Is laparoscopic hepatectomy superior to open hepatectomy for hepatocellular carcinoma?

The low perioperative morbidity and shorter hospital stay associated with laparoscopic hepatectomy have made it an often-used option at many liver centers, despite the fact that many patients with hepatocellular carcinoma have cirrhosis, which makes the procedure more difficult and dangerous. Type of surgical procedure proves not to be a primary risk factor for poor outcomes after hepatic resection for hepatocellular carcinoma, the available evidence clearly shows that laparoscopic hepatectomy is an effective alternative to the open procedure for patients with early-stage hepatocellular carcinoma, even in the presence of cirrhosis. Whether the same is true for patients with intermediate or advanced disease is less clear, since laparoscopic major hepatectomy remains a technically demanding procedure.     

A case of atypical caudate lobe hemangioma mimicking hepatocellular carcinoma:CT and angiographic manifestations

We report a case of caudate lobe hemangioma with an atypical CT enhancement pattern.In the present case, hemangioma exhibited a very subtle discontinuous peripheral rim enhancement at the post-enhanced arterial phase,and the peripheral enhanced zone had a moderately increased enhancement degree and with widened enhancement thickness during the portal-phase and delayed-phase.The stow enhancement rate for this caudate lobe hemangioma was due to sluggish perfusion by the small feeding arteries of caudate lobe branches as demonstrated by angiography.     

A case of atypical caudate lobe hemangioma mimicking hepatocellular carcinoma： CT and angiographic manifestations

We report a case of caudate lobe hemangioma with an atypical CT enhancement pattern. In the present case, hemangioma exhibited a very subtle discontinuous peripheral rim enhancement at the post-enhanced arterial phase, and the peripheral enhanced zone had a moderately increased enhancement degree and with widened enhancement thickness during the portal-phase and delayed-phase. The slow enhancement rate for this caudate lobe hemangioma was due to sluggish perfusion by the small feeding arteries of caudate lobe branches as demonstrated by angiography.     

Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease(CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma.     

CD40 in hepatocellular carcinoma: relevant or not?

The expression of the CD40 receptor in different tumours suggests that it might be involved in tumour development and proliferation. In this article, we discuss recent findings on CD40 expression in hepatocellular carcinoma, its possible biological role for tumour development, and different experimental therapeutic strategies such as gene therapy and immunotherapy protocols.     

Effectiveness of α-fetoprotein for hepatocellular carcinoma surveillance: the return of the living-dead?

Evaluation of: Singal AG, Conjeevaram HS, Volk ML et al. Effectiveness of hepatocellular surveillance in patients with cirrhosis. Cancer Epidemiol. Biomarkers Prev. 21(5), 793–799 (2012).

The evaluated article assesses the effectiveness in clinical practice of surveillance with ultrasound (US) and α-fetoprotein (AFP) in patients at risk of developing hepatocellular carcinoma. After a median follow-up of 3.5 years, among the 442 enrolled patients with cirrhosis, 41 developed tumor (annual incidence, 2.8%). Twenty-three hepatocellular carcinomas were diagnosed at Barcelona Clinic Liver Cancer early stage (single tumor <5?cm or ≤3 tumors each <3?cm). Two hundred and seventy one patients (61.3%) underwent ‘consistent’ (US done at least annually) surveillance, whereas 107 (24.2%) and 64 (14.5%) patients underwent ‘inconsistent’ and ‘no surveillance’, respectively. The per-patient sensitivity was 43.9% for US (58.1% excluding cases where US was inconsistently performed) and 65.9% for AFP >20?ng/ml. Specificity was 91.5% for US and 90.5% for AFP. The combination of the tests increased the sensitivity to 90.2%, with a small decrease in specificity (83.3%). In a real-world setting, the combination of US and AFP would be the most effective for hepatocellular carcinoma surveillance.     

Recommendations for the use of chemoembolization in patients with hepatocellular carcinoma: Usefulness of scoring system?

Several hepatocellular carcinoma (HCC) staging systems have been established, and a variety of country-specific treatment strategies are also proposed. The barcelona - clinic liver cancer (BCLC) system is the most widely used in Europe. The Hong Kong liver Cancer is a new prognostic staging system; it might become the reference system in Asia. Transarterial chemoembolization (TACE) is the most widely used treatment for HCC worldwide; but it showed a benefit only for intermediate stage HCC (BCLC B), and there is still no consensus concerning treatment methods and treatment strategies. In view of the highly diverse nature of HCC and practices, a scoring system designed to assist with decision making before the first TACE is performed or prior to repeating the procedure would be highly useful.     

Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?

BACKGROUND: The clinical usefulness of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable. OBJECTIVES: To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype. METHODS: A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor-nodes-metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity. RESULTS: Patients were divided into three AFP groups: normal (<20 ng/mL) [46%], elevated (21-400 ng/mL) [36%], and diagnostic (>400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (p= 0.0056), pain (p= 0.0025), Child-Pugh score (p= 0.001), tumor size, Okuda's and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1-4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001). CONCLUSION: The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.     

Biomarkers for hepatocellular carcinoma: What's new on the horizon?

Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.