Diagnosis Of Cholangiocarcinoma Research Articles

Deep Learning in Endoscopic Ultrasound: A Breakthrough in Detecting Distal Cholangiocarcinoma

Introduction: Cholangiocarcinoma (CCA) is a highly lethal malignancy originating in the bile ducts, often diagnosed late with poor prognosis. Differentiating benign from malignant biliary tumors remains challenging, necessitating advanced diagnostic techniques. Objective: This study aims to enhance the diagnostic accuracy of endoscopic ultrasound (EUS) for distal cholangiocarcinoma (dCCA) using advanced convolutional neural networks (CCNs) for the classification and segmentation of EUS images, specifically targeting dCCAs, the pancreas, and the bile duct. Materials and Methods: In this retrospective study, EUS images from patients diagnosed with dCCA via biopsy and an EUS-identified bile duct tumor were evaluated. A custom CNN was developed for classification, trained on 156 EUS images. To enhance the model’s robustness, image augmentation techniques were applied, generating a total of 1248 images. For tumor and organ segmentation, the DeepLabv3+ network with ResNet50 architecture was utilized, employing Tversky loss to manage unbalanced classes. Performance evaluation included metrics such as accuracy, sensitivity, specificity, and Intersection over Union (IoU). These methods were implemented in collaboration with the ADAPTED Research Group at the Technical University of Cluj-Napoca. Results: The classification model achieved a high accuracy of 97.82%, with precision and specificity both at 100% and sensitivity at 94.44%. The segmentation models for the pancreas and bile duct demonstrated global accuracies of 84% and 90%, respectively, with robust IoU scores indicating good overlap between predicted and actual contours. The application performed better than the UNet model, particularly in generalization and boundary delineation. Conclusions: This study demonstrates the significant potential of AI in EUS imaging for dCCA, presenting a robust tool that enhances diagnostic accuracy and efficiency. The developed MATLAB application serves as a valuable aid for medical professionals, facilitating informed decision-making and improving patient outcomes in the diagnosis of cholangiocarcinoma and related pathologies.

Cholangiocarcinoma: A Comprehensive Review and Update Guideline

Cholangiocarcinoma is a rare cancer of the gastrointestinal system. However, the prognosis for people with this disease has not improved in the last decade. CCA has a poor prognosis because most cases are diagnosed at an advanced stage and the availability of treatment options is limited. This literature review aims to provide information regarding the current understanding and guidelines for cholangiocarcinoma. In this literature review, we searched the National Center for Biotechnology Information (NCBI) and Google Scholar using the search keywords "Cholangiocarcinoma", "cholangiocarcinoma management", "cholangiocarcinoma guidelines" taken ScienceDirect, Researchgate, National Comprehensive Cancer Network, and PubMed published in the last 10 years. From various databases, the literature used and according to the selection criteria amounted to 50 articles In the latest articles and the Cancers NCCN Guidelines for Biliary Tract Cancer in 2023, CCA treatment is carried out based on the patient's profile. Targeted therapy is an additional treatment option today by targeting the molecular profile involved in the pathogenesis of CCA. The diagnosis of cholangiocarcinoma is made through histology, radiography, and laboratory examination. Based on the Cancers NCCN Guidelines for Biliary Tract Cancer in 2023, the treatment carried out consists of determining cancer staging, surgery, radiation therapy, and systemic therapy.

A case of hepatocellular carcinoma arising from the intraductal hepatic bile duct without parenchymal lesion.

Hepatocellular carcinoma (HCC) rarely presents as an intraductal tumor with no parenchymal lesions. Here, we present a case of HCC arising from an intrahepatic bile duct. A 74-year-old man who had been treated with direct-acting antiviral therapy for hepatitis C virus infection was referred to our hospital because of elevated serum prothrombin levels induced by vitamin K absence II (PIVKA-II). Initial imaging revealed no findings suspicious of HCC; however, repeat CT six months later revealed dilation of the intrahepatic bile ducts in the lateral segment of the liver. Cholangiography revealed a significant stricture of B3, and biopsy suggested adenocarcinoma. A left hepatectomy was performed with a preoperative diagnosis of intrahepatic cholangiocarcinoma. Although a surface nodule on the lateral segment of the liver, suspicious for intrahepatic metastasis, was found intraoperatively, radical resection was performed. Histopathological examination revealed a tumor filling the intrahepatic bile duct from the stump to the peripheral bile duct, with no infiltration into the liver parenchyma. The surface nodule is a dilated peripheral bile duct filled with a tumor with no extrabiliary invasion. Immunohistochemistry suggested HCC. No tumor lesions were observed in the hepatic parenchyma, and the tumor was finally diagnosed as HCC stemming from the biliary epithelium.

Bioinformatics analysis identifies WNK1 gene as a potential biomarker for cholangiocarcinoma diagnosis and immune infiltration

BackgroundCholangiocarcinoma (CHOL) is a malignant epithelial carcinoma of the digestive system with poor prognosis and high mortality. WNK lysine deficient protein kinase 1 (WNK1) is known to be associated with tumorigenesis in various cancers. However, the relationship between WNK1 and CHOL development, as well as the potential mechanisms involved, remains poorly understood. MethodsMicroarray datasets of CHOL (GSE22633 and GSE32879) were retrieved from the Gene Expression Omnibus (GEO) database. Functional enrichment and immunoinfiltration analyses were performed for genes co-expressed with WNK1. GraphPad Prism 9 was utilized for statistical data analysis and the construction of receiver operating characteristic (ROC) curves. The impact of WNK1 on the CHOL tumor microenvironment was analyzed using Tumor Immune Estimation Resource (TIMER), Venn diagrams, STRING, and TISIDB database for information on WNK1-related chemokines and chemokine receptors. Protein-protein interaction (PPI) networks were used to predict transcription factors and microRNAs interacting with WNK1 and the associated hub genes. ResultsDifferential expression of WNK1 was observed between CHOL and normal samples, suggesting its diagnostic value. Functional analysis showed that WNK1 and its associated genes were primarily enriched in pathways such as leukocyte transendothelial migration and chemokine signaling. Neutrophils were the only type of infiltrating immune cells associated with WNK1 in the CHOL tumor microenvironment (TME). VEGFA and ALB were identified as hub genes, and X-C motif chemokine receptor 1 (XCR1) and C-X-C motif chemokine ligand 5 (CXCL5) were identified as core chemokines and chemokine receptors related to WNK1 and neutrophil infiltration in CHOL. ConclusionsBased on network analysis and the summary of previous studies, it was proposed that CHOL tumor cells secrete CXCL5, leading to neutrophil recruitment to the tumor microenvironment. Vascular endothelial growth factor A (VEGFA) released by the infiltrating neutrophils is suggested to promote overexpression of WNK1 by tumor cells, activating the VEGFA downstream pathway to promote angiogenesis and tumor progression.

Role of [18F]FAPI-04 in staging and therapeutic management of intrahepatic cholangiocarcinoma: prospective comparison with [18F]FDG PET/CT

BackgroundFluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC).Materials and methodsPatients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI–avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann–Whitney U test, and McNemar’s test was used to assess the diagnostic accuracy between the two techniques.ResultsIn total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG.Conclusions[18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC.Trial registrationClinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1.

Artificial intelligence for ultrasonographic detection and diagnosis of hepatocellular carcinoma and cholangiocarcinoma

The effectiveness of ultrasonography (USG) in liver cancer screening is partly constrained by the operator’s expertise. We aimed to develop and evaluate an AI-assisted system for detecting and classifying focal liver lesions (FLLs) from USG images. This retrospective study incorporated 26,288 USG images from 5444 patients to train YOLOv5 model for FLLs detection and classification of seven different types of FLLs, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), focal fatty infiltration, focal fatty sparing (FFS), cyst, hemangioma, and regenerative nodules. AI model performance was assessed for detection and diagnosis of the FLLs on a per-image and per-lesion basis. The AI achieved an overall FLLs detection rate of 84.8% (95%CI:83.3–86.4), with consistent performance for FLLs ≤ 1 cm and > 1 cm. It also exhibited sensitivity and specificity for distinguishing malignant FLLs from other benign FLLs at 97.0% (95%CI:95. 9–98.2) and 97.0% (95%CI:95.9–98.1), respectively. Among specific FLL types, CCA detection rate was at 92.2% (95%CI:88.0–96.4), followed by FFS at 89.7% (95%CI:87.1–92.3), and HCC at 82.3% (95%CI:77.1–87.5). The specificities and NPVs for regenerative nodules were 100% and 99.9% (95%CI:99.8–100.0), respectively. Our AI model can potentially assist physicians in FLLs detection and diagnosis during USG examinations. Further external validation is needed for clinical application.

Serum targeted metabolomics uncovering specific amino acid signature for diagnosis of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a hepatobiliary malignancy which accounts for approximately 5–10 % of primary liver cancers and has a high mortality rate. The diagnosis of iCCA remains significant challenges owing to the lack of specific and sensitive diagnostic tests available. Hence, improved methods are needed to detect iCCA with high accuracy. In this study, we evaluated the efficacy of serum amino acid profiling combined with machine learning modeling for the diagnosis of iCCA. A comprehensive analysis of 28 circulating amino acids was conducted in a total of 140 blood samples from patients with iCCA and normal individuals. We screened out 6 differentially expressed amino acids with the criteria of |Log2(Fold Change, FC)| > 0.585, P-value < 0.05, variable importance in projection (VIP) > 1.0 and area under the curve (AUC) > 0.8, in which amino acids L-Asparagine and Kynurenine showed an increasing tendency as the disease progressed. Five frequently used machine learning algorithms (Logistic Regression, Random Forest, Supporting Vector Machine, Neural Network and Naïve Bayes) for diagnosis of iCCA based on the 6 circulating amino acids were established and validated with high sensitivity and good overall accuracy. The resulting models were further improved by introducing a clinical indicator, gamma-glutamyl transferase (GGT). This study introduces a new approach for identifying potential serum biomarkers for the diagnosis of iCCA with high accuracy.

Hybrid FDG-PET/MRI for Diagnosis and Clinical Management of Patients with Suspected Perihilar Cholangiocarcinoma: A Feasibility Pilot Study

PurposeRecently introduced hybrid 2-[18 F]-fluoro-2-deoxy-D-glucose (18 F-FDG) Positron Emission Tomography (PET) combined with Magnetic Resonance Imaging (MRI) may aid in proper diagnosis and staging of perihilar cholangiocarcinoma (pCCA). The aim of this study is to assess the effect of 18 F-FDG PET/MRI on diagnosis and clinical decision making in the pre-operative work up of pCCA.MethodsIn this single-centre pilot study patients with presumed resectable pCCA underwent state-of-the-art 18 F-FDG hybrid PET/MRI using digital silicone photomultiplier detectors integrated within a 3-Tesla bore. Data were collected on several baseline and imaging characteristics. The primary outcome measure was the added diagnostic information and the effect on clinical decision making. Secondary aim was to correlate quantitative PET signal intensity to patient- and tumour characteristics. High and low SUVmax subgroups related to the mean value were made. Significance of lesion- and patient characteristics with the high and low SUVmax subgroups, as well as TLR and TBR, was evaluated with Fisher’s exact test or Mann-Whitney-U test.ResultsIn total 14 patients were included (mean age 62.4 years, 64% male). Final diagnosis was pCCA in 10 patients (71.4%), follicular lymphoma in one patient (7.1%) and benign disease in the remaining three patients. FDG-PET/MRI added valuable diagnostic information in six (43%) patients and affected clinical decision making in two of these patients (14%) by increasing confidence for malignancy which lead to the decision for surgery on short term. High SUVmax values were seen in half of cases with pCCA and half of cases with non-cancerous lesions. In addition, high SUVmax values were directly associated with primary sclerosing cholangitis when present (p = 0.03).ConclusionSimultaneous 18 F-FDG-PET/MRI added diagnostic information in six of fourteen patients and influenced clinical decision making in two patients (14%) with presumed resectable pCCA.

Systematic comparison of deep-learning based fusion strategies for multi-modal ultrasound in diagnosis of liver cancer

For the diagnosis of liver cancer, conventional brightness mode (B-mode) can only provide morphological information. Multi-modal ultrasound, including shear-wave elastography (SWE) and contrast enhanced ultrasound (CEUS), can provide comprehensive diagnostic information on tumor microenvironment and tissue perfusion. The challenge is to effectively explore the multi-modal features of ultrasound. Besides, there are many fusion strategies currently available, but there is a lack of systematic comparative research on the various fusion strategies. In this study, we designed 'Lesions Pairing' to construct the dataset, addressing the challenge of small sample sizes in multi-modal learning. We then compared the effectiveness of different strategies and proposed hybrid-fusion strategies based on the combination of conventional layer-level fusion (i.e. early-fusion, mid-fusion and late-fusion), which can efficiently extract intra-/inter- modal information. Specifically, we first systematically compared different deep-learning-based fusion strategies for multi-modal ultrasound in the diagnosis of liver cancer. Secondly, based on the comparison results of a multimodal framework that integrates B-mode, SWE, CEUS ultrasound data, and clinical data simultaneously, we propose a hybrid-fusion strategies for the diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The experimental results showed that the area under the curve of the early-late fusion strategy combined with clinical data was 0.9854, which was superior to other single mode and other fusion strategies, increasing by 13.8–25.88 % and 2.22 %-9.79 %, respectively.

Biliary tract cancer

BackgroundBiliary tract cancers comprise a heterogeneous collection of malignancies usually described as cholangiocarcinoma of the intra- or extrahepatic bile duct, including perihilar cholangiocarcinoma and gallbladder cancer. MethodsA review of pertinent parts of the ESSO core curriculum for the UEMS diploma targets (Fellowships exam, EBSQ), based on updated and available guidelines for diagnosis, surgical treatment and oncological management of cholangiocarcinoma. ResultsFollowing the outline from the ESSO core curriculum we present the epidemiology and risk factors for cholangiocarcinoma, as well as the rationale for the current diagnosis, staging, (neo-)adjuvant treatment, surgical management, and short- and long-term outcomes. The available guidelines and consensus reports (i.e. NCCN, BGS and ESMO guidelines) are referred to. Recognition of biliary tract cancers as separate entities of the intrahepatic biliary ducts, the perihilar and distal bile duct as well as the gallbladder is important for proper management, as they each provide distinct clinical, molecular and treatment profiles to consider. ConclusionCore competencies in knowledge to the diagnosis, management and outcomes of biliary tract cancers are presented.

Sarcomatoid Cholangiocarcinoma: An Unusual Tumor Posing Diagnostic Challenges

AbstractSarcomatoid intrahepatic cholangiocarcinoma is an uncommon tumor that accounts for fewer than 1% of hepatobiliary system cancers. Frequently exhibits weight loss, fever, and stomach pain. This case study describes a 72-year-old woman who had been experiencing nausea, vomiting, and stomach pain for the previous 2 months. Histopathology and immunohistochemistry confirmed the diagnosis of sarcomatoid cholangiocarcinoma.

OS-076-YI Bile extracellular vesicles hold protein biomarkers for the early diagnosis of cholangiocarcinoma in individuals with primary sclerosing cholangitis

OS-076-YI Bile extracellular vesicles hold protein biomarkers for the early diagnosis of cholangiocarcinoma in individuals with primary sclerosing cholangitis

Outcome of patients with perihilar cholangiocarcinoma and previous biliary instrumentation: an observational study

BackgroundTo assess the outcome of previously untreated patients with perihilar cholangiocarcinoma who present to a cancer referral center with or without pre-existing trans-papillary biliary drainage.MethodsConsecutive patients with a diagnosis of perihilar cholangiocarcinoma presenting between January 1, 2013, and December 31, 2017, were identified from a prospective surgical database and by a query of the institutional database. Of 237 patients identified, 106 met inclusion criteria and were reviewed. Clinical information was obtained from the Electronic Medical Record and imaging studies were reviewed in the Picture Archiving and Communication System.Results73 of 106 patients (69%) presenting with a new diagnosis of perihilar cholangiocarcinoma underwent trans-papillary biliary drainage (65 endoscopic and 8 percutaneous) prior to presentation at our institution. 8 of the 73 patients with trans-papillary biliary drainage (11%) presented with and 5 developed cholangitis; all 13 (18%) required subsequent intervention; none of the patients without trans-papillary biliary drainage presented with or required drainage for cholangitis (p = 0.008). Requiring drainage for cholangitis was more likely to delay treatment (p = 0.012) and portended a poorer median overall survival (13.6 months, 95%CI [4.08, not reached)] vs. 20.6 months, 95%CI [18.34, 37.51] p = 0.043).ConclusionTrans-papillary biliary drainage for perihilar cholangiocarcinoma carries a risk of cholangitis and should be avoided when possible. Clinical and imaging findings of perihilar cholangiocarcinoma should prompt evaluation at a cancer referral center before any intervention. This would mitigate development of cholangitis necessitating additional drainage procedures, delaying treatment and potentially compromising survival.

Combined analysis of albumin in situ hybridisation and C reactive protein immunohistochemistry for the diagnosis of intrahepatic cholangiocarcinoma: towards a molecular classification paradigm

AimsIntrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several immunohistochemical markers have been proposed for iCCA, none...

Unveiling the potential of strain elastography in perihilar cholangiocarcinoma biopsies.

This study was conducted to investigate the effectiveness of strain elastography in guiding precise and sufficient tissue sampling for perihilar cholangiocarcinoma (CCA) biopsies. Our retrospective analysis included 23 liver biopsies conducted between March 2019 and July 2022 for suspected perihilar CCA. An experienced radiologist performed the biopsies via an ultrasound machine with elastography configuration. Tissue stiffness color maps were used for guiding when the biopsies were performed. Strain index value calculations were made by radiologists on recorded images. Patient demographics revealed a mean age of 65.17 ± 9.25years, with a gender distribution of six females and 17 males. Gray-scale examinations unveiled diverse echogenic characteristics in liver lesions. Elastography-guided biopsies demonstrated no need for repeats, while gray-scale biopsies necessitated re-biopsy in four patients, resulting in cholangiocarcinoma diagnosis (P = 0.037). Strain index values showcased strong inter- and intra-observer agreements (P < 0.001). Notably, no post-biopsy complications emerged in either study group. The diagnostic advantage of elastography, particularly in enhancing accuracy in challenging isoechoic lesions, was demonstrated, although the substantial overlap between strain index values of benign and malignant liver masses limits clinical usefulness of this technique.

Treatment of cholangiocarcinoma by pGCsiRNA-vascular endothelial growth factor in vivo.

The early diagnosis and treatment of cholangiocarcinoma may benefit from specific tumor markers to be used in clinical practice. To investigate whether the pGCsiRNA-vascular endothelial growth factor (VEGF) can affect the onset and progression of cholangiocarcinoma and its possible mechanism using the targeted therapy of nude mouse model of cholangiocarcinoma with attenuated Salmonella carrying the plasmid pGCsiRNA-VEGF. The nude mouse model of cholangiocarcinoma was established by tail vein injection of QBC939 cells and given attenuated Salmonella carrying the plasmid pGCsiRNA-VEGF. One month later, the tumor volume of nude mice was observed, and the tumor growth curve was plotted. The harvested tumors were weighed and detected for tissue structural changes and cell death status by hematoxylin-eosin staining. The protein and mRNA expressions of VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 were detected by Western blotting and PCR, respectively. The tumor volume and weight of the pGCsiRNA-VEGF group were significantly smaller than those of the mock and the si-scramble groups (P < 0.05). The expressions of VEGF, MMP2, and MMP9 at the transcriptional and translational levels were inhibited by pGCsiRNA-VEGF. PGCsiRNA-VEGF promoted tissue apoptosis and destroyed the tissue structure. In vivo silencing of VEGF can affect cell survival and inhibit cell migration, invasion, and development, probably by enhancing apoptosis and inhibiting the expressions of MMP2 and MMP9.

A new biomarker panel for differential diagnosis of cholangiocarcinoma: Results from an exploratory analysis.

Diagnosis of cholangiocarcinoma (CCA) can be challenging due to unclear imaging criteria and difficulty obtaining adequate tissue biopsy. Although serum cancer antigen 19-9 and carcinoembryonic antigen have been proposed as potential diagnostic aids, their use remains limited by insufficient sensitivity and specificity. This exploratory analysis aimed to identify individual- and combinations of serum biomarkers to distinguish CCA from hepatocellular carcinoma (HCC) and chronic liver disease (CLD) controls using samples from a published study. This prospective, multicenter, case-control study included patients aged ≥18 years at high-risk of HCC. Serum and ethylene diamine tetraacetic acid-plasma samples were collected prior to any treatment and confirmed diagnosis of HCC or CCA. Fourteen biomarkers (measured by electrochemiluminescence immunoassays or enzyme-linked immunosorbent assays) were subjected to univariate analysis and 13 included in a multivariate analysis (per selected combinations and exhaustive search). Overall, 55 CCA, 306 HCC, and 733 CLD control samples were analyzed. For distinguishing CCA from HCC, alpha-fetoprotein and matrix metalloproteinase-2 (MMP-2) showed the best individual performance (area under the curve (AUC) 86.6% and 84.4%, respectively); tissue inhibitor of metalloproteinase-1 (TIMP-1) was most able to distinguish CCA from CLD (AUC 94.5%) and from HCC + CLD (AUC 88.6%). The combination of MMP-2 and TIMP-1 was the best-performing two-marker panel, with AUC >90% for all comparisons. MMP-2 and TIMP-1 are promising biomarkers that could support differential diagnosis of CCA. Incorporating these assays into the diagnostic algorithm could provide additional diagnostic information in a non-invasive, rapid manner, and could supplement existing diagnostic methods.

Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma.

Cholangiocarcinoma often remains undetected until advanced stages due to the lack of reliable diagnostic markers. Our goal was to identify a unique secretory protein for cholangiocarcinoma diagnosis and differentiation from other malignancies, benign hepatobiliary diseases, and chronic liver conditions. We conducted bulk RNA-seq analysis to identify genes specifically upregulated in cholangiocarcinoma but not in most other cancers, benign hepatobiliary diseases, and chronic liver diseases focusing on exocrine protein-encoding genes. Single-cell RNA sequencing examined subcellular distribution. Immunohistochemistry and enzyme-linked immunosorbent assays assessed tissue and serum expression. Diagnostic performance was evaluated via receiver-operating characteristic (ROC) analysis. Inter-alpha-trypsin inhibitor heavy chain family member five (ITIH5), a gene encoding an extracellular protein, is notably upregulated in cholangiocarcinoma. This elevation is not observed in most other cancer types, benign hepatobiliary diseases, or chronic liver disorders. It is specifically expressed by malignant cholangiocytes. ITIH5 expression in cholangiocarcinoma tissues exceeded that in nontumorous bile duct, hepatocellular carcinoma, and nontumorous hepatic tissues. Serum ITIH5 levels were elevated in cholangiocarcinoma compared with controls (hepatocellular carcinoma, benign diseases, chronic hepatitis B, and healthy individuals). ITIH5 yielded areas under the ROC curve (AUCs) from 0.839 to 0.851 distinguishing cholangiocarcinoma from controls. Combining ITIH5 with carbohydrate antigen 19-9 (CA19-9) enhanced CA19-9's diagnostic effectiveness. In conclusion, serum ITIH5 may serve as a novel noninvasive cholangiocarcinoma diagnostic marker.

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Updates in Diagnosis and Endoscopic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.