Hepatocellular carcinoma in sub-Saharan Africa - the way forward.

Michael Kew's academic career spans five decades, representing the most proliferative and pioneering years of the expanded knowledge on all aspects of hepatocellular cancer (HCC). The preceding articles in this Festschrift bear testimony to his legacy, engagement, enthusiasm, dedication and ability to inspire others. His enormous contribution, mostly originating from research in sub-Saharan Africa (SSA), contributed immensely to the knowledge and evidence on which current understanding of the disease is based.

Striking Racial/Ethnic Disparities in Liver Cancer Incidence Rates and Temporal Trends in California, 1988-2012.

Background: Hepatocellular carcinoma (HCC) is characterized by disparate risk patterns by race/ethnicity. We examined HCC incidence patterns and temporal trends among detailed racial/ethnic populations, including disaggregated Asian-American subgroups. Methods: Using data from the population-based California Cancer Registry, we identified 41 929 invasive HCC cases diagnosed during 1988-2012. Patients were grouped into mutually exclusive racial/ethnic groups of non-Hispanic (NH) white, NH black, Hispanic, and NH Asian/Pacific Islander (API), as well as Asian subgroups of Chinese, Filipino, Japanese, Korean, Vietnamese, Cambodian, Laotian, and South Asian. Age-adjusted and age-specific incidence rates by sex, race/ethnicity, and time period were calculated. The average annual percent change (AAPC) in incidence rates was estimated using joinpoint regression. All estimates were provided with the 95% confidence intervals (CIs). Results: Aggregated NH API had higher HCC risk than NH whites, NH blacks, and Hispanics. When disaggregated, Southeast Asians (Vietnamese, Cambodians, and Laotians) had overall HCC incidence rates eight to nine times higher than NH whites and more than twice that of other ethnic Asians. Statistically significant rising temporal trends of HCC were found in NH whites, NH blacks, and Hispanics, especially those older than age 50 years. Overall HCC risk declined in Chinese males (AAPC = -1.3%, 95% CI = -2.0 to -0.6), but rose in Filipino (AAPC = +1.2%, 95% CI = 0.3 to 2.1) and Japanese males (AAPC = +3.0%, 95% CI = 0.4 to 5.6) and Vietnamese (AAPC = +4.5%, 95% CI = 0.7 to 8.5) and Laotian (+3.4%, 95% CI = 0.1 to 6.8) females. Conclusions: Our findings provide valuable information for the identification of at-risk ethnic subgroups of Asian Americans while underscoring the importance of disaggregating ethnic populations in cancer research.

Estimation of the Incidence of Hepatocellular Carcinoma and Cholangiocarcinoma in Songkhla, Thailand, 1989-2013, Using Multiple Imputation Method.

PURPOSE: Histological specimens are not required for diagnosis of liver and bile duct (LBD) cancer, resulting in a high percentage of unknown histologies. We compared estimates of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) incidences by imputing these unknown histologies. MATERIALS AND METHODS: A retrospective study was conducted using data from the Songkhla Cancer Registry, southern Thailand, from 1989 to 2013. Multivariate imputation by chained equations (mice) was used in re-classification of the unknown histologies. Age-standardized rates (ASR) of HCC and CCA by sex were calculated and the trends were compared. RESULTS: Of 2,387 LBD cases, 61% had unknown histology. After imputation, the ASR of HCC in males during 1989 to 2007 increased from 4 to 10 per 100,000 and then decreased after 2007. The ASR of CCA increased from 2 to 5.5 per 100,000, and the ASR of HCC in females decreased from 1.5 in 2009 to 1.3 in 2013 and that of CCA increased from less than 1 to 1.9 per 100,000 by 2013. RESULTS: of complete case analysis showed somewhat similar, although less dramatic, trends. CONCLUSION: In Songkhla, the incidence of CCA appears to be stable after increasing for 20 years whereas the incidence of HCC is now declining. The decline in incidence of HCC among males since 2007 is probably due to implementation of the hepatitis B virus vaccine in the 1990s. The rise in incidence of CCA is a concern and highlights the need for case control studies to elucidate the risk factors.

The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years?

BACKGROUND & AIMS: There has been remarkable progress in the management of hepatocellular carcinoma (HCC) during the last several decades, but its effect on the prognosis of HCC patient needs clarification. We analysed the changes that affected prognosis of HCC patients diagnosed over two different eras. METHODS: A retrospective study of 1318 patients diagnosed with HCC from 1986 to 2012 was conducted. Analysis was done according to two cohorts, cohort 1 (patients diagnosed with HCC from 1986 to 1992) and cohort 2 (patients diagnosed from 2006 to 2012). RESULTS: Hepatitis B virus was the most common cause of liver disease for both cohorts (66.2% and 66.0%). The proportion of patients with Barcelona Clinic Liver Cancer stage 0/A was significantly lower in cohort 1 than in cohort 2 (14.4% vs. 39.5%, P < 0.001). The proportions of patients diagnosed during surveillance and general health check-up were significantly higher in cohort 2 than in cohort 1 (28.6% vs. 10.6% and 26.3% vs. 7.9%, respectively) while those diagnosed during symptomatic evaluation was significantly higher in cohort 1 than in cohort 2 (45.1 vs. 81.4%, P < 0.001). Surgical resection rate was similar between the two cohorts (26.1% vs 26%) while the transcatheter arterial chemoembolization rate which was the highest in cohort 1 (40.6%) was overtaken by radiofrequency ablation in cohort 2 (55%) at BCLC stage 0/A. Median survival duration in cohort 2 was significantly longer than cohort 1 (65.0 vs. 7.9 months, P < 0.001). CONCLUSIONS: Implementation of national cancer surveillance and the advancement of treatment modalities have likely led to early detection of HCC and improvements in prognosis over the last 20 years.

Novel functional magnetic resonance imaging biomarkers for assessing response to therapy in hepatocellular carcinoma

The established and adapted image biomarkers based on size for tumor burden measurement continue to be applied to hepatocellular carcinoma (HCC) as size measurement can easily be used in clinical practice. However, in the setting of novel targeted therapies and liver directed treatments, simple tumor anatomical changes can be less informative and usually appear later than biological changes. Functional magnetic resonance imaging (MRI) has a potential to be a promising technique for assessment of HCC response to therapy. In this review, we discuss various functional MRI biomarkers that play an increasingly important role in evaluation of HCC response after treatment (AU)

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[Regularity of drugs compatibility of anti-hepatoma traditional Chinese medicine ancient prescriptions and risk evaluation of anti-hepatoma new drug research and development].

Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.

Overview: Liver disease and transplantation.

Australia has had a proud and enviable record of seminal contributions to hepatology, with many contributors. Thus, any attempt to summarize these contributions ab initio in a brief review article is a significant challenge, primarily because it is so easy to overlook or underestimate particular aspects. In this article, I have confined my comments primarily to the areas where the contributions have had a significant global impact and have clearly been recognized internationally. This means that many worthwhile Australian additions will be omitted if there was less apparent international impact. The first significant interest in liver disease in Australia was from the Melbourne group at the Walter and Eliza Hall Institute (WEHI) and Royal Melbourne Hospital, leading to seminal contributions to the description, diagnosis, aetiopathogenesis and therapy of autoimmune hepatitis and primary biliary cirrhosis. Others from Royal Prince Alfred Hospital in Sydney contributed substantially to the effects of immunosuppression of autoimmune hepatitis and to early descriptions of primary sclerosing cholangitis. Other areas where Australians have contributed significantly include steatohepatitis, iron metabolism (and in particular hemochromatosis), viral hepatitis (both at the molecular and clinical level), portal hypertension, and transplant immunology. The remarkable contribution of Professor Dame Sheila Sherlock to Australian hepatology is also summarized.

[The role of radiofrequency ablation in the treatment of malignant tumors. Openings and limits]. / A rádiófrekvenciás ablatio helye a malignus daganatok kezelésében. Lehetoségek és korlátok.

This review paper will provide a comprehensive summary about the role radiofrequency ablation in the palliative treatment of primary and metastatic hepatic tumours. Since the recommendations undergo a continuous change, we hope that this paper will generate further multidisciplinary approach in the technique and helps to outline up-to-date guidelines.

[Liver surgery after the millennium]. / Májsebészet az ezredforduló után.

Since 1906 according to the invitation of the Hungarian Surgical Society mainly surgeons have had the honour to give the János Balassa memorial lecture. In accordance with the traditions the first part of the lecture is a commemoration at János Balassa and the second part deals with the work of the invited lecturer. This year the 84th memorial lecture was held. The speaker besides reviewing János Balassa's biographical data pointed out his outstanding characteristics. Balassa was not only the founder of the first surgical school but a prominent intellectual leader in his age. He summarised the two basic conceptions of his oeuvre in the lecture that he held after being appointed to the leader of the surgical department; to raise surgery from the level of bunglers and barbers to the up-to-date surgical standards. His other statement is valid even today: surgery is equivalent with internal medicine among the clinical sciences but he did not intended to split them up. In the second part of the lecture the speaker presented his own work in hepatic surgery. He highlighted the present concerns of the history of hepatic surgery. He summarised separately the change of approaches in the indications of primary and secondary hepatic tumours. He determined the R0 resection as the basic factor of hepatic surgery. In his lecture he reported the alterations and expectations of surgery in hepatocellular carcinoma and metastatic hepatic tumours. He pointed out the increasing radicality in this field. He reviewed the new surgical techniques that give better results. He emphasised the importance of bloodless surgery in his own experience with Baron knack and different hepatic parenchyma separating techniques. He mentioned the role of oncology in connection with hepatic surgery, especially the results of molecular biology. In his lecture it stood out that he holds the long-term survival the most important result of hepatic surgery but he mentioned several other prognostic factors. Finally he gave an overview about the potential future of hepatic surgery.