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.

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.

Detection of hepatitis B virus DNA in paraffin-embedded intrahepatic and extrahepatic cholangiocarcinoma tissue in the northern Chinese population.

This study explored the importance of hepatitis B virus infection in cholangiocarcinoma pathogenesis in northern China. The clinical data of 66 patients with cholangiocarcinoma were analyzed. The hepatitis B virus gene was amplified using nested polymerase chain reaction, and the hepatitis B virus-related antigen was detected using immunohistochemistry in formalin-fixed, paraffin-embedded tissue from patients with intrahepatic cholangiocarcinoma (n = 23) and extrahepatic cholangiocarcinoma (n = 43). Hepatitis B surface antigen seropositivity was found in 52.2% (12/23) of intrahepatic cholangiocarcinoma cases and 13.9% (6/43) of extrahepatic cholangiocarcinoma cases. Hepatitis B virus DNA (X region) was detectable in 34.8% (8/23) of intrahepatic cholangiocarcinoma cases. Hepatitis B surface antigen and/or hepatitis B core antigen was detectable in 30.4% (7/23) of intrahepatic cholangiocarcinoma cases. All cases with detected viral protein were also positive for hepatitis B virus DNA. In contrast, no hepatitis B virus antigens or hepatitis B virus gene was detected in any of the 43 extrahepatic cholangiocarcinoma cases. Our findings strongly suggest that chronic hepatitis B virus infection is a significant risk factor for intrahepatic cholangiocarcinoma, but not for extrahepatic cholangiocarcinoma, in northern China. Hepatitis B virus infection is potentially independently associated with intrahepatic cholangiocarcinoma.

Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population.

UNLABELLED: Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer in the general population, we studied 62,279 white individuals from The Copenhagen City Heart Study and The Copenhagen General Population Study, randomly selected to reflect the adult Danish population aged 20 to 80+ years. Endpoints were recorded from January 1976 through May 2009. During a mean follow-up of, respectively, 31 and 4.4 years, 3124 participants developed symptomatic gallstone disease and 30 developed biliary cancer. The multifactorially adjusted hazard ratio for symptomatic gallstone disease was 1.9 (95% confidence interval, 1.7-2.1) in DH heterozygotes (prevalence, 12%), and 3.3 (2.3-4.6) in HH homozygotes (0.4%) versus noncarriers (P for trend <0.001). Mean age at onset of symptomatic gallstone disease was 56 years for noncarriers, 54 for DH heterozygotes, and 52 for HH homozygotes (P for trend <0.001). The fraction of all gallstones attributed to D19H was 11%. The multifactorially adjusted hazard ratio for biliary cancer was 4.0 (1.9-8.4) in DH heterozygotes and HH homozygotes combined versus noncarriers (P < 0.001). The fraction of all biliary cancers attributed to the D19H genotype was 27%. Finally, D19H genotype associated with stepwise increases in plasma levels of alanine aminotransferase and gamma glutamyltransferase of up to 14% and 25% in HH homozygotes, and with corresponding stepwise reductions in plasma levels of total and low-density lipoprotein cholesterol of up to 5% versus noncarriers (all comparisons, P for trend <0.001). CONCLUSION: In this general population cohort, ABCG8 D19H genotype was an important predictor of both symptomatic gallstone disease and biliary cancer.

Racial disparity in surgical mortality after major hepatectomy.

BACKGROUND: The relationship between surgical mortality and race has not been studied for major hepatectomy. We sought to quantify and explore the nature of racial disparities in surgical mortality after major hepatectomy in a nationally representative cohort of patients. STUDY DESIGN: We conducted a retrospective cohort study using data from the Nationwide Inpatient Sample (1998 to 2005). Adult patients undergoing major hepatectomy within 1 day of nontrauma admission were included. Logistic regression models were used to assess the variation of in-hospital mortality by race after adjustment for other risk factors. RESULTS: The study cohort consisted of 3,552 observations representing 17,794 patients undergoing major hepatectomy. Unadjusted analyses revealed that African-American patients had a two-fold increased odds of surgical mortality (odds ratio 2.22, 95% CI 1.38 to 3.57) relative to Caucasians. Even after adjustment for other risk factors, African Americans had a two-fold increased odds of surgical mortality (odds ratio 2.15, 95% CI 1.28 to 3.61) relative to Caucasians. Stratified analyses restricting the cohort to patients without comorbidities, those with neoplasms, those with private insurance, or those treated at high-volume hospitals all demonstrated racial disparities in surgical mortality. CONCLUSIONS: In-hospital mortality after major hepatectomy varies substantially by race. After adjustment for potential confounders, African-American patients have two-fold higher population-level odds of surgical mortality than Caucasian patients do. Our analyses suggest that clinical factors, insurance status, and hospital factors do not account for these differences. Additional studies to clarify the nature of this disparity and identify targets for intervention are warranted.

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.

Granular cell tumor of the biliary system: a report of 2 cases with cytologic diagnosis on endoscopic brushing.

BACKGROUND: Granular cell tumors (GCTs) of biliary system are rare. GCTs show a striking preponderance for young, black females, who generally present with obstructive jaundice. To our knowledge, these are the first 2 reports of GCT of biliary system identifed on endoscopic brushing cytology. CASES: In case 1, a 24-year-old, black woman presented with a 5-month history of pruritus. Radiographic studies demonstrated a mass in the distal common bile duct. Endoscopic biopsy and bile duct brushing were diagnosed as GCT. A Whipple procedure was confirmatory of GCT. In case 2, a 38-year-old, black female presented with a 7-month history of pruritus and jaundice. Radiographic studies showed a stricture of the common hepatic duct at the hilum. Endoscopic brushing cytology of the stricture yielded only a few sheets of granular cells that were missed on initial screening. Suspicion of cholangiocarcinoma prompted surgery, and final histopathology showed GCT. Both patients were well 1 1/2 and 6 years after presentation. CONCLUSION: GCT of the bile duct can be diagnosed on endoscopic brushing and should be considered in the cytologic differential diagnosis in the appropriate clinical settings.

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.

Cirrhosis and primary liver cancer amongst first generation migrants in England and Wales.

OBJECTIVE: To examine mortality from cirrhosis of the liver and primary liver cancer among first generation migrants to England and Wales. DESIGN: Comparison of standardised mortality ratios (SMRs) for cirrhosis of the liver and primary liver cancer in men and women aged 20-69, by country of birth for the five year period 1988-1992. SETTING: England and Wales. RESULTS: There was a statistically significant two-fold excess of mortality from cirrhosis of the liver among male migrants from East Africa (SMR 286), India (SMR 261) and Bangladesh (SMR 254) as well as men born in Scotland (SMR 253) and Ireland (SMR252). Among women, only those born in Scotland (SMR 254) and Ireland (SMR 237) showed significant excess mortality. For liver cancer, significant excess mortality occurred among men born in the Caribbean (SMR 312), Bangladesh (910) and the African Commonwealth other than East Africa (1014), with Scottish and Irish born men showing more moderate excesses (136 and 170, respectively). SMRs were elevated also in all groups of foreign-born women but, probably owing to the small numbers of deaths, none of the findings reached statistical significance. CONCLUSIONS: Of public health concern is the excess mortality from cirrhosis in first generation immigrants to England and Wales from Scotland and Ireland (men and women) and in male migrants from India, Bangladesh and East Africa. Of equal concern is increased mortality from liver cancer in all foreign-born groups of both sexes, particularly among Bangladeshis, and African-Caribbeans. As well as promoting sensible drinking among immigrant men, specific preventive measures for those of Bangladeshi, African-Caribbean origin may include selective screening for hepatitis B and C and other tumour markers. Screening for liver cancer using imaging techniques needs further investigation. The benefit/cost ratio should be assessed by the Screening Committees of the UK Departments of Health. At local level, variation in incidence and prevalence of hepatic disease and feasible prevention programmes should be assessed within developing health improvement programmes.

Obstructive jaundice in the South African black population.

We report the causes of obstructive jaundice in 56 black South African patients. Chronic pancreatitis and malignant biliary obstruction occurred with equal frequency. These two conditions may be difficult to differentiate clinically and radiologically, and only operative pancreatic biopsy may be diagnostic. Choledocholithiasis caused jaundice in only 7.1% of the patients, reflecting the relatively low prevalence of gallstones in this population.