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Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Engineered versions of adeno-associated virus (AAV) are commonly used in gene therapy but evidence revealing a potential oncogenic role of natural AAV in hepatocellular carcinoma (HCC) has raised concerns. The frequency of potentially oncogenic integrations has been reported in only a few populations. AAV infection and host genome integration in another type of liver cancer, cholangiocarcinoma (CCA), has been studied only in one cohort. All reported oncogenic AAV integrations in HCC come from strains resembling the fully sequenced AAV2 and partly sequenced AAV13. When AAV integration occurs, only a fragment of the AAV genome is detectable in later DNA or RNA sequencing. The integrated fragment is typically from the 3' end of the AAV genome, and this positional bias has been only partly explained. Three research groups searched for evidence of AAV integration in HCC RNAseq samples in the Cancer Genome Atlas (TCGA) but reported conflicting results. Results: We collected and analyzed whole transcriptome and viral capture DNA sequencing in paired tumor and non-tumor samples from two liver cancer Asian cohorts from Thailand (N = 147, 47 HCC and 100 intrahepatic cholangiocarcinoma (iCCA)) and Mongolia (N = 70, all HCC). We found only one HCC patient with a potentially oncogenic integration of AAV, in contrast to higher frequency reported in European patients. There were no oncogenic AAV integrations in iCCA patients. AAV genomic segments are present preferentially in the non-tumor samples of Thai patients. By analyzing the AAV genome positions of oncogenic and non-oncogenic integrated fragments, we found that almost all the putative oncogenic integrations overlap the X gene, which is present and functional only in the strain AAV2 among all fully sequenced strains. This gene content difference could explain why putative oncogenic integrations from other AAV strains have not been reported. We resolved the discrepancies in previous analyses of AAV presence in TCGA HCC samples and extended it to CCA. There are 12 TCGA samples with an AAV segment and none are in Asian patients. AAV segments are present in preferentially in TCGA non-tumor samples, like what we observed in the Thai patients. Conclusions: Our findings suggest a minimal AAV risk of hepatocarcinogenesis in Asian liver cancer patients. The partial genome presence and positional bias of AAV integrations into the human genome has complicated analysis of possible roles of AAV in liver cancer. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine the burden of intrahepatic cholangiocarcinoma (ICC) in Thailand and identify the prognostic factors for all-causes of death.Methods: We conducted a population-based study of ICC patients admitted during 2009-2013 using the Nationwide Hospital Admission Database, the National Health Security Office (NHSO). There was an average of 1,051,146 patients/year with diagnosis of gastrointestinal diseases (GI). All patients with a diagnosis of ICC (ICD10- C221) were included from a total of 72,479 admissions from 858 hospitals. The surgical resection procedures such as the radical pancreaticoduodenectomy, subtotal and partial hepatectomy were analyzed. Data for all patients were censored 1 year post-study or death, whichever came first.Results: A total of 34,325 patients with ICC during a 5-year study period (on average, 6865 patients/year, with the incidence rate of 14.6 per 100,000 population, per year. The ICC patients had a mean age of 63.8+/-11.6 years and 63% were males. The mean length of hospital stay was 6.4+/-7.3 days with a mean+/-SD cost of hospitalization of $595+/-$1160 USD per admission. There were 659 patients (1.9%) underwent surgical resection. The overall survival of ICC patients with surgery was significantly better than those patients without surgery. Hazard ratio of death for patients without surgery was 2.5 (95% CI of 2.3-2.7). Approximately 14% of the ICC patients died during hospitalization. The median overall survival of all patients after the first admission was 53 +/-0.6 days. From the multivariate analysis, factors related to all-causes of death were: patients' age >60 years (OR = 1.2, 95% CI; 1.1-1.3), length of hospital stay of >7 days (OR = 1.1, 95% CI; 1.02-1.2), male (OR = 1.3, 95% CI; 1.2-1.4), living in the northern part of Thailand (OR = 1.5, 95% CI; 1.3-1.8) and presence of complications during admission (OR = 1.3, 95% CI; 1.1-1.5).Conclusion: The disease burden of patients with ICC in Thailand is significant with the incidence rate of 14.6 per 100,000 population, per year during 2009-2013 and showed high mortality rate of 14%. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) requires histomorphological detection of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). However, these primary liver cancers (PLCs) have a wide variety of microscopic appearances resulting in difficulties and uncertainties in cHCC-CCA's diagnosis. This study aims to perform a clinicopathologic analysis on the diagnosis of PLCs at a tertiary referral hospital in Thailand using traditional morphologic studies., Methods: A 5-year retrospective analysis of pathologically diagnosed PLCs was conducted. Pathological features and clinical characteristics of cHCC-CCA and other PLCs with the histopathologic resemblance to cHCC-CCA were studied. The pathological diagnosis was rendered based on histomorphological context rather than immunoreactivity. A literature review containing diagnostic pitfalls of cHCC-CCA was carried out., Results: PLCs from a total of 295 patients were retrieved, and cHCC-CCA accounted for 1.4% (n = 4) of the malignancies. Histomorphological evaluation is the most reliable diagnostic modality for cHCC-CCA. Extremely uncommon variants of iCCA (i.e., mucinous iCCA and adenosquamous iCCA) and iCCA arising with hepatocellular nodular lesions (i.e., iCCA with nodular regenerative hyperplasia (NRH), and iCCA in cirrhosis) could have a histomorphologic resemblance to that of cHCC-CCA., Conclusions: Although there has been an exceedingly high incidence of iCCA in Thailand, such a commonness is not valid for cHCC-CCA in our series. Rare forms of iCCA could have a morphologic resemblance to that of cHCC-CCA. Regardless of the differentiation and immunophenotype, iCCA without a distinct HCC component should never be diagnosed as cHCC-CCA., (Copyright © 2021 Elsevier Inc. All rights reserved.)