Introduction

Biliary stricture (BS) diagnosis is challenging with limited diagnostic yields from imaging and tissue sampling. Raman spectroscopy (RS) is an optical method based on analysis of scattered monochromatic light. RS is able to provide tissue molecular “fingerprinting”.

Aims & Methods

The aim of this pilot study was to develop a methodology for in vivo RS in patients with BS. During ERCP, a fibre Raman probe (Endoscopic Fiber-Optic Raman Probe Bundle Fiber, Uni-Export Instruments, USA) was introduced transpapillary into the suspected malignant BS using an 8.5 Fr metal sheath. The Raman probe was placed in an adequate position under fluoroscopy control. Spectral BS measurements were performed (without fluoroscopy) 10-20 times for each patient (laser wavelength 785 nm, duration of each measurement 0.001-0.150 s). RS of normal bile duct and duodenal mucosa of each patient was subsequently performed. The final BS diagnosis was verified using brush cytology. The attained data was saved and analysed by a specialised biophysicist. All patients provided informed consent.

Results

A total of 20 patients (mean age 71, range 38 to 89, 45% males) with suspected malignant biliary stricture indicated for ERCP were measured, of which 11 had a final diagnosis of cholangiocarcinoma (CC). A total of 815 measurements were performed, of which 466 were subsequently analysed. In 5 (25%) cases, transpapillary insertion of an RS probe was not possible. No procedure-related complications were reported and no mechanical damage to the probe was observed. On visual analysis, the duodenal RS pattern differed from both normal bile duct and CC (Figure 1 and 2). Nevertheless, further data processing will be required to develop a discernible method to discriminate between CC and normal bile duct with a suitable level of selectivity and specificity.

Conclusion

Transpapillary Raman spectroscopy of biliary stricture is feasible. Although duodenal and biliary RS patterns were different, current data does not allow to fully discriminate between CC and normal bile duct.

Disclosure

The authors declare that there is no conflict of interest.

Introduction

Diagnosis of biliary obstructions is a challenge especially when histopathology is inconclusive. Indeterminate biliary strictures often require additional verification and a personalized approach.

Aims & Methods

This study investigates the prevalence, characteristics, and natural history of indeterminate biliary strictures. This retrospective study covers patients treated with ERCP because of jaundice due to biliary stricture(s) of unknown etiology. Exclusion criteria were prior liver transplantation, visible tumor, lithiasis, acute pancreatitis, PSC, or any known cause of dilated biliary ducts with subsequent biliary stricture diagnosed with imaging studies (US, CT, MRI, or EUS) and serology and clinical data. A diagnosis of potentially benign biliary stricture was based on cytology/histopathology evaluation of samples taken on primary ERCP. The study participants were monitored every 2–3 months with further endoscopic, imaging, and serological evaluations as needed.

Results

A total of 510 patients were treated with primary ERCP for biliary obstruction of indeterminate etiology. The 186 (36.5%) had biliary strictures with negative cytology/histopathology (category II per Papanicolaou guidelines), of these 55 (29.6%) had strictures in the liver hilum, 22 (11.8%) in the common bile duct (CBD), and 108 (58.1%) in the intrapancreatic region. Malignancy was confirmed in subsequent tests in 40 patients (21.5%). A benign cause was diagnosed in 77 cases (41.4%), including pancreatitis, PSC, ischemia, IgG4-SC, and Mirizzi syndrome, while 69 strictures (37.1%) remained indeterminate. Strictures in the liver hilum had a higher rate of eventual malignancy (30%) compared to CBD (23%) and intrapancreatic (16%) localization. Lithiasis was more common in intrapancreatic strictures (12%), while PSC was more frequent in hilar strictures (14%). During 6-month follow-up of the 69 indeterminate cases: 17 patients received a diagnosis (8 lithiasis, 5 malignancies, 2 chronic pancreatitis, 1 benign neoplasm, 1 IgG4-SC), 4 patients died from unrelated causes, 48 cases (25.8% of the potentially benign stricture group) remained indeterminate.

Conclusion

A quarter of benign biliary strictures remain indeterminate in 6 months follow-up, while 20% of patients with indeterminate receive diagnosis of malignancy.

Introduction

Malignant biliary strictures are mainly secondary to biliopancreatic cancer, and inevitably affect the nutritional status of these icteric patients. Deterioration of this nutritional status conditions therapeutic management, particularly surgery.
The aim of this study is to assess the nutritional status of patients with biliary stenosis.

Aims & Methods

All patients with non-operable malignant biliary stenosis who underwent endoscopic biliary drainage were included from 2015 to 2022 in a single-center descriptive and analytical study. Patients with advanced WHO 3/4 impairment of general condition were excluded. Nutritional status was assessed before and after the procedure (3-6 months) on the basis of weight, BMI, weight change, nutritional risk index (NRI), albumin and CRP levels. The various data collected were analyzed using SPSS software.

Results

200 patients were included: mean age 59 years (18-96 years) with no clear gender predominance (sex ratio=1.04). The etiology of malignant biliary stenosis was dominated by cholangiocarcinoma in 112 cases (56%), followed by pancreatic cancer in 64 cases (34%), extrinsic compression in 16 cases (8%) and ampulloma in 8 cases (4%). Endoscopic biliary drainage was performed in 192 cases (96%), bilio-digestive anastomosis in 6 cases (3%) and trans-hepatic drainage in 2 cases (1%). Pre-therapeutic nutritional assessment showed that: 100% of patients had significant weight loss with a mean of 21.91%, 71.5% had anorexia and 47% were underweight (BMI < 18.5 kg/m2), 83.5% had hypoalbuminemia and 84% had elevated CRP. An improvement in nutritional status was noted 3 to 6 months after biliary drainage, with an improvement in: underweight from 47% to 17%, severe undernutrition from 61.5% to 22.06%, anorexia from 71.5% to 18.61% and an increase in mean albumin level from 29g/l to 34.52g/l and a decrease in mean CRP level from 61.73 mg/l to 26 mg/l. The 6-month survival rate was 72.5% (n=145).

Conclusion

Malignant biliary strictures are essentially linked to cholangiocarcinomas, with a clear impact on nutritional status, represented by weight loss in all cases, anorexia in around ¾ of cases and underweight in around 50%. The impact of biliary drainage on nutritional status is clear, since there is an improvement in the various clinical and biological factors assessing the latter.

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

A biliary stricture is a narrowing of intrahepatic and/or extrahepatic biliary system with upstream dilatation¹; 70-80% of biliary strictures are malignant¹ therefore histological diagnosis is necessary to distinguish benign from malignant causes and guide management. Strictures without confirmed histology are referred to unexplained biliary strictures². ESGE (European Society of Gastrointestinal Endoscopy) guidelines recommend an integrated diagnostic approach that combines multiple techniques to improve diagnostic accuracy. Endoscopic ultrasound(EUS) has demonstrated high sensitivity for evaluating biliary strictures and unexplained common bile duct (CBD) dilatation, due to its ability to provide high-resolution images of CBD walls and surrounding structures, so is the preferred diagnostic modality for both imaging and tissue acquisition(TA), even in absence of abnormal laboratory test.¹ The introduction of ancillary techniques, as DFI (Detective Flow Imaging), which enables the detection of low-velocity blood flow without the use of contrast media, represents a potential useful addition in the diagnostic algorythm³.

Aims & Methods

The aim of this single-centre retrospective study is to validate the role of EUS-DFI in characterizing unexplained biliary strictures and CBD dilatation. We included consecutive patients (pts) with unexplained biliary strictures/CBD dilatation who underwent biliopancreatic EUS between January 2024 and April 2025 at the Digestive Diseases Unit of Sant’Andrea University Hospital, Rome. During EUS, biliary stricture (lesions or thickening of CBD wall) were described as hypoechoic or isoechoic. DFI was performed to evaluate strictures: if microvascularization was observed, vascular pattern was classified as regular or irregular⁴. Results were compared with the final diagnosis, defined by histopathology and/or ≥6 months clinical follow-up as gold standard. TA was performed with EUS-FNB (fine needle biopsy) and/or ERCP(Endoscopic Retrograde Cholangiopancreatography) intraductal biopsies/brushing.

Results

Of 13 patients included, 8(61.5%) were male, median age 72 (range 56-86). All underwent Magnetic Resonance Imaging/Contrast-Enhanced Computed Tomography as first line imaging: 3(23%) had a perihilar stricture, 9(69%) a medio-distal, 1(8%) had “in toto” CBD thickening. Among the 13 strictures, EUS identified 10(76.9%) lesions, with a mean diameter of 17 mm (median 16 mm; range, 5–35 mm), and 3(23.1%) CBD wall thickening. Twelve (92%) strictures were hypoechoic, 1(8%) was isoechoic. EUS-TA was performed in all pts, revealing 7(54%) cases of malignancies, of whome 5 cholangiocarcinoma and 2 pancreatic ductal adenocarcinoma (PDAC), 3(23%) high-grade dysplasia, and 3(23%) fibroinflammatory disease on histopatological evaluation. All pts underwent DFI-EUS. Microvascularization was detected in 12 cases (92%), with an irregular pattern observed in 9 pts. Among these, 5 (55.6%) were diagnosed with cholangiocarcinoma, 1(11.1%) with PDAC infiltrating CBD, and 3(33.3%) with high-grade dysplasia. The 3 benign strictures demonstrated a homogeneous pattern. One case (8%), corresponding to a PDAC, appeared hypovascular on DFI.

Conclusion

In a small cohort of patients with unexplained or indeterminate biliary strictures, the novel DFI-EUS technique proved to be feasible for assessing microvascularization in CBD stenosis and revealed characteristic irregular patterns or hypovascularization in malignant lesions. Further prospective studies with a larger patient population are needed to confirm these preliminary findings.

References

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