Risk For CCA Research Articles

Polymorphism of genes encoding drug-metabolizing and inflammation-related enzymes for susceptibility to cholangiocarcinoma in Thailand.

Cholangiocarcinoma (CCA) is an intractable cancer, and its incidence in northeastern Thailand is the highest worldwide. Infection with the liver fluke Opisthorchis viverrini (OV) has been associated with CCA risk. However, animal experiments have suggested that OV alone does not induce CCA, but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters. Therefore, in humans, other environmental and genetic factors may also be involved. To examine relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes. This hospital-based case-control study enrolled 95 case-control pairs matched by age (± 5 years) and sex. We examined relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes, serum anti-OV, alcohol consumption, and smoking. Polymorphisms of CYP2E1, IL-6 (-174 and -634), IL-10 (-819), and NF-κB (-94) and their co-occurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed. Although CCA risk was not significantly associated with any single polymorphism, persons with the GSTT1 wild-type and CYP2E1 c1/c2 + c2/c2 genotype had an increased risk (OR = 3.33, 95%CI: 1.23-9.00) as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype. The presence of anti-OV in serum was associated with a 7- to 11-fold increased risk, and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms. In addition to infection with OV, gene-gene interactions may be considered as one of the risk factors for CCA development.

Biliary Tract Malignancies Related to Gallbladder Polyps, Primary Sclerosing Cholangitis, and Choledochal Cysts.

Biliary Tract Malignancies Related to Gallbladder Polyps, Primary Sclerosing Cholangitis, and Choledochal Cysts.

Integrative radiomics expression predicts molecular subtypes of primary clear cell renal cell carcinoma

To identify combined positron-emission tomography (PET)/magnetic resonance imaging (MRI)-based radiomics as a surrogate biomarker of intratumour disease risk for molecular subtype ccA and ccB in patients with primary clear cell renal cell carcinoma (ccRCC). PET/MRI data were analysed retrospectively from eight patients. One hundred and sixty-eight radiomics features for each tumour sampling based on the regionally sampled tumours with 23 specimens were extracted. Sparse partial least squares discriminant analysis (SPLS-DA) was applied to feature screening on high-throughput radiomics features and project the selected features to low-dimensional intrinsic latent components as radiomics signatures. In addition, multilevel omics datasets were leveraged to explore the complementing information and elevate the discriminative ability. The correct classification rate (CCR) for molecular subtype classification by SPLS-DA using only radiomics features was 86.96% with permutation test p=7×10-4. When multi-omics datasets including mRNA, microvascular density, and clinical parameters from each specimen were combined with radiomics features to refine the model of SPLS-DA, the best CCR was 95.65% with permutation test, p<10-4; however, even in the case of generating the classification based on transcription features, which is the reference standard, there is roughly 10% classification ambiguity. Thus, this classification level (86.96-95.65%) of the proposed method represents the discriminating level that is consistent with reality. Featured with high accuracy, an integrated multi-omics model of PET/MRI-based radiomics could be the first non-invasive investigation for disease risk stratification and guidance of treatment in patients with primary ccRCC.

Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a systematic review and meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA).MethodsA search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics.ResultsSeven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36–2.79, I2=76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52–3.24, I2=67%) and 1.55 (95%CI: 1.03–2.33, I2=69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41–2.75, I2=71%), 2.09 (95%CI, 1.49–2.91, I2=42%) and 2.05 (95%CI, 1.59–2.64, I2=0%) for all CCAs, iCCA, and eCCA, respectively.ConclusionsThis meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted.Trial registrationThe protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573).

No Evidence That Azathioprine Increases Risk ofCholangiocarcinoma in Patients With Primary SclerosingCholangitis.

Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Patients with PSC also can have inflammatory bowel diseases (IBDs) or features of autoimmune hepatitis (AIH), and therefore are treated with azathioprine. Azathioprine has been associated with an increased risk for malignancy, therefore we investigated whether azathioprine use affects the risk of CCA in persons with PSC. We performed a retrospective study of well-defined patients with PSC using data collected from 3 large-volume, tertiary care centers in Germany and Norway. We analyzed data from 638 patients (70% men; 5900 patient-years of follow-up evaluation); 91 patients had received azathioprine therapy (considered to be effective at 90 days after first intake). Risk analysis was performed using the Cox proportional hazard model when risks competing with study end points were present. Of patients who received azathioprine treatment, 3.3% developed CCA, compared with 6.8% of patients without azathioprine treatment. However, azathioprine did not significantly affect the risk for CCA (hazard ratio, 0.96; 95% confidence interval, 0.29-3.13; P= .94). The only factor associated with an increased risk of CCA was age 35 years or older at PSC diagnosis (hazard ratio, 3.87; 95% confidence interval, 1.96-7.67; P < .01). Patient sex, concomitant IBD, or AIH did not affect the risk of CCA. Overall, the cumulative 10-year incidence of CCA was 4.6% and the cumulative 15-year incidence was 7.7%. A retrospective analysis of patients with PSC treated at tertiary centers in Europe found no evidence that azathioprine significantly affects the risk of CCA. Azathioprine therefore should not be withheld from patients with PSC and concomitant IBD and/or AIH.

Surveillance of Populations at Risk of Cholangiocarcinoma Development in Rural Communities of Thailand Using the Korat-CCA Verbal Screening Test

Cholangiocarcinoma (CCA) is a serious problem in Thailand, particularly in the northeastern region. Active surveillance in rural communities with an appropriat low-cost screening tool is required to facilitate early detection. Therefore, this study aimed to investigate the population at risk of CCA in Bua Yai district, Nakhon Ratchasima province, Northeastern Thailand using the Korat-CCA verbal screening test (KCVST) during June to October 2015. Reliability of KCVST demonstrated a Cronbach alpha coefficient=0.75 Stepwise-multiple regression showed that alcohol consumption was important for CCA screened, followed by agriculture and pesticide use, under-cooked cyprinoid fish consumption, praziquantel use, naïve northeastern people, opisthorchiasis, family relatives with CCA, and cholangitis or cholecystitis or gallstones, respectively. Population at risk for CCA was classified to low risk (63.4%), moderate risk (33.7%), and high risk (1.32%) for CCA. When CCA was screened using ultrasonography, 4 of 32 high risk participants had an abnormal biliary tract with dilated bile ducts. This study indicates that KCVST is a potential useful too which decrease the cost of large scale CCA screening.

GIS Database and Google Map of the Population at Risk of Cholangiocarcinoma in Mueang Yang District, Nakhon Ratchasima Province of Thailand.

Cholangiocarcinoma (CCA) is a serious problem in Thailand, particularly in the northeastern and northern regions. Database of population at risk are need required for monitoring, surveillance, home health care, and home visit. Therefore, this study aimed to develop a geographic information system (GIS) database and Google map of the population at risk of CCA in Mueang Yang district, Nakhon Ratchasima province, northeastern Thailand during June to October 2015. Populations at risk were screened using the Korat CCA verbal screening test (KCVST). Software included Microsoft Excel, ArcGIS, and Google Maps. The secondary data included the point of villages, sub-district boundaries, district boundaries, point of hospital in Mueang Yang district, used for created the spatial databese. The populations at risk for CCA and opisthorchiasis were used to create an arttribute database. Data were tranfered to WGS84 UTM ZONE 48. After the conversion, all of the data were imported into Google Earth using online web pages www.earthpoint.us. Some 222 from a 4,800 population at risk for CCA constituted a high risk group. Geo-visual display available at following www.google.com/maps/d/u/0/ edit?mid=zPxtcHv_iDLo.kvPpxl5mAs90 and hl=th. Geo-visual display 5 layers including: layer 1, village location and number of the population at risk for CCA; layer 2, sub-district health promotion hospital in Mueang Yang district and number of opisthorchiasis; layer 3, sub-district district and the number of population at risk for CCA; layer 4, district hospital and the number of population at risk for CCA and number of opisthorchiasis; and layer 5, district and the number of population at risk for CCA and number of opisthorchiasis. This GIS database and Google map production process is suitable for further monitoring, surveillance, and home health care for CCA sufferers.

Distribution of the Population at Risk of Cholangiocarcinoma in Bua Yai District, Nakhon Ratchasima of Thailand Using Google Map.

Cholangiocarcinoma (CCA), a major problem of health in Thailand, particularly in Northeastern and Northern regions, is generally incurable and rapidly lethal because of presentation in stage 3 or 4. Early diagnosis of stage 1 and 2 could allow better survival. Therefore, this study aimed to provide a distribution map of populations at risk for CCA in BuaYai district of Nakhon Ratchasima province, Northeast Thailand. A cross-sectional survey was carried out in 10 sub-districts and 122 villages, during June and November 2015. The populations at risk for CCA were screened using the Korat CCA verbal screening test (KCVST) and then risk areas were displayed by using Google map (GM). A total of 11,435 individuals from a 26,198 population completed the KCVST. The majority had a low score of risk for CCA (1-4 points; 93.3%). High scores with 6, 7 and 8 points accounted for 1.20%, 0.13% and 0.02%. The population at risk was found frequently in sub-district municipalities, followed by sub-district administrative organization and town municipalities, (F=396.220, P-value=0.000). Distribution mapping comprised 11 layers: 1, district; 2, local administrative organization; 3, hospital; 4, KCVST opisthorchiasis; 5, KCVST praziquantel used; 6, KCVST cholelithiasis; 7, KCVST raw fish consumption; 8, KCVST alcohol consumption; 9, KCVST pesticide used; 10, KCVST relative family with CCA; and 11, KCVST naive northeastern people. Geovisual display is now available online. This study indicated that the population at high risk of CCA in Bua Yai district is low, therefore setting a zero model project is possible. Key success factors for disease prevention and control need further study. GM production is suitable for further CCA surveillance and monitoring of the population with a high risk score in this area.

Spatial Distribution of the Population at Risk of Cholangiocarcinoma in Chum Phaung District, Nakhon Ratchasima Province of Thailand

Cholangiocarcinoma (CCA) is a serious health problem in Thailand, particularly in northeastern and northern regions, but epidemiological studies are scarce and the spatial distribution of CCA remains to be determined. A database for the population at risk is required for monitoring, surveillance and organization of home health care. This study aim was to geo-visually display the distribution of CCA in northeast Thailand, using a geographic information system and Google Earth. A cross-sectional survey was carried out in 9 sub-districts and 133 villages in Chum Phuang district, Nakhon Ratchasima province during June and October 2015. Data on demography, and the population at risk for CCA were combined with the points of villages, sub-district boundaries, district boundaries, and points of hospitals in districts, then fed into a geographical information system. After the conversion, all of the data were imported into Google Earth for geo-visualization. A total of 11,960 from 83,096 population were included in this study. Females and male were 52.5%, and 47.8%, the age group 41-50 years old 33.3%. Individual risk for CCA was identifed and classified by using the Korat CCA verbal screening test as low (92.8%), followed by high risk (6.74%), and no (0.49%), respectively. Gender (X2-test=1143.63, p-value= 0.001), age group (X2-test==211.36, p-value=0.0001), and sub-district (X2-test=1471.858, p-value=0.0001) were significantly associated with CCA risk. Spatial distribution of the population at risk for CCA in Chum Phuang district was viewed with Google Earth. Geo-visual display followed Layer 1: District, Layer 2: Sub-district, Layer 3: Number of low risk in village, Layer 4: Number of high risk in village, and Layer 5: Hospital in Chum Phuang District and their related catchment areas. We present the first risk geo-visual display of CCA in this rural community, which is important for spatial targeting of control efforts. Risk appears to be strongly associated with gender, age group, and sub-district. Therefor, spatial distribution is suitable for the use in the further monitoring, surveillance, and home health care for CCA.

Population-Based Intervention for Liver Fluke Prevention and Control in Meuang Yang District, Nakhon Ratchasima Province, Thailand.

Opisthorchiasis is still a major health problem in rural communities of Thailand. Infection is associated with cholangiocarcinoma (CCA), which is found frequently in Thailand, particularly in the northeastern. Therefore, this study aimed to evaluate the effectiveness of health intervention in the population at risk for opisthorchiasis and CCA. A quasi-experimental study was conducted in Meuang Yang district, Nakhon Ratchasima province, northeastern Thailand, between June and October 2015. Participants were completed health intervention comprising 4 stations; 1, VDO clip of moving adult worm of liver fluke; 2, poster of life cycle of liver fluke; 3, microscopy with adult and egg liver fluke; and 4, brochure with the knowledge of liver fluke containing infection, signs, symptoms, related disease, diagnosis, treatment, prevention, and control. Pre-and-post-test questionnaires were utilized to collect data from all participants. Students paired t-tests were used to analyze differences between before and after participation in the health intervention. Knowledge (mean difference=-7.48, t=-51.241, 95% CI, -7.77, -7.19, p-value =0.001), attitude (mean difference=-9.07, t=-9.818, 95% CI=-10.9, -7.24, p-value=0.001), and practice (mean difference=-2.04, t=-2.688, 95% CI=-3.55, -0.53, p-value=0.008), changed between before and after time points with statistical significance. Community rules were concluded regarding: (1) cooked cyprinoid fish consumption; (2) stop under cooked cyprinoid fish by household cooker; (3) cooked food consumption; (4) hygienic defecation; (5) corrected knowledge campaign close to each household; (6) organizing a village food safety club; (7) and annual health check including stool examination featuring monitoring by village health volunteers and local public health officers. The results indicates that the present health intervention program was effective and easy to understand, with low cost and taking only a short time. Therefore, this program may useful for further work at community and provincial levels for liver fluke prevention and control.

Biliary multifocal chromosomal polysomy and cholangiocarcinoma in primary sclerosing cholangitis.

Polysomy detected by fluorescence in situ hybridization (FISH) is associated with cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC). However, a subset of PSC patients with polysomy do not manifest CCA even after long-term follow-up. It is unknown if patients with chromosomal gains detected by FISH in multiple areas of the biliary tree (i.e., multifocal polysomy, MFP) are more likely to be diagnosed with CCA than patients with unifocal polysomy (UFP). Therefore, our aim is to determine whether patients with MFP are more likely to manifest CCA compared with patients with other chromosomal abnormalities including UFP and other FISH subtypes. We performed a retrospective review of PSC patients without a mass lesion who underwent FISH testing at our institution from 1 January 2005 to 1 July 2013. Three-hundred and seventy-one PSC patients were included. Compared with patients with UFP, those with MFP were more likely to have weight loss (32 vs. 9%), suspicious cytology (45 vs. 13%) and develop serial polysomy (91 vs. 35%). MFP was associated with CCA (hazard ratio (HR), 82.42; 95% confidence interval (CI), 24.50-277.31) and was the strongest predictor of cancer diagnosis. Suspicious cytology (HR, 26.31; 95% CI, 8.63-80.24) and UFP (HR, 13.27; 95% CI, 3.32-53.08) were also predictive of CCA. MFP, UFP and suspicious cytology remained associated with CCA in the multivariable model. Compared with other FISH subtypes, MFP is the strongest predictor of CCA. However, patients with UFP and suspicious cytology (regardless of FISH status) are also at an increased risk for CCA.

Histological confirmation of periductal fibrosis from ultrasound diagnosis in cholangiocarcinoma patients

Cholangiocarcinoma (CCA) has no specific clinical signs and symptoms and non-specific bio- and tumor-markers in the early disease stage. Usually patients present to tertiary care with advanced disease stage. In order to detect early cases of CCA that may present as a mass, dilatation of intrahepatic duct or combination, ultrasonography is accepted as a powerful imaging tool. A smaller mass or bile duct segmental dilatation requires further imaging for characterization, including computerized tomography (CT) or magnetic resonance imaging (MRI). We examined whether liver echo pattern was correlated with high risk for CCA in an endemic area of Opisthorchis viverrini (Ov). Ov infestation caused chronic inflammation of the biliary tree by periductal fibrosis (PDF), which may subsequently lead to CCA development. In our study, a World Health Organization classification of pattern of increased periportal echo (IPE) for schistosomiasis was applied. Two CCA patients gave consent for operation. Histopathological diagnosis showed both had cholangiocarcinoma with periductal fibrosis of the non-tumorous area of the liver. Ultrasonography was used to compare the non-tumorous area with parenchymal echo pattern and was shown to have an early CCA detection role and a surveillance role in an endemic area of Ov by detection of PDF.

Higher incidence of clear cell adenocarcinoma of the cervix and vagina among women born between 1947 and 1971 in the United States

Although the association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma of the cervix and vagina (CCA) was first reported among young women, subsequent case reports and cohort studies suggest that an elevated risk for CCA may persist with age. Data from the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program were used to construct indirect standardized incidence ratios (SIR) comparing CCA risk among women born during the exposure period 1947 through 1971, when DES was prescribed to pregnant women, to the relevant time period for nonexposed women born before or after DES exposure period. CCA incidence among the women born before the DES exposure period (ages 30–54 at diagnosis of CAA) or after the DES exposure period (ages 15–29 at diagnosis) were used to calculate the expected rates for women born during the DES exposure period. Among women aged 15–29 years, CCA risk increased with age and peaked in the 25–29 year age group, but the risk estimates were unstable (SIR = 6.06; 95% CI: 0.97, −251.07, SEER data). Among women aged 40–54 years, CCA risk was greatest in the 40–44 year age group (SIR = 4.55; 95% CI: 1.11, 40.19, SEER data and SIR = 3.94; 95% CI: 1.06, 33.01, NPCR/SEER data) and remained significantly elevated throughout this age group in the combined data set. Risk was not elevated among women aged 30–39 years. The observed risk of CCA, if causally related to DES exposure, reflects a persistent health impact from in utero exposure that is widespread in the general population. When assessing a woman’s cancer risks, whether her mother took DES while pregnant may still be a relevant aspect of the medical history for women born during the period of DES use in pregnancy.

S1900 Both Hepatitis C and B Virus Were Major Underlying Etiologies for Hepatocellular Carcinoma (HCC) in Vietnamese Americans While the Vast Majority of HCC Cases in Chinese Americans Were Associated With Hepatitis B Virus

patients (5.94%) were diagnosed with CCA. Patients received a mean number of 1.65 MRIs, 0.93 ERCPs, 0.34 CT scans, and 0.69 ultrasounds as screening tests during the observation period. 4 patients were found to have CCA on MRI, while 2 were diagnosed by biliary aspirate or brushings. The group with CCA was slightly older (63.5 years vs 53.0 years, p= 0.025). There was no significant difference in creatinine levels (1.42 vs 0.87, p=0.46), bilirubin levels (5.34 vs 3.26, p=0.39) or INR (1.16 vs 1.13, p=0.75). Those with CCA had a slightly higher MELD score (14.26 vs 10.62), but the difference was not significant (p= 0.335). As expected, CA 19-9 levels appeared higher among the CCA group, but were not significantly different (148.5 vs 89.4, p=0.63). There were no independently predicted factors that were associated with the development of CCA. In Kaplan-Meier survival analysis, oneyear survival in patients with CCA was statistically different than those without CCA (94.5% vs 77%, log rank = 0.01). In a multivariate one-year survival model, none of the imaging modalities studied were independent predictors of the diagnosis of CCA. Patients without CCA underwent more MRI/MRCPs, C T scans, and total imaging tests. Conclusion: Using clinical characteristics to stratify patients with PSC at risk for CCA remains problematic, as no parameters were found to impact risk. Using imaging techniques to screen for CCA did not appear to improve survival. Mean numbers of imaging tests based on CCA status

High lifetime risk of cancer in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) patients are at risk for developing cholangiocarcinoma (CCA) and colorectal carcinoma (CRC). Our aim was to assess the risk of malignancies and their influence on survival. Data from PSC patients diagnosed between 1980 and 2006 in two university hospitals were retrieved. The Kaplan-Meier method and a time-dependent Cox regression model were used to calculate risks of malignancies and their influence on survival. Two hundred and eleven patients were included, 143 (68%) were male and 126 (60%) had inflammatory bowel disease (IBD). Median transplantation-free survival was 14 years. The risk of CCA after 10 and 20 years was 9% and 9%, respectively. In patients with concomitant IBD the 10-year and 20-year risks for CRC were 14% and 31%, which was significantly higher than for patients without IBD (2% and 2% (P=0.008)). CCA, cholangitis, and age at entry were independent risk factors for the combined endpoint death or liver transplantation. Risk factors for the endpoint death were CCA, CRC, age, and symptomatic presentation. Patients with PSC and IBD have a high long-term risk of developing CRC and this risk is about threefold higher than the risk for CCA. Both malignancies are associated with decreased survival.

Serum antibody response to Opisthorchis viverrini antigen as a marker for opisthorchiasis-associated cholangiocarcinoma

The liver flukes Opisthorchis viverrini and Clonorchis sinensis chronically infect over 30 million people in south-eastern Asia, resulting in significant morbidity and a predispoisition to cholangiocarcinoma (CCA). Liver fluke-associated CCA carries a poor prognosis, partly because it is often detected at a late and advanced stage. The development of improved diagnostic methods, particularly for early CCA, may improve chances of survival and cure. Accordingly, we explored the use of immunological responses to liver fluke antigens as a potential means of identifying individuals at high risk for liver fluke-associated CCA. Serum antibody responses to O. viverrini adult worm homogenate and metacercaria homogenate (MH) were studied using enzyme-linked immunosorbent and immunoblot assays in 65 infected residents of an opisthorchiasisendemic area in Thailand. Antibody levels correlated with liver ultrasonography (U/S) findings, and immunoblot analysis revealed a 91 93 kDa MH doublet recognized only by sera of individuals with severe liver U/S findings, including CCA. These results suggest that serum antibody responses to liver fluke antigens may be useful in the identification of infected individuals who are at high risk for liver fluke-associated CCA.