Diagnosis Of Cholangiocarcinoma Research Articles

Molecular therapeutic targets for cholangiocarcinoma: Present challenges and future possibilities.

A diagnosis of cholangiocarcinoma (CCA) is implicit with poor prognosis and limited treatment options, underscoring the near equivalence of incidence and mortality rates in this disease. In less than 9years from genomic identification to FDA-approval of the corresponding inhibitors, fibroblast growth factor receptor 2 (FGFR2) rearrangements and isocitrate dehydrogenase 1 (IDH1) mutations became exemplary successes of precision oncology in subsets of patients with CCA. However, clinical trial results from multikinase inhibitors in unselected populations have been less successful, while the impact of immunotherapies are only beginning to impact this setting. Development of future therapeutics is incumbent with new challenges. Many driver alterations occur in tumor suppressor-like genes which are not directly druggable. Therapeutically, this will require identification of ensuant "non-oncogene addiction" involving genes which are not themselves oncogenes but become tumor survival dependencies when a specific driver alteration occurs. The low recurrence frequency of genomic alterations between CCA patients will require careful evaluation of targeted agents in biomarker-enrolled trials, including basket trial settings. Systematic expansion of candidate drug targets must integrate genes affected by non-genetic alterations which incorporates the fundamental contribution of the microenvironment and immune system to treatment response, disease facets which have been traditionally overlooked by DNA-centric analyses. As treatment resistance is an inevitability in advanced disease, resistance mechanisms require characterization to guide the development of combination therapies to increase the duration of clinical benefit. Patient-focused clinical, technological and analytical synergy is needed to deliver future solutions to these present therapeutic challenges.

Malignant lesions of the extrahepatic biliary system

This article provides an overview of recent advances in the diagnosis and treatment of extrahepatic cholangiocarcinomas (EH-CCAs), focusing on the role of endoscopy, surgery, and transplantation. It reviews optimal evaluation and management of patients with EH-CCA, including a careful integration of clinical information, imaging studies, cytology and/or histology, as well as a coordinated multidisciplinary approach. It reviews additional therapy such as radio- or chemotherapy either in the neoadjuvant or adjuvant setting. Furthermore, it addresses palliative approaches as well as emerging targeted therapy and immunotherapy. EH-CCAs account for nearly 90% of biliary tract malignancies and present an ongoing challenge for hepatobiliary surgeons.

The role of positron emission tomography in the diagnosis and treatment of oncological diseases of the hepatobiliary system

The article highlights the role of PET and SIRT in the diagnosis and treatment of cholangiocarcinoma and HCR. In HCR, PET can be useful in detecting distant metastases, assessing overall and recurrence-free survival. In the case of cholangiocarcinoma, PET is more diagnostically informative than CT when detecting distant metastases and plays an important role in predicting recurrence after surgical resection. Data on the use of various types of radiopharmaceuticals and their combinations are provided. A comparison of their sensitivity and specificity is presented, which showed the best results when using the combination of FDG + choline. The effectiveness of PET in the selection of patients before transplantation, the ability to assess the distribution of activity and to quantify the absorbed dose in SIRT, which in turn allows to predict the therapeutic response and outcome, has been demonstrated. Different types of microspheres for SIRT are considered, in particular, 90Y-resin, 90Y-glass, and 166Ho-poly-L-lactic acid (PLLA). Among them, the most interesting are 166Ho microspheres, which have the advantage of being able to perform diagnostics and treatment with the same radiological label, i.e., to be used in a theranostic approach, theoretically reducing discrepancies between the planning and treatment procedure. SIRT can be used both alone and in combination with other types of treatment at different stages of tumor disease.

IGG4-related Sclerosing Cholangitis Mimicking Cholangiocarcinoma: A Case Report

Introduction: IgG4-related sclerosing cholangitis may have variable clinical presentations and may sometimes mimic cholangiocarcinoma. We present a case of a 42-year-old male with IgG4-related sclerosing cholangitis who was initially diagnosed as cholangiocarcinoma. Case report: A 42-year-old gentleman presented with history of progressive jaundice for one month associated with generalized weakness and loss of appetite. His total and direct bilirubin were 5.7 and 4.8 mg/dl, respectively, with an ALP of 1570 U/L. CECT revealed an ill-defined soft tissue enhancing component infiltrating the lumen of the common hepatic duct, distal cystic duct, and proximal common bile duct. In addition, the MRCP of the patient showed an ill-defined lesion around the gall-bladder neck that was effacing a part of the distal cystic duct and a long segment of common hepatic duct suspicious of cholangiocarcinoma. With a provisional diagnosis of cholangiocarcinoma, the patient was subjected to diagnostic laparoscopy, which revealed scirrhous tissue encasing the proper hepatic artery and portal vein and prominent lymph nodes around the hepatoduodenal ligament. There were no ascites or evidence of peritoneal metastasis. Biopsy of the lesion revealed inflammatory cells comprising of lymphocytes, plasma cells, and eosinophils; there were no atypical or malignant cells. IgG-4 marker was positive and immuno-reactive in 5-6% of plasma cells. The patient’s symptoms were completely relieved after three months of steroid therapy. Conclusion: IgG4 -related sclerosing cholangitis can mimic cholangiocarcinoma. Although the disease is rare and its diagnosis remains challenging, knowledge of the disease is valuable when considering the differential diagnosis of obstructive jaundice.

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.

An Integrated Microfluidic System for Cholangiocarcinoma Diagnosis from Bile by Using Specific Affinity Probes

An Integrated Microfluidic System for Cholangiocarcinoma Diagnosis from Bile by Using Specific Affinity Probes

O-L02 Evaluation of the Utility of Prognostic Models for Patients Diagnosed with Peri-hilar Cholangiocarcinoma

Abstract Background Several potential prognostic models have been developed to stratify patients with peri-hilar cholangiocarcinoma (PHC) by Overall Survival (OS). The American Joint Committee on Cancer (AJCC) staging system is a post-resectional model utilising tumour-specific pathological parameters to stratify and predict OS. The Mayo Clinical (MC) scoring system has been developed utilising primarily clinical, serological, and radiological variables to predict survival in all patients with a diagnosis of peri-hilar cholangiocarcinoma. The objective of this study was to evaluate the utility of these models in determining prognosis for all patients presenting to a tertiary treatment centre with PHC. Methods Three hundred and two patients diagnosed with PHC referred to a regional tertiary referral centre between 2008 and 2019 had their demographic and survival data retrospectively analysed from a prospectively held database linked to Hospital Episode Statistics and Somerset Cancer Registry data. One hundred and twenty seven patients were surgically explored. Eight-four patients underwent resection. One-hundred and seventy-four (57.6%) patients underwent palliative endoscopic therapy. Univariate and multivariate modelling was utilised to determine significant prognostic variables. Concordance Indices (C-Indices) were constructed for the prognostic models to determine internal validity within the cohort. Results Multivariate analysis demonstrated that: pre-interventional ECOG status (p < 0.001); serum albumin (p < 0.001); bilirubin levels (p < 0.001); CA 19-9 levels (p < 0.001) and resectional status (p < 0.001) were significant predictors of OS. Patients stratified by the MC scoring system to early-stage disease had a significantly longer OS compared to patients fulfilling late-stage criteria (p < 0.001). The predictive C-Indices for the MC model obtained significance in discriminating OS for the entire cohort (p < 0.05) and un-resected patients (p < 0.05). Neither model attained significant concordance for accurately discriminating OS in post-resectional patients. Conclusions The predictive performance of the stated prognostic models for OS have poor utility. Simple pre-interventional serological, functional and radiological variables appear to provide better prognostic indication of OS. Variables not incorporated in the AJCC registry have a significant effect upon post-resectional OS and require full incorporation in to model prognostication.

Moving forward in the treatment of cholangiocarcinoma.

Despite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.

Development and validation of a machine learning-based nomogram for prediction of intrahepatic cholangiocarcinoma in patients with intrahepatic lithiasis.

Accurate diagnosis of intrahepatic cholangiocarcinoma (ICC) caused by intrahepatic lithiasis (IHL) is crucial for timely and effective surgical intervention. The aim of the present study was to develop a nomogram to identify ICC associated with IHL (IHL-ICC). The study included 2,269 patients with IHL, who received pathological diagnosis after hepatectomy or diagnostic biopsy. Machine learning algorithms including Lasso regression and random forest were used to identify important features out of the available features. Univariate and multivariate logistic regression analyses were used to reconfirm the features and develop the nomogram. The nomogram was externally validated in two independent cohorts. The seven potential predictors were revealed for IHL-ICC, including age, abdominal pain, vomiting, comprehensive radiological diagnosis, alkaline phosphatase (ALK), carcinoembryonic antigen (CEA), and cancer antigen (CA) 19-9. The optimal cutoff value was 2.05 µg/L for serum CEA and 133.65 U/mL for serum CA 19-9. The accuracy of the nomogram in predicting ICC was 82.6%. The area under the curve (AUC) of nomogram in training cohort was 0.867. The AUC for the validation set was 0.881 from The Second Affiliated Hospital of Wenzhou Medical University, and 0.938 from The First Affiliated Hospital of Fujian Medical University. The nomogram holds promise as a novel and accurate tool to predict IHL-ICC, which can identify lesions in IHL in time for hepatectomy or avoid unnecessary surgical resection.

Latest advances in cholangiocarcinoma

Biliary tract cancers include cholangiocarcinoma (CCA) and gallbladder cancer (GBC). Despite being considered rare tumours, their incidence is increasing, especially due to an increased incidence of intrahepatic cholangiocarcinoma (iCCA).1 The majority of patients are diagnosed at late stages, mainly due to challenges at the time of diagnosis.2 This means that for the majority of patients, the only treatment option available is palliative management; thus, prognosis remains poor with a 5-year survival of around 5%-15% when all stages are analysed together.1 This current special issue includes an overview of the main areas of interest in the field of cholangiocarcinoma.3 Firstly, aiming to improve patients’ outcomes, early diagnosis is key. In order to achieve this, in depth knowledge of current endoscopic diagnostic techniques is crucial.4 In addition, the development of new strategies and technologies is the only way of securing adequate early diagnosis and acquisition of tissue to secure sufficient sample for diagnostic and molecular profiling purposes. Endoscopy is also key for the management of one of the most common and clinically relevant complications identified on patients with biliary malignancies: malignant biliary obstruction. Malignant biliary obstruction is considered one of the oncological emergencies and its early release is of much importance to avoid life threatening complications and prevent early and potentially avoidable clinical deterioration. Secondly, treatment for patients with the advanced disease currently relies on the use of palliative chemotherapy.1 However, the emergence of targeted therapies is rapidly changing this,5 especially for iCCA which are most likely to harbour targetable alterations such as fibroblast growth factor receptor (FGFR)-2 fusions and isocitrate dehydrogenase (IDH)-1 mutations, within others. Despite recent studies supporting the role of these precision medicine strategies in cholangiocarcinoma, lots of unanswered questions remain and will need specific research to better understand, not only primary and secondary resistance to these treatments, but also adequate sequencing and combination strategies.6 Thirdly, none of the advances on diagnosis and treatment strategies could have taken place without a close collaboration between basic, translational and clinical researchers. Such collaborations allow identification of diagnostic biomarkers, predictive tools for adequate treatment selection and also understanding of acquired secondary resistance to novel therapies. Within the field of cholangiocarcinoma, many unmet needs can be identified and lots of effort is going into getting this sorted with the aim of moving the field forward.7 In summary, diagnosis and management of cholangiocarcinoma is a rapidly evolving field that requires teamwork and multidisciplinary collaboration to benefit our current and future patients. The articles included in this special issue provide an overview of the current knowledge and unanswered questions for some of the main topics of interest.4, 6, 7 Dr Angela Lamarca received funding from The Christie Charity and the European Union's Horizon 2020 Research and Innovation Programme [grant number 825510, ESCALON]. Travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan and Delcath; speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA, QED and Servier; advisory honoraria from EISAI, Nutricia Ipsen, QED, Roche and Servier; member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Data sharing is not applicable to this article as no new data were created or analysed in this study.

Proteomic analysis of serum and serum exosomes, and their application in intrahepatic cholangiocarcinoma

外泌体是由各种类型细胞在正常或非正常生理情况下分泌释放至细胞外且携带多种生物活性分子的细胞外囊泡,在细胞间通讯和免疫应答等生物过程中发挥着重要作用。肝内胆管癌是一种胆道上皮恶性肿瘤,早期无明显临床症状且生存率较低,目前常用的诊断手段包括依赖于影像设备的诊断方式和灵敏度及特异性较低的诊断标志物等,这些手段的不足对发展新的特异性标志物提出了需求。该文对血清中的外泌体进行了分离和表征,并采用液相色谱-质谱技术针对健康组与肝内胆管癌患者组的血清样本和血清外泌体样本进行了无标记定量蛋白质组学分析,分别从两种类型样本中鉴定并筛选到271和430种可信蛋白质。基于血清样本和血清外泌体样本的可信蛋白质定量表达值进行多维统计分析都能将健康组与肝内胆管癌患者组良好地区分开。对血清样本中鉴定到的蛋白质进行差异蛋白质筛选,肝内胆管癌患者组相对于健康组有15个上调和8个下调蛋白质;对血清外泌体样本中鉴定到的蛋白质进行差异蛋白质筛选,肝内胆管癌患者组相对于健康组有33个上调和18个下调蛋白质;基于两种样本筛选到的差异蛋白质中仅有4个是重复的,且基于血清外泌体样本的51个差异蛋白质中有35个蛋白质属于外泌体蛋白质数据库。针对差异蛋白质进行生物学信息分析,与差异蛋白质相关的分子功能、生物过程和信号通路主要涉及天然免疫反应、炎症反应和凝血等过程。该研究为发现肝内胆管癌的潜在生物标志物和探究肝内胆管癌的发生、发展和转移等过程提供了参考和借鉴价值。此外,通过比较研究发现血清外泌体样本能够获得较多的差异蛋白质和生物学信息,证明了外泌体作为组学分析样本的价值和应用潜力。

Efficacy of percutaneous image-guided biopsy for diagnosis of intrahepatic cholangiocarcinoma.

To evaluate the efficacy of percutaneous biopsy for diagnosing intrahepatic cholangiocarcinoma (IHCCA). Retrospective review of biopsy and pathology databases from 2006 to 2019 yielded 112 patients (54F/58M; mean age, 62.9years; 27 cirrhotic) with IHCCA who underwent percutaneous biopsy. Data regarding the lesion, biopsy procedure technique, and diagnostic yield were collected. If biopsy was non-diagnostic or discordant with imaging, details of repeat biopsy or resection/explant were gathered. A control group of 100 consecutive patients (56F/44M; mean age, 63years, 5 cirrhotic) with focal liver lesions > 1cm was similarly assessed. Mean IHCCA lesion size was 6.1 ± 3.6cm, with dominant lesion sampled in 78% (vs. satellite in 22%). 95% (n = 106) were US guided and 96% were core biopsies (n = 108), typically 18G (n = 102, 91%), median 2 passes. 18 patients (16%) had discordant/ambiguous pathology results requiring repeat biopsy, with two patients requiring 3-4 total attempts. A 4.4% minor complication rate was seen. Mean time from initial biopsy to final diagnosis was 60 ± 120days. Control group had mean lesion size of 2.9 ± 2.5cm and showed a non-diagnostic rate of 3.3%, both significantly lower than that seen with CCA, with average time to diagnosis of 21 ± 28.8days (p = 0.002, p = 0.001). IHCCA is associated with lower diagnostic yield at initial percutaneous biopsy, despite larger target lesion size. If a suspicious lesion yields a biopsy result discordant with imaging, the radiologist should recommend prompt repeat biopsy to prevent delay in diagnosis.

Research Progress of Circulating Tumor Cells in the Evaluation of Early Cholangiocarcinoma

Epidemiological data show that the incidence rate of cholangiocarcinoma (CCA) has been increasing over the past 20 years. Due to its concealment of clinical manifestations, most patients are diagnosed with CCA at a late stage. On this premise, this review not only discusses the research progress related to CCA diagnosis, but also focuses on the concept of circulating tumor cell (CTC), its evaluation value, application, and prospects for the early diagnosis of extrahepatic cholangiocarcinoma.

Analysis of Post-operative Adjuvant Chemotherapy Versus Adjuvant Chemoradiation Therapy Outcomes in Non-metastatic Cholangiocarcinoma: an NCDB Review

BackgroundEach year, approximately 8000 cases of cholangiocarcinoma are recorded in the USA. Surgical resection is considered to be the only curative option. Despite surgery as a curative approach, many patients will require adjuvant therapies in the form of chemotherapy (ChT) or chemoradiotherapy (CRT). As such, we sought to analyze outcomes in patients with non-metastatic cholangiocarcinoma receiving adjuvant ChT or CRT following surgical resection.MethodsWe queried the National Cancer Database (NCDB) for patients with a diagnosis of non-metastatic cholangiocarcinoma between the years 2010 and 2015 who underwent adjuvant ChT or CRT following surgery. Overall survival (OS) was calculated using Kaplan Meier method. Cox proportional hazard ratios were used to identify predictors of overall survival, and logistic regression was used to identify predictors of receiving each treatment.ResultsA total of 875 patients were identified who met the above eligibility criteria. Of these patients, 818 received adjuvant chemotherapy alone with 57 patients receiving adjuvant chemoradiation therapy. The median OS in patients receiving CRT was 19.8 months versus 11.9 months for ChT (p value < 0.0238). The 1- and 5-year survival rates between ChT and CRT were 50% vs 61% and 6% vs 13%, respectively (hazard ratio 0.7005; 95% CI 0.51–0.97; p value < 0.0294).ConclusionThe results of this study suggest a potential benefit of chemoradiation therapy in the adjuvant setting, although the trends appear to show rare utilization. Given the limitations of our study, prospective corroboration is warranted.

A Mouse Model of Cholangiocarcinoma Uncovers a Role for Tensin-4 in Tumor Progression.

Earlier diagnosis and treatment of intrahepatic cholangiocarcinoma (iCCA) are necessary to improve therapy, yet limited information is available about initiation and evolution of iCCA precursor lesions. Therefore, there is a need to identify mechanisms driving formation of precancerous lesions and their progression toward invasive tumors using experimental models that faithfully recapitulate human tumorigenesis. To this end, we generated a mouse model which combines cholangiocyte-specific expression of KrasG12D with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced inflammation to mimic iCCA development in patients with cholangitis. Histological and transcriptomic analyses of the mouse precursor lesions and iCCA were performed and compared with human analyses. The function of genes overexpressed during tumorigenesis was investigated in human cell lines. We found that mice expressing KrasG12D in cholangiocytes and fed a DDC diet developed cholangitis, ductular proliferations, intraductal papillary neoplasms of bile ducts (IPNBs), and, eventually, iCCAs. The histology of mouse and human IPNBs was similar, and mouse iCCAs displayed histological characteristics of human mucin-producing, large-duct-type iCCA. Signaling pathways activated in human iCCA were also activated in mice. The identification of transition zones between IPNB and iCCA on tissue sections, combined with RNA-sequencing analyses of the lesions supported that iCCAs derive from IPNBs. We further provide evidence that tensin-4 (TNS4), which is stimulated by KRASG12D and SRY-related HMG box transcription factor 17, promotes tumor progression. We developed a mouse model that faithfully recapitulates human iCCA tumorigenesis and identified a gene cascade which involves TNS4 and promotes tumor progression.

Diagnostic Accuracy of tumor marker CA 19-9 in patients with cholangiocarcinoma taking ERCP as gold standard test”

Background: Majority of the cases of Cholangiocarcinoma at presentation are unresectable, it’s diagnosis at an early stage is pivotal but generally difficult due to lack of easy availaibility of confirmatory test at the moment in our country. Endoscopic Retrograde Cholangiopancreatography (ERCP) is not only helpful in reaching the diagnosis Aim: To find out the diagnostic accuracy of tumour marker CA 19-9, in suspected patients of Cholangiocarcinoma taking ERCP as gold standard test Methods: This cross sectional study was conducted in general and private clinics of Department of Gastroenterology of the Fatima Memorial Hospital Lahore from, October 21, 2014 to April 20, 2015. Sampling technique used was probability purposive sampling. Results: A total of 150 suspected patients of cholangiocarcinoma were included in the study in which 61 (40.7%) were male and 89(59.3%) were female with total mean age of 56.32±14.13 years. Among the studied patients, 88(58.7%) were found positive for malignant stricture on ERCP and CBD brushing cytology. Sensitivity, specificity and accuracy of the tumour marker CA 19-9 was 53.4%, 66.1% and 58% respectively. Conclusions: CA 19-9 is a very important tumor marker in making diagnosis of cholangiocarcinoma and in our country due to lack of easy access/availability to invasive diagnostic methods like endoscopic ultrasonography (EUS) and fine needle aspiration (FNA) of the tumor. It should be used as routine early diagnostic modality in suspected cases of Cholangiocarcinoma. Keywords: Cholangiocarcinoma, Cancer antigen (CA) 19-9, ERCP, biliary brushing and cytology

Serum epithelial membrane protein 1 serves as a feasible biomarker in extrahepatic cholangiocarcinoma.

Extrahepatic cholangiocarcinoma is a malignancy that originates from bile duct epithelium with an unfavorable prognosis. Epithelial membrane protein 1 was first discovered in 1995, functioning as an oncogene or anti-tumor gene in various cancers. However, the clinical role of epithelial membrane protein 1 extrahepatic cholangiocarcinoma remained unclear. Differentially expressed genes were identified using Gene Ontology and the Kyoto Encyclopedia and Genomes pathway analysis. Out of 183 extrahepatic cholangiocarcinoma patients and 61 healthy controls, the expression level of epithelial membrane protein 1 was detected and compared using reverse transcription-quantitative polymerase chain reaction analysis and western blot assay. Meanwhile, the diagnosis and prognosis of EMP1 in ECCA were measured by receiver operating characteristic and Kaplan-Meier analysis. Finally, the relationship between epithelial membrane protein 1 expression and clinicopathological indexes were compared to further verify the clinical role of epithelial membrane protein 1 in extrahepatic cholangiocarcinoma. After analyzing data from GSE76297, GSE89749, and GSE26566GO, we found 1554 down-regulated and 1065 up-regulated genes. Through Gene Ontology and Kyoto Encyclopedia and Genomes analysis, extracellular matrix organization, extracellular structure organization, cholesterol metabolism, interleukin-17 signaling pathway, and vitamin digestion and absorption were significantly enriched and involved in targeted differentially expresses genes. Epithelial membrane protein 1 messenger ribonucleic acid was notably decreased in serum samples from extrahepatic cholangiocarcinoma patients, compared with that in healthy controls. Receiver operating characteristic analysis revealed that the area under the curve of epithelial membrane protein 1 messenger ribonucleic acid for the diagnosis of extrahepatic cholangiocarcinoma was 0.9281 (95% CI = 0.8967-0.9595). Moreover, the correlation analysis presented that epithelial membrane protein 1 expression was negatively correlated with lymph node metastasis, tumour node metastasis stage, cancer antigen 19-9 level, and carcinoembryonic antigen level. Aberrant expression of epithelial membrane protein 1 contributed to distinguishing extrahepatic cholangiocarcinoma patients and healthy controls, and a low expression level of epithelial membrane protein 1 indicated an unfavorable prognosis. Hence, epithelial membrane protein 1 was a feasible and credible biomarker for extrahepatic cholangiocarcinoma diagnosis and prognosis, with high accuracy, sensitivity, and specificity.

Thrombospondin-2 as a diagnostic biomarker for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma

PurposeDistal cholangiocarcinoma and pancreatic ductal adenocarcinoma are malignancies with poor prognoses that can be difficult to distinguish preoperatively. Thrombospondin-2 has been proposed as a novel diagnostic biomarker for early pancreatic ductal adenocarcinoma. The aim of the present study was to evaluate thrombospondin-2 as a diagnostic and prognostic biomarker in combination with current biomarker CA 19-9 for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma.MethodsThrombospondin-2 was measured in prospectively collected serum samples from patients who underwent surgery with a histopathological diagnosis of distal cholangiocarcinoma (N = 51), pancreatic ductal adenocarcinoma (N = 52) and benign pancreatic diseases (N = 27) as well as healthy blood donors (N = 52) using an enzyme-linked immunosorbent assay.ResultsThrombospondin-2 levels (ng/ml) were similar in distal cholangiocarcinoma 55 (41–77) and pancreatic ductal adenocarcinoma 48 (35–80) (P = 0.221). Thrombospondin-2 + CA 19-9 had an area under the curve of 0.92 (95% CI 0.88–0.97) in differentiating distal cholangiocarcinoma and pancreatic ductal adenocarcinoma from healthy donors which was superior to CA 19-9 alone (P < 0.001). The diagnostic value of adding thrombospondin-2 to CA 19-9 was larger in early disease stages. Thrombospondin-2 did not provide additional value to CA 19-9 in differentiating the benign disease group; however, heterogeneity was notable in the benign cohort. Three of five patients with autoimmune pancreatitis patients had greatly elevated thrombospondin-2 levels. Thrombospondin-2 levels had no correlation with prognoses.ConclusionsSerum thrombospondin-2 in combination with CA 19-9 has potential as a biomarker for distal cholangiocarcinoma and pancreatic cancer.

Brush Cytology, Forceps Biopsy, or Endoscopic Ultrasound-Guided Sampling for Diagnosis of Bile Duct Cancer: A Meta-Analysis.

Endoscopic sampling is essential for tissue diagnosis of cholangiocarcinoma (CCA). To evaluate and compare the diagnostic sensitivities of endoscopic retrograde cholangiopancreatography-guided brush cytology biopsy, and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with CCA. A comprehensive literature search through multiple databases was conducted for articles published between January 1995 and August 2020. The pooled rates of sensitivity for the diagnosis of CCA and of adverse events were compared among brushing, biopsy, brushing & biopsy, and EUS-FNA. In total, 1123 patients with CCA (32 studies), 719 patients (20 studies), 358 patients (13 studies), and 422 patients (17 studies) were tested by brushing, biopsy, brushing & biopsy, and EUS-FNA, respectively. The pooled diagnostic sensitivity was 56.0% (95% confidence interval (CI) 48.8-63.1%, I2 = 83.0%) with brushing, 67.0% (95% CI 60.2-73.5%, I2 = 72.5%) with biopsy, 70.7% (95% CI 64.1-76.8%, I2 = 42.7%) with brushing & biopsy, and 73.6% (95% CI 64.7-81.5%, I2 = 74.7%) with EUS-FNA. The diagnostic sensitivity was significantly lower for brushing than for biopsy, brushing & biopsy, or EUS-FNA. No significant difference was noted in diagnostic sensitivities among biopsy, brushing & biopsy, and EUS-FNA. Adverse events were comparable between the groups. Intraductal biopsy, brushing & biopsy, and EUS-FNA had comparable efficacy and safety for the diagnosis of CCA. Brushing was the least sensitive diagnostic tool compared with intraductal biopsy or EUS-FNA. Given the modest diagnostic sensitivities of intraductal biopsy and EUS-FNA in the diagnosis of CCA, further studies for complementing these techniques with biomarkers may be needed.

Cholangioscopy in primary sclerosing cholangitis: a case series of benign features.

Background and AimsCholangioscopy is useful in establishing a visual diagnosis of cholangiocarcinoma (CCA), but this is harder to achieve in primary sclerosing cholangitis (PSC) because of the stricture-forming nature of the disease. Furthermore, it can be harder to differentiate malignant from benign features of the underlying inflammation. This case series demonstrates the varied features of nonmalignant inflammatory findings in PSC.MethodsA single experienced endoscopist performed cholangioscopy for PSC cases referred for ERCP.ResultsCholangioscopy in these 5 cases without CCA demonstrated the features of acute and chronic inflammation, acute inflammatory mass, dominant stricture, acute cholangitis in a duct with features of chronic inflammation with a large pigmented stone, and fibrostenotic disease. Cholangioscopic maneuvers such as advancement across strictures after balloon dilation, targeted mucosal biopsy, and electrohydraulic lithotripsy (EHL) of impacted stones are demonstrated. The relevant radiographic and histopathologic features of the disease accompany each case description. Regarding long-term prognosis, 1 case of acute inflammatory mass and a case of worsening liver function required a liver transplant evaluation, whereas the other 3 cases remain stable.ConclusionsCholangioscopic features of benign disease in PSC are varied. Knowledge of these features is essential in differentiating between benign and malignant findings. These features, combined with biopsy and cytology evaluation, can help in tailoring management in patients with benign PSC.