Peroral cholangioscopy: past, present and future
Article information
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the evaluation of biliary strictures and the management of bile duct stones. However, standard ERCP techniques sometimes fail for both indications. In such situations, peroral cholangioscopy (POCS), which allows direct visualization of the bile duct, can play a significant role in diagnosis and treatment. Direct visualization using POCS can help differentiate between malignant and benign conditions and is more accurate in defining the extent of cholangiocarcinoma. Furthermore, POCS enables visually guided biopsies. Certain types of difficult bile duct stones, such as impacted and intrahepatic stones, require POCS for visually guided lithotripsy. Recent advancements in POCS will broaden its applicability and improve its diagnostic utility. In this review, we provide perspectives on the past, present, and future of POCS.
INTRODUCTION
Endoscopic retrograde cholangiopancreatography (ERCP) is well-established for the diagnosis and management of patients with biliary diseases, such as biliary strictures and bile duct stones.1-3 Nevertheless, indeterminate biliary strictures can be difficult to diagnose with standard techniques. A meta-analysis reported that the pooled sensitivity and specificity of forceps biopsy via ERCP were 48.1% and 99.2%, respectively.4 These results have an inherent limitation under fluoroscopic guidance. In the management of bile duct stones, approximately 90% can be extracted using a retrieval basket or balloon catheter following endoscopic sphincterotomy.5 However, complete stone extraction can be challenging in cases involving impacted or intrahepatic stones.6 In such cases, peroral cholangioscopy (POCS) plays a significant role.
POCS allows visualization of biliary strictures, offering the advantages of POCS-guided biopsy resulting in improved diagnostic accuracy compared to fluoroscopy-guided biopsy.7-9 Lithotripsy using electrohydraulic lithotripsy (EHL) or yttrium aluminum garnet laser in combination with POCS enables the fragmentation of difficult stones which are impacted (common bile duct, cystic duct, or intrahepatic duct) and difficult to reach intrahepatic stones, leading to complete clearance of bile duct stones.10-12 POCS is also utilized for antegrade stone removal via the endoscopic ultrasound (EUS)-guided hepaticogastrostomy route. Recently, there have been several advancements in POCS. Thinner POCS has been introduced, making it available for balloon enteroscopy-assisted ERCP in patients with surgically altered anatomy.13,14 Moreover, artificial intelligence (AI) has been integrated into POCS for the diagnosis of biliary strictures.15,16 In this review, we provide perspectives on the past, present, and future of POCS.
HISTORY OF PERORAL CHOLANGIOSCOPY
The first report of POCS in English was published in 1976, by Nakajima et al.17 They reported passing a thin caliber “baby” endoscope down the operating channel of a standard duodenoscope (“mother” scope). This procedure required two skilled endoscopists and in 1977, Urakami et al.18 reported the insertion of an 8.8 mm diameter fiberscope “directly” into the bile duct. The advantage of this technique was that it required only one operator. In 1984, Fuji et al.19 successfully performed the direct POCS in seven out of eight cases using an oblique-view prototype with a double-angle mechanism. Although there were advantages and disadvantages to both the mother-baby system as well as direct cholangioscopy (Tables 1, 2), neither system was widely utilized even after the introduction of the video baby scope.
Deficiencies of mother-baby peroral cholangioscopy
Direct peroral cholangioscopy
In 2005, Boston Scientific introduced the first generation of single operator cholangioscopes (SpyGlass Direct Visualization System; Boston Scientific). The first generation of spyglass utilized a catheter with four-way tip control and a separate channel for water infusion and optics utilized an optical fiber that was passed down through one of the channels.8 Use of a reusable optical fiber had many disadvantages including poor and unstable images, inconsistent orientation of the working channel and the need to frequently adjust the optical fiber. Fortunately, Boston Scientific made significant improvements with a second-generation spyglass which now incorporated a CCD chip (SpyGlass DS). The system maintained its excellent functional utility with four-way tip deflection and multiple channels to allow water infusion, suction, and a working channel. The visualization challenges of the first-generation instrument were completely solved by the digital version.
REVIEW OF PERORAL CHOLANGIOSCOPY SYSTEMS
Mother-baby
Since it was first reported in the 1970s, the mother-baby system has the longest history in POCS. The advantage of the mother-baby system is that it can be easily inserted from the duodenoscope into the bile duct under guidewire guidance, similar to the insertion of a basket catheter. With the advent of the video baby scope, resolution improved and provided for image enhancement functions such as narrow-band imaging (NBI) making it easier to differentiate mucosal lesions in the bile duct.20
The latest POCS (CHF-B290; Olympus Medical Systems) is equipped with texture and color enhancement imaging as part of the new-generation image-enhanced endoscopy (IEE) system (EVIS X1; Olympus Medical Systems).21 These functions enhance the clarity of structural changes, particularly at the edges of lesions (Fig. 1).22,23 Compared to the previous CHF-B260, the CHF-B290 has improved observation performance, durability, and operability. The observation depth has been refined to 1.5 to 2.0 mm, allowing for higher-resolution imaging at close range. Additionally, increased light intensity has enhanced the clarity of NBI. The rubber thickness of the bending section has been approximately doubled while maintaining the same outer diameter of the scope, reducing the risk of damage. Despite reducing the distal tip outer diameter to 3.3 mm, the channel diameter has been expanded to 1.3 mm, improving the ease of forceps insertion and making water irrigation and suction more efficient than before. Despite these improvements the disadvantages outlined in Table 1 remain.
Peroral cholangioscopy findings using texture and color enhancement imaging (TXI). (A) White light imaging. A protruded lesion is observed. (B) TXI imaging. TXI showing the structural change clearer than white light imaging.
Direct POCS
In the direct POCS, an ultra-slim gastroscope is advanced in a monorail fashion over a guidewire or with balloon assistance into the bile duct.24 This approach requires endoscopic sphincterotomy or distal duct dilation to allow advancement of the cholangioscope through the papilla. The advantages of the direct POCS include wider availability of compatible endoscopes, high-quality images (including IEE system), and larger forceps channel for larger biopsies and a wider range of accessories. On the other hand, it is more difficult to insert the scope if the common bile duct is not sufficiently dilated, and stabilizing its position can sometimes be challenging (Table 2). To overcome these limitations, multi-bending ultra-slim scopes have been attempted and reported as useful.25-27 These direct POCSs have limited available but if there are future developments, they may become more widely adopted. In recent years, for patients with surgically altered anatomy requiring a POCS approach, it has become possible to insert a direct scope using a balloon endoscope. If the bile duct is narrow, the overtube can be left in place, and a slim endoscope can be used for observation or stone extraction.28,29
Single operator POCS
Primarily because of its superb functionality and ease of use, the SpyGlass Direct Visualization System has become the dominant system when performing cholangioscopy.8 Its functionality attributes include four-way tip deflection, a separate water infusion channel, digital imaging, a separate working channel and quick connection (“plug and play”). The independent water infusion channel allows for water irrigation and suction even while forceps are in use. The scope’s angle can be semi-fixed, enhancing the stability of operations. However, the image quality is inferior to standard endoscope's which may limit its diagnostic capability. Over time, image quality has improved with the introduction of the digital versions of the SpyGlass (SpyGlass DS and SpyGlass DS II; Boston Scientific) equipped with a CCD chip.30 The image resolution has improved by 4 to 5 times compared to previous versions, and the light intensity is sufficient, ensuring a clear view even in the dilated bile duct. Now, most of newly POCS are single-operator POCS due to its conveniency.13,14 Single-operator POCS is originally designed for use by a single operator. However, in some facilities, a two-operator method is employed, allowing one operator to focus on the mother scope and the other on the baby scope for more efficient operation. The single use aspect of single operator cholangioscopy is undoubtedly advantageous toward preventing infection, the fact that it is fully disposable results in significant increased costs per use. The cost factor severely limits its utilization particularly in Asia and Europe.
Table 3 shows the characteristics of each available POCS. Endoscopists must understand the advantages and disadvantages of each POCS system in order to choose the appropriate one for each individual case.
Characteristics of each available POCS
MANAGEMENT OF BILIARY DISEASES USING PERORAL CHOLANGIOSCOPY
Bile duct strictures
Establishing a diagnosis and indeterminant biliary strictures can be quite challenging. Although forceps biopsy with ERCP under fluoroscopic guidance is considered the gold standard, its diagnostic accuracy is relatively poor. A recent meta-analysis reported that the diagnostic sensitivity of combining brush cytology and biopsy was 59.4%.4 In fact, biliary strictures cannot be accurately diagnosed using fluoroscopy alone, as the fluoroscopic characteristics of benign and malignant conditions overlap. To overcome this limitation, tissue acquisition is critical and toward this end, POCS has proven to be very beneficial.
The value of POCS in evaluating indeterminant biliary strictures is both its ability to image the characteristics of the lesion and determine the extent of spread as well as guiding the precise location to biopsy. The use of POCS is limited to areas that can be accessed. Thus, POCS is usually not helpful for lesions in the cystic duct, gallbladder, and second and third-degree intrahepatic biliary radicles.
Criteria had been proposed for POCS images to differentiate benign from malignant biliary strictures (Fig. 2).20,31-33 The Monaco classification33 is based on eight visual criteria for suspecting malignancy and distinguishing between benign and malignant biliary strictures (Table 4).33 Among these criteria, the presence of papillary projections (odds ratio, 7.2; p=0.025) and the presence of ulcers (odds ratio, 10.3; p=0.01) have been identified as strong factors associated with malignancy. Recently, a new classification, the Mendoza classification, has been reported.34 In this classification, five criteria were incorporated based on the Monaco classification33: the presence of tortuous and dilated vessels, irregular nodulations, raised intraductal lesions, an irregular surface with or without ulcerations, and friability. The diagnostic intraclass correlation was almost perfect for neoplastic (0.90) and non-neoplastic (0.90) diagnoses. The overall diagnostic accuracy using these criteria was 77%. In a systematic review and meta-analysis of the diagnostic yield of POCS visual findings, the pooled sensitivity and specificity for diagnosing malignant biliary strictures were 93% (95% confidence interval [CI], 88%–96%) and 86% (95% CI, 75%–92%), respectively.35 Furthermore, POCS can detect the superficial extension of cholangiocarcinoma in detail. It has been reported that POCS provides a more accurate diagnosis of superficial cholangiocarcinoma extension compared to ERCP alone.36 An international multicenter study evaluated the usefulness of POCS in mapping pancreaticobiliary neoplasia. By mapping the bile duct with POCS, the surgical plan was altered for 32 of 105 patients with bile duct lesions.37 This study demonstrates the effectiveness of direct visualization using POCS.
Peroral cholangioscopy findings. (A, B) A case of cholangiocarcinoma. Irregular surface in the mucosa and tortuous, dilated vessels are observed. (C, D) A case of benign biliary stricture. Smooth mucosa without vascular proliferation and well-organized granular mucosa with low height, without papillary tumors, are observed.
Despite improvements in accuracy, the visual criteria for differentiating malignant from benign conditions is still suboptimal. Additionally, in order to administer chemo or radiation therapy, a tissue diagnosis must be established (Fig. 3). In a systematic review and meta-analysis of the diagnostic yield of POCS-guided biopsy, the pooled sensitivity and specificity for diagnosing malignant biliary strictures were 82% (95% CI, 76%–87%) and 98% (95% CI, 95%–99%), respectively.35 However, POCS-guided biopsies have limitations which include limited maneuverability, tight bands, and the small tissue samples obtained with current biopsy forceps. These limitations may be overcome by improved POCS design such as a tighter bending radius and larger working channel to provide for larger and better designed biopsy forceps.
Peroral cholangioscopy-guided biopsy is performed on an indeterminate biliary stricture with dedicated forceps; open forceps (A) and closed (B).
Confocal laser endomicroscopy (CLE) is an endoscopic imaging technique that provides in vivo histological assessment in real time, known as a ‘virtual biopsy’. Probe-based CLE (pCLE; CholangioFlex, Cellvizio; Mauna Kea Technologies) has been cited in the recent American Society for Gastrointestinal Endoscopy (ASGE) guidelines for the management of biliary neoplasia as a useful alternative to the existing diagnostic workup.38 Therefore, if the definitive diagnosis using POCS is difficult, pCLE would be beneficial. However, pCLE is usually performed under fluoroscopic guidance through a catheter during ERCP. Therefore, it may be doubtful whether the confocal miniprobe is properly applied to the site of interest. To overcome this limitation, pCLE under the direct view of POCS has been reported as useful (Fig. 4).39-42
Probe-based confocal laser endomicroscopy (pCLE) under the direct view of peroral cholangioscopy (POCS). (A) Cholangiogram showing the hilar biliary stricture (arrow). (B, C) pCLE under the direct view of POCS is performed. Probe is attached to the lesion under POCS. (D) pCLE findings. Dark clumps (arrow) indicating malignancy is observed.
Bile duct stones
Bile duct stones are one of the most commonly encountered biliary diseases, and currently, endoscopic removal following endoscopic sphincterotomy is the standard treatment.43 Most bile duct stones can be cleared using standard techniques but some stones are considered “difficult” and require ancillary technologies and techniques. In general, “difficult stones” are defined as stones greater than 15 mm in diameter, impacted stones (bile duct, cystic duct, or intrahepatic duct), and a stone of any size proximal to a biliary stricture or a stone of any size greater than the diameter of the distal bile duct.6 POCS-guided lithotripsy plays a significant role to extract these difficult stones (Fig. 5). It has been reported that for cases of difficult stones where the bile duct stone diameter/distal bile duct diameter ratio exceeds 1 and impacted stones, POCS-guided lithotripsy should be considered the first-line treatment.44
A case of large and multiple bile duct stones. (A) Cholangiography showing large and multiple bile duct stones. (B, C) Peroral cholangioscopy-guided electrohydraulic lithotripsy is performed to fragment the stones. (D) Complete stone extraction is achieved.
POCS-guided lithotripsy includes techniques such as EHL and laser lithotripsy. Two meta-analyses have been reported on POCS-guided lithotripsy for bile duct stones; the complete stone removal rate was 91–94%, with a complication rate of 6.1% to 8.9%, and requiring an average of 1.3 procedures for complete stone removal.45,46 Intrahepatic stones are also good indications for POCS-guided lithotripsy. A latest study using the single-operator POCS (SpyGlas DS) evaluated the treatment outcomes for intrahepatic stones, reporting a high clearance rate of 94% in cases where stone removal using standard baskets and balloon catheters failed.47 Impacted stones constitute the strongest for indication for POCS-guided lithotripsy. Among 53 patients with Mirizzi syndrome, stone clearance was achieved in 48 patients (90.6%) using POCS-guided lithotripsy.10
In recent years, the utility of EUS-guided antegrade intervention has been reported for treating bile duct stones in patients with altered anatomy.48 It is often performed using a two-stage approach after fistula creation. When necessary, lithotripsy is performed, followed by balloon dilation of the duodenal papilla, allowing the stones to be pushed antegradely into the intestinal tract. POCS can also be inserted through the hepatico-gastrostomy fistula after dilation to 10 Fr or larger.49,50 POCS is inserted through the forceps channel of a duodenoscope. POCS allows direct visualization and lithotripsy of the stones, and after stone removal, it can visually confirm the absence of residual stones. Larger studies are needed to firmly establish the safety and efficacy of this approach.
Adverse events related to POCS
Adverse events related to POCS include cholangitis, pancreatitis, bleeding, and perforation. A systematic review evaluating the safety of POCS for biliary stricture assessment, summarizing 11 studies on POCS-guided biopsy, reported an adverse event rate of 7%, with acute cholangitis being the most common adverse event (1.8%).51 A meta-analysis summarizing 49 studies on POCS-guided lithotripsy reported an early complication rate of 7% during POCS. The estimated incidence rates of pancreatitis, cholangitis, perforation, and other adverse events were 2%, 4%, 1%, and 3%, respectively, with cholangitis being the most frequent complication.52 A study comparing POCS performed for diagnosing biliary strictures and POCS-guided lithotripsy reported complication rates of 7 out of 66 cases (10.6%) for diagnostic purposes versus 5 out of 34 cases (14.7%) for therapeutic procedures, concluding that there is no significant difference in the adverse events rate between POCS-guided lithotripsy and POCS for diagnostic purposes (p=0.54).53 It has been reported that no administration of antibiotics before the procedure was found to be a statistically significant risk factor for the development of fever after the procedure (p<0.01).54 There have been reports suggesting that direct POCS can cause air embolism. This complication has been largely obviated by the use of CO2 instead of air but embolism still remains a concern when performing direct POCS.55
FUTURE OF PERORAL CHOLANGIOSCOPY
Recently, there have been several advancements in POCS. Thinner POCS (eyeMAX; Micro-Tech) with an approximately 9-Fr diameter has been launched.14,56 Smaller diameter POCS could improve visualization and therapy within small ducts such as strictures, the cystic duct, and intrahepatic ducts. ERCP in patients with surgically altered anatomy is considered challenging. The usefulness of balloon enteroscopy-assisted ERCP has been reported.57-59 However, since the forceps channel of a balloon enteroscope is limited to 3.2 mm (<10 Fr), POCS is not possible with existing instruments. Thinner POCS now play a significant role in balloon enteroscopy-assisted ERCP, making it possible to perform POCS-guided biopsy and POCS-guided lithotripsy.14,51 In addition to diagnosing biliary strictures, POCS is also sometimes used to assist in the placement of guidewires into the cystic duct or intrahepatic bile ducts. Thinner POCS may improve the success rate of guidewire placement as it is more flexible.
Tissue acquisition with POCS-guided biopsy remains a challenge because existing POCS forceps produce a very small specimen. The new POCS system (eyeMAX) also includes an 11-Fr POCS with a 2.0 mm forceps channel diameter, allowing the use of larger biopsy forceps cups for POCS-guided biopsy. It has been reported that biopsies using eyeMAX were performed in 65.3% of the study cohort, with adequate tissue samples obtained in 96.8% of cases.60 Although this is early data, it is expected that larger biopsy forceps will improve POCS-guided tissue acquisition.
Improving endoscopic diagnosis using AI has been increasingly adopted, and there are now several reports on POCS diagnosis using AI (Table 5).15,61-64 All reports indicate a high diagnostic accuracy rate. Robles-Medranda et al.15 reported that in a comparison between AI and four experts and four non-experts, AI had significantly higher diagnostic accuracy than one expert and two non-experts.63 Overall, AI had a diagnostic accuracy rate of 80%, while the expert group had 75.4%, and the non-expert group had 67.2%, demonstrating AI's superiority.15 Similarly, Zhang et al.64 compared the diagnostic accuracy between AI, novices, and experts, reporting accuracy rates of 93%, 84.5%, and 88.6%, respectively; with AI demonstrating superior performance. Compared to the gastrointestinal tract, there are fewer cases where diagnostic POCS is performed. Thus, endoscopists have less experience in interpreting images from the biliary tree. This is an ideal situation where AI should be able to improve accuracy in diagnoses.
Reports on peroral cholangioscopy diagnosis using artificial intelligence
The ASGE has noted that POCS may be performed in select specialty centers and that its technique complements routine ERCP, requiring additional training once basic ERCP techniques are mastered.65 They also emphasized that trainees should understand the potential applications of this advanced technique in managing indeterminate biliary and pancreatic strictures, intraductal papillary mucinous tumors of the pancreas, and intraductal stones. Therefore, POCS should be performed by experienced endoscopists, and the learning process will be smoother when carried out by skilled endoscopists. A cohort study conducted in the U.S. reported that endoscopists with experience in fewer than 25 cases had lower accuracy in using POCS to diagnose indeterminate biliary strictures.66
CONCLUSIONS
The 50th anniversary of the first report of POCS will be celebrated in 2026. This review has provided a history of the development of POCS, a summary of the currently available instrumentation, and existing data on the safety and efficacy of POCS in the evaluation of biliary strictures and the treatment of bile duct stones. Finally, it offers a glimpse toward the future of this technology. Challenges remain in advancing the technology to improve diagnostic accuracy and therapeutic efficacy, while also broadening its applications and reducing complications. AI will undoubtedly play a role in improving diagnosis. The future is bright for this technology and endoscopists should look forward to ways it will improve the care of their patients.
Notes
Conflicts of Interest
Robert Hawes is a consultant for GIE Medical, Olympus America Inc., Fujifilm, and Apollo Endosurgery. The other authors have no potential conflicts of interest.
Funding
None.
Author Contributions
Conceptualization: all authors; Data curation: all authors; Formal analysis: all authors; Investigation: all authors; Supervision: RH; Validation: all authors; Writing–original draft: YT; Writing–review & editing: all authors.