Brush cytology is a widely used diagnostic method in conjunction with intraductal biopsies during endoscopic retrograde cholangiopancreatography, but its diagnostic yield remains a limitation. This study evaluated the efficacy of biliary cytology using a newly developed brush device with rapid on-site cytological evaluation (ROSE) for detecting malignant biliary strictures (MBSs).

In total, 58 patients with suspected intrinsic MBS identified by intraductal ultrasound were enrolled. After achieving tissue sampling with ROSE through a maximum of two brushing passes, a transpapillary forceps biopsy (TPB) was performed. The primary outcome was diagnostic accuracy, and the secondary outcomes were technical success, sampling adequacy, and procedure-related adverse events.

Biliary cytology with ROSE was technically successful in all patients (58/58), with a sampling adequacy of 96.6% (56/58). The technical success and sampling adequacy of TPB were 94.8% (55/58) and 91.4% (53/58), respectively. Brush cytology with ROSE and TPB yielded sensitivity rates of 91.8% and 85.7%, specificity rates of 88.9% for both, and accuracy rates of 88.9% for both. The receiver operating characteristic curve comparing the diagnostic accuracies of brush cytology with ROSE and TPB combined versus TPB alone showed a significantly higher value for the combined approach (0.93) than TPB alone (0.87) (p = 0.010).

Biliary brush cytology using a novel brush device with ROSE is effective and can be used complementarily to TPB in patients with suspected MBS.

Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.

Background/Objectives: Endobiliary brushing is usually performed in the diagnosis of indeterminate biliary strictures; however, in this setting, brush cytology is limited by a low diagnostic yield and sensitivity. Here, we compared the catheter flushing method (CFM) with the conventional cytologic method (CCM) in terms of cellularity and diagnostic performance. Methods: Endobiliary brushings were obtained during endoscopic retrograde cholangiopancreatography (ERCP) from patients with biliary strictures enrolled at six tertiary hospitals. Additionally, the CFM was performed after brushing. Using liquid-based cytologic preparations of samples, we assessed the diagnostic performance of the CCM using Pap staining and the CFM using methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence staining. Results: From a total of 399 patients (malignant, 253; benign, 146), 374 CCM samples and 361 CFM samples contained adequate cells, with no significant difference in diagnostic yield (93.7% vs. 90.5%, respectively; p = 0.088). The sensitivity of the CFM (90.3%) was significantly higher than that of the CCM (75.1%; p < 0.001), with no significant difference in accuracy between methods (81.2% vs. 82.6%, respectively; p = 0.608). Conclusions: The diagnostic yield of the CFM was comparable to that of the CCM. Additionally, the diagnostic performance of the CFM was comparable to that of the CCM. These findings indicate that the CFM could be an additional brush cytology method for sample collection in patients with indeterminate biliary strictures. Incorporating both the CCM and CFM might be expected to improve the diagnostic yield of brush cytology in the biliary strictures. Further prospective comparative studies between the CCM and CFM using the same staining method are needed to validate these findings.

This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment.

We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions.

The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61).

Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.

Cholangiocarcinoma is a rare malignancy of the biliary tract with a relatively poor prognosis. As a gastroenterologist, our main role is to differentiate between benign and malignant biliary disease, help achieve a diagnosis, and palliate jaundice related to biliary obstruction. This article focuses on summarizing the various tools currently available for endoscopic evaluation and management of cholangiocarcinoma.

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.

Pancreaticobiliary cancer (PB Ca) is a lethal disease, and a useful diagnostic marker is urgently needed. A correlation between the human microbiota and malignant gastrointestinal diseases was recently reported.

To investigate the efficacy of the duodenal microbiota for diagnosing PB Ca.

We recruited 22 patients with benign pancreaticobiliary diseases (benign group) and 12 patients with PB Ca (malignant group). The duodenal microbiota of each patient was analyzed by the 16S rDNA terminal restriction fragment length polymorphism method. Patient characteristics, tumor markers, and relative abundances of the duodenal microbiota were compared between the benign and malignant groups.

Cancer antigen 19-9 (CA19-9), Bifidobacterium, Clostridium cluster XVIII, and Prevotella levels differed significantly between the benign and malignant groups. Clostridium cluster XVIII had the greatest area under the receiver operating characteristic curve (AUC) among the four factors with respect to diagnosing PB Ca (cutoff value: 3.038%; sensitivity: 58.3%; specificity: 95.2%; AUC: 0.81). The combination of Clostridium cluster XVIII (cutoff value: 3.038%) and CA19-9 Levels (cutoff value: 18.8 U/mL) showed 91.7% sensitivity and 71.4% specificity for diagnosing PB Ca.

The duodenal microbiota may be useful for PB Ca screening.

Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens.

During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining.

In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P < .0001).

The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).

Patients with cholangiocarcinoma have poor survival since the majority of patients are diagnosed at a stage precluding surgical resection, due to locally irresectable tumors and/or metastases. Optimization of diagnostic strategies, with a principal role for tissue diagnosis, is essential to detect cancers at an earlier stage amenable to curative treatment. Current barriers for a tissue diagnosis include both insufficient tissue sampling and a difficult cyto- or histopathological assessment. During endoscopic retrograde cholangiopancreatography, optimal brush sampling includes obtaining more than one brush within an individual patient to increase its diagnostic value. Currently, no significant increase of the diagnostic accuracy for the new cytology brush devices aiming to enhance the cellularity of brushings versus standard biliary brush devices has been demonstrated. Peroral cholangioscopy with bile duct biopsies appears to be a valuable tool in the diagnostic work-up of indeterminate biliary strictures, and may overcome current technical difficulties of fluoroscopic-guided biopsies. Over the past years, molecular techniques to detect chromosomal instability, mutations and methylation profiling of tumors have revolutionized, and implementation of these techniques on biliary tissue during diagnostic work-up of biliary strictures may be awaited in the near future. Fluorescence in situ hybridization has already been implemented in routine diagnostic evaluation of biliary strictures in several centers. Next-generation sequencing is promising for standard diagnostic care in biliary strictures, and recent studies have shown adequate detection of prevalent genomic alterations in KRAS, TP53, CDKN2A, SMAD4, PIK3CA, and GNAS on biliary brush material. Detection of DNA methylation of tumor suppressor genes and microRNAs may evolve over the coming years to a valuable diagnostic tool for cholangiocarcinoma. This review summarizes optimal strategies for biliary tissue sampling during endoscopic retrograde cholangiopancreatography and focuses on the evolving molecular techniques on biliary tissue to improve the differentiation of benign and malignant biliary strictures.

Sensitivities of various sampling methods to detect malignant biliary strictures remain suboptimal. Irrigation during digital single operator cholangioscopy (dSOC) is done routinely for visualization of the duct. The aim of this study was to evaluate improvement of the sensitivity for detecting malignant biliary strictures when adding aspiration fluid cytology (AFC) from the irrigated fluid during cholangioscopy to cholangioscopic biopsy (CBx).

We conducted a retrospective analysis of patients at a tertiary medical center who underwent CBx for evaluation of their biliary strictures. We included patients who had aspiration of fluid from the bile duct after CBx and were sent for cytology from January 2017 to October 2017. Diagnosis was made on the basis of final pathology or follow-up over 9 months.

Fifty-six patients had CBx obtained, out of which 35 patients had AFC in conjunction. Twenty-two (62%) patients were male and the average age was 65 years. Considering atypical cells as benign, the sensitivity, specificity, positive and negative predictive values (PPV, NPV) for CBx were 62.5%, 100%, 100%, and 76% respectively. When CBx combined with AFC, the above statistics went up to 81.25%, 100%, 100%, and 86.36% respectively. When atypical cells were considered malignant, the sensitivity, specificity, PPV and NPV for CBx were 81.25%, 84.21%, 81.25%, 84.21% and increased to 93.75%, 78.94%, 78.94%, and 93.75% respectively after adding AFC results.

For patients with biliary stricture, addition of AFC dSOC guided biopsies, significantly improves the sensitivity for detecting malignancy.

Pancreaticobiliary malignancies arise from different areas within the pancreas and biliary tree. Endoscopic ultrasound (EUS) is a well-recognized diagnostic and therapeutic modality in the treatment of pancreaticobiliary diseases, and more specifically, pancreaticobiliary malignancies. Traditionally used for diagnostic purposes, EUS plays a critical role in tissue sampling and cancer staging. The emergence of the new field of interventional EUS has allowed EUS to also play a critical role in therapeutic management. Novel interventional EUS procedures such as EUS-guided gastrojejunostomy (EUS-GE), EUS-guided biliary drainage (EUS-BD), and EUS-guided gallbladder drainage (EUS-GLB) can be utilized to treat complications of pancreaticobiliary malignancies such as gastric outlet obstruction, obstructive jaundice, and cholecystitis. In addition, interventional EUS procedures can be utilized for the palliation of unresectable malignancies both for source control with EUS-radiofrequency ablation (EUS-RFA) and for the treatment of abdominal pain refractory to opioid medications with EUS-guided celiac axis neurolysis. However, patient selection remains a critical component in both diagnostic and therapeutic interventions and must be tailored to individual patient wishes, disease pathology, and overall prognosis.

Extracellular vesicles (EVs) are released from all cells. Bile directly contacts bile duct tumor; bile-derived EVs may contain high concentrations of cancer biomarkers. We performed a proteomic analysis of human bile-derived EVs and identified a novel biomarker of cholangiocarcinoma (CCA). EVs were isolated using ultracentrifugation, and chelating agents, ethylenediaminetetraacetic acid and ethylene glycol tetraacetic acid (EDEG) and phosphate buffered saline (PBS) were used as dissolution solutions. Bile was collected from 10 CCA and 10 choledocholithiasis (stones) cases. Proteomic analysis was performed; subsequently, ELISA was performed using the candidate biomarkers in a verification cohort. The vesicles isolated from bile had a typical size and morphology. The expression of exosome markers was observed. RNA was more abundant in the EDEG group. The proportion of microRNA was higher in the EDEG group. EDEG use resulted in the removal of more contaminants. Proteomic analysis identified 166 proteins as CCA-specific. ELISA for Claudin-3 revealed statistically significant difference. The diagnostic accuracy was AUC 0.945 and sensitivity and specificity were 87.5%. We report the first use of EDEG in the isolation of EVs from human bile and the proteomic analysis of human bile-derived EV-proteins in CCA. Claudin-3 in bile-derived EVs is a useful biomarker for CCA.

In the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC), differentiation from extrahepatic cholangiocarcinoma (ECC) is extremely important but is still a clinical challenge. This study aimed to elucidate the usefulness of peroral cholangioscopy (POCS) for the differential diagnosis between IgG4-SC and ECC.

POCS findings for bile duct stricture were retrospectively evaluated in 17 patients with IgG4-SC diagnosed at the Hiroshima University Hospital and 53 patients with surgically resected infiltrating ECC. Mucosal surface, dilated vessels (tortuosity, caliber alteration, and disruption), and easily bleeding were compared between the groups.

The stricture sites of IgG4-SC evaluated by POCS were 10 extrapancreatic bile ducts and 9 intrapancreatic bile ducts. In patients with IgG4-SC, smooth mucosal surface was observed in 89% (17/19), dilated vessels in 58% (11/19) [tortuosity 82% (9/11), caliber alteration 18% (2/11), and disruption 9% (1/11)], and easily bleeding in 0%. Irregular mucosal surface and easily bleeding were observed significantly more frequently in ECC (both P <  0.001). The frequency of caliber alteration and disruption of dilated vessels was significantly less in IgG4-SC (P <  0.001 and 0.005, respectively). The sensitivity and specificity of POCS in the diagnosis of ECC were 96 and 89%, respectively. Dilated vessels in IgG4-SC were observed significantly more frequently in the extrapancreatic bile duct, especially the hilar bile duct (P = 0.006). Concerning image evaluation, the interobserver agreement was κ = 0.719, and the intraobserver agreement was κ = 0.768 and 0.754.

Characteristic POCS findings of the stricture sites in IgG4-SC were smooth mucosal surface, dilated vessels without caliber alteration and disruption, and lack of easily bleeding. These POCS findings are extremely useful for distinguishing between IgG4-SC and ECC.

Identifying malignant biliary strictures using endobiliary brushing cytology specimens is important for treatment decision-making and prognosis prediction. The sensitivity of brushing cytology specimens based on Papanicolaou (Pap) staining is low, which hampers accurate diagnosis of indeterminate strictures. Here, we assessed the diagnostic value of immunohistochemical (IHC) and immunofluorescence (IF) staining for methionyl-tRNA synthetase 1 (MARS1).

Endobiliary brushing cytology specimens were obtained during ERCP from 80 patients with an extrahepatic biliary stricture. Pap and MARS1 IF staining were performed on liquid-based cytology slides derived from these specimens. Sections of bile duct adenocarcinoma and normal bile duct tissue were obtained from 45 patients who underwent surgery for malignant biliary stricture, and MARS1 levels were evaluated by IHC staining.

MARS1 IF staining was applied to brushing cytology specimens, and the results showed strong signals in malignant biliary structures but not in the negative for malignancy specimens. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 70.4%, 96.2%, 97.4%, 56.8%, and 78.8%, respectively, for conventional Pap staining and 98.1%, 96.1%, 98.1%, 96.2%, and 97.5%, respectively, for MARS1 IF (P < .0001). When IHC staining was used, MARS1 was detected in 45 bile duct adenocarcinoma sections but not in 15 normal bile duct sections. Moreover, MARS1 mRNA and protein levels were significantly higher in bile duct adenocarcinoma sections according to polymerase chain reaction and Western blot, respectively.

The high sensitivity and accuracy of MARS1 IF staining enabled detection of malignancy in patients with indeterminate biliary stricture. Further prospective studies are needed to validate our findings. (Clinical trial registration number: KCT 0003285.).

The diagnosis of biliary strictures can be challenging. There are no systematic reviews studying same-session endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of biliary strictures.

A systematic review was conducted on studies analyzing same-session EUS and ERCP for tissue diagnosis of suspected malignant biliary strictures. The primary outcome was the accuracy of each method individually compared to the two methods combined. The secondary outcome was the accuracy of each method in pancreatic and biliary etiologies. In the meta-analysis, we used Forest plots, summary receiver operating characteristic curves, and estimates of the area under the curve for intention-to-treat analysis.

Of the 12,132 articles identified, six were included, resulting in a total of 497 patients analyzed. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of the association between the two methods were: 86%, 98%, 12.50, 0.17, and 96.5%, respectively. For the individual analysis, the sensitivity, specificity and accuracy of EUS-FNA were 76%, 100%, and 94.5%, respectively; for ERCP-based tissue sampling, the sensitivity, specificity, and accuracy were 58%, 98%, and 78.1%, respectively. For pancreatic lesions, EUS-FNA was superior to ERCP-based tissue sampling. However, for biliary lesions, both methods had similar sensitivities.

Same-session EUS-FNA and ERCP-based tissue sampling is superior to either method alone in the diagnosis of suspected malignant biliary strictures. Considering these results, combination sampling should be performed when possible.

Determining the cause of suspected biliary stricture is often challenging in clinical practice. We aimed to compare the diagnostic yields of endoscopic ultrasound-guided tissue sampling (EUS-TS) and endoscopic retrograde cholangiopancreatography-guided tissue sampling (ERCP-TS) in patients with suspected biliary stricture at different primary lesions.

We enrolled patients who underwent same-session EUS- and ERCP-TS for the evaluation of suspected biliary stricture. Forceps biopsy and/or brush cytology of intraductal lesions and fine-needle aspiration for solid mass lesions were performed during ERCP and EUS, respectively.

One hundred and twenty-five patients treated at our institution between January 2011 and September 2016, were initially considered for the study. However, 32 patients were excluded due to loss of follow-up (n=8) and ERCP-TS on the pancreatic duct (n=20) or periampullary lesions (n=4). Of the 93 patients included, 86 had a malignant tumor including cholangiocarcinoma (n=39), pancreatic cancer (n=37), and other malignancies (n=10). Seven patients had benign lesions. EUS-TS had higher rate of overall diagnostic accuracy than ERCP-TS (82.8% vs. 60.2%, p=0.001), and this was especially true for patients with a pancreatic lesion (84.4% vs. 51.1%, p=0.003).

EUS-TS was found to be superior to ERCP-TS for evaluating suspected biliary strictures, especially those caused by pancreatic lesions.

Benign and malignant biliary strictures are common indications for endoscopic retrograde cholangiopancreatography. Diagnosis involves high-quality cross-sectional imaging and cholangiography with various endoscopic sampling techniques. Treatment options include placement of plastic biliary stents and self-expanding metal stents, which differ in patency duration and cost effectiveness. Whether the etiology is benign or malignant, a multidisciplinary strategy should be implemented. This article will discuss general principles of biliary stenting in both benign and malignant conditions.

Biliary ductal cancer (BDC) is a lethal disease; however, diagnosing BDC is challenging. Biliary biopsies are performed to pathologically diagnose BDC, but the appropriate parameters for biliary biopsy [number of biliary biopsies, number of endoscopic retrograde cholangiopancreatography (ERCP) sessions, etc.] are unknown.

To clarify what constitutes an adequate method for biliary biopsy.

In total, 95 patients who underwent endoscopic biliary biopsy without choledochoscopy and who were pathologically diagnosed with BDC were enrolled in this study. The patients were divided into two groups. Seventy-six patients who were diagnosed by biliary biopsy were defined as the positive group (P group), and nineteen patients who were not diagnosed by biliary biopsy were defined as the negative group (N group). The patient characteristics and ERCP-related procedures were compared between the P and N groups.

The numbers of ERCP sessions and biliary biopsies were significantly different between the two groups [ERCP sessions (one/two), P group 72/4 vs N group 15/4, P value = 0.048; number of biliary biopsies, P group 2 (1-6) vs N group 2 (1-7), P value = 0.039]. In a multivariate analysis, fewer than 2 ERCP sessions was an independent factor influencing the positivity of the biliary biopsies.

This study clarified that ERCP and biliary ductal biopsy should only be performed once. If biliary cancer is not pathologically diagnosed after the first ERCP session, other methods (Endoscopic ultrasonography-guided fine needle aspiration or choledochoscopy-guided biliary ductal biopsy) should be employed.

Balloon-assisted cholangioscopy allows mucosal assessment of the biliary tree with pediatric endoscopes. No validated optical criteria exist to differentiate benign from neoplastic biliary lesions. We aimed to identify, validate, and revalidate optical features differentiating benign from neoplastic biliary lesions. Furthermore, we aimed to determine whether cholangioscopic appearance allows endoscopists to accurately differentiate benign from neoplastic biliary lesions.

Baseline: from 44 de-identified balloon-assisted cholangioscopy videos, a blinded investigator analyzed potential optical features distinguishing benign from neoplastic biliary lesions.

during the initial "teaching phase," 20 endoscopists viewed video clips of 11 optical features identified in the baseline study. At the subsequent "test phase," 20 further video clips were assessed by the endoscopists blinded to clinical details and questionnaires completed for the presence or absence of optical features, favored diagnosis and diagnostic confidence. Revalidation: The six identified optical features from the validation study with at least moderate agreement were revalidated the same way 12 months later assessing 20 new lesions.

Baseline: 11 optical features were found to differentiate benign from neoplastic biliary lesions. Validation and revalidation: six optical features demonstrated at least moderate interobserver agreement (irregular margin, dark mucosa, adherent mucous, papillary projections, tubular, or branched/disorganized surface structures). Endoscopists correctly diagnosed lesions as benign in 89% and neoplastic in 83%. When highly confident, endoscopists correctly diagnosed 96% of benign and 87% neoplastic lesions.

Six features were validated and revalidated to differentiate benign from neoplastic biliary lesions. When highly confident with a diagnosis, endoscopists usually differentiate benign from neoplastic biliary lesions.

Single-operator, per-oral cholangiopancreatoscopy (SOPCP) enables direct biliopancreatic ductal visualization, targeted tissue sampling, and therapeutic intervention. At Karolinska University Hospital, SOPCP was introduced early and has since been extensively utilized according to a standardized protocol. We analysed the clinical value of SOPCP in the diagnosis and treatment of biliopancreatic diseases in a single high volume center.

All SOPCP procedures performed between March 2007 and December 2014 were retrospectively reviewed. Each procedure's diagnostic yield and therapeutic value was evaluated using a predefined 4 grade scale; 1 - no diagnostic or therapeutic value, 2 - information gained did not impact clinical decision-making and in case of a therapeutic intervention, did not alter the clinical course of the patient, 3 - information gained had an impact on clinical decision-making and in the case of a therapeutic intervention, assisted subsequent disease management, and finally, 4 - information gained was essential and critical for clinical decision-making and in case of a therapeutic intervention, solved the clinical problem requiring no further therapeutic actions. Descriptive statistics were used to analyse results, with uni- and multivariate analyses completed to assess risk of adverse events.

During the study period, 365 SOPCP procedures were performed. We found SOPCP of pivotal importance (grade 4) in 19% of cases, and of great clinical significance (grade 3) in 44% of cases. SOPCP did not affect clinical decision-making or alter clinical course (grade 1 and 2) in 37% of cases.

SOPCP offers direct access to the biliopancreatic ducts for both diagnostic and therapeutic purposes, adding significant clinical value in 64% of cases.

As this is a purely observational and retrospectively registered study in which the assignment of the medical intervention was not at the discretion of the investigator, it has not been registered in a registry.

A new device with metallic wires for scrape cytology was developed.

To compare the diagnostic performance of scrape cytology and conventional cytology during endoscopic retrograde cholangiopancreatography for biliary strictures.

A total of 420 cases with biliary stricture underwent transpapillary bile cytology. Among them, there are 79 cases with scrape cytology using the new device (scrape group) and 341 cases with conventional cytology (control group). Seventy-two and 174 cases underwent biliary biopsy at the same time as bile cytology in the scrape and control group, respectively.

The sensitivity for malignancy of bile cytology in the scrape and control group was 41.2% [pancreatic cancer (PC): 23.1%, biliary cancer (BC): 52.5%] and 27.1% (PC: 16.3%, BC: 38.0%), respectively (P = 0.023). When analyzed PC and BC, respectively, there was no significant difference between the two groups. In the both groups, the sensitivity was significantly higher for BC than PC. In the scrape group, there was no difference in the sensitivity between cytology and biopsy [39.7% (PC: 17.4%, BC: 55.3%)], but in the control group, a significantly lower sensitivity was observed with cytology than biopsy (36.4% (PC: 19.7%, BC: 50.0%)) (P = 0.046). When analyzed PC and BC, respectively, there was no significant difference between cytology and biopsy. The sensitivity of combined cytology and biopsy was 55.6% (PC: 30.4%, BC: 71.1%) in the scrape group and 47.0% (PC: 24.6%, BC: 64.3%) in the control group.

Scrape bile cytology for biliary strictures may be superior to conventional cytology.

In this study, we determined the efficacy of the cell death biomarker cytokeratin 18 for diagnosing biliary tract cancer (BTC). We recruited 36 patients with BTC (Malignant group) and 45 patients with benign biliary tract disease (Benign group) for this study. We used M30 and M65 as cell death biomarkers. M30 levels indicate apoptosis, and M65 levels indicate both apoptosis and necrosis. M30 and M65 levels were significantly higher in the Malignant group than in the Benign group (142.4 ± 117.0 vs 48.9 ± 71.2 U/l, P < 0.001; 1513.3 ± 837.4 vs 882.2 ± 831.2 U/l, P = 0.001). The diagnosability of M30 was the highest of the four markers (CEA, CA19-9, M30, M65) (cut-off value: 74.429 U/l, sensitivity: 72.2%, specificity: 77.1%, AUC: 0.771). The sensitivity of M30 (cut-off value: 74.429 U/l) was significantly higher than that of biliary cytology (76% (19/25) vs 12% (3/25), P < 0.001), and the accuracy of M30 was significantly higher than that of biliary cytology (78.3% (36/46) vs 52.2% (24/46), P = 0.015). The sensitivity of M30 (cut-off value: 74.429 U/l) was significantly higher than that of biliary cytology and brush cytology (72.4% (21/29) vs 24.1% (7/29), P < 0.001). In conclusion, cell death biomarkers were increased in patients with BTC, and M30 could efficiently diagnose BTC.