Incidence Of Cholangiocarcinoma Research Articles

Incidence and Long-Term Outcomes of Biliary Tract Cancers in Olmsted County, Minnesota from 1976 to 2018.

Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research.

Development of machine learning models for patients in the high intrahepatic cholangiocarcinoma incidence age group

BackgroundIntrahepatic cholangiocarcinoma (ICC) has a poor prognosis and is understudied. Based on the clinical features of patients with ICC, we constructed machine learning models to understand their importance on survival and to accurately determine patient prognosis, aiming to develop reference values to guide physicians in developing more effective treatment plans.MethodsThis study used machine learning (ML) algorithms to build prediction models using ICC data on 1,751 patients from the SEER (Surveillance, Epidemiology, and End Results) database and 58 hospital cases. The models’ performances were compared using receiver operating characteristic curve analysis, C-index, and Brier scores.ResultsA total of eight variables were used to construct the ML models. Our analysis identified the random survival forest model as the best for prognostic prediction. In the training cohort, its C-index, Brier score, and Area Under the Curve values were 0.76, 0.124, and 0.882, respectively, and it also performed well in the test cohort. Kaplan–Meier survival analysis revealed that the model could effectively determine patient prognosis.ConclusionsTo our knowledge, this is the first study to develop ML prognostic models for ICC in the high-incidence age group. Of the ML models, the random survival forest model was best at prognosis prediction.

Factors associated with fruit and vegetable consumption among people in the highest risk area for Cholangiocarcinoma in Thailand

Background: Over the past 30 years, the incidence of cholangiocarcinoma (CCA) in the Northeast of Thailand has been high and has tended to increase. Fruits and vegetables (FV) were accepted as protective factors against CCA. The prevalence of FV consumption among Northeast people is lower than recommended, which is a significant health problem that must be urgently solved. Objectives: This study investigated the factors associated with FV consumption among people in Ubon Ratchathani, one of the high-risk areas of Thailand. Methods: A multi-stage sampling method was used to select the population aged 40 years and over. Data were analyzed using descriptive and inferential statistics. A logistic regression analysis was performed to identify the factors associated with FV consumption. Results: Out of the total 744 respondents, only 11.83% consumed FV according to the standard of <400 grams/day. The bio-social factor regarding an average family income of more than 15,000 Baht had a 10.54 times greater effect on FV consumption (AOR=10.54, 95% CI: 7.59-20.57). Purchasing FVs from mobile sales trucks (AOR=4.11, 95% CI: 1.69-9.97) and receiving information from radio (AOR=1.97, 95% CI: 1.14-3.39) were associated with standard FV consumption. However, a good level of attitude had decreased the risk of FV consumption (AOR=0.30, 95% CI: 0.18-0.49). Conclusion: The prevalence of FV consumption among the study population is considerably low. Family income, purchasing from mobile sales trucks, receiving information from radio, and having a positive attitude were associated with standard FV consumption among people in Thailand's highest-risk area for CCA. Relevant organizations should organize activities to provide people of every economic status with knowledge and attitude on FV consumption via radio or social media and support access to quality and safe mobile sales trucks to meet consumption standards and prevent as well as reduce the risk of CCA.

Clinical significance of small extracellular vesicles in cholangiocarcinoma.

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

Per-oral cholangioscopy in patients with primary sclerosing cholangitis: a 12-month follow-up study.

Background and study aims Patients with primary sclerosing cholangitis (PSC) have a 9% to 20% lifetime incidence of cholangiocarcinoma (CCA). Per-oral cholangioscopy (POCS) added to endoscopic retrograde cholangiography (ERC) could potentially improve detection of CCA occurrence. We prospectively assessed POCS identification of 12-month CCA incidence in PSC patients undergoing ERC. Patients and methods Consecutive patients with PSC, an indication for ERC, and no prior liver transplantation were enrolled. During the index procedure, POCS preceded planned therapeutic maneuvers. The primary endpoint was ability for POCS visualization with POCS-guided biopsy to identify CCA during 12-month follow-up. Secondary endpoints included ability of ERC/cytology to identify CCA, repeat ERC, liver transplantation, and serious adverse events (SAEs). Results Of 42 patients enrolled, 36 with successful cholangioscope advancement were analyzed. Patients had a mean age 43.5±15.6 years and 61% were male. Three patients diagnosed with CCA had POCS visualization impressions of benign/suspicious/suspicious, and respective POCS-guided biopsy findings of suspicious/positive/suspicious for malignancy at the index procedure. The three CCA cases had ERC visualization impressions of benign/benign/suspicious, and respective cytology findings of atypical/atypical/suspicious for malignancy. No additional patients were diagnosed with CCA during median 11.5-month follow-up. Twenty-three repeat ERCs (5 including POCS) were performed in 14 patients. Five patients had liver transplantation, one after CCA diagnosis and four after benign cytology at the index procedure. Three patients (7.1%) had post-ERC pancreatitis. No SAEs were POCS-related. Conclusions In PSC patients, POCS visualization/biopsy and ERC/cytology each identified three cases of CCA. Some patients had a repeat procedure and none experienced POCS-related SAEs.

Microsatellite markers for Opisthorchis felineus to understand its genetic diversity and transmission patterns of opisthorchiosis.

Opisthorchis felineus is a food-borne trematode which causes opisthorchiosis and affects mainly the liver and bile ducts of the liver with a possible risk of bile duct carcinogenesis resulting in cholangiocarcinoma. In Russia, O. felineus is mainly endemic in Western Siberia (Ob and Irtysh river basins) and occurs throughout the Volga, Kama, Don, and Dnepr river basins. The prevalence, intensity, and clinical significance of human infections and the incidence of cholangiocarcinoma vary geographically in endemic regions. Currently, there is substantial evidence on genetic variation of O. felineus, but information on the population genetic structure is so far very scarce. Because microsatellite DNA of this parasite is not available, we for the first time isolated sufficient microsatellite loci to examine the genetic diversity and population structure of O. felineus, using multiple nuclear loci approach. A total of ten highly polymorphic microsatellite loci from a constructed enriched genomic DNA library were characterized, using 29 samples representing huge O. felineus metapopulation extended in latitude over 5000km from Middle Europe to Western Siberia. At least three populations can be discerned as result of analysis of the microsatellite loci genetic diversity. Based on the results for the first time, a hypothesis was put forward about the formation of a modern habitat of O. felineus.

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

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. 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. 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. 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. Our findings suggest that demographic factors were associated with BTC stages and BTC survival.

Cystatins from the Human Liver Fluke Opisthorchis viverrini: Molecular Characterization and Functional Analysis.

A high incidence of cholangiocarcinoma (bile duct cancer) has been observed in Thailand. This usually rare cancer has been associated with infection with the human liver fluke, Opisthorchis viverrini. Secretions of the parasite that interact with the host are thought to be a major component of its pathogenicity and proteolysis is a key biological activity of the secreted molecules. In this study, we present a molecular analysis of cysteine proteinase inhibitors (cystatins) of Opisthorchis viverrini. Six cDNA coding sequences of Opisthorchis viverrini cystatins, OvCys1-6, were cloned from the adult stage of the parasite using RT-PCR. Based on their sequences, OvCys1 and OvCys2 are classified as type 1 cystatins, while OvCys3-6 are classified as type 2 cystatins, with each containing a signal peptide and only one C-terminal disulfide bond. Their C-terminal region sequences are diverse compared with other cystatin members. Cystatins OvCys1, 3 and 4 were found in crude worm extracts and excretory-secretory (ES) products from the adult parasite using Western blot detection, while the other isoforms were not. Thus, OvCys1, 3 and 4 were selected for inhibition analysis and immune reactivity with Opisthorchis viverrini-infected hamster sera. OvCys1, 3, and 4 inhibited mammalian cathepsin L more effectively than cathepsin B. The pH range for their full activity was very wide (pH 3-9) and they were heat stable for at least 3 h. Unlike Fasciola gigantica cystatins, they showed no immune reactivity with infected hamster sera based on indirect ELISA. Our findings suggest that Opisthorchis viverrini cystatins are not major antigenic components in the ES product of this parasite and that other effects of Opisthorchis viverrini cystatins should be investigated.

Surgical management of intrahepatic and hilar cholangiocarcinoma: liver resection versus liver transplantation

The incidence of cholangiocarcinoma is increasing worldwide. Patients present with abdominal pain, whereas weight loss and malaise are symptoms of advanced disease. Jaundice occurs when there is hilar obstruction by the tumor. Surgical management involves resection of the affected hepatic segments or liver transplantation, which requires a dedicated multidisciplinary team approach, and promising outcomes are seen in high-volume centres. The authors employed a search strategy for databases like PubMed and Google Scholar. The authors then reviewed the articles using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines and compared data concerning postoperative complications, recurrence rates, five-year survival rates and prognosis. Liver resection confers long-term survival in patients with intrahepatic cholangiocarcinoma, though the prognosis and morbidity of this procedure are still gloomy. Liver transplantation could be an option, either in early stages diagnosed in the context of chronic liver diseases or locally advanced tumors, when neoadjuvant treatments have achieved sustained tumor response without extrahepatic tumor spread.

Lanatoside C decelerates proliferation and induces apoptosis through inhibition of STAT3 and ROS-mediated mitochondrial membrane potential transformation in cholangiocarcinoma.

Introduction: The incidence of cholangiocarcinoma (CCA) has increased worldwide in recent years. Given the poor prognosis associated with the current management approach of CCA, new therapeutic agents are warranted to improve the prognosis of this patient population. Methods: In this study, we extracted five cardiac glycosides (CGs) from natural plants: digoxin, lanatoside A, lanatoside C, lanatoside B, and gitoxin. Follow-up experiments were performed to assess the effect of these five extracts on cholangiocarcinoma cells and compounds with the best efficacy were selected. Lanatoside C (Lan C) was selected as the most potent natural extract for subsequent experiments. We explored the potential mechanism underlying the anticancer activity of Lan C on cholangiocarcinoma cells by flow cytometry, western blot, immunofluorescence, transcriptomics sequencing, network pharmacology and in vivo experiments. Results: We found that Lan C time-dependently inhibited the growth and induced apoptosis of HuCCT-1 and TFK-1 cholangiocarcinoma cells. Besides Lan C increased the reactive oxygen species (ROS) content in cholangiocarcinoma cells, decreased the mitochondrial membrane potential (MMP) and resulted in apoptosis. Besides, Lan C downregulated the protein expression of STAT3, leading to decreased expression of Bcl-2 and Bcl-xl, increased expression of Bax, activation of caspase-3, and initiation of apoptosis. N-acetyl-L-cysteine (NAC) pretreatment reversed the effect of Lan C. In vivo, we found that Lan C inhibited the growth of cholangiocarcinoma xenografts without toxic effects on normal cells. Tumor immunohistochemistry showed that nude mice transplanted with human cholangiocarcinoma cells treated with Lan C exhibited decreased STAT3 expression and increased caspase-9 and caspase-3 expression in tumors, consistent with the in vitro results. Conclusion: In summary, our results substantiates that cardiac glycosides have strong anti-CCA effects. Interestingly the biological activity of Lan C provides a new anticancer candidate for the treatment of cholangiocarcinoma.

Utility of circulating tumor DNA for identifying genetic mutations in cholangiocarcinoma of East Asian patients.

e16332 Background: Cholangiocarcinoma, also referred to as bile duct cancer, is a major global health concern. The diagnosis of this cancer is often difficult due to its lack of distinctive symptoms and its tendency to present at advanced stages. However, the recent emergence of blood liquid biopsy as a diagnostic tool has shown great potential for detecting and managing cholangiocarcinoma. The use of blood liquid biopsy in East Asian populations, where the incidence of cholangiocarcinoma is particularly high, has the potential to improve the accuracy of diagnosis, prognosis, and targeted treatment planning. Methods: The study cohort contains 53 Chinese cholangiocarcinoma patients, the examination of DNA from tumor tissue (tDNA), blood (cfDNA), and blood leukocytes (gDNA) was performed using 680 gene targeted capture sequencing and analyzing for CNV, fusion, SNV, indel, MSI, and TMB. The sequencing depth was 2200X for tDNA, 20000X for bDNA, and 10000X for gDNA. In the tissue samples evidence of PD-L1 expression was examined. The TMB was classified as high (TMB-H) with a cutoff > 10 mutations/megabase and low (TMB-L) < 10. Microsatellite instability-high (MSI-H) was identified in cases where instability was observed > 20% of 117 loci, and the microsatellite stable (MSS) rate was determined to be < 20%. Results: In a cohort of 53 patients, a thorough analysis of tissue and blood samples was conducted to detect somatic mutations. 146 (38.1%) shared mutations were found in both tDNA and cfDNA, while 211 (55.09%) and 25 (6.53%) unique mutations were found in tDNA and cfDNA respectively. Of the 64 mutations found in CNV, 5 (7.81%) were shared in tDNA and cfDNA, 52 (81.25%) were unique in tissues, and 7 (10.93%) were unique in blood. High frequency mutated genes were also revealed as TP53, KRAS, SMAD4, LRP1B, and ARID1A, which were consistent with the results from the IntoGen database (4 cohorts, 393 samples). Notably, LRP1B (11.32%, 6/53) was not detected in the validation cohort. 96.23% of the samples showed consistent tTMB vs. bTMB outcomes, with only 1 sample exhibiting high PD-L1 expression and TMB-L, MSS, and 1 sample (out of 52 with MSS) having TMB-H and PD-L1 expression less than 1%. Conclusions: The results of the mutation analysis suggest that relying solely on cfDNA for molecular typing of cholangiocarcinoma is not sufficient. This highlights the importance of testing tissue samples in order to accurately detect tumor mutations in cholangiocarcinoma. Further research is needed to determine the significance of LRP1B, a gene that was frequently mutated in the study cohort but not found in the validation cohort, in the diagnosis and treatment of cholangiocarcinoma.

Characteristics and clinical outcomes in young-onset cholangiocarcinoma.

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. 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. 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). Patients with young-onset cholangiocarcinoma may represent a demographically and clinically distinct group from those with more typical-onset disease.

Trends in incidence, treatments, and clinical outcomes of cholangiocarcinoma diagnosed in British Columbia, Canada, from 2005 through 2019.

522 Background: While only accounting for 3% of gastrointestinal malignancies, cholangiocarcinoma (CC) has poor prognosis. New targeted therapies are on the horizon and understanding the potential size of the population eligible for such therapies is of importance. Contemporary incidence and outcomes in Canada have not been studied. Methods: Patients diagnosed with CC between 2005-2019 in British Columbia were identified using the BC Cancer Registry. Patient characteristics, treatments received and outcomes were collected and analyzed. Results: A total of 1520 patients were identified. Median age at diagnosis was 69 (interquartile 61-76) and 52% were female, 594 patients presented with localized disease (39%) of whom 416 had disease recurrence. The proportion of intrahepatic CC (ICC) rose from 17% in 2005-2009 to 44% in 2015-2019 while the incidence of extrahepatic (ECC) and gallbladder (GB) cancers followed populational trends. More patients with ICC had stage IV cancer at the time of diagnosis (64% vs 43% for ECC and 45% for GB, p&lt;0.01). Treatments received are shown in the table. Among 1086 patients with recurrent or metastatic disease, 54% and 14% respectively received first- and second-line chemotherapy. Overall survival (OS) was 13.7 months [HR 0.43 (95% CI 0.37-0.49)] with 1 line of treatment and 21.3 months with 2 lines [HR 0.30 (95% CI 0.24-0.37)], compared to 4.8 months with best supportive care. On multivariate analysis, ECOG, first and second-line treatment and liver-directed therapy remained associated with improved outcomes while tumor site or time period did not. Conclusions: The incidence of CC is rising and most patients present with advanced disease. Treatment attrition is high and few patients receive second line therapies. The outcomes of patients receiving first line, second line and liver-directed therapies are significantly better than those receiving supportive care only. Understanding contemporary trends in presentation and treatment patterns is essential as we consider strategies to improve implementation and access of emerging novel therapies in this setting. [Table: see text]

A glimpse into the future of cholangiocarcinoma: Predicting the future incidence based on the current epidemiological data.

616 Background: Cholangiocarcinoma (CCA) is an aggressive, heterogenous group of neoplasms that arise from the epithelial lining of bile ducts that have dismal poor prognosis. A recent epidemiological study in the United States demonstrated a steady increase in the incidence of cholangiocarcinoma from 2001 to 2017 with a predominant increase in the intrahepatic sub-type (iCCA). We sought to evaluate the future incidence of cholangiocarcinoma stratified based on the subtype, age, sex, and race, that could possibly help plan prevention, control, and treatment strategies for this cancer. Methods: We obtained histologically confirmed cases of cholangiocarcinoma (ICD-0-3 Site: C220, C21, and C240) from National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) 18 registries between 2000 to 2017 and predicted the incidence between the years 2018-2029. We applied age-period-cohort models to estimate future cholangiocarcinoma incidence rates (per 100, 000) and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: A total of 12,737 and 8,395 patients with iCCA and extra-hepatic cholangiocarcinoma (eCCA) were included in the final analysis. The median age of iCCA cohort was 64 (range: 20-79) years and 46.4% were females whereas in eCCA the median age was 66 (range: 20-79) years and 43.8% were females. The overall observed age-adjusted incidence of iCCA between 2000-2017 was 1.07, which is predicted to increase to 2.13 by 2029 (99% increase) with a predominant increase in incidence rate observed in the age groups 70-79 and White males and females. Interestingly, incidence rate remained stable in Black and Asian males and in Asian females. Similarly, as compared to 2001-2017, the incidence of eCCA is projected to increase from 0.74 to 1.01 by 2029 (36.5% increase) with predominant increase noted in Black and Hispanic cohorts. In contrast, we noticed a relatively stable and decreasing incidence rate in White and Asian females, respectively. Conclusions: We predict an overall increased incidence of both iCCA and eCCA over the next decade especially in certain subgroups warranting the urgent need for preventive strategies. Further epidemiological studies are needed to determine the etiological factors contributing to predicted increase in incidence rate.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma incidence between 2006 and 2015 in China: estimates based on data from 188 population-based cancer registries.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common subtypes of primary liver cancer, but nationwide incidence of both liver cancer subtypes have never been reported in China. We aimed to estimate the most recent incidence of HCC and ICC and temporal trends in China based on the most updated data from high qualified population-based cancer registries (covering 13.1% of the national population), in comparison to those in the United States at the same period. We used data from 188 Chinese population-based cancer registries covering 180.6 million population of China to estimate the nationwide incidence of HCC and ICC in 2015. And 22 population-based cancer registries' data were used to estimate the trends of HCC and ICC incidence from 2006 to 2015. Multiple imputation by chained equations method was used to impute liver cancer cases with unknown subtype (50.8%). We used data from 18 population-based registries from the Surveillance, Epidemiology, and End Results program to analyze incidence of HCC and ICC in the United States. In China, an estimated 301,500 and 61,900 newly diagnosed HCC and ICC occurred in 2015. The overall age-standardized rates (ASRs) of HCC incidence decreased by 3.9% per year. For ICC incidence, the overall ASR was relatively stable, but increased in the population of over 65 years old. Subgroup analysis by age showed that the ASR of HCC incidence had the sharpest decline in population who were less than 14 years old and received neonatally hepatitis B virus (HBV) vaccination. In the United States, though the incidence of HCC and ICC were lower than those in China, the overall HCC and ICC incidence increased by 3.3% and 9.2% per year. China still faces with a heavy burden of liver cancer incidence. Our results may further support the beneficial effect of Hepatitis B vaccination on reduction of HCC incidence. Both healthy lifestyle promotion and infection control are needed for future liver cancer control and prevention for China and the United States.

Strategy for ERCP stenting in cholangiocarcinoma

Considering the steadily growing incidence of cholangiocarcinoma (CCA) worldwide, there is a constant need to re-evaluate and re-think its pathophysiology, diagnostic modalities, and mostly important, its treatment. No matter the histopathological appearance, endoscopic procedures - mainly Endoscopic Retrograde Cholangiopancreatography (ERCP) with stenting - are often used in the treatment of CCA complications, such as biliary obstruction when biliary drainage is indicated. Indications for preoperative biliary drainage in surgical cases are adjusted to each patient’s status. On the contrary, palliative drainage is the first option for relieving symptoms and improving the quality of life in the context of locally advanced and unresectable CCA. Further, concern about stenting techniques depends on the stricture location: Bismuth-Corlette types I and II are usually endoscopically drained with one stent placed in biliary tract, while for types III and IV, even bilateral stenting may prove inadequate. Stents used in ERCP are either plastic or self-expandable metallic stents (SEMS). Though plastic stents show some advantages over SEMS in terms of removability and possibility to adapt to a biliary tree which allows potential reinterventions, SEMS are better in terms of patency, lower complications number, and success of drainage. Besides ERCP, echo-endoscopic drainage is also an option, especially when ERCP approach has not yielded a successful drainage. The aim of this study was to show the potential of ERCP stenting in CCA treatment, its possible pitfalls, and the need to consider multiple levels of ERCP-related care.

Patterns of Regional Lymph Node Recurrence after Surgery for Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma: A Retrospective Analysis in a Single Institution

<h3>Purpose/Objective(s)</h3> The overall incidence of cholangiocarcinoma (CCA) has increased progressively worldwide over decades. CCAs are highly aggressive, which renders a dismal prognosis with high recurrence rates after dissection and disappointing 5-year survival rate (7%-20%). Surgical resection remains the mainstay of potentially curative therapy for intrahepatic CCA (iCCA) or combined hepatocellular carcinoma (HCC)-CCA. Most patients develop recurrent disease after surgery and extrahepatic recurrence was found in 40% patients. Postoperative radiotherapy (RT) has been considered an adjuvant treatment modality. However, no consensus has been reached regarding to the clinical target volume (CTV) of RT. We aim to investigate the patterns of regional recurrence after surgery for iCCA and combined HCC-CCA to give insights on CTV delineation. <h3>Materials/Methods</h3> Medical records of iCCA and combined HCC-CCA patients who underwent surgery at Cancer Hospital of Chinese Academy of Medical Sciences between 2010 to 2019 were retrospectively reviewed. Patients were included in this study if they 1) had been pathologically diagnosed with iCCA or combined HCC-CCA; 2) underwent surgical resection; and 3) had been diagnosed with first recurrent event in regional LNs. Patients were excluded if they had adjuvant radiotherapy. All available follow-up imaging studies were thoroughly reviewed. Patterns of recurrence were categorized as local (intrahepatic), regional (regional LNs) and distant failure. Regional failures as first site of recurrence were further evaluated. <h3>Results</h3> A total of 53 patients were included in analysis, 42 of which had iCCA and 11 had combined HCC-CCA. The median age was 59 years (35-70) for all patients. The proportion of patients with history of hepatitis B and elevated AFP was higher in combined HCC-CCA group than in iCCA group. 67.9% patients underwent R0 resection and the median number of dissected LNs is 5 (0-31). Hepatic hilar is the most common recurrent region for both groups followed by portal vein-vena cava (high risk stations). Recurrence rates at left gastric, paracardial, diaphragmatic, common hepatic, celiac trunk and superior mesenteric artery are similar and moderate (medium risk stations). There is much less recurrence at other LN regions with likelihood less than 10% (low risk stations). A total of 20.8% patients had skip metastases. 13.2% patients had recurrence at medium risk stations without recurrence at high-risk stations and 7.6% patients had recurrence at high and low risk stations without recurrence at medium risk stations. A figure of 3-dimentional distribution of recurrent LNs was created. A standard patient was selected and all recurrent LNs were contoured on her CT images according to relationship between LNs and vessels. <h3>Conclusion</h3> This study created a LN recurrence map of surgically resected iCCA and combined HCC-CCA patients, which might be helpful for radiation oncologists in CT-guided delineation of postoperative CTV.

S44 The Incidence of Cholangiocarcinoma Among Primary Sclerosing Cholangitis Patients Is Lower Than Previously Reported

S44 The Incidence of Cholangiocarcinoma Among Primary Sclerosing Cholangitis Patients Is Lower Than Previously Reported

RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma.

BackgroundRecently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNAs may regulate the progression of a variety of tumors, and tsRNAs is expected to become a new diagnostic biomarker of cancer. However, the expression of tsRNAs is obscure and should be elucidated in CCA.MethodsHigh‐throughput RNA sequencing technology (RNA‐seq) was utilized to determine the overall expression profiles of tsRNAs in three pairs CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The target genes of dysregulated tsRNAs were predicted and the biological effects and potential signaling pathways of these target genes were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to validate 11 differentially expressed tRFs with 12 pairs CCA and adjacent normal tissues.ResultsHigh‐throughput RNA‐seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated, such as tRF‐21‐YLKZKWE5D，tRF‐16‐9NF5W8B，tRF‐27‐78YLKZKWE52，tRF‐19‐RLXN48KP，tRF‐33‐IK9NJ4S2I7L7DV，tRF‐19‐F8DHXYIV, and 294 tsRNAs were downregulated (tRF‐20‐739P8WQ0, tRF‐34‐JJ6RRNLIK898HR, tRF‐17‐VL8RPY5, tRF‐23‐YP9LON4VDP, tRF‐39‐EH623K76IR3DR2I2, tRF‐17‐18YKISM, tRF‐19‐Q1Q89PJZ, etc.) in CCA compared with adjacent normal tissues (|log2 [fold change] | ≥ 1 and p value <0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF‐34‐JJ6RRNLIK898HR, tRF‐38‐0668K87SERM492V, and tRF‐39‐0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, cAMP signaling pathway and in growth hormone synthesis, secretion and action, etc. qRT‐PCR result showed that tRF‐34‐JJ6RRNLIK898HR/tRF‐38‐0668K87SERM492V/tRF‐39‐0668K87SERM492E2 was downregulated (p = 0.021), and tRF‐20‐LE2WMK81 was upregulated in CCA (p = 0.033).ConclusionDifferentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the tumor progression and have potential to be diagnostic biomarkers and therapeutic targets of CCA.

Temporal Changes in Cholangiocarcinoma Incidence and Mortality in the United States from 2001 to 2017.

BackgroundPrevious studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015.Patients and MethodsPatients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3: C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA.ResultsForty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%).ConclusionsCCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification.