Immunohistochemical expression of mismatch repair genes:A screening tool for predicting mutator phenotype in liver fluke infection-associated intrahepatic cholangiocarcinoma

AIM： To clarify possible contributions of DNA mismatch repair （MMR） system in carcinogenesis of liver fluke infection-associated intrahepatic cholangiocarcinoma （ICC） by using immunohistochemical assay. METHODS： A total of 29 ICC samples, which had been assessed for genomic instability by a PCR-based method, were used for study. They were examined immunohistochemically to demonstrate protein expression of two MMR genes, hMSH2 and hMLH1. Results obtained were compared with their mutator phenotype assessed previously. RESULTS： Either hMSH2 or hMLH1 protein was obviously expressed in 28 of 29 （96.6%） ICC samples. Positive nuclear localization of hMSH2 or hMLH1 protein was observed in 86.2% （25/29） or 93.1% （27/29） ICC cases, respectively, while their negative nuclear reactivity was only detected in 13.8% （4/29） or 6.9% （2/29） ICC cases analyzed, respectively. CONCLUSION： Our study, probably for the first time, showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associatedcholangiocarcinogenesis. These results confirm previous findings on mutational status of these genes assessed through a PCR-based method. The immunohistochemical analysis has proven to be an effective and sensitive approach for screening MMR deficiency regardless of somatic inactivation or promoter hypermethylation of hMSH2 and/or hMLH1 gene. Furthermore, immunohistochemistry is more advantageous compared to mutator phenotyping assay in terms of simplicity, less time consuming and cost effectiveness for screening possible involvements of target MMR genes in tumorigenesis.

Examining ecosystem(dis-)services on liver fluke infection in rural Northeast Thailand

Background The direct reliance of humans on and their interactions with freshwater ecosystems in the Lower Mekong Basin have given rise to parasitic infections,which is particularly prevalent in Northeast Thailand where raw fish consumption is practiced.This study examined the interactions between environments,ecosystem(dis-)services,human raw fish consumption habits,and raw fish dish sharing on liver fluke infection risk.Method Water fecal contents and the first intermediate snail host were sampled between June and September of 2019.One hundred twenty questionnaires were surveyed in two villages of different environmental surroundings,one next to a river and the other located inland,in Northeast Thailand.Multivariate regression analyses using linear mixed effect models assessed the influence of social,behavioral and perceptual factors on raw fish consumption frequency,willingness to avoid consumption and liver fluke infection status.Social network analysis compared the degree of raw fish dish sharing between the villages and assessed the probable influence of connections to fish procurement locations and sharing activities on liver fluke infection risk.Results High abundance of the first intermediate snail host and presence of fecal contamination in water could endanger both villages to ecosystem disservices of parasitic transmission.The river-side village relied more on provisioning ecosystem services than the inland village(29.7%vs.16.1%of villages)to consume raw fish as their main source of protein.Males in both villages(64.5 and 40.4 days/year for the respective villages)are also likely to consume koi pla and pla som,higher risk fish dishes,more frequently than females(4.1 and 4.3 days/year for the respective villages).The consumption habits of both villages were driven mostly by deriving cultural ecosystem services.Participation in raw fish dish sharing activities significantly reduced the odds of an individual being willing to avoid the consumption(Odds ratio=0.19).Network analysis suggested that river-side villagers had a more direct raw fish dish sharing interaction and they procured fish from multiple locations;these characteristics might potentially account for more liver fluke infected households in the village.Conclusion Villagers’raw fish consumption is driven by deriving cultural ecosystem services,and the geographic settings of the villages potentially affect villagers’fish procurement locations and infection risk.The findings underscore the linkages between villagers and their surrounding ecosystem environments as pertinent determinants for foodborne parasitic disease risk.

Characteristics and outcomes of cholangiocarcinoma by region in Thailand: A nationwide study

AIM To identify the potential risk factors of cholangiocarcinoma, we determined the characteristics of cholangiocarcinoma patients among 5 different regions of Thailand. METHODS All patients diagnosed with cholangiocarcinoma between 2008 and 2013 were identified using the Nationwide Hospital Admission Data registry(n = 39421). Baseline characteristics, comorbidities and survival were abstracted. RESULTS The annual incidence during the study period was stable in all regions. Most patients lived in the Northeast(62.8%), followed by the North(16.9%), Central(12.3%), Bangkok(5.4%), and South(n = 2.6%) regions(P < 0.0001). Significantly more cholangiocarcinoma patients had diabetes, cirrhosis, and chronic viral hepatitis B/C infection than noncholangiocarcinoma participants(diabetes: 11.42% vs 5.28%; cirrhosis: 4.81% vs 0.92%; hepatitis B: 0.74% vs 0.12%; and hepatitis C: 0.50% vs 0.10%, P < 0.0001 for all, respectively). The overall 1-year mortality rate was 81.7%, with a stable trend over time. CONCLUSION Diabetes and chronic liver diseases may be associated with cholangiocarcinoma in the Thai population.