Risk Factor For Cholangiocarcinoma Research Articles

Hepatitis B and C Virus Infection and Cholangiocarcinoma: A Case-Control Study in Turkey

Hepatitis B and C virus (HBV and HCV) infection have been proposed as risk factors for cholangiocarcinoma, but the results are in- consistent through different reports. This study is to carry out a hospital-based case-control study to investigate the association bet- ween HBV and HCV infection and cholangiocarcinoma in Turkey. A total of 127 cases and 48 matched controls were included in the study. There were 89 cases with extrahepatic cholangiocarcinoma, 10 cases with intrahepatic cholangiocarcinoma and 28 ca- ses with gallbladder cancer. The patients and controls were questioned on smoking, alcohol drinking, history of cholecystolithiasis, choledocholithiasis and hepatolithiasis. Blood from all participants were tested for HBsAg, Anti-HBs, Anti-HBc IgG and Anti-HCV. The prevalence of smoking, alcohol drinking, cholecystolithiasis, choledocolithiasis, hepatolithiasis, anti-HCV, HBsAg and anti- HBs/anti-HbcIgG did not differ significantly between the patients and controls (p>0.05). In the subgroup analysis there was no sig- nificantly more prevalent risk factor except smoking in intrahepatic cholangiocarcinoma (p= 0.019). In conclusion, HBV or HCV in- fection were not found to be risk factors for development of CC in this study.

Colangitis esclerosante

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology, characterized by inflammatory and fibrotic changes along the intrahepatic and extrahepatic biliary tree. These changes result in irregular and segmentary stenosis and dilatations of biliary ducts, and progress to biliar obliteration, disappearance of intrahepatic biliary ducts, and, finally, the development of liver cirrhosis. PSC is associated with inflammatory bowel disease, mainly ulcerative cholitis, in 75% of cases. Patients with PSC present an increased risk of development of a cholangiocarcinoma. PSC is the more frequent risk factor for cholangiocarcinoma in western countries. No specific treatment in order to modify the natural history of PSC is available. In selected cases, liver transplantation is the only therapeutic option which increases survival in these patients.

Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma

Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.

Risk factors for cholangiocarcinoma in high-risk area of Thailand: Role of lifestyle, diet and methylenetetrahydrofolate reductase polymorphisms

Background and aim: Cholangiocarcinoma (CCA) is the most common cancer in Northeast Thailand. Endemicity of Opisthorchis viverrini (OV) – a known carcinogen – is responsible, but although infection is very common, the lifetime risk of CCA is only 5%. Other co-factors must exist, including aspects of lifestyle or diet along with variations in genetic susceptibility to them. Change in methylenetetrahydrofolate reductase (MTHFR) activity may influence both DNA methylation and synthesis. This study investigates risk factors for CCA with a focus on lifestyle, diet and MTHFR polymorphisms. Methods: Nested case–control study within cohort study was conducted. 219 subjects with primary CCA were each matched with two non-cancer controls from the same cohort on sex, age at recruitment and presence/absence of OV eggs in stool. Lifestyle and dietary data were obtained at recruitment. MTHFR polymorphisms were analyzed using PCR with high resolution melting analysis. The associations were assessed using conditional logistic regression. Results: Consumption of alcohol, raw freshwater fish and beef sausage increased the risk of CCA, while fruit and/or vegetables consumption reduced risk. There were interactions between MTHFR and preserved freshwater fish and beef. These dietary items are either a source of OV or of pre-formed nitrosamine, folate and antioxidants that are of possible relevance in OV carcinogenesis. Conclusions: Primary prevention of CCA in high-risk population is based upon efforts to reduce OV infection. Reduced consumption of alcohol and preserved meats, and increased consumption of dietary folate, actions with a wider preventive potential, may also help in the reduction of CCA burden.

Risk factors for cholangiocarcinoma

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy after hepatocellular cancer. CC accounts for approximately 10%-25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of CC. There are several established risk factors for CC, including parasitic infections, primary sclerosing cholangitis, biliary-duct cysts, hepatolithiasis, and toxins. Other less-established potential risk factors include inflammatory bowel disease, hepatitis C virus, hepatitis B virus, cirrhosis, diabetes, obesity, alcohol drinking, tobacco smoking, and host genetic polymorphisms. In studies where the distinction between intra- and extrahepatic CC was used, some potential risk factors seem to have a differential effect on CC, depending on the site. Therefore, the consistent use of a more refined classification would allow a better understanding of risk factors for CC.

Protective effect of melatonin against Opisthorchis viverrini-induced oxidative and nitrosative DNA damage and liver injury in hamsters

The liver fluke, Opisthorchis viverrini, is the risk factor of cholangiocarcinoma, which is a major health problem in northeastern Thailand. Production of reactive oxygen and nitrogen species during the host's response leads to oxidative and nitrosative stress contributing to carcinogenesis. We investigated the protective effect of melatonin against O. viverrini-induced oxidative and nitrosative stress and liver injury. Hamsters were infected with O. viverrini followed by oral administration of various doses of melatonin (5, 10, and 20 mg/kg body weight) for 30 days. Uninfected hamsters served as controls. Compared to the levels in O. viverrini-infected hamsters without melatonin treatment, the indoleamine decreased the formation of oxidative and nitrosative DNA lesions, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-nitroguanine, in the nucleus of bile duct epithelium and inflammatory cells, in parallel with a reduction in 3-nitrotyrosine. Melatonin also reduced the expression of heme oxygenase-1 and cytokeratin 19, nitrate/nitrite levels, and bile duct proliferation in the liver. Alanine transaminase activity and the levels of 8-isoprostane and vitamin E were also dose dependently decreased in the plasma of melatonin-treated hamsters. Melatonin reduced the mRNA expression of oxidant-generating genes [inducible nitric oxide synthase, nuclear factor-kappa B (NF-κB), and cyclooxygenase-2] and proinflammatory cytokines (TNF-α and IL-1β), accompanied by an increase in the expression of antioxidant genes [nuclear erythroid 2-related factor 2 (Nrf2) and manganese superoxide dismutase]. Thus, melatonin may be an effective chemopreventive agent against O. viverrini-induced cholangiocarcinoma by reducing oxidative and nitrosative DNA damage via induction of Nrf2 and inhibition of NF-κB-mediated pathways.

Accumulation of miscoding etheno-DNA adducts and highly expressed DNA repair during liver fluke-induced cholangiocarcinogenesis in hamsters

Infection by Opisthorchis viverrini, a risk factor for cholangiocarcinoma (CCA) may act through chronic inflammation, oxidative stress and lipid peroxidation (LPO)-related damage and growth stimuli. 1, N 6-Etheno-2′-deoxyadenosine (ɛdA), and 3, N 4-etheno-2′-deoxycytidine (ɛdC), markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients. In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model, in O. viverrini-infected hamsters that had received N-nitrosodimethylamine (NDMA, 12.5 ppm in dw) for 2 months. ɛdA- and ɛdC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method, from 21 up to 180 days post- O. viverrini-infection. In inflamed areas of the liver, etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct. Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters, treated with or w/o NDMA when compared with untreated controls. Levels were found highest in the liver of O. viverrini-infected plus NDMA-treated hamsters. Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development. Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase (ALP) activity, bile duct hyperplasia, dysplasia, precancerous lesions, and CCA appearance. Also elevated expression of alkyladenine DNA glycosylase (AAG), which excises 1, N 6-ethenoadenine (ɛA) was linked to higher adduct formation, suggesting imbalanced repair. Our results implicate accumulation of inflammation-related, promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis.

Involvement of MMP‐9 in peribiliary fibrosis and cholangiocarcinogenesis via Rac1‐dependent DNA damage in a hamster model

Peribiliary fibrosis caused by chronic infection with Opisthorchis viverrini (OV) is a risk factor of cholangiocarcinoma (CCA) in northeastern Thailand. Matrix metalloproteinases (MMPs) are enzymes capable of degrading and remodeling the extracellular matrix in the process of fibrosis and carcinogenesis. We examined MMPs expression and their role in fibrogenesis and cholangiocarcinogenesis in hamsters treated with OV and N-nitrosodimethylamine (NDMA). We assessed the time profiles of MMPs, inducible nitric oxide synthase (iNOS), Rac1, α-smooth muscle actin (α-SMA) and DNA lesions (8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG) in relation to fibrosis and CCA development. Histopathology revealed OV and NDMA synergistically induced peribiliary fibrosis time-dependently, and CCA occurred at 3 months, whereas OV or NDMA alone induced less fibrosis. Hydroxyproline levels in the liver and plasma were positively associated with the expression of collagen I and α-SMA. MMP-9 expression was significantly increased and correlated with the accumulation of myofibroblast, fibrosis levels and cholangiocarcinogenesis. MMP-9 activity was correlated with iNOS, and immunocolocalization was observed in inflammed tissues, early and invasive CCA. OV and NDMA synergistically induced MMP-9 expression in association to Rac1. In addition, Rac1 was colocalized with iNOS, and 8-nitroguanine, in inflammed tissues and CCA. Formation of 8-nitroguanine and 8-oxodG increased with tumor progression. The results suggest that MMP-9 expression is associated with the accumulation of peribiliary fibrosis in conjunction to the induction of iNOS and Rac1 that may potentiate DNA damage and cholangiocarcinogenesis.

Proteomic identification of peroxiredoxin 6 for host defence againstOpisthorchis viverriniinfection

Opisthorchis viverrini infection causes opisthorchiasis and is a risk factor for cholangiocarcinoma via chronic inflammation. To investigate the mechanism of O. viverrini -induced liver disease, we applied a proteomic approach to examine alterations in hepatic protein levels in O. viverrini -infected hamsters. Two-dimensional gel electrophoresis (2DE) revealed that O. viverrini infection induced upregulation (1.5- to 4.3-fold) of 25 proteins and downregulation (1.5 to 2.5-fold) of 24 proteins compared with uninfected animals. Expression of proteins related to stress response, DNA replication and repair, and cell structure was significantly increased, whereas that of proteins associated with normal liver function, such as metabolism, blood volume maintenance and fatty acid cycle was decreased. Among the upregulated proteins, a 2.7-fold increase in peroxiredoxin 6 (Prdx6), an antioxidant protein, was confirmed by 2DE and immunoblot analysis, Western blot and quantitative PCR. Immunohistochemical analysis showed that Prdx6 expression was observed mainly in the cytoplasm of inflammatory cells. These results suggest that Prdx6 is important for host defence against O. viverrini infection. This study provides basic information for Prdx6 as a potential biomarker and therapeutic target for opisthorchiasis.

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case–control study in China

The risk factors for cholangiocarcinoma are incompletely defined in China, especially for intrahepatic cholangiocarcinoma (ICC). We evaluated the risk factors for both ICC and extrahepatic cholangiocarcinoma (ECC). A case-control study in which cases were cholangiocarcinoma patients referred to Peking Union Medical College Hospital (PUMCH) between 1998 and 2008 and controls were healthy individuals. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on liver disease, family history, diabetes, smoking and drinking were collected by a retrospective review of the patients' records and health examination reports or by interview. A total of 190 patients (61 ICC; 129 ECC) and 380 age- and sex-matched controls were enrolled. HBsAg (P<0.001) and anti-HBc without HBsAg (P=0.001) were significantly related to ICC. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were 18.1 (95% CI: 7.5-44.0) and 3.6 (95% CI: 1.7-7.6) respectively. Diabetes mellitus (P=0.007), cholecystolithiasis (P=0.004) and previous cholecystectomy (P<0.001) were significantly associated with ECC. The prevalence of cirrhosis was higher in ICC than that in ECC (P<0.001). Furthermore, on excluding the ICC patients with cirrhosis, ICC patients showed significant independent associations with HBsAg (OR: 7.3; 95% CI: 3.1-17.2) and anti-HBc without HBsAg (OR: 2.4; 95% CI: 1.1-5.2). Cirrhosis and chronic hepatitis B virus infection are risk factors for ICC, while cholecystolithiasis, diabetes and previous cholecystectomy are risk factors for ECC.

Cholangiocarcinoma

Cholangiocarcinoma is a rare, primary cancer of the biliary tree that can be difficult to diagnose with all imaging modalities. The presenting clinical symptoms of nausea, vomiting, and jaundice can be consistent with classic cholecystitis symptoms, increasing the risk of a missed diagnosis. The most often seen risk factor for cholangiocarcinoma is primary sclerosing cholangitis (PSC). In most cases, the initial diagnostic finding is intrahepatic ductal dilatation. Once an actual mass is seen, liver transplantation is the necessary treatment plan because of likely hepatic metastasis. There is a slight recurrence rate of cholangiocarcinoma even in a transplanted liver. A high percentage of cases are treated with only palliative care. This case presents a classic example of cholangiocarcinoma at the porta hepatis, involving a hyperechoic mass in a dilated common bile duct with abnormalities of the intrahepatic bile ducts and gallbladder.

Cholangiocarcinoma in USA- versus Asian-born Asians: Is viral hepatitis a factor?

Aim: Though liver and biliary tract cancers are more common in Asian countries they are increasing in incidence in the USA. This study attempted to clarify the risk factor profile for immigrant Asians compared with the USA population. Methods: A retrospective review was made of 128 cholangiocarcinoma cases presenting to a tertiary referral center from 1996–2007. Data were collected on patient characteristics, risk factors, tumor characteristics, treatment and survival. We then compared Asian immigrants (n = 40) to USA-born Asians (n = 46). Results: In our cohort, the mean age was 66.7 years, of whom 54% were men, 51% had cholelithiasis, 51% were smokers, 41% used alcohol, 10% had hepatitis C and 27% had hepatitis B. In four patients, one each had sclerosing cholangitis, liver flukes, choledochal cyst and previous biliary tract surgery. The distribution of tumors was as follows: 43 intrahepatic (ICC) and 85 extrahepatic cholangiocarcinoma (ECC) including 43 proximal, nine middle and 33 distal tumors. Immigrants were more likely to be younger (mean age 63 vs 70 years old) and to have ICC than ECC (50% vs 26%) and hepatitis B (46% vs 14%). There was no significant difference between groups in hepatitis C, smoking, alcohol, cholelithasis, resectability or survival. Conclusion: Traditionally described risk factors for cholangiocarcinoma are not as evident in this largely Asian cohort. Asian immigrants were more likely to have ICC and have hepatitis B though whether hepatitis B is directly carcinogenic to the biliary tract is not clear. Immigrant status did not seem to have an effect on outcome from cholangiocarcinoma.

Risk factors for biliary tract and ampullary carcinomas and prophylactic surgery for these factors

Curative resection is the only treatment for biliary tract cancer that achieves long-term survival. However, patients with advanced biliary tract cancer have only a limited prognosis even after radical surgical resection. Thus, to improve the longterm results, the early detection of biliary tract cancer and subsequent cure seem to be essential. The purpose of this study was to review the literature concerning the risk factors for cancerous and precancerous lesions of the biliary tract, and prophylactic surgery for these factors. It has been reported that pancreaticobiliary maljunction (PBM) with bile duct dilatation is a risk factor for gallbladder cancer and bile duct cancer, while PBM without bile duct dilatation is a risk factor for gallbladder cancer. Thus, in the former group, a prophylactic excision of the common bile duct and gallbladder should be recommended, while in the later group, a prophylactic cholecystectomy without bile duct resection may be the appropriate surgical procedure. It has also been reported that primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. Patients with PSC often develop advanced cholangiocarcinoma with a poor prognosis. In patients with PSC, therefore, strict follow-up should be recommended. Adenoma and dysplasia have been regarded as precancerous lesions of gallbladder cancer. A polypoid lesion of the gallbladder that is sessile, has a diameter greater than 10 mm, and /or grows rapidly, is highly likely to be cancerous and should be resected. Although gallstones seem to be closely associated with gallbladder cancer, there is no evidence of a direct causal relationship between gallstones and gallbladder cancer. Thus, a cholecystectomy is not advised for asymptomatic cholecystolithiasis. Controversy remains as to whether adenomyomatosis of the gallbladder and porcelain gallbladder are associated with gallbladder cancer. With respect to ampullary carcinoma, adenoma of the ampulla is considered to be a precancerous lesion. This article discusses the risk factors for cancerous and precancerous lesions of the biliary tract and prophylactic treatment for these factors.

Intrahepatic Cholangiocarcinoma with Old Infestation of Schistosoma japonicum: Report of a Case

We report a rare case of intrahepatic cholangiocarcinoma associated with old infestation of Schistosoma japonicum. The patient was a 76-year-old Japanese man who had lived his childhood in an endemic area of this parasite. He presented with jaundice and computed tomography showed a 4-cm, hypodense tumor in segment VIII of the liver. Microscopically, the resected mass was composed of well-differentiated adenocarcinoma cells. Fibrosis and inflammation were seen around the dilated peripheral portal veins embolized with dead S. japonicum eggs. Our search of the literature found only one other case of cholangiocarcinoma coincident with S. japonicum, suggesting that it is not a risk factor for cholangiocarcinoma, although the inflammation and fibrosis caused by the S. japonicum eggshells may predispose to carcinogenesis. However, there is no evidence supporting this hypothesis. More data are necessary to evaluate the differences in clinicopathological findings between cholangiocarcinoma concomitant with S. japonicum and the usual type of cholangiocarcinoma.

Advances in the diagnosis, evaluation and management of cholangiocarcinoma

Cholangiocarcinoma is an enigmatic malignancy of the biliary tract that has recently been shown to be increasing in incidence globally. There has been recent progress in identifying potential risk factors for the tumor, and in the use of emerging technologies for diagnosis and palliative treatment. Hepatitis B and C, cirrhosis and alcohol have been described as risk factors for cholangiocarcinoma. A morphology-based classification for cholangiocarcinoma is proposed that will facilitate future descriptive epidemiology, diagnosis and comparative therapeutic studies. Diagnosis may be improved by new approaches to enhance the diagnostic yield and utility of biliary cytology. The role of new imaging approaches such as positron emission tomography scanning, endoscopic ultrasound or optical coherence tomography for diagnosis are being examined and defined. Long-term results for transplantation protocols for curative intent in non-resectable localized disease have been described. Photodynamic therapy looks extremely promising for adjunct therapy of intrahepatic mass lesions. Recent advances in the epidemiology, classification, diagnosis and therapy of cholangiocarcinoma are expected to enhance the evaluation and management of patients with this devastating malignancy.

Primary Sclerosing Cholangitis and Cholangiocarcinoma

Primary sclerosing cholangitis (PSC), a cholestatic liver disease characterized by fibrosing inflammatory damage of the biliary tree, is a risk factor for cholangiocarcinoma (CCA). Indeed, the prevalence of CCA in patients with PSC ranges from 7 to 13%. The major challenges of CCA in PSC patients relate to lack of methods for early diagnosis and the absence of effective treatment. Early diagnosis of CCA in PSC is delayed because its clinical presentation can mimic benign dominant biliary strictures. Moreover, biliary and serum tests to diagnose development of CCA in PSC are limiting, although the use of advanced cytologic techniques for aneuploidy and chromosomal aberrations are promising in this regard. As a result, current therapies do not extend survival with the exception of protocol liver transplantation available to a selected group of patients. Future studies should emphasize deciphering the sequence of events that transform the inflammatory changes of the biliary tree to cancer. Only then will chemoprevention, early diagnosis, and therapy of CCA in patients with PSC improve.

Hepatolithiasis associated with cholangiocarcinoma.

Intrahepatic stone is common in East Asia. Hepatolithiasis is a risk factor for cholangiocarcinoma but it is difficult to make an accurate diagnosis before operation. The effect of intrahepatic stone on diagnosis, treatment and survival in patients with coexistent cholangiocarcinoma was investigated. Between 1981 and 1994, 33 patients with hepatolithiasis and associated cholangiocarcinoma were identified and compared respectively to 18 patients with intrahepatic cholangiocarcinoma alone. Patients with intrahepatic stones had a significantly longer duration of symptoms, a higher frequency of previous biliary surgery but a lower rate of preoperative diagnosis. Surgical resection was the treatment of choice and was performed in 18 of 33 patients with cholangiocarcinoma and stones and in nine of 18 with intrahepatic cholangiocarcinoma alone. Significantly inferior 5-year survival rates were found in patients with hepatolithiasis: two of 32 versus four of 14 for all cases and two of 17 versus four of nine for resectable cases (P < 0.05). These survival differences may be attributed to delayed diagnosis, lower diagnostic rate and relatively fewer curative resections in the patients with stone-containing cholangiocarcinoma.

Letter To The Editor: The Prevalence Of Hepatitis C Seropositive And Opisthorchiasis Among The Patients With Cholangiocarcinoma

Cholangiocarcinoma is the malignancy of the biliary duct system, originating in the liver and terminating at the ampulla of Vater. It is a tumor that arises from the intrahepatic or extrahepatic biliary epithelium. The etiology of most bile duct cancers remains undetermined. Presently, these malignant biliary tract diseases are common cancerous diseases among the people in the Southeast Asia, with the world highest prevalence at the northeastern Thailand and Laos (1). Concerning the pathogenesis, it has been suggested that longstanding inflammation, as with primary sclerosing cholangitis or chronic parasitic infection, could play a role by inducing hyperplasia, cellular proliferation, and, ultimately, malignant transformation (2). This carcinoma tends to grow slowly and to infiltrate the walls of the ducts, dissecting along tissue planes and leading to biliary tract obstruction. Opisthorchiasis, an important intestinal parasite infection with high prevalence in tropical countries, is proposed to be linked to the very high incidence rate of cholangiocarcinoma in the Northeast of Thailand (3). Liver fluke or Opisthorchis viverri is the corresponding pathogen for this infection (3). In addition to opisthorchiasis, hepatitis virus-associated chronic hepatitis or cirrhosis has recently been suggested to be involved in the pathogenesis of cholangiocarcinoma(4, 5). Here, we reported the prevalence of hepatitis C seropositive among the Thai patients with cholangiocarcinoma. We retrospectively reviewed on the medical records of all cholangiocarcinoma patients who admitted to King Chulalongkorn Memorial Hospital during year 1992 to 2001. In each case, the cholangiocarcinoma had been diagnosed from the final histopathological results. A total of 30 cases with known hepatitis C serology and stool examination result were selected for further prevalence study. The data collated from the records also included the sex and age of each patient. A total of 30 patients with cholangiocarcinoma, who admitted to King Chulalongkorn memorial Thailand during 1992 – 2001, with known hepatitis C serology was selected for further prevalence study. Of the total 30 cases (16 males and 14 females), the hepatitis C seropositive was found in 4 cases (2 males and 2 females, giving the total prevalence rate equaled to 13.3 % (12.5 % for male and 14.3 % for female). Concerning stool examination, opisthorchis viverrini eggs were detected in 2 cases (1 male and 1 female) giving the total prevalence rate equaled to 6.7 % (6.3 % for male and 7.1 % for female). All cases with opisthorchiasis also have hepatitis C seropositive. One of the relating risk for development of cholangiocarcinoma is chronic infection. According to the recent study of Donato et al (4) , HCV is a risk factor for cholangiocarcinoma. Here, we can demonstrate a high rate (13.3 %) of hepatitis C seropositive among the cholangiocarcinoma patients. This prevalence was about 5 times higher in comparison with the Thai local population (about 2.6 %)(6). These findings can state the high hepatitis C seropositive rate among the cholangiocarcinoma patients. In addition, the co-presentation of hepatitis C seropositive and opisthorchiasis in some cases also implies for a higher risk. Since the hepatitis C infection is believed to be one of the risk to development of the cholangiocarcinoma and both Letter To The Editor: The Prevalence Of Hepatitis C Seropositive And Opisthorchiasis Among The Patients With Cholangiocarcinoma 2 of 3 cholangiocarcinoma and hepatitis C infection are common in Thailand (1), the screening for hepatitis C, adding to the routine screening for liver fluke by stool examination, may be a useful strategy for decrease of the high rate of cholangiocarcinoma in Thailand. Further long-term study to study the relation of hepatitis C infection and cholangiocarcinoma is recommended.

An increasing incidence of cholangiocarcinoma: Why?

An increasing incidence of cholangiocarcinoma: Why?

Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis

Inflammation mediated by infection is an important factor causing carcinogenesis. Opisthorchis viverrini (OV) infection is a risk factor of cholangiocarcinoma (CHCA), probably through chronic inflammation. Formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) were assessed in the liver of hamsters infected with OV. We newly produced specific anti-8-nitroguanine antibody without cross-reaction. Double immunofluorescence staining revealed that 8-oxodG and 8-nitroguanine were formed mainly in the same inflammatory cells and epithelium of bile ducts from day 7 and showed the strongest immunoreactivity on days 21 and 30, respectively. It is noteworthy that 8-oxodG and 8-nitroguanine still remained in epithelium of bile ducts on day 180, although amount of alanine aminotransferase activity returned to normal level. A time course of 8-nitroguanine was associated with iNOS expression. Furthermore, this study demonstrated that HO-1 expression and subsequent iron accumulation may be involved in enhancement of oxidative DNA damage in epithelium of small bile ducts. In conclusion, nitrative and oxidative DNA damage via iNOS expression in hamsters infected with OV may participate in CHCA carcinogenesis.