Introduction

Cholangiocarcinoma defines a group of tumors with a poor prognosis arising from the epithelial cells of the bile ducts. They can occur anywhere along the biliary tree. The diagnosis of cholangiocarcinoma represents a real challenge, given the difficulties of accessing a cytological diagnosis. Anatomopathological diagnosis remains the “gold standard”, but in certain situations, biliary-MRI may suffice to make a positive diagnosis.

Aims & Methods

The aim of our work is to study the contribution of biliary-MRI to the diagnosis of extrahepatic cholangiocarcinoma.
This is a retrospective descriptive monocentric study extending over a 02-year period (January 2021-August 2023) collecting cases of extrahepatic cholangiocarcinoma hospitalized in the Hepato-Gastro-Enterology and Proctology Department "Medicine B".
We only included patients whose diagnosis was evoked by the radiological appearance of biliary MRI.

Results

27 patients were included in our study, with a mean age of 65.5 ± 10 years. Male predominance was observed, with 16 men (59.2%) and 11 women (40.7%), so, a M/F sex ratio of 1.45.
The circumstances of discovery were dominated by altered general condition, which was reported in 18 patients (66.6%), jaundice in 16 (59.2%), and angiocholitis in 11 (40.7%). Biologically, median total bilirubin was 203 [129- 264], median CEA 6 [3- 120], and median CA 19-9 976 [60- 1933].
The tumor was distal in 6 patients (22.2%), and hilar in 21 (77.7%), including 13 cases (48.1%) classified as bismuth IV, 3 cases (11.1%) as bismuth III; bismuth II in 3 (11.1%), and bismuth I in one (3.7%). The process was infiltrative in 25 cases (92.5%), budding in 2 cases (7.4%), and stenosing in 19 cases (70.3%). In all our patients, the cholangiocarcinoma presented as an irregular process, enhanced late and progressively after contrast injection, with diffusion restriction, and with different signal intensities: Hyposignal T1 in 19 cases (70.3%), iso signal T1 in 07 cases (25.9%), hyper signal T2 in 14 cases (51.8%), intermediate signal T2 in 11 patients (40.7%), and iso signal T2 in 2 patients (7.4%). Liver metastases were noted in 9 patients: bilobar in 8 (29.6%) and unilobar in one (3.7%).
The diagnosis of cholangiocarcinoma was confirmed histologically in 11 patients (40.7%). Only 3 patients (11.1%) underwent surgery, while treatment was palliative in 25 patients (92.5%).

Conclusion

The definitive diagnosis of cholangiocarcinoma remains histological, but Biliary-MRI plays an essential role. Our study showed that late and progressive enhancement with T1 hyposignal and T2 hypersignal were the most frequent cholangiographic sequences in the diagnosis of extrahepatic cholangiocarcinoma.

Introduction

Drug-induced hepatotoxicity is one of the main forms of iatrogenic pathology, which is often under-diagnosed. Numerous drugs are implicated and can cause hepatic damage reproducing the whole spectrum of non-iatrogenic liver pathology, ranging from a simple transient disturbance of the liver balance to fulminant, life-threatening hepatitis.

Aims & Methods

The aim of our work is to study the etiological profile and therapeutic management of drug-induced hepatitis.
This is a retrospective descriptive monocentric study from January 2010 to August 2023 of patients with drug-induced hepatitis in the Hepato-Gastro-Enterology and Proctology Department “Medicine B”.
Diagnosis was based on the elimination of infectious, immunological and toxic causes of hepatitis. For all patients, viral serologies for hepatotropic viruses and a pharmacovigilance investigation were carried out before concluding that the cause was drug-induced.

Results

194 patients were included in our study, with a mean age of 44.2 years, ranging from 23 to 84 years. Female predominance was observed, with 110 women (56.7%) versus 84 men (43.2%), so, a F/H sex ratio of 1.3.
In 59 cases (30.4%), liver damage was discovered by chance during a biological check-up. In the other cases, clinical manifestations were dominated by jaundice in 112 patients (57.7%), followed by asthenia in 42 patients (21.6%), pruritus in 35 cases (18%) and fever in 17 cases (8.7%). Liver function tests showed cytolysis in 97 cases (50%), mixed disease in 74 patients (38.1%), and cholestasis in 23 patients (11.8%). The time to onset of clinical or biological signs of hepatotoxicity ranged from 03 days to 09 months. Severe acute hepatitis occurred in 70 cases (36%), including 48 cases (24.7%) of fulminant hepatitis. Viral serologies were negative in all cases. Liver biopsy was consistent with drug-induced hepatitis in 35 cases (18%). The main drugs implicated were anti-tuberculosis drugs in 110 cases (56.7%), followed by immunosuppressants, particularly azathioprine in 44 cases (22.6%), then paracetamol in 23 cases (11.8%), antidepressants in 6 cases (3%), and non-steroidal anti-inflammatory drugs (NSAIDs) in 3 cases (1.5%). Other drugs were less frequently associated with liver dysfunction, such as: allopurinol, fluconazole (1 case: 0.5%), synthetic antithyroid drugs (1 case: 0. 5%), antiepileptics (Carbamazepine) (1 case: 0.5%), hypolipidemics (1 case: 0.5%), ciprofloxacin (1 case: 0.5%), anti TNF (Adalimumab) (1 case: 0.5%), and anti-angoretics (1 case: 0.5%).
Discontinuation of the treatment in question was considered in all patients. Patients with fulminant acute hepatitis were managed in intensive care, and N-acetylcysteine was introduced in patients admitted for paracetamol-induced hepatitis. The outcome was favorable in 160 patients (82.4%), while 34 patients (17.5%) died.

Conclusion

Drug-induced hepatitis is a delicate condition, given its polymorphic presentation and the diversity of potentially hepatotoxic drugs prescribed. Diagnosis is based on the elimination of other possible causes of liver dysfunction, a suggestive or compatible chronology between the administration of the drug and the onset of hepatitis, and a favorable evolution after discontinuation of the drug. Prevention requires compliance with prescribing rules, early detection of signs of therapeutic intolerance and rigorous monitoring of progress under treatment.

Introduction

The biliary tract cancers (BTC) are among the most frequent differential diagnosis of the obstructive cholestasis. Accurate diagnosis remains challenging, as conventional tools such as brush cytology and CA 19-9 lack sufficient sensitivity and histological confirmation is often difficult. The subsequent management of this condition involves the use of biliary tract stenting via endoscopic retrograde cholangiography to facilitate optimal bile flow. We have recently reported that biliary stents are a potential source of molecular biomarkers, including the microbiome.

Aims & Methods

The aim of this study was to investigate the potential of biliary stent microbiome patterns as a biomarker for BTC. Patients diagnosed with obstructive cholestasis of various aetiologies, including malignant disease, BTC and non-malignant disease (NM) including inflammatory and postoperative stenosis, were prospectively enrolled. The study was conducted in 3 steps including discovery, confirmation and validation cohorts to ensure reliability and reproducibility. The discovery cohort comprised a total of 123 patients (28 with BTC, 54 other malignancies and 69 NM). The confirmation cohort comprised 54 patients (16 with BTC) with the inclusion of stents from alternative time points or independent stents as part of the multi-stenting management from the same time point. The validation cohort included stents from 38 independent patients (11 with BTC). The DNA was extracted and subsequently analysed using 16S rRNA gene sequencing. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated.

Results

There were significant differences in the stent-derived microbiome between BTC and patients with other conditions. BTC was associated with a higher abundance of following taxa Bacillales, Peptoniphilaceae, Erysipelotrichaceae and Actinomyces while Fusobacteriaceae, Klebsiella, Dialister and Anaeroglobus was increased in the non-malignant cohort. The calculation of the microbiome-based prediction score was performed by utilising the abundance of the significantly different taxa and applying logarithmic normalisation. ROC analysis on the testing cohort, revealed an AUC of 0.82 (95%-CI: 0.73 to 0.90, p < 0.0001) in prediction of BTC based on the microbial score. To confirm the data, independent analyses were performed using the confirmation cohort revealing comparable results with the AUC of 0.85 (95%-CI: 0.74 to 0.97, p < 0.0001). In the subsequent phase, an independent validation cohort was used to confirm the robustness of the findings. ROC analysis yielded an AUC of 0.83 (95% CI: 0.71–0.96, p = 0.0014), demonstrating promising reproducibility of the microbiome-based score as a diagnostic tool.

Conclusion

Patients with biliary stenosis exhibit distinct biliary microbial alterations. Using stent-derived microbiome data analysis, we developed a novel microbiome-based score to estimate the probability of BTC in patients with cholestasis. Results from both validation and confirmatory cohorts strongly support the utility of this tool for predicting BTC in patients with biliary stenosis.

Introduction

The sensitivity and accuracy of diagnosis for extrahepatic cholangiocarcinoma (EHCC) can be greatly improved by Spyglass DS choledochoscope, which can realize direct observation and biopsy . Studies have shown that endoscopic radiofrequency ablation (RFA) could prolong stent patency and survival in patients with unresectable extrahepatic cholangiocarcinoma (EHCC) . However, there are few reports about Spyglass DS choledochoscopy and endoscopic RFA therapy in the same stage of diagnosis and treatmen for unresectable EHCC.

Aims & Methods

Aim: To investigate the feasibility and safety of Spyglass DS combined with endoscopic RFA)for unresectable EHCC on the same stage.
Methods A total of 90 patients with extrahepatic bile duct obstruction treated in Hangzhou First People's Hospital from January 2013 to January 2022 were divided into two groups according to the diagnosis and treatment process: conventional group: ERCP + cytobrush/ Spyglass DS cholangioscopy first, and ERCP + RFA again when the pathological results were positive; simultaneous group: ERCP was performed via Spyglass DS cholangioscopy to examine the bile duct and biopsy the lesion under direct vision, and RFA was performed on the same stage for patients identified as malignant tumor. The success rate of procedure, recovery of liver function, the number of ERCPs and the incidence of postoperative adverse events were compared between the two groups.

Results

The sensitivity of Spyglass DS choledochoscope biopsy for EHCC was 87.5% (35/40) significantly higher than that of the cell brush group (38.9% (14/36), and the difference was statistically significant (P<0.05); All patients in both groups successfully completed endoscopic RFA with a 100% of procedure success rate; there was no statistically significant difference in the improvement of bilirubin between the two groups (P>0.05); the mean number of ERCPs in simultaneous group was significantly less than that in conventional group (1.00 vs. 2.59, P<0.001), which was statistically different; the incidence of postoperative adverse events between the two groups was 14.7% (5/34) vs. 14.3% (5/35), with no statistical significance (P=0.889).

Conclusion

Spyglass direct vision diagnosis + biopsy combined with RFA for unresectable extrahepatic cholangiocarcinoma can significantly improve the diagnostic sensitivity, reduce the number of ERCPs, and not increase the incidence of postoperative adverse events, which is a safe and effective diagnosis and treatment method with a high cost-benefit ratio.

Disclosure

NO

Introduction

Indeterminate biliary strictures pose a significant diagnostic challenge, as they can result from a wide spectrum of both benign and malignant conditions. Differentiating between these is crucial due to different management strategies. Conventional methods like endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology have limited sensitivity, often leading to repeated procedures and delays in treatment. Peroral cholangioscopy (POC) offers direct bile duct visualization and targeted biopsies, improving diagnostic accuracy. Modern systems, like the SpyGlass™ DS, enhance procedure feasibility and image quality.

Aims & Methods

Aims: The aim of our study is to assess the effectiveness of single-operator peroral cholangioscopy system (POCS) with its digital version SpyGlass^TM Direct Visualization System with SpyBite biopsies as a promising modality for accurate diagnosis of biliary strictures.
Method: We performed a two-center retrospective analysis of prospective database from March 2019 to March 2025. Each patient underwent peroral cholangioscopy using SpyGlass^TM Direct Visualization System with SpyBite biopsies for the diagnosis of indeterminate biliary strictures.

Results

We identified 162 patients who underwent peroral cholangioscopy during the study period (96 males and 66 females). The medium age of the patients was 63.04 years. There was 100 % technical success of the procedure. All patients underwent POCS due to indeterminate biliary strictures. Before the procedure CT scan was performed and positive for biliary stenosis in 115 (70.9%) of the cases. The biliary stenoses were located as follows: 20 (12.3%) in the distal common bile duct, 29 (17.9%) in the proximal common bile duct, 102 (62.9%) at the hepatic hilum and 11 (6.7%) in the intrahepatic bile ducts.
Benign disease was diagnosed in 39 (24.07 %) of the patients. Visual impression for malignant desease (at least one of the following- tortuous dilated vessels, friability and easily bleeding, infiltrative stricture, polipoid mass, nodular eleveted lesion, vegetative mass, fish-egg lesion, finger - like villiform lesion and irregular papillary or granular lesion) was found in 123 (75.9%) of the patients. The most reliable correlation with malignancy was found to be the presence of infiltrative strictures - 113 (69.7%) patients. A final diagnosis of cholagiocarinoma was established in 84
(51.8%) of them. In 39 (24.07%) patients, no tumor cells were found in the specimen. Visual impression accuracy with SpyGlass was 100% (with 100% sensitivity and 100% specificity). SpyBite biopsies accuracy was 69.05 % (with 68. 3% sensitivity and 100% specificity).

Conclusion

POC has proven valuable in evaluating indeterminate biliary strictures, offering advantages over ERCP by allowing real-time visualization and targeted biopsies. Our study supports POC's superior accuracy, especially in identifying malignant lesions, with visual impression achieving up to 100% sensitivity and specificity. However, POC adoption is limited by operator expertise, the need for standardized interpretation, and availability. While adverse events are rare (<10%), careful patient selection is essential. In conclusion, POC holds substantial promise as a key diagnostic tool for indeterminate biliary strictures, with ongoing improvements enhancing its clinical role.

Disclosure

No conflict of interest

Introduction

Recent genomic analysis of biliary tract carcinoma has revealed the distinct genetic features based on their primary sites and is expected to help develop primary site-specific treatments. However, the exact primary site of perihilar cholangiocarcinoma (phCCA), which is located between the intrahepatic and extrahepatic bile ducts, is virtually unknown. A precise diagnosis of the primary tumor site of phCCA is urgently necessary to select appropriate treatment and improve prognosis.

Aims & Methods

This study aims to identify the primary site of phCCA by molecular pathological analysis. We analyzed a total of 358 surgically treated invasive CCA operated at the National Cancer Centre Central Hospital Tokyo, Japan from 1990 to 2013. The primary site of the tumor was evaluated based on bile duct stenosis location on preoperative image findings, detailed macroscopic observation in the resected specimen and histological tumor localization using elastic fiber staining. Hilar CCA (hCCA) was defined as a tumor originating in the upper common, right or left hepatic duct without macroscopic mass formation in liver. The analysis set included 39 cases of mass-forming type intrahepatic CCA (iCCA-MF) and 9 cases of extrahepatic CCA (eCCA) in which both frozen and formalin-fixed paraffin-embedded specimens were available. The validation set included 60, 100, 85, 14, 36, and 15 cases of iCCA-MF, eCCA, hCCA, periductal infiltrating intrahepatic CCA (iCCA-PI), periductal infiltrating plus mass-forming intrahepatic CCA (iCCA-PI+Mass), and iCCA-MF with perihilar invasion, respectively. First, transcriptome analysis was performed using the analysis set to identify candidate genes differentially expressed between eCCA and iCCA-MF. Second, immunohistochemical staining of the candidate genes was performed on the analysis set to determine the evaluation criteria. Finally, immunostaining of the candidate markers was performed on the validation set to evaluate the expression levels of each CCA subtype and statistically analyze the comparison between hCCA and the other CCA subtypes.

Results

Candidate genes included Serpin Family A Member 1 (SEPRINA1), Claudin18 (CLDN18), and Mesothelin (MSLN) as positive cases, with their immunohistochemical staining evaluation criteria of ≥33%, ≥5%, and ≥1+ (positive intensity), respectively. The immunohistochemical expression of each three molecules in the analysis set between eCCA and iCCA-MF revealed SERPINA1 at 0% vs. 82% (P < 0.01), CLDN18 at 100% vs. 41% (P < 0.01), and MSLN at 100% vs. 48% (P < 0.01). Similarly, a statistically significant difference was observed in the expression of each of the three molecules in the validation set. However, no significant difference was found in the immunohistochemical expression of the three molecules between eCCA and hCCA. Conversely, SERPINA1 expression in iCCA-MF cases with perihilar invasion was significantly different from that in cases of hCCA with microscopic hepatic parenchyma invasion, but not significantly different from that in cases of iCCA-PI+Mass. Furthermore, clustering analysis of the combination of three molecule expressions revealed that CCA was divided into three subgroups, consisting of iCCA-MF, iCCA-PI+Mass and iCCA-PI, and hCCA and eCCA.

Conclusion

We demonstrated molecular pathologically that the primary tumor site of phCCA can be identified and clinicopathologically classified in detail. In particular, we succeeded in showing that hCCA is classified into the same group as eCCA.