Clinical implications of pediatric biliary intraepithelial neoplasia diagnosed from a choledochal cyst specimen.

BACKGROUND: Biliary intraepithelial neoplasia (BilIN), a noninvasive precursor of cholangiocarcinoma, can manifest malignant transformation. Since cholangiocarcinoma (CCA) may progress due to chronic inflammation in the bile ducts and gallbladder, choledochal cysts are considered a precursor to CCA. However, BilIN has rarely been reported in children, to date. METHODS: We reviewed medical records of patients (< 18 years of age, n = 329) who underwent choledochal cyst excision at Asan Medical Center from 2008 to 2022. BilIN was diagnosed in 15 patients. Subsequent analyses were performed of the demographics, surgical procedures, clinical course, and outcomes in these patients. Subgroup analysis and multivariate logistic regression test were performed to identify factors influencing BilIN occurrence. RESULTS: The mean age of the patients included in our study was 40.1 ± 47.6 months. In 15 patients, BilIN of various grades was diagnosed. Todani type I was prevalent in 80% of the patients. The median age at surgery was 17 months. During a mean follow-up of 63.3 ± 94.0 months, no adverse events such as stone formation in the remnant intrapancreatic common bile duct and intrahepatic duct or cholangiocarcinoma were observed, indicating a favorable outcome until now. CONCLUSIONS: The potential progression of choledochal cysts to BilIN in children was demonstrated. These results could underscore the importance of early and comprehensive excision of choledochal cysts, including resection margins for associated lesions and more thorough postoperative surveillance in patients with or at risk of BilIN.

Characteristics and malignancy rates of adult patients diagnosed with choledochal cyst in the West: a systematic review.

BACKGROUND: The approach to patients with choledochal cysts (CCs) remains varied and subject to institutional practices. Owing to the rarity of the disease, the optimal treatment remains poorly defined, particularly in the adult population. This study aimed to review the literature on adult patients with CCs to evaluate trends of diagnosis and management in Western countries. METHODS: A literature search of 3 electronic databases was performed on adult patients diagnosed with CCs in Western institutions. A review of published literature was completed with comprehensive screening by 2 independent reviewers. Studies were analyzed, and data on surgical approach, malignancies, and follow-up were collected. Findings are presented in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: Of the 3488 articles retrieved, 21 studies evaluated Western adults with CCs for a combined population of 1337 patients. The most common Todani subtypes included types I (64%) and IV (22%). Symptoms at presentation included abdominal pain and jaundice, although many were asymptomatic. Ultrasound was used most frequently for diagnosis, followed by computed tomography and endoscopic cholangiopancreatography. The combined malignancy rate was 10.9%, with cholangiocarcinoma being the most prevalent. Complete extrahepatic cyst resection was standard for type I and IV CCs. Among malignancies, 18.5% and 16.4% were observed in patients with prior resection and internal drainage, respectively. CONCLUSIONS: A significant proportion of patients who undergo resection of CC disease harbor malignancy. Cancer risk seems reduced but not eliminated with complete resection, which remains the standard treatment. Additional studies are needed to standardize guidelines for the diagnosis and postoperative care of patients in Western countries.

Spatio-Temporal Analysis of Cholangiocarcinoma in a High Prevalence Area of Northeastern Thailand: A 10-Year Large Scale Screening Program.

BACKGROUND: Cholangiocarcinoma (CCA) is experiencing a global increase, particularly in Northeast Thailand, which has the highest global incidence rates. However, there is a paucity of studies on CCA screening, especially in high-risk populations. This study aimed to investigate the distribution and spatial patterns of CCA in Northeast Thailand over a ten-year screening period. METHODS: The study included CCA patients from the Cholangiocarcinoma Screening and Care Program (CASCAP) between 2013 and 2022, which encompasses 20 provinces and 282 districts in Northeast of Thailand. CCA data were based on pathological diagnosis to determine the distribution and spatial patterns. RESULTS: Of the 2,515 CCA patients, approximately two-thirds were males (63.98%), and the majority were aged over 55 years (72.72%), with a mean age of 61.12 ± 9.13 years. The highest percentage of CCA cases occurred in 2014 at 19.01% of all patients, followed by 2018 at 15.23%. The overall CCA incidence rate in Northeast Thailand over ten years was 32 per 100,000 population. Hotspot statistical analysis identified high-scoring geographic clusters in the upper and middle regions, showing a tendency to expand from hotspot areas into nearby areas. CONCLUSION: The distribution of CCA in Northeast Thailand has continued to rise over the past decade, particularly in the upper and middle regions. Targeted screening in high-risk areas and increased awareness of CCA risks are crucial to mitigate its impact.

Modeling the persistence of Opisthorchis viverrini worm burden after mass-drug administration and education campaigns with systematic adherence.

Opisthorchis viverrini is a parasitic liver fluke contracted by consumption of raw fish, which affects over 10 million people in Southeast Asia despite sustained control efforts. Chronic infections are a risk factor for the often fatal bile duct cancer, cholangiocarcinoma. Previous modeling predicted rapid elimination of O. viverrini following yearly mass drug administration (MDA) campaigns. However, field data collected in affected populations shows persistence of infection, including heavy worm burden, after many years of repeated interventions. A plausible explanation for this observation is systematic adherence of individuals in health campaigns, such as MDA and education, with some individuals consistently missing treatment. We developed an agent-based model of O. viverrini which allows us to introduce various heterogeneities including systematic adherence to MDA and education campaigns at the individual level. We validate the agent-based model by comparing it to a previously published population-based model. We estimate the degree of systematic adherence to MDA and education campaigns indirectly, using epidemiological data collected in Lao PDR before and after 5 years of repeated MDA, education and sanitation improvement campaigns. We predict the impact of interventions deployed singly and in combination, with and without the estimated systematic adherence. We show how systematic adherence can substantially increase the time required to achieve reductions in worm burden. However, we predict that yearly MDA campaigns alone can result in a strong reduction of moderate and heavy worm burden, even under systematic adherence. We predict latrines and education campaigns to be particularly important for the reduction in overall prevalence, and therefore, ultimately, elimination. Our findings show how systematic adherence can explain the observed persistence of worm burden; while emphasizing the benefit of interventions for the entire population, even under systematic adherence. At the same time, the results highlight the substantial opportunity to further reduce worm burden if patterns of systematic adherence can be overcome.

Impact of socio-economic environment on incidence of primary liver cancer in France between 2006 and 2016.

BACKGROUND AND AIMS: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHOD: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. RESULTS: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9-10.66] per 100 000 person-years, Q2 11.43 [10.48-12.47] (p < .0001), Q3 11.81 [10.82-12.89] (p < .0001), Q4 12.26 [11.25-13.37] (p < .001) and Q5 11.53 [10.57-12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). CONCLUSION: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies.

Update on the risk factors for opisthorchiasis and cholangiocarcinoma in Thailand.

This study aimed to identify the recent risk factors for Opisthorchis viverrini infection and cholangiocarcinoma (CCA) to improve disease prevention. The participants were divided into the following 3 groups based on their health status: healthy control (nonOV and nonCCA), those with O. viverrini infection (OV), and those with CCA. A questionnaire was used to explore their lifestyle and behaviors. Multivariate logistic regression and backward elimination were used to identify the significant risk factors. The results showed that the significant risk factors for both O. viverrini infection and CCA were age>50 years (odd ratio (OR)=8.44, P<0.001, 95% confidence intervals (CI) 2.98-23.90 and OR=43.47, P=0.001, 95% CI 14.71-128.45, respectively) and raw fish consumption (OR=8.48, P< 0.001, 95% CI 3.18-22.63 and OR=3.15, P=0.048, 95% CI 1.01-9.86, respectively). A history of O. viverrini infection was identified as an additional risk factor for CCA (OR=20.93, P=0.011, 95% CI 2.04-215.10). This study provided an update on the risk factors for O. viverrini infection and CCA. Asymptomatic patients with O. viverrini infection, particularly those>50 years old, should be carefully monitored to prevent CCA.

Influence of misconceptions and inappropriate eating behaviors on Opisthorchis viverrini infection among at-risk populations undergoing cholangiocarcinoma screening in Northeastern Thailand.

Raw or undercooked freshwater fish consumption contributes to persistent Opisthorchis viverrini infection in Northeast Thailand. This study aims to assess the relationship between misconceptions, unhealthy eating habits, and O. viverrini infection. Data were obtained from the Cholangiocarcinoma Screening and Care Program in Northeast Thailand from 2019 to 2021. Participants were screened for O. viverrini annually over the following 2 years using the Kato-Katz technique. Misconceptions and unhealthy eating habits were assessed through questionnaires. The relationship between these factors and O. viverrini infection was evaluated using adjusted risk ratios (ARRs) and 95% confidence intervals (CIs) from generalized estimating equations under binomial regression framework. Of 5375 participants screened for O. viverrini over 3 years, infection rates were 21.53%, 10.7%, and 4.6% each year, respectively. Out of those, 636 participants responded to questions regarding misconceptions. Results showed that participants who believed in the efficacy of putting lime or red ants in Koi pla (raw fish salad) or eating Koi pla with white whiskey to kill parasites, and early-stage cholangiocarcinoma can be cured, were 41% (ARR, 1.41; 95% CI, 1.03-1.94) and 57% (ARR, 1.57; 95% CI, 1.06-2.33), respectively, more likely to be infected with O. viverrini. Our study confirms that belief in using lime or red ants in Koi pla or eating Koi pla with white whiskey to make it cooked, or early-stage cholangiocarcinoma can be cured, increases O. viverrini infection risk in high-risk populations. Changing health beliefs and eating habits is necessary to reduce O. viverrini infection and its risk to cholangiocarcinoma.

Epidemiology and Control of Opisthorchis viverrini Infection: Implications for Cholangiocarcinoma Prevention.

It is known that Opisthorchis viverrini (OV) is the most significant risk factor for the development of cholangiocarcinoma (CCA); hence, it is also known as carcinogenic parasite. Effective control and elimination of OV infection should significantly reduce O. viverrini-related CCA. This chapter includes details of the three recently developed innovative tools, namely the Isan cohort database software, an OV-RDT for screening of O. viverrini, and an ultrasound telecommunication system. Past and current control programs, i.e., education, medication, and sanitation were discussed and stressed the need for a comprehensive control program which encompasses primary, secondary, and tertiary patient care programs for confirmation and management of suspected CCA cases. The approach of mathematical modeling for control of OV and CCA was also briefly described. Additionally, we highlighted the current progress toward control of OV and CCA in Thailand and potential for expansion into nearby countries in Southeast Asia.

Community Awareness and Education: In the West and Southeast Asia.

Although cholangiocarcinoma (CCA) or bile duct cancer is considered rare, worldwide it is the second most common primary liver cancer. The incidence is increasing globally, and mortality is high owing to its aggressiveness, late diagnosis, and refractory nature. In this chapter, the awareness of cholangiocarcinoma in the West and in Southeast Asia, particularly Thailand, is explored. The background to this cancer in each region is described, and the challenges faced by both by healthcare professionals and patients are uncovered. Although there is a growing number of organisations working at every level in each region to improve the situation for those with cholangiocarcinoma, there remains little awareness of the public health importance of this cancer. However, it is with health agencies and those at government level that hopes for an improved future for all those with cholangiocarcinoma must lie.

Synopsis.

Cholangiocarcinoma (CCA) is the second most common primary liver cancer worldwide. Despite the severity of the disease and its impact on individuals, families, and communities, there remains an overall lack of awareness and interest in this disease. The information contained in the chapters of this book shows that this is indeed a significant public health and socioeconomic problem with varying levels of country-specific awareness. In Southeast Asia liver fluke, O. viverrini related CCA is endemic with the highest incidence worldwide in northeast Thailand, yet it is treatable and preventable. The chapters highlight significant advances in our knowledge of the biology and epidemiology of the O. viverrini species complex, intermediate hosts, systematics, population genetics, and the complexity of the three-host life cycle. A comprehensive conceptual framework has been developed to assist in understanding the complexity of molecular mechanisms of CCA carcinogenesis and cancer development which can result in improvement of targeted CCA therapy. There have been many advances in understanding the pathology of CCA in the biliary tract, including advances in prognosis and molecular pathogenesis. The development of different modalities and their advantages for diagnosis have increased diagnostic accuracy, providing reliable information allowing appropriate treatment and management programs to be selected for each patient. Particularly exciting is the recent development of a urine antigen assay which has revolutionized the diagnostic approach of opisthorchiasis due to its simplicity, the non-invasive nature of sample collection, and its ease of use in field settings. Significant in-roads and advances have been made in the surgical and systemic treatment of CCA patients. Additionally, a sophisticated data collection and analysis system, the Isan Cohort, has been developed and established for the treatment and control of CCA. Importantly, a greater understanding has been made of the social, community, religious, and anthropological issues initiating and sustaining the eating behavior of raw, partially cooked, and/or fermented fresh water fish. Specially designed education programs/curricula, based on currently available multidisciplinary hard data targeting school children, have been introduced since the inception of the Cholangiocarcinoma Screening and Care Program (CASCAP) and the subsequent strategic Fluke Free Thailand Model. The education program is being expanded to other provinces in Thailand and in the near future to other Southeast Asian countries, initially to Lao PDR, where the Fluke Free Lao PDR program has already been implemented. Despite advances that have been made in many disciplines focused on O. viverrini related CCA, raising awareness of CCA at all levels, particularly across endemic regions, is still needed, as is raising the awareness of CCA globally. As parasites and parasite related diseases have no borders, it is critical that an effective common strategic plan is instigated and established between all countries where liver fluke, O. viverrini related CCA is a significant public health problem, thereby increasing the quality of life and life expectancy of millions of people who suffer from this insidious disease.

Development of Fruit and Vegetable Consumption Promotion Model in a High-Risk Population for Cholangiocarcinoma in Thailand: An Action Research.

OBJECTIVE: This study aimed to develop a model for promoting fruit and vegetable consumption  in Thailand's high-risk population for cholangiocarcinoma (CCA). METHODS: Action research was used as a guiding framework for model development. Participants were divided into groups for process development and evaluation. Group discussions and practice notes were utilized as tools for process development. Data were collected through questionnaires. Qualitative data were categorized and analyzed using content analysis. Descriptive and inferential statistics were applied to analyze quantitative data. RESULTS: The model development process, following the PAOR framework (Planning, Action, Observation, Reflection), involved fruit and vegetable consumption promotion.  The model, named the "NONGBO NO-CCA Model" included various components: active involvement of villagers in planning, objective sharing of experiences and brainstorming to identify CCA prevention strategies, establishment of networks to support community healthcare, enhancement of community self-reliance through utilization of local resources, and encouragement of chemical-free and environmentally friendly fruit and vegetable cultivation. Following model development, at-risk individuals demonstrated a statistically significant improvement in knowledge, attitude, and practice (p<0.001). CONCLUSION: The findings indicate that at-risk individuals exhibited improvements in knowledge, attitude, and practice. Knowledge gains may be attributed to educational training activities, improved attitudes may result from networking processes, and modifications in practice behaviors may be influenced by community participation. Therefore, active involvement in community development can serve as a guiding principle for effective proactive CCA prevention.

Temporal Trends of Stages and Survival of Biliary Tract Cancers in the United States and Associations with Demographic Factors.

BACKGROUND: The incidence of cholangiocarcinoma and gallbladder cancer has been increasing and decreasing respectively in the United States, whereas their mortality has been declining since 1980, which suggests improved overall survival of biliary tract cancers (BTC). We aimed to investigate temporal trends of BTC stages and survival and their associations with demographic factors. METHODS: A total of 55,163 patients with BTC collected from 2000 to 2018 from the NCI Surveillance, Epidemiology, and End Results 18 registry were included in this study. We assessed the temporal trend of BTC stages with diagnosis years using the annual percentage of change (APC) in the proportion of the stages. We estimated the association of BTC survival and stages with diagnosis years and demographic factors using the Cox regression models. RESULTS: While localized BTC proportion remained little changed from 2006 to 2018, the proportion of regional and distant BTCs significantly decreased (APC = -2.3%) and increased (APC = 2.7%), respectively, through the years. The overall and cancer-specific survival increased from 41.0% and 47.3% in 2000 to 2004 to 51.2% and 53.8% in 2015 to 2018, respectively. Patients with BTC who were older, Black, unmarried, or had lower socioeconomic status (SES) had significantly poorer overall survival. CONCLUSIONS: We found that distant and regional BTC significantly increased and decreased, respectively, and the BTC survival significantly improved over time. Age, sex, race, SES, and marital status were significantly associated with overall survival and less evidently with cancer-specific survival of patients with BTC. IMPACT: Our findings suggest that demographic factors were associated with BTC stages and BTC survival.

Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma.

BACKGROUND: It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. METHODS: We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. RESULTS: Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. CONCLUSIONS: In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. IMPACT: The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.

Regional variation in routes to diagnosis of cholangiocarcinoma in England from 2006 to 2017.

BACKGROUND: Incidence of cholangiocarcinoma (CCA) is rising, with overall prognosis re-maining very poor. Reasons for the high mortality of CCA include its late presentation in most patients, when curative options are no longer feasible, and poor response to systemic therapies for advanced disease. Late presentation presents a large barrier to improving outcomes and is often associated with diagnosis via mergency presentation (EP). Earlier diagnoses may be made by Two Week Wait (TWW) referrals through General practitioner (GP). We hypothesise that TWW referrals and EP routes to diagnosis differ across regions in England. AIM: To investigate routes to diagnosis of CCA over time, regional variation and influencing factors. METHODS: We linked patient records from the National Cancer Registration Dataset to Hospital Episode Statistics, Cancer Waiting Times and Cancer Screening Programme datasets to define routes to diagnosis and certain patient characteristics for patients diagnosed 2006-2017 in England. We used linear probability models to investigate geographic variation by assessing the proportions of patients diagnosed via TWW referral or EP across Cancer Alliances in England, adjusting for potential confounders. Correlation between the proportion of people diagnosed by TWW referral and EP was investigated with Spearman's correlation coefficient. RESULTS: Of 23632 patients diagnosed between 2006-2017 in England, the most common route to diagnosis was EP (49.6%). Non-TWW GP referrals accounted for 20.5% of diagnosis routes, 13.8% were diagnosed by TWW referral, and the remainder 16.2% were diagnosed via an 'other' or Unknown route. The proportion diagnosed via a TWW referral doubled between 2006-2017 rising from 9.9% to 19.8%, conversely EP diagnosis route declined, falling from 51.3% to 46.0%. Statistically significant variation in both the TWW referral and EP proportions was found across Cancer Alliances. Age, presence of comorbidity and underlying liver disease were independently associated with both a lower proportion of patients diagnosed via TWW referral, and a higher proportion diagnosed by EP after adjusting for other potential confounders. CONCLUSION: There is significant geographic and socio-demographic variation in routes to diagnosis of CCA in England. Knowledge sharing of best practice may improve diagnostic pathways and reduce unwarranted variation.

Clinical Characterization of HCC/CCA Mixed Cancers in a Population-based Cohort.

BACKGROUND AND AIMS: Primary liver cancer (PLC) ranks among of the most common cancers worldwide. Within this group, a minority of cases displays characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), known as combined hepatocellular cholangiocarcinoma (cHCC- CCA). Currently, there is no specific standardized therapy for these mixed tumors. Therefore, the aim of our study was to analyze the clinical course, treatment and outcome of cHCC-CCA patients in a European population-based registry. METHODS: We investigated 9,144 patients with PLC (6,622 HCC, 2,356 iCCA, and 166 cHCC-CCA) diagnosed between 2009 and 2020. All data were obtained from Clinical Cancer Registry of Baden-Württemberg (BW), Germany. RESULTS: In all three groups patients were predominantly male (82%, 57%, and 68% for HCC, iCCA and cHCC-CCA groups, respectively). 48% of cHCC-CCA patients were diagnosed as stage IV cancers, which was more than for HCC (31%) but less compared to CCA (64%). Overall median survival of cHCC-CCA patients was worse compared to HCC (9-13 months vs. 15.5 months, p<0.001) and rather comparable to CCA (11.8 months). CONCLUSIONS: Our data demonstrated that cHCC-CCA tumors appear to have a distinct clinical course with worse overall survival compared to HCC. Thus, identification of these cancers by histopathology is essential in order to further characterize this tumor entity and to provide accurate treatment to these patients.

Characteristics and clinical outcomes in young-onset cholangiocarcinoma.

BACKGROUND: While the incidence of cholangiocarcinoma is rising, little is known about young-onset disease. We compared clinical characteristics and outcomes between patients with young-onset cholangiocarcinoma, diagnosed between the ages of 18 and <50 years, and patients with typical-onset cholangiocarcinoma, diagnosed at age 50 years or greater. METHODS: We used the National Cancer Database to identify patients with young-onset cholangiocarcinoma (n = 2520) and typical-onset cholangiocarcinoma (n = 23,826). We compared the frequency of demographic and clinical characteristics between the two groups. We compared overall survival between the two groups using multivariable Cox regression analysis after adjusting for age, gender, race/ethnicity, comorbidity, facility type, tumor location, tumor stage, surgical status, and receipt of radiotherapy, chemotherapy and surgery. RESULTS: When compared to patients with typical-onset disease (median age 68 years), patients with young-onset cholangiocarcinoma (median age 44 years) were more likely to be non-White (35.0% vs. 27.4%, p < 0.01), and had lower overall comorbidity burden. Patients with young-onset disease had a greater proportion of intrahepatic cholangiocarcinoma (56.0% vs. 45.5%, p < 0.001) and stage IV disease (50.5% vs. 43.5%, p < 0.001). Younger patients were more likely than typical-onset patients to receive definitive surgery (30.9% vs. 25.0%, p < 0.001), radiation (27.7% vs. 19.6%, p < 0.001) and chemotherapy (73.1% vs. 50.1%, p < 0.001). In adjusted analyses, patients with young-onset disease had a 15% decreased risk of death, compared with patients with typical-onset disease (HR 0.85 [95% CI 0.80-0.89], p < 0.001). CONCLUSIONS: Patients with young-onset cholangiocarcinoma may represent a demographically and clinically distinct group from those with more typical-onset disease.

Association between sleep traits and primary liver cancer: A Mendelian randomization analysis.

BACKGROUND: Primary liver cancer (PLC) is the sixth most frequently occurring cancer, representing one of the top 5 leading causes of cancer-related mortality worldwide. Recently, researchers have focused more on the impact of living habits on the incidence and development of tumours. This study reports a relationship between sleep traits and PLC. METHODS: In this study, we used published genome-wide association studies to obtain exposure factors of 6 sleep traits. Mendelian randomization (MR) analysis was used to assess the causal relationship between sleep traits and PLC via inverse-variance weighted (IVW), MR Egger and weighted median. Sensitivity analysis was used to reduce the bias. RESULTS: Our investigation revealed that there was a negative correlation between sleep duration and the group of liver and bile duct cancer by IVW (p-value = .042), and this result was similarly observed in the liver cell carcinoma group by Weighted Median (p-value = .026). In contrast, there was a positive correlation found between napping during the day and primary liver cancer in the cohorts of liver and bile duct cancer (p-value = .030), liver cell carcinoma (p-value = .043) and malignant neoplasm of other and unspecified parts of the biliary tract (p-value = .016) by IVW. Furthermore, our study also revealed a positive correlation between insomnia and malignant neoplasm of the liver and intrahepatic bile ducts by IVW (p-value = .022). CONCLUSIONS: Overall, our study indicates that insomnia and nap during the day may be risk factors of PLC and adequate night sleep might keep us away from PLC.

Incidence, Mortality, and Survival Trends in Cancer of the Gallbladder and Extrahepatic Bile Ducts in Lithuania.

Background and Objectives: Gallbladder cancer is a rare type of cancer, with aggressive clinical behavior. Limited treatment options provide poor survival prognosis. We aimed to investigate the incidence, mortality trends, and survival of gallbladder and extrahepatic bile duct cancer in Lithuania between 1998 and 2017. Materials and Methods: The study was based on the Lithuanian Cancer Registry database. The study included all cases of cancer of the gallbladder and extrahepatic bile ducts reported to the Registry in the period 1998-2017. Age-specific and age-standardized incidence rates were calculated. In addition, 95% confidence intervals for APC (Annual Percent Change) were calculated. Changes were considered statistically significant if p was <0.05. Relative survival estimates were calculated using period analysis according to the Ederer II method. Results: Age-standardized rates for gallbladder cancer and extrahepatic bile duct cancer among females decreased from 3.91 to 1.93 cases per 100.000 individuals between 1998 and 2017, and from 2.32 to 1.59 cases per 100.000 individuals between 1998 and 2017 among males. The highest incidence rates were found in the 85+ group with 27.5/100,000 individuals in females and 26.8/100,000 individuals in males. The 1-year as well as 5-year relative survival rates of both genders were 34.29% (95% CI 32.12-36.48) and 16.29% (95% CI 14.40-18.27), respectively. Conclusions: Incidence and mortality from gallbladder and extrahepatic bile duct cancer decreased in both sexes in Lithuania. Incidence and mortality rates were higher in females than in males. Relative 1-year and 5-year survival rates showed a steady increase during the study period among males and females.