 HCC nodules were randomly allocated to SR (n = 54) and ultrasound-guided PTA with microwave or radiofrequency energy (n = 51) RESULTS The complete tumor elimination rates in SR and PTA groups were similar (100% vs 947%) and the local recurrence rates were both 0 There were no significant differences in distance recurrence rate (167% vs 275%, P = 0182) and time to the first recurrence (49 month vs 96 month, P = 0130) between the SR and PTA groups One, 2-, and 3-year disease-free survival rates were 824%, 824% and 824%, respectively, in SR group, whereas they were 785%, 615% and 513% in PTA group, respectively The difference between these two groups was statistically not significant (P = 0128) The overall survival rates in SR group were 913%, 864% and 864% at 1, 2, and 3 years, respectively, and those in PTA group were 935%, 871% and 871%, respectively There was no significant difference between these two groups (P = 0808) Compared with SR, PTA required less treatment time (27 min vs 145 min, P < 0005), less necessity for blood transfusion (0 patient vs 7 patients, P = 0013) and less hospital-stay (52 d vs 191, P < 0005) There was no significant difference in the rate of treatment-related complication between the two groups (111% for SR vs 78% for PTA, P = 0742) At day 7 and day 30 after treatment, the numbers of patient with physical status (WHO Performance Status grades) of grade 0 - 1 were 32 and 44 in PTA group, respectively, significantly more than 16 and 33 in SR group (P = 0001 and P = 0004, respectively) CONCLUSION Besides minimal invasiveness, easy to access and cost saving, PTA achieved equivalent local therapeutical effectiveness and 3-year survival outcomes as SR did, and may be considered as a one of the first-choice treatment modality for treatment of early-stage HCC

[Surgical resection versus percutaneous thermal ablation for early-stage hepatocellular carcinoma: a randomized clinical trial]

Tumor cells co-express vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) that interact each other to support a self-sustainable cell growth. So far, this autocrine VEGF loop is not reported in human intrahepatic cholangiocarcinoma (ICC). Apatinib is a highly selective VEGFR2 inhibitor, but its effects on ICC have not been investigated. In this study, we reported that VEGF and phosphorylated VEGFR2 were expressed at a significantly high level in ICC patient tissues (P<0.05). In vitro, treating ICC cell lines RBE and SSP25 with recombinant human VEGF (rhVEGF) induced phosphorylation of VEGFR1 (pVEGFR1) and VEGFR2 (pVEGFR2); however, only the VEGFR2 played a role in the anti-apoptotic cell growth through activating a PI3K-AKT-mTOR anti-apoptotic signaling pathway which generated more VEGF to enter this autocrine loop. Apatinib inhibited the anti-apoptosis induced by VEGF signaling, and promoted cell death in vitro. In addition, Apatinib treatment delayed xenograft tumor growth in vivo. In conclusion, the autocrine VEGF/VEGFR2 signaling promotes ICC cell survival. Apatinib inhibits anti-apoptotic cell growth through suppressing the autocrine VEGF signaling, supporting a potential role for using Apatinib in the treatment of ICC.

/pdf/apatinib-inhibits-vegf-signaling-and-promotes-apoptosis-in-3uref53a7e.pdf

Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma

Bile leakage after hepatectomy for hepatolithiasis: risk factors and management.

AIM: To evaluate the long-term outcome and surgical indications of hepaticojejunostomy (HJ) for the treatment of hepatolithiasis.

METHODS: Three hundred and fourteen elective cases with hepatolithiasis but without biliary stricture or cystic dilatation treated in the past 10 years were reviewed retrospectively. The patients were divided into HJ group and T tube drainage group according to biliary drainage procedure. Furthermore, four subgroups were subdivided by hepatectomy as a balance factor, group A1: hepatectomy+HJ; group A2: choledochoctomy+HJ; group B1: hepatectomy + choledochoctomy T tube drainage; group B2: choledochoctomy + T tube drainage. The stone residual rate, surgical efficacy and long-term outcome were compared among different procedures.

RESULTS: There was no surgical mortality among all patients. The total hospital mortality was 1.6%. The overall stone residual rate after surgical clearance was 25.9%. There was no statistical difference between HJ group and T tube drainage group in terms of stone residual rate after surgical clearance, however, after postoperative choledochoscopic lithotripsy, the total stone residual rate of T tube drainage group was significantly lower than that of HJ group (0.5% vs 16.7%, P < 0.01). Hepatectomy + choledochoctomy tube drainage achieved the optimal therapeutic effect, only 8.2% patients suffered from an attack of cholangitis postoperatively, which was significantly lower than that of hepatectomy + HJ (8.2% vs 22.0%, P = 0.034). The major reason for postoperative cholangitis was stone residual in the HJ group (16/23, 70.0%), and stone recurrence in the T tube drainage group (34/35, 97.1%). The operative times were significantly prolonged in those undergoing HJ, and the operative morbidity of HJ was higher than those of T tube drainage.

CONCLUSION: The treatment result of HJ for hepatolithiasis is not satisfactory in this retrospective study due to high rate of stone residual and postoperative cholangitis. HJ could not drain residual stone effectively. HJ may hinder post-operative choledochoscopic lithotripsy, which is the optimal management for postoperative residual stone. The indications of HJ for hepatolithiasis should be strictly selected.

Hepaticojejunostomy for hepatolithiasis: A critical appraisal

AIM: To evaluate the therapeutic efficacy of systemic chemoimmunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: Twenty-six patients with advanced HCC were treated by using systemic chemo-immunotherapy (PIAF regimen), which consisted of cisplatin (20 mg/m 2 ) intravenously daily for 4 consecutive day, doxorubicin (40 mg/m 2 ) intravenously on day 1, 5-fluorouracil (400 mg/m 2 ) intravenously daily for 4 consecutive day, and human recombinant α -interferon-2a (5 Mu/m 2 ) subcutaneous injection daily for 4 consecutive day. The treatment was repeated every 3 wk, with a maximum of six cycles. RESULTS: A total of 90 cycles of PIAF treatment were administered, with a mean number of 3.9 cycles per patient. Eight patients received six cycles of treatment (group A), and the remaining 18 were subjected to two to five cycles (group B). There were 0 complete response, 4 partial responses, 9 static diseases and 13 progressive diseases, with a disease control rate of 50% (13/26). The 1-year survival rate was 24.3%, with a median survival time of 6.0 mo. Group A had a remarkably better survival as compared with group B, the 1- and 2-year survival rates were 62.5% vs 6.1% and 32.3% vs 0%, and a median survival time was 12.5 mo vs 5.0 mo (P = 0.001). CONCLUSION: Systemic chemo-immunotherapy using PIAF regimen represented an effective treatment and could improve the survival rate and prolong the survival time in selected patients with advanced HCC.

Jiaming Lai

Papers

[Surgical resection versus percutaneous thermal ablation for early-stage hepatocellular carcinoma: a randomized clinical trial]

Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma

Bile leakage after hepatectomy for hepatolithiasis: risk factors and management.

Hepaticojejunostomy for hepatolithiasis: A critical appraisal

Systemic chemo-immunotherapy for advanced-stage hepatocellular carcinoma