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.

A Glance at Aflatoxin Research in Mozambique.

In Mozambique, aflatoxin research started in the 1960's and has been carried through apparently unrelated efforts according to opportunities. However, they can be grouped in two sets: early epidemiological studies and recent agricultural research. Early investigators found a strong correlation between aflatoxin contamination and primary liver cancer. Since then, there have been efforts to examine the extent of contamination, especially in groundnuts and maize. More recent investigations and interventions aimed mostly to reduce the level of contamination, enough to allow such commodities to gain acceptance in the international market. The current status of knowledge is still marginal but the increasing involvement of local authorities, academia, and international organizations seems promising.

Frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from gastric cancer: A SEER-based study.

The hematogenous metastatic pattern of gastric cancer (GC) was not fully explored. Here we analyzed the frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from GC patients. Data queried for this analysis included GC patients from the Surveillance, Epidemiology, and End Results Program database from 2010 to 2014. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). All statistical tests were two-sided. Totally, there were 19 022 eligible patients for analysis. At the time of diagnosis, there were 7792 patients at stage IV, including 3218 (41.30%) patients with liver metastasis, 1126 (14.45%) with lung metastasis, 966 (12.40%) with bone metastasis and 151 (1.94%) with brain metastasis. GC patients with lung or liver metastasis have a higher risk of bone and brain metastasis than those without lung nor liver metastasis. Intestinal subtype had significantly higher rate of liver and lung metastasis, while diffuse type was more likely to have bone metastasis. Proximal stomach had significantly higher risk to develop metastasis than distal stomach. African-Americans had the highest risk of liver metastasis and Caucasian had the highest prone to develop lung and brain metastasis. The median survival for patients with liver, lung, bone, and brain metastasis was 4 months, 3 months, 4 months and 3 months, respectively. It is important to evaluate the status of bone and brain metastasis in GC patients with lung or liver metastasis. Knowledge of metastatic patterns is helpful for clinicians to design personalized pretreatment imaging evaluation for GC patients.

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.

Aretaeus of Cappadocia (ca 1st-3rd century AD): views on hepatic cancer.

Aretaeus lived in an era when cancer was known to be a fatal disease. He had understood both liver's capacity to regenerate, and its vital role for the body's homeostasis, and proposed the treatment to confront hepatic cancer. Although human's anatomy was well studied, especially in the Alexandrian School, and a plethora of surgical instruments and techniques were available, he had suggested a more holistic-palliative approach for hepatic cancer by applying a suitable dietetic regime, pain killers and psychological support.

[Retention of contrast media in the history of radiology : Sequelae of the former use of thorotrast and new challenges]. / Kontrastmittelretention in der Geschichte der Radiologie : Folgen der früheren Thorotrastanwendungen und neue Herausforderungen.

Detection of gadolinium deposits in patients who have repeatedly been administered intravenous gadolinium chelates have given rise to concern regarding the long-term safety of magnetic resonance imaging (MRI) contrast media. Nevertheless, negative long-term clinical effects have not yet been observed. In some publications parallels have been drawn to the sequelae of thorotrast that was formerly used for arterial angiography. In this article the history of thorotrast use is briefly described and in particular why, despite warnings, this substance was used frequently and worldwide. A brief summary of the results of the German Thorotrast Study revealed that high excess rates were only observed for primary malignant liver tumors after a 15-year or longer latency period and to a lesser degree of leukemias, as well as for severe local complications due to paravascular injections, particularly in the neck region. Based on this historical review, we will venture to take stock of the outcome from the "success story" of this contrast agent.

Time trend analysis of primary liver cancer incidence in Sihui county of Guangdong Province, China (1987-2011).

BACKGROUND: Southern China is an endemic area for primary liver cancer (PLC), but it is unclear if rates have changed in recent decades. We evaluated PLC incidence and estimated the effects of age, period of diagnosis, and birth cohort in Sihui City, Guangdong Province, China. METHODS: Age-standardized rates (ASRs) of PLC were examined for both males and females from 1987 to 2011. Joinpoint regression analysis was conducted to estimate the annual percent changes in PLC incidence. The age-period-cohort (APC) model was used to investigate the effects of age, diagnosis period, and birth cohort on the relative risk (RR) of PLC. RESULTS: A total of 2988 PLC cases were identified in this period, with average ASRs of 51.1/100,000 for males and 11.7/100,000 for females. Joinpoint regression analysis revealed increasing PLC incidence throughout the entire period in both males (average annual change of 1.65 %) and females (0.20 %). RRs increased gradually in both sexes from the youngest age group (30-34 years) to the oldest (80-84 years). In males, the RR decreased during diagnosis period from 1987-1991 to 1997-2001 and remained stable thereafter. In females, RRs fluctuated with diagnosis period throughout the entire period. Incidence tended to increase with birth cohort from 1905-1909 to 1975-1979 in both males and females; however, female incidence plateaued in the youngest cohorts born between 1955 and 1974, while incidence in males increased sharply in the cohorts born between 1965 and 1974. According to APC analysis, the full age-period-cohort (APC) model fit the data best, and the period-cohort (PC) model would be enough to explain variability of rates in females. CONCLUSION: The PLC incidence rate in males of Sihui City has increased more significantly than female over the last 25 years. Despite the age effect in male, this trend mainly reflects the effects of risk factors that are present in early life (birth cohort) and period change in both genders.

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.

International trends in primary liver cancer incidence from 1973 to 2007.

BACKGROUND: Primary liver cancer (PLC) is a common cancer worldwide, especially in developing countries. Several previous studies using different datasets have summarized PLC incidence rates and trends in different populations. However, with changes in exposure to risk factors and the implementation of preventive measures, the epidemiology of PLC worldwide may have changed. METHODS: We extended the analyses using the latest data from Cancer Incidence in Five Continents over the 35-year period 1973-2007 from 24 populations in Americas, Asia, Europe and Oceania using Joinpoint regression analysis. We examined age-standardized rates (ASRs) of PLC by histologic subtypes for both males and females in 24 populations during the period 2003-2007. RESULTS: We found that during the period 2003-2007, the highest ASRs for PLC were observed in some Asian populations, ranging from 19.0 to 26.7 per 100,000 in males and 4.8 to 8.7 per 100,000 in females. The international trends between 1973 and 2007 showed that ASRs for PLC were declining in several Asian populations. In contrast, ASRs for PLC were increasing in some European, American and Oceanian populations. CONCLUSIONS: Although the reasons were not fully clear for these trends, public health measures in Asian populations and HCV transmission in European, American and Oceanian populations were likely to have contributed to these patterns. Meanwhile, other possible risk factors such as the consumption of alcohol, obesity, and nonalcoholic fatty liver disease should also be concerned for the burden of PLC.

Discovery of why acute lymphoblastic leukaemia cells are killed by asparaginase: Adventures of a young post-doctoral student, Bertha K Madras.

A surprising finding was made by JG Kidd (1909-1991) that guinea pig serum could make tumours disappear in mice. A later finding made by JD Broome (1939-) showed that asparaginase could suppress or kill tumour cells. However, the major mystery was why were only tumour cells but not normal cells affected by the asparaginase? The biology underlying this mechanism was unravelled by a young post-doctoral student, Bertha K Madras (1942-) who hypothesized that cells with low asparagine synthetase are those that die following treatment with asparaginase. To test her theory, Madras developed an assay for asparagine synthetase. The hypothesis was supported by the results that cells with normal asparagine synthetase were protected, while cells with low levels of this enzyme were killed by asparaginase. The findings provide a clinical guide for the use of asparaginase in acute lymphoblastic leukaemia in children and adults.

[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.