Gallbladder and extrahepatic bile duct cancers in the Americas: Incidence and mortality patterns and trends

Trends in gallbladder cancer incidence and mortality in populations across the Americas can provide insight into shifting epidemiologic patterns and the current and potential impact of preventative and curative programs. Estimates of gallbladder and extrahepatic bile duct cancer incidence and mortality for the year 2018 were extracted from International Agency for Research on Cancer (IARC) GLOBOCAN database for 185 countries. Recorded registry-based incidence from 13 countries was extracted from IARCs Cancer Incidence in Five Continents series and corresponding national deaths from the WHO mortality database. Among females, the highest estimated incidence for gallbladder and extrahepatic bile duct cancer in the Americas were found in Bolivia (21.0 per 100,000), Chile (11.7) and Peru (6.0). In the US, the highest incidence rates were observed among Hispanics (1.8). In the Chilean population, gallbladder cancer rates declined in both females and males between 1998 and 2012. Rates dropped slightly in Canada, Costa Rica, US Whites and Hispanics in Los Angeles. Gallbladder cancer mortality rates also decreased across the studied countries, although rising trends were observed in Colombia and Canada after 2010. Countries within Southern and Central America tended to have a higher proportion of unspecified biliary tract cancers. In public health terms, the decline in gallbladder cancer incidence and mortality rates is encouraging. However, the slight increase in mortality rates during recent years in Colombia and Canada warrant further attention. Higher proportions of unspecified biliary tract cancers (with correspondingly higher mortality rates) suggest more rigorous pathology procedures may be needed after surgery.     

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992–2013) to conduct a population-based, case–control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63–41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73–10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03–7.75]), gallbladder cancer (2.06 [1.27–3.33]) and ampulla of Vater cancer (6.29 [4.29–9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30–6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94–8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers.     

Biliary brush cytology in the assessment of biliary strictures at a tertiary center in Iran

Background: Confirmation of cholangiocarcinoma and other malignant bile duct stenosis is challenging. The aim of the current study was to assess the accuracy of brush cytology for diagnosis of malignant biliary strictures. Methods: 105 patients with hepatic biliary strictures undergoing ERCP were included in this study. Prospectively collected data included symptoms, results of biochemical testing and imaging procedures, as well as details of ERCP. Exclusion criteria were: 1) strictures that would not permit passage of guidewire and brush accession; and 2) post-operative strictures. Brushings of the bile duct strictures were performed. All patients were followed for at least 6 months. The final diagnosis was confirmed following surgery, histopathological diagnosis of the lesion, radiological infiltration of adjacent organs or metastases, or after at least a 6-month follow-up. Results: 88 brush samples from 88 patients were of appropriate quality. The overall diagnostic sensitivity and specificity for malignant nature of biliary strictures were 40.7% and 100%, respectively. The sensitivity was 66.6 % for ampullary carcinomas, 36.3% for pancreatic cancer and 32.5% for cholangiocarcinomas. Conclusions: Despite the low sensitivity, due to the relative ease and safety, brush cytology should remain the first choice for diagnosis of causes of biliary strictures.     

Prognostic factors in gallbladder and biliary tract cancer

Background. Cancers of the gallbladder and bile ducts are uncommon neoplasms with poor survival. Prognostic factors are not well defined because of the scant number of patients reported through series of cases. Methods. We reviewed the medical records of patients with cancer of the bile ducts and gallbladder between the years 1979 and 1998, and analyzed their characteristics according to location (gallbladder, extrahepatic biliary tract, intrahepatic biliary tract, and Klatskin tumors). Results. One hundred and sixty-eight patients were included; the mean follow-up time was 238 ± 54 d. The tumor found at more advanced stages was the biliary tract tumor. Overall survival time was 254 ± 40 d. Location did not influence survival. The factors significantly associated to increased survival were age at diagnosis less than 50 yr (p=0.0065), surgical treatment (p<0.001), adjuvant chemotherapy and radiotherapy (p<0.001 and p=0.0072, respectively), surgical treatment with curative purpose (p<0.001), stage of the disease (p<0.0001), absence of jaundice (p=0.0425), and absence of weight loss (p=0.0446). In the multivariate analysis the significant variables were age, surgical treatment, adjuvant chemotherapy, surgery with curative purpose, stage of the disease, and absence of jaundice. Conclusions. Cancers of the bile ducts are neoplasms known to have a poor prognosis. Chemotherapy was an independent survival factor despite the context, there is need of future studies to define its role on this disease.     

The relationship between vegetable/fruit consumption and gallbladder/bile duct cancer: A population‐based cohort study in Japan

Vegetable and fruit consumption may have a protective effect against several types of cancers. However, the effect on biliary cancers is unclear. We investigated the association of vegetable/fruit consumption with the risks of gallbladder cancer (GBC), intrahepatic bile duct cancer (IHBDC) and extrahepatic bile duct cancer (EHBDC) in a population‐based prospective cohort study in Japan. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model, and the exposure level was categorized into quartiles, with the lowest group used as the reference. A total of 80,371 people aged 45 to 74 years were enrolled between 1995 and 1999, and followed up for 1,158,632 person‐years until 2012, during which 133 GBC, 99 IHBDC, and 161 EHBDC cases were identified. Increased consumption of total vegetable and fruit was significantly associated with a decreased risk of EHBDC (HR = 0.49; 95% CI: 0.29–0.81 for the highest group; p trend = 0.005). From the analysis of relevant nutrients, significantly decreased risk of EHBDC was associated with folate and insoluble fiber (HR = 0.48, 0.53; 95% CI: 0.28–0.85, 0.31–0.88 for the highest group; p trend = 0.010, 0.023; respectively), and a significant trend of decreased EHBDC risk associated with vitamin C was observed (p trend = 0.029). No decreased risk of GBC and IHBDC was found. Our findings suggest that increased vegetable/fruit consumption may decrease a risk of EHBDC, and folate, vitamin C, and insoluble fiber might be key contributors to the observed protective effect.     

Malignant melanoma incidence in Connecticut (United States): time trends and age-period-cohort modeling by anatomic site

This study examined time trends and age-period-cohort patterns in the incidence of cutaneous malignant melanoma (CMM) by gender and anatomic site in Connecticut (United States) between 1950 and 1989, using data from the population-based Connecticut Tumor Registry. A total of 8,249 invasive CMM incident cases were included. Cases were grouped into melanomas of the head and neck, upper limb, lower limb, and trunk. Between 1950 and 1989, rates increased substantially for all sites. The largest relative increases occurred in melanoma of the upper limb for both males and females; the largest absolute increase occurred for melanoma of the trunk in males; and the smallest increase occurred in head and neck melanoma in females. Recent trends for time periods 1970–89 among birth cohorts 1930–69 indicated that the rate of increase of CMM is slowing substantially among males, but not among females. Nevertheless, continued overall increases in CMM incidence are likely in Connecticut in the 1990s in both genders, with a decrease in the male-female ratio. The age-period-cohort patterns were significantly different between the genders and among anatomic sites, suggesting different trends in carcinogenic exposures (mainly ultraviolet radiation from the sun) or etiologic distinctions between males and females and among the sites.This study was supported by the National Institute of Health grant # CA-62986, and #CA-30931. Dr Dubrow received support from a National Cancer Institute Preventive Oncology Academic Award (K07-CA01463).     

Trends in colorectal cancer incidence in Norway 1962–2006: an interpretation of the temporal patterns by anatomic subsite

There have been rapid increases in the incidence of colorectal cancer in Norway since the 1960s, and rates rank among the highest worldwide. The primary objectives are to describe trends in left‐ and right‐sided colon cancer and rectal cancer by calendar period and birth cohort and to generate hypotheses as to the etiological factors in operation. Although the age‐adjusted incidence rates of both colon and rectal cancer increased in Norway in both sexes up to the 1980s, subsite‐ and age‐specific analyses reveal a deceleration in the rate of increase thereafter, apparent in the rates of both left‐sided colon and rectal cancer. Overall trends in incidence of right‐sided colon cancer continue to increase in both sexes. Rates in both left‐ and right‐sided colon cancers have tended to stabilize or decrease among successive generations born after 1950, however, while incidence rates of rectal cancer appear to be increasing in recent generations. The all‐ages rates are thus in keeping with the commonly reported “left to right shift” of colon cancer, although standardization masks important observations. The cohort patterns provide further evidence that factors earlier in life are important, and while the complex etiology makes interpretation difficult, modifications in diet, obesity and physical activity in Norway are likely among the drivers of the trends in one or more of the colorectal subsites examined. In summary, the recent downturn in the disease at younger ages provides some reason for optimism, although possible increases in rectal cancer among recent birth cohorts are of concern.     

Biliary tract cancer and stones in relation to chronic liver conditions: A population-based study in Shanghai, China

Biliary tract cancers are relatively rare but fatal tumors. Apart from a close link with gallstones and cholangitis, risk factors for biliary tract cancer are obscure. Chronic liver conditions, including liver cirrhosis, have been linked to a higher risk of biliary tract cancer. In a population-based case-control study conducted in Shanghai, China, we investigated the relationships of a history of chronic hepatitis and liver cirrhosis as well as a family history of liver cancer with biliary tract cancer risk. The study included 627 patients with biliary tract cancers (368 gallbladder, 191 bile duct and 68 ampulla of Vater), 1,037 patients with biliary stones (774 gallbladder stones and 263 bile duct stones) and 959 healthy subjects randomly selected from the population. Bile duct cancer was associated with self-reports of chronic liver conditions, including a history of chronic hepatitis (OR = 2.0, 95% CI 0.9-4.4), liver cirrhosis (OR = 4.7, 95% CI 1.9-11.7) and a family history of primary liver cancer (OR = 2.0, 95% CI 1.0-3.9). The excess risk persisted after adjustment for gallstones and were more pronounced among subjects without gallstones (OR = 5.0, 95% CI 1.3-20.0 and OR = 4.9, 95% 2.0-12.2, respectively). History of liver conditions was also associated with an excess of biliary stones (OR = 1.9, 95% CI 1.2-3.0). No association was found for cancers of the gallbladder and ampulla of Vater. A history of chronic hepatitis and cirrhosis may be risk factors for extraheptic bile duct cancer. Given that chronic infection with hepatitis B virus (HBV) is the most common cause of liver disease in China, serologic markers of HBV need to be measured in future studies to examine the link between HBV and bile duct cancer.     

Sex disparities in colorectal cancer incidence by anatomic subsite,race and age

Although incidence of colorectal cancer (CRC) in the United States has declined in recent years, rates remain higher in men than in women and the male‐to‐female incidence rate ratio (MF IRR) increases progressively across the colon from the cecum to the rectum. Rates among races/ethnicities other than Whites or Blacks have not been frequently reported. To examine CRC rates by sex across anatomic subsite, age and racial/ethnic groups, we used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program for cases diagnosed among residents of 13 registries during 1992–2006. Incidence rates were expressed per 100,000 person‐years and age‐adjusted to the 2000 US Standard Population; MF IRR and 95% confidence intervals were also calculated. Among each racial/ethnic group, the MF IRR increased fairly monotonically from close to unity for cecal cancers to 1.81 (Hispanics) for rectal cancers. MF IRRs increased with age most rapidly for distal colon cancers from <1.0 at ages <50 years to 1.4–1.9 at older ages. The MF IRR for rectal cancers also rose with age from about 1.0 to 2.0. For proximal cancer, the MF IRR was consistently <1.5; among American Indian/Alaska Natives, it was <1.0 across all ages. The MF IRRs for CRC vary markedly according to subsite and age but less by racial/ethnic group. These findings may partially reflect differences in screening experiences and access to medical care but also suggest that etiologic factors may be playing a role.     

Colorectal cancer incidence in the United States, 1999‐2004

BACKGROUND:

By using recent national cancer surveillance data, the authors investigated colorectal cancer (CRC) incidence by subpopulation to inform the discussion of demographic‐based CRC guidelines.

METHODS:

Data included CRC incidence (1999‐2004) from the combined National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program databases. Incidence rates (age‐specific and age‐adjusted to the 2000 US standard population) were reported among individuals ages 40 to 44 years, 45 to 49 years, 50 to 64 years, and ≥65 years by sex, subsite, disease stage, race, and ethnicity. Rate ratios (RR) and rate differences (RD) were calculated to compare CRC rates in different subpopulations.

RESULTS:

Incidence rates were greater among men compared with women and among blacks compared with whites and other races. Incidence rates among Asians/Pacific Islanders (APIs), American Indians/Alaska Natives (AI/ANs), and Hispanics consistently were lower than among whites and non‐Hispanics. Sex disparities were greatest in the population aged ≥65 years, whereas racial disparities were more pronounced in the population aged <65 years. Although the RD between blacks and whites diminished at older ages, the RD between APIs and whites, between AI/ANs and whites, and between non‐Hispanics and Hispanics increased with increasing age. By subsite, blacks had the highest incidence rates compared with whites and other races in the proximal and distal colon; the reverse was true in the rectum. By stage, whites had higher incidence rates than blacks and other races for localized and regional disease; for distant and unstaged disease, blacks had higher incidence rates than whites.

CONCLUSIONS:

The current findings suggested differences that can be considered in formulating targeted screening and other public health strategies to reduce disparities in CRC incidence in the United States. Cancer 2009. Published 2009 by the American Cancer Society.     

The relationship between cancer incidence,stage and poverty in the United States

We extend a prior analysis on the relation between poverty and cancer incidence in a sample of 2.90 million cancers diagnosed in 16 US states plus Los Angeles over the 2005–2009 period by additionally considering stage at diagnosis. Recognizing that higher relative disparities are often found among less‐common cancer sites, our analysis incorporated both relative and absolute measures of disparities. Fourteen of the 21 cancer sites analyzed were found to have significant variation by stage; in each instance, diagnosis at distant stage was more likely among residents of high‐poverty areas. If the incidence rates found in the lowest‐poverty areas for these 21 cancer sites were applied to the entire country, 18,000 fewer distant‐stage diagnoses per year would be expected, a reduction of 8%. Conversely, 49,000 additional local‐stage diagnoses per year would be expected, an increase of 4%. These figures, strongly influenced by the most common sites of prostate and female breast, speak to the trade‐offs inherent in cancer screening. Integrating the type of analysis presented here into routine cancer surveillance activities would permit a more complete understanding of the dynamic nature of the relationship between socioeconomic status and cancer incidence.     

Gallstones and the risk of biliary tract cancer: a population-based study in China

We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0-33.4), 8.0 (95% CI 5.6-11.4), and 4.2 (95% CI 2.5-7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR=34.3, 95% CI 19.9-59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P<0.001). Gallstone weight in gallbladder cancer was significantly higher than in gallstone patients (4.9 vs 2.8 grams; P=0.001). We estimate that in Shanghai 80% (95% CI 75-84%), 59% (56-61%), and 41% (29-59%) of gallbladder, bile duct, and ampulla of Vater cancers, respectively, could be attributed to gallstones.     

Thyroid cancer incidence attributable to overdiagnosis in the United States 1981–2011

Papillary thyroid cancer incidence has increased in the United States from 1978 through 2011 for both men and women of all ages and races. Overdiagnosis is partially responsible for this trend, although its magnitude is uncertain. This study examines papillary thyroid cancer incidence according to stage at diagnosis and estimates the proportion of newly diagnosed tumors that are attributable to overdiagnosis. We analyzed stage specific trends in papillary thyroid cancer incidence, 1981–2011, using the Surveillance, Epidemiology and End Results national cancer registries. Yearly changes in early and late‐stage thyroid cancer incidence were calculated. We estimate that the proportion of incident papillary thyroid cancers attributable to overdiagnosis in 2011 was 5.5 and 45.5% in men ages 20–49 and 50+ and 41.1 and 60.1% in women ages 20–49 and 50+, respectively. Overdiagnosis has resulted in an additional 82,000 incident papillary thyroid cancers that likely would never have caused any clinical symptoms. The detection of early‐stage papillary thyroid cancer outpaced that of late‐stage disease from 1981 through 2011, in part due to overdiagnosis. Further studies into the prevention, risk stratification and optimal treatment of papillary thyroid cancer are warranted in response to these trends.     

Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005

BACKGROUND:

Studies have reported an increasing incidence of thyroid cancer since 1980. One possible explanation for this trend is increased detection through more widespread and aggressive use of ultrasound and image‐guided biopsy. Increases resulting from increased detection are most likely to involve small primary tumors rather than larger tumors, which often present as palpable thyroid masses. The objective of the current study was to investigate the trends in increasing incidence of differentiated (papillary and follicular) thyroid cancer by size, age, race, and sex.

METHODS:

Cases of differentiated thyroid cancer (1988‐2005) were analyzed using the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) dataset. Trends in incidence rates of papillary and follicular cancer, race, age, sex, primary tumor size (<1.0 cm, 1.0‐2.9 cm, 3.0‐3.9 cm, and >4 cm), and SEER stage (localized, regional, distant) were analyzed using joinpoint regression and reported as the annual percentage change (APC).

RESULTS:

Incidence rates increased for all sizes of tumors. Among men and women of all ages, the highest rate of increase was for primary tumors <1.0 cm among men (1997‐2005: APC, 9.9) and women (1988‐2005: APC, 8.6). Trends were similar between whites and blacks. Significant increases also were observed for tumors ≥4 cm among men (1988‐2005: APC, 3.7) and women (1988‐2005: APC, 5.70) and for distant SEER stage disease among men (APC, 3.7) and women (APC, 2.3).

CONCLUSIONS:

The incidence rates of differentiated thyroid cancers of all sizes increased between 1988 and 2005 in both men and women. The increased incidence across all tumor sizes suggested that increased diagnostic scrutiny is not the sole explanation. Other explanations, including environmental influences and molecular pathways, should be investigated. Cancer 2009. © 2009 American Cancer Society.     

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m²); normal (18.5-22.9 kg/m²); overweight (23-24.9 kg/m²); and obese (25+ kg/m²). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.     

中国食管癌高发区磁县上消化道癌两个时期发病率的比较与分析

  目的  探讨我国食管癌高发区磁县上消化道癌不同时期发病率情况。  方法  分析磁县2003~2012年上消化道癌发病资料,计算年度发病率,中国人口结构标化发病率(简称中标率)和世界人口结构标化发病率(简称世标率),并分割为前后两个时期,进行年度及各年龄组比较。  结果  2003~2012年上消化道癌粗发病率为165.36/10万。其中2003~2007年粗发病率为171.55/10万,2008~2012年粗发病率为151.41/10万,后5年发病率较前5年有所降低;其中食管癌2003~2012年粗发病率为108.05/10万,前后两个时期比较(2003~2007年为116.87/10万,2008~2012年为99.58/10万),后5年较前5年明显下降;贲门癌2003~2012年总体粗发病率为31.21/10万,两个时期比较(2003~2007年为29.11/10万,2008~2012年为33.23/10万)后5年较前5年有所升高;远端胃癌2003~2012年总体粗发病率为26.10/10万,两个时期比较(2003~2007年粗发病率为25.57/10万,2008~2012年为26.60/10万)后5年较前5年略有增高。  结论  食管癌发病下降明显,但仍是磁县居民发病的首位,贲门癌明显上升,远端胃癌男性增高明显,而女性略有下降,提示需重点开展贲门癌及远端胃的防治,早诊早治非常重要。