Race, ethnicity, and socioeconomic factors in cholangiocarcinoma: What is driving disparities in receipt of treatment?

BACKGROUND AND OBJECTIVES: Race/ethnicity and socioeconomic factors are associated with worse cancer outcomes. Our aim was to determine the association of these factors with receipt of surgery and multimodality therapy for cholangiocarcinoma. METHODS: Patients with cholangiocarcincoma in the National Cancer Database were identified. Racial/ethnic groups were defined as non-Hispanic White, non-Hispanic Black, Asian, and Hispanic. Socioeconomic factors were insurance status, income, and education. RESULTS: Of 12 095 patients with non-metastatic cholangiocarcinoma, 42% received surgery. Black race was associated with decreased odds of receiving surgery (odds ratio [OR]: 0.66l; P < .001) compared to White patients. Socioeconomic factors accounted for 21% of this disparity. Accounting for socioeconomic and clinicopathologic variables, Black race (OR: 0.73; P < .001), uninsured status (OR: 0.43; P < .001), and Medicaid insurance (OR: 0.63; P < .001) were all associated with decreased receipt of surgery. Of 4808 patients who received surgery, 47% received multimodality therapy. There were no racial/ethnic or socioeconomic differences in receipt of multimodality therapy once patients accessed surgical care. Similar results were seen in patients with advanced disease who received chemotherapy as primary treatment. CONCLUSION: Racial/ethnic and socioeconomic disparities exist in treatment for cholangiocarcinoma, however only for primary treatment. In patients who received surgery or chemotherapy, there were no disparities in receipt of multimodality therapy. This emphasizes the need to improve initial access to health care for minority and socioeconomical disadvantaged patients.

Imaging features of combined hepatocellular and cholangiocarcinoma compared with those of hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in a Chinese population.

AIM: To determine the enhanced computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) in Chinese patients. MATERIALS AND METHODS: Patients with histopathologically proven cHCC-CC (n=54) were compared with hepatocellular carcinoma (HCC; n=41) and cholangiocellular carcinoma (CCC; n=41) patients. Clinical information was measured in all patients. Tumour size, tumour margins, signs of cirrhosis, pseudocapsule, capsular retraction, rim enhancement, intrahepatic biliary dilatation, portal vein thrombosis, upper abdominal lymphadenopathy, were assessed on CT and/or MRI. The dynamic pattern of enhancement was also assessed. RESULTS: The majority (81.5%) of cHCC-CC patients had positive hepatitis B serology. The presence of cirrhosis and tumour blood vessels was comparable in cHCC-CC and HCC, but significantly lower in CCC (p>0.05). The presence of ill-defined margin and regional lymphadenopathy was comparable in cHCC-CC and CCC, but significantly lower in HCC (p>0.05). The pseudocapsule, capsular retraction, biliary dilatation, rim enhancement, and abnormal perfusion were significantly different between the three types of lesions, with cHCC-CC being intermediate between HCC and CCC. Nearly half of the cHCC-CC tumours (25; 46.3%) showed the wash-in and wash-out enhancement pattern; the gradual, persistent, and mixed patterns were seen in 12 (22.2%), 5 (9.3%), and 12 (22.2%) tumours, respectively. CONCLUSION: The majority of cHCC-CC tumours occur against a background of positive hepatitis B serology and cirrhosis. Imaging findings vary widely between cHCC-CC tumours. In the present series, the enhancement pattern of cHCC-CC tumours was HCC-like in most cases.

Racial, Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic Cholangiocarcinoma in the United States; 1995-2014.

INTRODUCTION AND AIM: Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014). MATERIAL AND METHODS: We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality. RESULTS: Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year allcause mortality (HR = 1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, and Blacks and American Indians/Alaska Natives. CONCLUSION: The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.

Occult hepatitis B virus infection in Chinese cryptogenic intrahepatic cholangiocarcinoma patient population.

BACKGROUND: There is no information available about occult hepatitis B virus (HBV) infection (OBI) in individuals with intrahepatic cholangiocarcinoma (ICC). GOALS: To investigate the correlation between OBI and ICC. STUDY: A retrospective case-control study was conducted. The cases were 183 cryptogenic ICC patients (group I), and the controls were 549 healthy individuals (group II). The cases and controls were matched for age, sex, and inhabitancy. Adjusted odds ratios and 95% confidence intervals were calculated. Intrahepatic total HBV DNA in 63 paraffin-embedded samples was collected from patients in group I (n=44), HBV-associated ICC patients (n=3), and hepatic cavernous hemangioma patients with seronegative HBsAg (hepatitis B S antigen) (group III; n=16). We determined the levels of serum and intrahepatic HBV DNA and compared the level of intrahepatic HBV DNA in 44 cryptogenic patients from group I with the level in the patients from group III. RESULTS: Compared with group II, group I had a lower prevalence of anti-HBs (antibody against HBsAg) and a higher prevalence of anti-HBe (antibody against hepatitis B e antigen) and anti-HBc (antibody against hepatitis B c antigen). Multivariate analysis confirmed that anti-HBe and anti-HBc positivity were associated with ICC. The odds ratios and 95% confidence intervals for anti-HBe and anti-HBc were 2.482 and 1.482-4.158, 4.556 and 2.938-7.066, respectively. Compared with group III, cryptogenic ICC cases showed more frequent detection of intrahepatic total HBV DNA (63.64% vs. 18.75%, P=0.002). CONCLUSIONS: OBI may represent an important risk factor for ICC. HBsAg seroclearance does not signify eradication of HBV and may not entirely prevent the development of ICC.

Peripheral intrahepatic cholangiocarcinoma occurring in patients without cirrhosis or chronic bile duct diseases: epidemiology and histopathology of distant nontumoral liver in 57 White patients.

BACKGROUND/AIM: Peripheral intrahepatic cholangiocarcinoma (ICC) occurring mainly in the absence of cirrhosis represents an increasing subgroup of primary liver tumors in Western countries. Histopathologic changes in the non-neoplastic liver in this context are not well characterized. PATIENTS AND METHODS: We assessed the clinical characteristics and histopathologic changes in the distant nontumoral liver of 57 consecutive White patients (34 men, mean age 59 years) referred to one medical and one surgical liver institution over a 16-year period who developed a peripheral ICC in the absence of cirrhosis or bile duct disease. RESULTS: High alcohol consumption was observed in 11 patients (20%), 38 patients (66%) had a BMI of 25 kg/m or more, 22 patients (40%) had diabetes, two patients had hepatitis B virus infection, two others had hepatitis C virus infection, three patients had genetic hemochromatosis, and two patients had cutaneous porphyria tarda. The distant nontumoral liver was normal in 10 patients (18%). The two main histopathologic changes observed were macrovesicular steatosis (>10% of hepatocytes) in 38 patients (66%), including 11 patients (19%) with steatohepatitis, and moderate or intense hepatocyte iron overload in 22 patients (38%). CONCLUSION: This study shows a high prevalence of macrovesicular steatosis associated or not with steatohepatitis and iron overload in patients who develop peripheral ICC in the absence of cirrhosis or bile duct disease.

Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review.

BACKGROUND AND AIM: A number of studies have shown that hepatitis virus infections may be associated with cholangiocarcinoma (CC). However, the relationship between hepatitis B virus (HBV) infection and CC, especially intrahepatic cholangiocarcinoma (ICC), is still controversial. METHODS: Relevant studies were identified by searching PUBMED, EMBASE and Web of Science Datebases up to September 2011. Pooled risk estimates were calculated using a random-effects model. Potential sources of heterogeneity were performed by subgroup analyses. A total of 18 papers were included in this meta-analysis. RESULTS: The pooled risk estimate of all studies showed a statistically significant increased risk of CC among individuals with HBV infection (rate ratio [RR]: 2.66; 95% confidence interval [CI]: 1.97, 3.60). Compared with those without HBV infection, persons with HBV infection had an increased risk of intra-CC (ICC) (RR: 3.42; 95% CI: 2.46, 43.74), extrahepatic CC (OR: 1.46; 95% CI: 0.98, 2.17), and CC (OR: 2.03; 95% CI: 1.15, 3.56). In a subgroup analysis of HBV infection and risk of ICC, the pooled risk estimate of studies in Asians (RR: 3.63; 95% CI: 2.56, 5.13) was higher than that in non-Asians (RR: 1.93; 95% CI: 0.78, 4.76). A Begg funnel plot and Egger test revealed no evidence for publication bias. CONCLUSIONS: This meta-analysis shows that HBV is associated with increased risk of CC, especially for ICC. Further investigation is needed to focus on the mechanism by which HBV may be involved in the pathogenesis of CC.

Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation.

OBJECTIVES: To investigate whether Helicobacter spp. infection and the cagA of H. pylori are associated with hepatobiliary pathology, specifically biliary inflammation, cell proliferation and cholangiocarcinoma (CCA). METHODS: Helicobacter species including H. pylori, H. bilis and H. hepaticus were detected in the specimens using the polymerase chain reaction (PCR). Biliary inflammation of the liver and gallbladders was semi-quantitatively graded on hematoxylin and eosin (H&E)-stained slides. Biliary proliferation was evaluated by immunohistochemistry using the Ki-67-labelling index. RESULTS: Helicobacter pylori was found in 66.7%, 41.5% and 25.0% of the patients in the CCA, cholelithiasis and control groups (P < 0.05), respectively. By comparison, H. bilis was found in 14.9% and 9.4% of the patients with CCA and cholelithiasis, respectively (P > 0.05), and was absent in the control group. The cagA gene of H. pylori was detected in 36.2% and 9.1% of the patients with CCA and cholelithiasis, respectively (P < 0.05). Among patients with CCA, cell inflammation and proliferation in the liver and gallbladder were significantly higher among those DNA H. pylori positive than negative. CONCLUSIONS: The present findings suggest that H. pylori, especially the cagA-positive strains, may be involved in the pathogenesis of hepatobiliary diseases, especially CCA through enhanced biliary cell inflammation and proliferation.

Genetic factors in the pathogenesis of cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is increasing in incidence, but its pathogenesis remains poorly understood. Chronic inflammation of the bile duct and cholestasis are major risk factors, but most cases in the West are sporadic. Genetic polymorphisms in biliary transporter proteins have been implicated in benign biliary disease and, in the case of progressive familial cholestasis, have been associated with childhood onset of CC. In the current study, five biologically plausible candidate genes were investigated: ABCB11 (BSEP), ABCB4 (MDR3), ABCC2 (MRP2), ATP8B1 (FIC1) and NR1H4 (FXR). METHODS: DNA was collected from 172 Caucasian individuals with confirmed CC. A control cohort of healthy Caucasians was formed. Seventy-three SNPs were selected using the HapMap database to capture genetic variation around the five candidate loci. Genotyping was undertaken with a competitive PCR-based system. Confirmation of Hardy-Weinberg equilibrium and Cochran-Armitage trend testing were performed using PLINK. Haplotype frequencies were compared using haplo.stats. RESULTS: All 73 SNPs were in Hardy-Weinberg equilibrium. Four SNPs in ABCB11 were associated with altered susceptibility to CC, including the V444A polymorphism, but these associations did not retain statistical significance after Bonferroni correction for multiple testing. Haplotype analysis of the genotyped SNPs in ATP8B1 identified significant differences in frequencies between cases and controls (global p value of 0.005). CONCLUSION: Haplotypes in ATP8B1 demonstrated a significant difference between CC and control groups. There was a trend towards significant association of V444A with CC. Given the biological plausibility of polymorphisms in ABCB11 and ATP8B1 as risk modifiers for CC, further study in a validation cohort is required.

Epidemiology of hilar cholangiocarcinoma in Egypt: single center study.

BACKGROUND/AIMS: Cholangiocarcinoma is the second most frequent malignant tumor of the liver after hepatocellular carcinoma. The incidence rates of hilar cholangiocarcinoma (CC) vary greatly among different areas of the world, this variation is related to distribution of risk factors. The aim of this work is to study epidemiology and possible risk factors in the North East delta of Egypt. METHODOLOGY: This study included 440 patients with hilar cholangiocarcinoma who were admitted to the Gastrointestinal Surgical Center, Mansoura University between January 1995 and October 2004. After complete evaluation by thorough history, clinical examination, biochemical assessment including liver function tests, kidney function tests, blood picture and serology of viral markers, tumor markers and radiological investigation. RESULTS: The mean age was 54.49 +/- 12.8 (range 23 to 82 year). Male to female ratio was 1.7:1, with increasing annual incidence from 22 patients at 1995 up to 68 patients in 2003 and 60 patients in the first 10 months of 2004. Hilar CC is common in patients coming from rural areas especially in Dakahlia government area (41%). All patients presented with jaundice, while weight loss was presented in 41%, and right upper abdominal pain in 37% of patients. Positive history of schistosomiasis infection was encountered in 66.5% while typhoid infection was in 52% of patients with high prevalence of both in rural versus urban (89% vs. 13%, p < 0.001 & 66% vs. 25%, p < 0.001). Laboratory assessment revealed 238 (54%) patients HCV positive while HBs antigen positive in 10 (2%) with high significant increase of HCV in rural versus urban (70% vs. 16%, p < 0.001). Gallstones was significantly higher in rural versus urban (28% vs. 40%, p = 0.016). The laboratory data showed highly significant increase in serum alkaline phosphatase, CA19.9 (26.9 +/- 1 4.4mg/dL, 56.3 +/- 30.6 KAU, 517.8 +/- 279.2 u/mL respectively). CONCLUSIONS: We conclude that, the number of newly diagnosed cases increases annually, it is common in males especially in farmers and rural residents. Liver cirrhosis, HCV, bilharziasis, chronic typhoid infection and gallstones can be possible risk factors for hilar cholangiocarcinoma in Egypt.

Racial and ethnic variations in the epidemiology of intrahepatic cholangiocarcinoma in the United States.

BACKGROUND/AIMS: Despite the global increase in the incidence of intrahepatic cholangiocarcinoma, regional variations occur. To assess the potential contribution of racial/ethnic factors, we assessed the epidemiology of these cancers in different racial and ethnic groups in the United States. METHODS: Disease prevalence, mortality and survival rates for different racial and ethnic groups were obtained from the surveillance, epidemiology and end results survey database. RESULTS: The age-adjusted prevalence was highest for Hispanics (1.22 per 100 000) and lowest for Blacks (0.3 per 100 000). Age-adjusted mortality rates were higher for American Indian/Alaska Natives and Asian/Pacific Islanders compared with other groups. However, mortality rates increased by greater than 3.5% annual for all racial or ethnic groups except for American Indian/Pacific Islanders in whom mortality rates decreased by 0.2% annually. The increase in mortality rates was greatest for Hispanic women aged between 40 and 49 years. Prevalence and survival were significantly higher in Hispanic women in contrast to gender differences observed in other groups. CONCLUSIONS: Significant racial and ethnic variations occur in the epidemiology of intrahepatic cholangiocarcinoma within geographically defined regions in the United States These may reflect genetic, socioeconomic or cultural predispositions to cancer.

Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?

BACKGROUND/AIMS: The incidence of intrahepatic cholangiocarcinoma (ICC) has been reported to be increasing in the USA. The aim of this study is to examine whether this is a true increase or a reflection of improved detection or reclassification. METHODS: Using data from the Surveillance Epidemiology and End Results (SEER) program, incidence rates for ICC between 1975 and 1999 were calculated. We also calculated the proportions of cases with each tumor stage, microscopically confirmed cases, and the survival rates. RESULTS: A total of 2864 patients with ICC were identified. The incidence of ICC increased by 165% during the study period. Most of this increase occurred after 1985. There were no significant changes in the proportion of patients with unstaged cancer, localized cancer, microscopic confirmation, or with tumor size <5 cm during the period of the most significant increase. The 1-year survival rate increased significantly from 15.8% in 1975-1979 to 26.3% in 1995-1999, while 5-year survival rate remained essentially the same (2.6 vs. 3.5%). CONCLUSIONS: The incidence of ICC continues to rise in the USA. The stable proportions over time of patients with early stage disease, unstaged disease, tumor size <5 cm, and microscopic confirmation suggest a true increase of ICC.

Gall bladder cancer, extrahepatic bile duct cancer and ampullary carcinoma in New Zealand: Demographics, pathology and survival.

INTRODUCTION: The aim of present paper was to document the incidence of gall bladder cancer, cancer of the extrahepatic bile ducts and ampullary carcinoma in New Zealand. METHODS: Data were collected from the New Zealand Cancer Registry from 1980 to 1997 and combined with national census statistics to give crude and age standardized incidence rates. RESULTS: Over the 18-year study period, 226 carcinomas of the ampulla of Vater, 608 gall bladder cancers, and 486 extrahepatic cholangiocarcinomas were registered. The age standardized incidence rates for gall bladder carcinoma in all New Zealanders were 0.41/100 000 in men and 0.74/100 000 in women. The age standardized incidence rates for gall bladder cancer in Maori were 1.49/100 000 in Maori men and 1.59/100 000 in Maori women. The corresponding age standardized incidence rates for extrahepatic bile duct cancers were 0.67/100 000 in men and 0.45/100 000 in women. There were insufficient cases to calculate an age standardized incidence in Maori or Pacific Islanders. For carcinoma of the ampulla, the age standardized rates were 0.34/100 000 in men and 0.25/100 000 in women. There were insufficient cases to calculate an age standardized incidence rate for Maori or Pacific Islanders. When histology was defined adenocarcinoma was the most common form of cancer occurring in 66% of gall bladder cancers, 91% of extrahepatic bile duct cancers and 70% of ampullary cancers. Most tumours were advanced at presentation with regional or distant metastases present in 72% of gall bladder cancers, 63% of extrahepatic bile duct cancers and 69% of ampullary tumours at diagnosis. Survival was poor with median survivals of 86 days, 151 days and 440 days recorded for gall bladder cancer, extrahepatic bile duct cancer and ampullary cancer, respectively. CONCLUSIONS: The demographic profile, pathology and survival of patients with gall bladder cancer, extrahepatic bile duct cancer and ampullary carcinoma are similar in New Zealand to that of other Western countries. However New Zealand Maori have a relatively high incidence of gall bladder cancer, and the incidence is equal in both Maori men and women, while cancers of the extra-hepatic bile duct and ampulla of Vater are rare in Maori. In comparison, cancers of the gall bladder, extrahepatic bile ducts and ampulla are rare in Pacific Islanders.

Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States.

Clinical observations suggest a recent increase in intrahepatic biliary tract malignancies. Thus, our aim was to determine recent trends in the epidemiology of intrahepatic cholangiocarcinoma in the United States. Reported data from the Surveillance, Epidemiology, and End Results (SEER) program and the United States Vital Statistics databases were analyzed to determine the incidence, mortality, and survival rates of primary intrahepatic cholangiocarcinoma. Between 1973 and 1997, the incidence and mortality rates from intrahepatic cholangiocarcinoma markedly increased, with an estimated annual percent change (EAPC) of 9.11% (95% CI, 7.46 to 10.78) and 9.44% (95%, CI 8.46 to 10.41), respectively. The age-adjusted mortality rate per 100,000 persons for whites increased from 0.14 for the period 1975-1979 to 0.65 for the period 1993-1997, and that for blacks increased from 0.15 to 0.58 over the same period. The increase in mortality was similar across all age groups above age 45. The relative 1- and 2-year survival rates following diagnosis from 1989 to 1996 were 24.5% and 12.8%, respectively. In conclusion, there has been a marked increase in the incidence and mortality from intrahepatic cholangiocarcinoma in the United States in recent years. This tumor continues to be associated with a poor prognosis.