Incidence Of Cholangiocarcinoma Research Articles

Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence.

Simple SummaryA potential relationship between cholangiocarcinoma and metabolic disorders has been suggested, but there is a lack of published data. This study aimed to describe the prevalence of metabolic disorders in a cohort of 122 patients with cholangiocarcinoma and report clinical outcomes. We found a prevalence of 42.6% of metabolic disorders. There was no significant difference in overall survival between patients with or without metabolic disorders, although there was a better survival in the subgroup of patients undergoing surgical resection. This indicates a need to better explore the association between cholangiocarcinoma in a metabolic background.Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (“metabolic disorder group”) and (2) without any of these features (“non-metabolic-disorder group”). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1–17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The “metabolic disorder group” (n = 52) had a median survival of 15.5 months (95% CI 10.9–33.9) vs. 11.5 months (95% CI 8.4–16.5) in the “non-metabolic-disorder group” (n = 70) (HR: 1.10; 95% CI 0.62–1.94). Patients with resectable disease in the “metabolic group” had longer survival than patients in the “non-metabolic group” (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6–26.9); HR = 0.12, 95% CI 0.03–0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background.

Fields of Life and Death: Cholangiocarcinoma, Food Consumption, and Masculinity in Buddhist Rural Thailand

The Mekong region presents a record incidence of cholangiocarcinoma (bile duct cancer). Scientists identify correlations between the development of this aggressive disease and the consumption of raw fish in local dishes. While made aware of these correlations by comprehensive health campaigns, some villagers in Thailand’s notoriously neglected Northeast refuse to cook the fish before consumption: a phenomenon that puzzles medical experts and policy makers. Based on ethnographic data, this paper suggests that practices surrounding the consumption of raw food in the area have become taboo. Rather than disappearing, they now play a key role in bonding rituals where rural masculinities are expressed via spectacles of risk taking that transgress normative ideals of manhood as epitomised by urban men and Buddhist monks.

Current status of Clonorchis sinensis and clonorchiasis in Korea: epidemiological perspectives integrating the data from human and intermediate hosts.

Clonorchis sinensis is a carcinogenic liver fluke that causes clonorchiasis in humans. Clonorchiasis is prevalent in East Asian countries, and approximately 15–20 million individuals are estimated to be infected with this fluke globally. This review highlights the current status of C. sinensis and clonorchiasis in Korea from the epidemiological perspective involving the analysis of humans and intermediate hosts. Despite the recent decline in C. sinensis infection rate in Korea, C. sinensis infections remain endemic in 5 major river basins (Han-gang, Geum-gang, Seomjin-gang, Yeongsan-gang and Nakdong-gang; gang means river) with a high incidence of cholangiocarcinoma. A noticeable pattern involves increasing mild infections among patients diagnosed positive for C. sinensis eggs. The infection rate of C. sinensis metacercariae in the second intermediate host, freshwater fish, is also maintained at a substantial level. Thus, the One Health approach integrating different sectors and disciplines is recommended to accelerate and sustain control of C. sinensis, thereby leading to successful eradication. Health promotion via information dissemination and health education should be extended to prevent the consumption of raw freshwater fish by residents living in high-risk areas.

The Proportion of Occupationally Related Cholangiocarcinoma: A Tertiary Hospital Study in Northeastern Thailand.

Simple SummaryNortheastern Thailand has the world’s highest incidence rate of cholangiocarcinoma (CCA), whereas a consequence, approximately 14,000 patients die annually. In most cases, the causal factors are identified, but, for some, they remain unknown. Legally imported industrial chemicals such as 1,2-dichloropropane (1,2-DCP), dichloromethane (DCM), and asbestos fibers are defined as occupational causes of CCA. An investigation into these vis-à-vis the diagnosis of occupationally related CCA in Thailand has not been conducted, but is important for understanding the potential magnitude of the problem. The current study found that the proportion of occupationally related CCA was approximately 5.5%, as well as a lower proportion of occupational history taken by treating physicians. Improving physician skills and developing an assistive tool for exploring occupational history might improve the documentation of work-related conditions.Northeastern Thailand registers the highest worldwide incidence of cholangiocarcinoma (CCA). Most of the cases are associated with liver flukes, while unknown causes comprise approximately 10–30% of cases, and these could be due to occupational exposures. Our aim was to determine the magnitude of occupational causes of CCA in a tertiary hospital in northeastern Thailand. We conducted a cross-sectional study with a sample of 220 patients between March and November 2021. Descriptive statistics were used to analyze the findings. Clinical information and telephone interviews were used to explore significant occupational histories. An occupational consensus meeting was held with two occupational physicians, an industrial hygienist, and a hepatobiliary surgeon to decide on the final diagnosis. The response rate was 90.9% (200/220). Based on the medical records and telephone interviews, researchers found that 11 participants had significant exposure. After occupational consensus, it was agreed that the eleven had possible occupational causes, 5.5% (11/200)–54.5% (6/11) being due to asbestos fibers, 45.5% (5/11) due to dichloromethane, and 9.1% (1/11) due to 1,2-dichloropropane. Only 4% (8/200) had occupational histories collected by their treating physicians. Taken together, occupationally related CCA appears to have been underestimated, so improving occupational history taking is needed to properly identify and classify work-related CCA—both for patient treatment and occupational hazard prevention.

From the Editor’s Desk...

From the Editor’s Desk...

The association of family history of primary liver cancer with cholangiocarcinoma: USA case-control study.

403 Background: The incidence of cholangiocarcinoma (CCA), particularly intrahepatic cholangiocarcinoma (IHC) has exponentially increased in the United States since 2007. While cholangiocarcinomas share some common characteristics, increasing evidence suggests that different subtypes of CCA have divergent tumor microenvironments, pathobiology and distinct epidemiologic features and risk factors. The correlation between family history of cancer and cholangiocarcinoma remains to be determined. This study aims to address the connection between positive family history of primary liver cancer and development of cholangiocarcinoma, including intrahepatic cholangiocarcinoma (IHC) and extrahepatic cholangiocarcinoma (EHC), in USA. Methods: At The University of Texas M. D. Anderson Cancer Center, we studied 429 patients with pathologically confirmed cholangiocarcinoma (308 IHC, 121 EHC) and 1,075 healthy controls. All subjects were interviewed for their family history of cancer, including the number of relatives with cancer, the type of cancer, the subjects’ relationship with the relative, and the age at which the relative was diagnosed. Results: Independent of hepatitis B virus (HBV) and hepatitis C virus (HCV), a family history of cancer was significantly associated with IHC and EHC, the estimated ORs and 95% CI were 1.6 (1.2-2.2) and 1.6 (1.1-2.5) for IHC and EHC respectively. Primary liver cancer in first-degree relatives was significantly associated with EHC development (OR 9.4 [95% CI, 2.9-30.7]). No significant association was observed for IHC, (OR 1.7 [95% CI, 0.5-5.9]). The prevalence of family history of primary liver cancer in first-degree members was recorded in 6.6% of EHC patients and in 1.6% of IHC patients. Multiple relatives with primary liver cancer were observed in 5 patients (4.1%) among EHC subjects but less common in IHC (1%). All estimated ORs were adjusted for age, sex, race, smoking, alcohol, Hepatitis virus infection, diabetes, and obesity. Conclusions: First-degree family history of primary liver cancer is associated with EHC development in USA independent of known risk factors for CCA. Further research exploring the genetic–environment interactions associated with EHC is warranted. Focused efforts in identifying the population at increased risk for developing EHC are necessary and may lead to new screening and surveillance strategies.

Characteristics and trends in treatment utilization in young-onset cholangiocarcinoma.

386 Background: Although the incidence of cholangiocarcinoma is rising, little is known about the demographic and clinical characteristics of patients with young-onset cholangiocarcinoma (YOCC), diagnosed at age &lt; 50 years. The objective of this study was to compare patients with YOCC, and patients with typical-onset cholangiocarcinoma (TOCC; diagnosed age &gt;50 years), and to describe trends in treatment utilization and factors associated with survival in YOCC. Methods: We identified patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and hilar cholangiocarcinoma from the National Cancer Database (NCDB) between 2004 and 2016. Patients were classified as either having YOCC or TOCC. Categorical variables were compared using the chi-square test with Bonferroni correction. Multivariate survival analyses were performed using the Cox-regression model after adjusting for age, gender, race/ethnicity, comorbidity index, insurance status, laterality, definitive surgery, radiotherapy, and chemotherapy. Results: We identified 26,346 patients, of which 2,520 had YOCC (9.6%, median age 44 years) and 23,826 had TOCC (90.4%, median age 68 years). Patients with YOCC were more likely to be non-White (YOCC 35.0% vs. TOCC 27.4%, p &lt;0.01) and had lower overall comorbidity burden. Patients with YOCC were more likely to present with stage IV disease (YOCC 50.5% vs. TOCC 43.5%, p &lt;0.001) and have intrahepatic cholangiocarcinoma (YOCC 56.0% vs. TOCC 45.5%, p&lt;0.001). Patients with YOCC were more likely to receive definitive surgery (YOCC 30.9% vs. TOCC 25.0%, p &lt;0.001) radiation (YOCC 27.7% vs. TOCC 19.0%, p&lt;0.001), and chemotherapy (YOCC 73.1% vs. TOCC 50.4%, p&lt;0.001). In adjusted analyses, patients with YOCC had a 21% decreased risk of death compared to patients with TOCC [HR 0.79 (95% CI 0.75-0.83), p&lt;0.001)]. This remained true for subgroups of patients with intrahepatic disease and those who underwent definitive surgery. Conclusions: YOCC constitutes a small but distinct subgroup of cholangiocarcinoma. Patients with YOCC were more likely to be non-White and present with intrahepatic cholangiocarcinoma disease. Despite being more likely to be diagnosed with advanced stage cholangiocarcinoma, patients with YOCC had better overall survival.

Tumor Microenvironment and its Implications for Antitumor Immunity in Cholangiocarcinoma: Future Perspectives for Novel Therapies.

The incidence of cholangiocarcinoma (CCA) has been increasing over the past few years. Although there are surgery, chemotherapy and other conventional treatment methods, the effect is not as expected. At present, immunotherapy has become the research frontier of cancer treatment, and CCA tumor microenvironment (TME) is becoming a hot exploration direction of immunobiology. TME can affect tumor progression through changes in metabolism, secretion and immunity. Accordingly, understanding the role played by immune cells and stromal cells in TME is important for the study of CCA immunotherapy. This review will discuss the interactions between immune cells (including CD8+ T cells, CD4+ T cells, macrophages, natural killer cells, dendritic cells, myeloid suppressor cells, mast cells, and neutrophils) and stromal cells (including cancer-associated fibroblasts, endothelial cells) in the TME of CCA. In addition, we will also discuss current research results on TME of CCA and recent advances in immunotherapy.

Widening Health Disparities: Increasing Cholangiocarcinoma Incidence in an Underserved Population.

Cholangiocarcinoma is a relatively rare malignancy with high mortality. In the U.S., incidence rates of cholangiocarcinoma have increased, particularly affecting younger age groups and Hispanic and Asian individuals. We investigated the incidence of cholangiocarcinoma in a largely under-represented, minority population. We performed a retrospective cohort study from 2005 to 2017 among adults in a county-funded healthcare system in Harris County, Texas. Incidence rate ratios were computed to compare age-standardized rates using U.S. standard population between 2 time periods: 2005-2011 and 2012-2017. We identified 139 cholangiocarcinoma cases (64% intrahepatic, 36% extrahepatic). The median age at diagnosis was 57 years; 62% were Hispanic, and 56% were born outside the U.S. The incidence rate increased from 1.2 to 2.4 per 100,000 person-years (rate ratio 2.1 [95% confidence interval {CI}: 1.5, 3.0]). Hispanic individuals and those aged 40-69 years had the highest rate of incidence increase (respectively, rate ratio: 2.5 [95% CI: 1.6, 4.0] and rate ratio: 2.0 [95% CI: 1.2, 3.0]) between time periods. In 2012-2017, the risk of cholangiocarcinoma among patients with diabetes was 1.4 times relative to those without (relative risk: 1.4; 95% CI: 1.1, 1.5) and 1.2 times among those who were overweight/obese relative to those who were not (relative risk: 1.2; 95% CI: 1.1, 1.6). Incidence of cholangiocarcinoma doubled during the 12-year study period, with Hispanic and middle-aged individuals disproportionately affected. Individuals with diabetes mellitus and those who were overweight or obese had a high risk of being diagnosed with cholangiocarcinoma in the later time period. Further studies should focus on preventing and improving earlier diagnosis of cholangiocarcinoma among Hispanics.

Cholangiocarcinogenesis and targeted therapy for cholangiocarcinoma

Cholangiocarcinoma includes a highly heterogeneous group of malignant tumors of the biliary tract, developing from the epithelium of the intra- and extrahepatic bile ducts. The incidence of cholangiocarcinoma is growing worldwide and currently accounts for about 15% of all primary neoplastic diseases of the liver and up to 3% of malignant neoplasms of the gastrointestinal tract. The asymptomatic course of these tumors in combination with a very aggressive course and low sensitivity to cytotoxic therapy contributes to a fairly high mortality rate from this disease, amounting to up to 2% in the structure of cancer mortality in the world. The high heterogeneity of cholangiocarcinoma at the genomic, epigenetic and molecular levels significantly reduces the effectiveness of the available treatments. In recent decades, new diagnostic tools and treatment methods have been developed to improve the results of treatment of patients with cholangiocarcinoma. The prevalence of BRAF gene mutations is associated with the occurrence of various tumors, including cholangiocarcinoma. Currently, more than 30 mutations in the BRAF gene with oncogenic potential have been registered. Basically, the V600 codon is affected, an amino acid change occurs, which ultimately leads to the fact that the BRAF protein becomes constantly active, even in the absence of growth factors. Dabrafenib is an inhibitor of the BRAF protein, which is permanently overactive in mutated cells. The use of dabrafenib as monotherapy leads to the development of resistance after 6–7 months. Dabrafenib is used with trametinib, a MEK inhibitor that also blocks the Ras-Raf-MEK-MAPK kinase pathway, to prevent the resistance.

Sequence of CX-4945 and Cisplatin Administration Determines the Effectiveness of Drug Combination and Cellular Response in Cholangiocarcinoma Cells In Vitro.

The incidence of cholangiocarcinoma (CCA) is increasing worldwide and current single chemotherapeutic drug treatments are ineffective. CX-4945 and cisplatin are currently in clinical trial for CCA treatment. We assessed the effects of the sequence of administration of CX-4945 and cisplatin applied in combination treatments on their efficacy in CCA cells in vitro. CCA cell viability was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Apoptosis was examined using flow cytometry. The percentage of cells positive for phosphorylated H2A histone family member X (γ-H2AX) were measured using both flow cytometry and immunofluorescence. CCA cell viability was reduced to 50% after 24 h of treatments with CX-4945 and cisplatin as single agents. Interestingly, treatment with cisplatin 6 h prior to CX-4945 treatment induced significantly more DNA damage and apoptosis than CX-4945 treatment followed by cisplatin. Unexpectedly, CX-4945 treatment followed by cisplatin was less effective than single treatment in RMCCA-1 CCA cells. In addition, a 1:1 ratio of each drug was the most effective combination in these cells. These data demonstrate that the combination of CX-4945 and cis platin acts additively when cisplatin is applied first, at least in part due to increased DNA damage and apoptosis. Furthermore, treatment with CX-4945 prior to cisplatin treatment reduces the efficacy of this drug combination in CCA cells.

Arctigenin inhibits cholangiocarcinoma progression by regulating cell migration and cell viability via the N-cadherin and apoptosis pathway

Northeast Thailand has the highest incidence of cholangiocarcinoma (CCA) in the world. The lack of promising diagnostic markers and appropriate therapeutic drugs is the main problem for metastatic stage CCA patients who have a poor prognosis. N-cadherin, a cell adhesion molecule, is usually upregulated in cancers and has been proposed as an important mediator in epithelial-mesenchymal transition (EMT), one of the metastasis processes. Additionally, it has been shown that arctigenin, a seed isolated compound from Arctium lappa, can inhibit cancer cell progression via suppression of N-cadherin pathway. In this study, we investigated the protein expression of N-cadherin and its correlation with clinicopathological data of CCA patients, as well as the impact of arctigenin on KKU-213A and KKU-100 CCA cell lines and its underlying mechanisms. Immunohistochemistry results demonstrated that high expression of N-cadherin was significantly associated with severe CCA stage (p = 0.027), and shorter survival time (p = 0.002) of CCA patients. The mean overall survival times between low and high expression of N-cadherin were 31.6 and 14.8months, respectively. Wound healing assays showed that arctigenin significantly inhibited CCA cell migration by downregulating N-cadherin whereas upregulating E-cadherin expression. Immunocytochemical staining revealed that arctigenin suppressed the expression of N-cadherin in both CCA cell lines. Furthermore, flow cytometry and western blot analysis revealed that arctigenin significantly reduced CCA cell viability and induced apoptosis via the Bax/Bcl-2/caspase-3 pathway. This research supports the use of N-cadherin as a prognostic marker for CCA and arctigenin as a potential alternative therapy for improving CCA treatment outcomes.

Dichloromethane increases mutagenic DNA damage and transformation ability in cholangiocytes and enhances metastatic potential in cholangiocarcinoma cell lines

Dichloromethane (DCM), a widely used chlorinated solvent, is classified by IARC (2017) as probably carcinogenic to humans. Exposure to DCM has been associated with increased incidence of cholangiocarcinoma (CCA) in humans. This study aimed to investigate how DCM could contribute to CCA development by investigating the effects of DCM on DNA damage and cell transformation in cholangiocytes (MMNK-1) and on metastatic potential as measured by invasion and cell migration in malignant CCA cell lines (HuCCA-1 and RMCCA-1). MMNK-1 cells treated with the non-cytotoxic concentration of DCM (25 μM, 24 h) significantly increased the levels of mutagenic DNA adducts including 8-hydroxydeoxyguanosine, 8-OHdG, (1.84-fold, p < 0.01) and 8-nitroguanine (1.96-fold, p < 0.01) and enhanced cell transformation by 1.47-fold (p < 0.01). In addition, the expression of various genes involved in carcinogenesis, namely, NFE2L2 (antioxidative response), CXCL8 (inflammation), CDH1 (cell adhesion), MMP9 (tissue remodeling) and MKI67 (cell proliferation) were altered in cholangiocytes treated with DCM. When MMNK-1 cells were transformed by DCM, the expression of all the aforementioned genes was also increased. In malignant cell lines (HuCCA-1 and RMCCA-1), DCM treatment resulted in increased CXCL8 and MMP9 transcription and decreased CDH1 transcription accompanied by increased invasion and migration capabilities of these cells. Taken together, this study demonstrated that DCM exposure could be linked to the development of CCA.

Circ_HIPK3 Knockdown Inhibits Cell Proliferation, Migration and Invasion of Cholangiocarcinoma Partly via Mediating the miR-148a-3p/ULK1 Pathway.

BackgroundThe incidence of cholangiocarcinoma (CCA) is on the rise in recent years, and its pathogenesis may be associated with the deregulation of circular RNAs (circRNAs). Hence, we aimed to investigate the role of circRNA homeodomain interacting protein kinase 3 (circ_HIPK3) in CCA.MethodsThe expression of circ_HIPK3, miR-148a-3p and unc-51 like kinase 3 (ULK1) mRNA was detected using quantitative real-time polymerase chain reaction (qPCR). The role of circ_HIPK3 in cell proliferation was detected by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay and colony formation assay. Cell apoptosis and cell cycle progression were investigated using flow cytometry assay. Cell migration and invasion were detected by transwell assay. The protein levels of ULK1 and migration/invasion-associated markers were measured using Western blot. The putative relationship between miR-148a-3p and circ_HIPK3 or ULK1 was validated by dual-luciferase reporter assay. The role of circ_HIPK3 was also investigated in vivo.ResultsCirc_HIPK3 was overexpressed in CCA tissues and cells. In function, circ_HIPK3 knockdown inhibited CCA cell proliferation, migration and invasion and induced apoptosis and cycle arrest. It was confirmed that miR-148a-3p was a target of circ_HIPK3, and ULK1 was a target of miR-148a-3p. Circ_HIPK3 regulated ULK1 expression by targeting miR-148a-3p. Rescue experiments showed that miR-148a-3p inhibition reversed the effects of circ_HIPK3 knockdown. Besides, miR-148a-3p enrichment-blocked cell proliferation, migration and invasion were recovered by ULK1 overexpression. In vivo, circ_HIPK3 knockdown inhibited solid tumor growth.ConclusionCirc_HIPK3 knockdown blocked CCA malignant development partly via regulating the miR-148a-3p/ULK1 pathway.

The Clinical Management of Cholangiocarcinoma in the United States and Europe: A Comprehensive and Evidence-Based Comparison of Guidelines.

The incidence of cholangiocarcinoma has doubled over the last 15 years with a similar rise in mortality, which provides the impetus for standardization of evidence-based care through the establishment of guidelines. We compared available guidelines on the clinical management of cholangiocarcinoma in the United States and Europe, which included the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG) and the International Liver Cancer Association (ILCA) guidelines. There is discordance in the recommendation for biopsy in patients with potentially resectable cholangiocarcinoma and in the recommendation for use of fluorodeoxyglucose positron emission tomography scans. Similarly, the recommendation for preoperative biliary drainage for extrahepatic and perihilar cholangiocarcinoma in the setting of jaundice is inconsistent across all four guidelines. The BILCAP (capecitabine) and ABC-02 trials (gemcitabine with cisplatin) have provided the strongest evidence for systemic therapy in the adjuvant and palliative settings, respectively, but all guidelines have refrained from setting them as standard of care, given heterogeneity in the study cohorts and ABC-02's negative intention-to-treat results. Future progress in enhancing survivorship of patients with cholangiocarcinoma would likely entail improvements in diagnostic biomarkers and novel systemic therapies. Based on recent results from studies of targeted therapy, future iterations of the guidelines will likely incorporate molecular profiling.

Decreasing trends in cholangiocarcinoma incidence and relative survival in Khon Kaen, Thailand: An updated, inclusive, population-based cancer registry analysis for 1989-2018.

BackgroundCholangiocarcinoma (CCA) is a leading cause of cancer death in northeastern Thailand. We reported on the incidence of CCA using only one method. In the current study, we used three different statistical methods to forecast future trends and estimate relative survival.MethodsWe reviewed the CCA cases diagnosed between 1989 and 2018 recorded in the population-based Khon Kaen Cancer Registry (KKCR). Annual percent change (APC) was calculated to quantify the incidence rate trends using Joinpoint regression. Age-period-cohort models (APC model) were used to examine the temporal trends of CCA by age, calendar year, and birth cohort. We projected the incidence of CCA up to 2028 using three independent approaches: the Joinpoint, Age-period-cohort, and Nordpred models. Survival assessments were based on relative survival (RS).ResultsThe respective APC in males and females decreased significantly (-3.1%; 95%CI: -4.0 to -2.1 and -2.4%; 95%CI: -3.6 to -1.2). The APC model—AC-P for male CCA—decreased according to a birth-cohort. The CCA incidence for males born in 1998 was 0.09 times higher than for those born in 1966 (Incidence rate ratios, IRR = 0.09; 95%CI: 0.07 to 0.12). The relative incidence for female CCA similarly decreased according to a birth-cohort (IRR = 0.11; 95%CI: 0.07 to 0.17). The respective projection for the age-standardized rate for males and females for 2028 will be 7.6 per 100,000 (102 patients) and 3.6 per 100,000 (140 patients). The five-year RS for CCA was 10.9% (95%CI: 10.3 to 11.6).ConclusionThe incidence rate of CCA has decreased. The projection for 2028 is that the incidence will continue to decline. Nevertheless, the survival of patients with CCA remains poor.

Progress toward improving outcomes in patients with cholangiocarcinoma.

Purpose of review:To provide an update on latest advances in treatment of cholangiocarcinoma.Recent findings:Incidence of cholangiocarcinoma has been increasing over the past decade. A better understanding of the genetic landscape of cholangiocarcinoma and its risk factors resulted in earlier diagnosis and treatment option expansion to targeted therapy with FGFR inhibitors, and liver transplantation for early perihilar cholangiocarcinoma and early intrahepatic cholangiocarcinoma. IDH1/2 inhibition for intrahepatic cholangiocarcinoma is an emerging targeted therapy approach. Data supports benefits of adjuvant therapy for a subset of patients undergoing surgical resection. Approaches combining different treatment modalities such as chemotherapy, surgery, radiation therapy appear promising.Summary:Earlier diagnosis and genetic characterization provided additional treatment options for patients with previously incurable cholangiocarcinoma. A precision medicine approach with a focus on actionable genetic alterations and combination of treatment modalities are actively being explored and will further improve outcomes in our patients with cholangiocarcinoma.

Incidence of Cholangiocarcinoma in Patients with History of Colorectal Cancer. Multicenter Experience

Introduction: Cholangiocarcinoma (CCA) represents one the most common primary malignancy of the liver. Cirrhosis, HCV infection, Cholestatic diseases represent well known predisposing factors. Late diagnosis of CAA is associated with a poor prognosis. History of colorectal cancer (CRC) is supposed to be a risk factor. Method: Data were retrospectively collected from two different HPB surgical centers in Italy (Ancona, Roma-Gemelli) to identify all patients with CCA and CRC between January 2000 to December 2018. All the data from patient history, surgical and oncological treatments were examinated. Histopatological examination of both CCA and CRC characteristics were analised. Genetics characteristics of both tumours were collected. Results: A total of 26 patients developed biopsy-proven CCA after CRC. The median time between CRC and CCA diagnosis was 111,7 months. All the CRC were successfully treated with surgery and 5 patients underwent adjuvant chemotherapy. Median age at the CCA diagnosis was 66,8 years. 23 (88,4%) patients underwent R0 surgical treament. 3 patients underwent palliative treatments. After a median followup of 73,4 months, 5 years survival was 61,5%. Conclusions: To our knowledge, this is the largest series of patients with CCA and CRC. Treatment can allow a significant 5 year survival. It is also mandatory a follow up for CAA in CRC patients.

Laparoscopic Type IV Choledochal Cyst Excision with Roux-En-Y Hepaticojejunostomy

Introduction: Choledochаl cysts represent а rare congenital cystic dilation of the biliary tract. Nearly 25% are diagnosed in the first year of life with and incidence of approximately 1/200 000 live births in western countries, although these numbers are significantly higher in East Аsiаn populations. Presentation typically occurs in childhood, with jaundice, fever or an abdominal mass. Although benign, choledochаl cysts cаn be аssociаted with various complications including malignant transformation. In western countries, the incidence of cholangiocarcinoma has been reported to reach 12% in some series, with higher reports in Asian countries. Other hurdles include cholangitis, pancreatitis, and cholelithiаsis. The modified Todani classification is employed to describe the various types of choledocal cysts (I-V). Type I, a fusiform dilation of the common bile duct, is the most common. Type IV is the second most prevalent, with extension of the cysts into the intrahepatic ducts. Types II, II and V are less frequent. This video intends to present the laparoscopic excision of a type IV choledocal cyst with intracorporeal Roux-en-Y hepaticojejunostomy with a specific attention on technical detail and education. Methods: A 49 year old female with no relevant prior medical history presented with a history of abdominal comfort. Results: An abdominal CT scan showed common biliary duct dilation and an MRi revealed the existence of a type IVa choledochаl cyst. Laparoscopic cyst excision was proposed and accepted. The patient was submitted to surgery on January 2021, initiated oral intake on day 2 and was discharged at day 7 without any hurdles. Conclusion: Laparoscopic choledochal cyst excision is a safe procedure with decreased morbidity and in-hospital stay days compared with an open approach. The authors consider that the video quality and surgical procedure can successfully contribute to the education and training of surgery residents and also contribute to share expertise and consolidate knowledge to surgeons.

Opisthorchosis is a topical health problem (problem overview and analysis)

The purpose of the research is analyzing literature sources to establish the role of opisthorchosis in health care and assessing the relevance of histological and histochemical methods in determining the efficacy of drugs against helminths which are causative agents of opisthorchosis.Materials and methods. We analyzed literature sources on the study of opisthorchosis, its pathogen spread and its significance for public health. We also reviewed the official documentation of the annual reports presented on the official websites.Results and discussion. In 2018, more than 19.0 thousand cases of opisthorchosis were recorded in the country (rate is 12.99 per 100 thousand population), which made up 79.5% of all recorded bio-helminthosis in the population. Opisthorchosis is characterized by long course and proceeds with frequent exacerbations. The most serious complication is cancer in the liver, bile ducts and pancreas, which are organs of opisthorchis parasitism. The works of many authors reveal the connection and high incidence of cholangiocarcinoma in patients with opisthorchosis in countries with endemic sites of Opisthorchiidae family representative’s infection. Long-term opisthorchosis infection reduces the efficacy of anthelmintic therapy and leads to the appearance of the disease recurrent forms. Opisthorchis viverrini was officially recognized as a Group 1 biological carcinogen by the International Agency for Research on Cancer in 2009. The carcinogenic role of O. felineus has not yet been sufficiently studied. However, life cycles, morphology and localization in the human body of O. viverrini and O. felineus are similar. In the list of established medicinal products with opisthorchocidal action, special attention and interest are paid to herbal products. Histological and histochemical research methods confirmed the efficacy against such herbal preparations as ecorsol, erlim and artemisin.