INTRODUCTION: CHALLENGES IN THE DIAGNOSIS OF BILIARY STRICTURES
The etiologies of biliary strictures are diverse, ranging from benign conditions to primary malignancies of the bile duct, as well as extrinsic compression by tumors arising from adjacent organs such as the pancreas or lymph nodes. Because benign disorders also present a wide spectrum of manifestations, it is not uncommon to encounter cases that are diagnostically challenging. Accurate differentiation is directly linked to prognosis, quality of life, and the selection of appropriate treatment strategies, including endoscopic management versus curative surgery. By contrast, the major malignant causes of biliary strictures are cholangiocarcinoma, pancreatic cancer, and ampullary cancer, which are often diagnosed at an advanced stage. Conventional endoscopic retrograde cholangiopancreatography (ERCP)-based tissue acquisition methods (brush cytology and transpapillary forceps biopsy) are characterized by high specificity but insufficient sensitivity. A meta-analysis reported that the sensitivity of brush cytology for malignant biliary strictures was 45%, that of forceps biopsy was 48.1%, and even the combination of the two yielded a sensitivity of only 59% [1,2].
Cases in which the etiology cannot be determined despite crosssectional imaging and repeated ERCP-based sampling are referred to as indeterminate biliary strictures (IBS) and represent a major clinical problem. Therefore, there has been a growing need for novel diagnostic techniques that enable direct visualization of the biliary lumen and targeted sampling of suspicious lesions. Peroral cholangioscopy (POCS) has attracted attention as a promising solution to this issue [3]. In this review, we summarize current evidence on the technological development and diagnostic utility of POCS, as well as its integrated applications in combination with interventional endoscopic ultrasound (EUS).
TECHNOLOGICAL EVOLUTION OF POCS
1. Historical background and early systems
Cholangioscopy was introduced more than 60 years ago for the intraoperative evaluation of bile duct stones. POCS was first applied clinically in 1976, allowing direct visualization and biopsy of biliary lesions [4]. In the early days, mother–baby fiberoptic systems were the mainstream approach; however, the fragility of the baby scope and the lack of dedicated accessories made visually guided, targeted biopsy difficult and hampered widespread adoption [5]. Early retrograde cholangioscopy required a duodenoscope with a large-caliber working channel [6], but subsequent advances in optics, outer diameter, and bending mechanisms led to the development of cholangioscopes that could be inserted through the working channel of a standard therapeutic duodenoscope [7].
2. POCS and image-enhanced endoscopy
To overcome the limitations of fiberoptic systems, a digital imaging system that provides high-resolution images was developed [4]. In particular, the concomitant use of narrow-band imaging (NBI) has been shown to enhance the depiction of surface architecture and vascular patterns compared with white-light imaging [8]. In a multicenter prospective study, the diagnostic accuracy for mucosal cancer extension with ERCP alone (73.5%) improved to 92.9% with POCS plus NBI [4]. Image-enhanced endoscopy (IEE) modalities such as NBI can also be incorporated into direct POCS (D-POCS) [9]. The NBI system is based on a modification of spectral characteristics by narrowing the spectral bandwidth with an optical color-separation filter. The filter cuts all illumination wavelengths except for two central wavelengths (415 nm and 540 nm). The 415-nm wavelength mainly provides information on superficial mucosal capillaries and pit patterns, whereas the 540-nm wavelength provides information on slightly deeper, thicker subepithelial vessels [10]. NBI enhances visualization of mucosal structures and microvascular patterns, which may improve the detection of malignant biliary lesions. A prospective study by Shin et al. [11] demonstrated that the use of NBI during POCS significantly improved diagnostic performance for IBS, achieving a diagnostic accuracy of 91.3%, compared with 82.8% with conventional white-light imaging. These findings suggest that NBI may serve as a useful adjunctive modality for improving visual assessment during POCS.
3. Direct POCS
Direct POCS (D-POCS) is a technique in which an ultrathin endoscope (e.g., GIF-XP290N, CHF-Y0010) is advanced directly into the bile duct via the papilla. It provides extremely high-resolution images, allows the use of IEE, and enables satisfactory tissue acquisition through a 2.0-2.2-mm instrument channel [9,12]. However, conventional D-POCS sometimes required dedicated accessories (such as balloon catheters) to achieve successful biliary intubation. To overcome this limitation, a multibending, ultraslim endoscope (e.g., the prototype CHFY0010) was developed, enabling insertion into sharply angulated bile ducts without device assistance [13]. In addition, a novel mother–baby POCS system has been developed. This system has an outer diameter of 3.5 mm and a relatively large, 2.0-mm accessory channel, which is expected to permit more efficient suction and the use of a broader range of ERCP devices [14].
4. Single-operator cholangioscopy
The representative POCS images and their key characteristics are summarized. The CHF-B290 offers an observation depth ranging from 1.5 to 20 mm with enhanced near-focus image quality (Fig. 1A). This improvement allows closer endoscopic observation, enabling detailed visualization of fine mucosal surface patterns and vascular architecture. In addition, NBI, an imageenhancement technology developed by Olympus that enhances the visibility of superficial mucosal vessels and tissue structures, facilitates high-precision diagnostic assessment of the bile and pancreatic ducts.
Boston Scientific Corporation currently provides two POCS systems. The SpyGlass system (Boston Scientific Corporation, Marlborough, MA, USA), introduced in 2007 [3], consists of a disposable access and delivery catheter (SpyScope; 10 Fr), a reusable fiberoptic probe (SpyGlass Fiber Optic Probe; 6,000-pixel imaging), and dedicated miniature biopsy forceps (SpyBite) for visually guided, targeted sampling (Fig. 1B). The SpyScope catheter can be deflected in four directions and is introduced through a standard duodenoscope with a 4.2-mm working channel. In addition, the Scivita Medical single-use video cholangioscope (Scivita Medical Technology Co., Ltd., Suzhou, China), which is scheduled for commercial release in the near future, is available in two sizes (working channel/outer diameter: 2.0 mm, 11 Fr; and 1.2 mm, 8.9 Fr) and offers high-resolution digital imaging with electronic zoom and freeze-frame capabilities (Fig. 1C).
In addition to conventional single-operator cholangioscopy (SOC) platforms, several catheter-type and flexible POCS systems have also been developed to address specific clinical needs. The DRES Slim Scope (Japan Lifeline Co., Ltd., Tokyo, Japan) is an ultraslim catheter-type peroral cholangioscope (Fig. 1D). This device consists of a catheter-type sheath with an outer diameter of 2.3 mm, incorporating two independent lumens and a high-resolution digital camera. It can also be used as a catheter for common bile duct cannulation.
The eyeMAX system (Micro-Tech Co., Ltd., Nanjing, China) incorporates state-of-the-art complementary metal-oxidesemiconductor and LED technology, providing high-resolution imaging with 160,000 pixels (Fig. 1E). Two scope diameters (3.2 mm and 3.9 mm) are available according to lesion location. The system allows one-touch image freezing and resumption and supports two instrument channel options: 1.2 mm for the 3.2-mm scope and 2.0 mm for the 3.9-mm scope. The 11-Fr eyeMAX has been reported; owing to its 2.0-mm channel, it allowed procurement of larger specimens than the conventional SpyScope™ DS II (mean specimen area 2.96 mm2 vs. 1.80 mm2) and showed higher diagnostic accuracy (96.0% vs. 80.9%) [15].
Although not shown in the figures, a disposable flexible POCS system, the YSNJ-CHD-1 (Guangzhou Yueshen Medical Equipment Co., Ltd., Guangzhou, China), has also been commercially released by Guangzhou Yueshen Medical Equipment. This system features a dual light source, a dedicated large 2.0-mm working channel designed for irrigation, and four-way steering capability. The image processing unit is equipped with a 10.1-inch touchscreen display (1,280×800 resolution), high-definition multimedia interface (HDMI) and audio visual (AV) outputs, and a removable rechargeable battery supporting up to 4 hours of operation. In addition, a removable secure digital memory card (SD card) is incorporated for image and video storage.
Through these technological innovations, POCS has evolved from a mere visualization tool into a high-precision diagnostic modality that supports clinical decision-making. In the following sections, we outline the diagnostic utility and clinical applications of POCS.
DIAGNOSTIC UTILITY OF POCS
1. Usefulness for indeterminate biliary stricture
POCS is particularly useful in patients with IBS in whom ERCP-based tissue sampling has yielded negative results. By enabling visually guided, targeted biopsy, POCS can improve diagnostic performance. In IBS patients, the diagnostic outcomes of POCS-guided forceps biopsy (SpyBite biopsy) have been shown to be superior to those of conventional brush cytology and standard forceps biopsy. In one prospective study, SpyBite biopsy achieved a sensitivity of 76.5% and a specificity of 100%, whereas the sensitivity of brush cytology and standard forceps biopsy was reported to be 5.8% and 29.4%, respectively [5]. Furthermore, the sensitivity of visual impression obtained with the SpyGlass system has been reported to range from 78% to 95%, and the diagnostic accuracy of SpyBite biopsy has ranged from 61% to 93% [4,16]. A prospective randomized multicenter trial by Gerges et al. showed that digital SOC (DSOC)-guided biopsy significantly improved diagnostic sensitivity compared with ERCP-guided brushing (68.2% vs. 21.4%) in IBS [17]. The diagnostic performance of DSOC may be influenced by several factors, including lesion location and morphology, the presence of inflammation, prior stent placement, endoscopist experience, and the quality of tissue acquisition, as systematically reported by Jang et al. [18] Furthermore, optimization of specimen processing and the number of biopsy samples may also improve diagnostic yield, as suggested by Bang et al. [19]
2. Visual diagnostic criteria
On POCS, the following findings have been described as suggestive of malignancy: tumor vessels (irregular dilation and tortuosity) (Fig. 2A), irregular mucosal surface (Fig. 2B), nodularity (Fig. 2C), papillary/villous protrusions (Fig. 2D), fine granular or fish-egg-like appearance (Fig. 2E), and easy contact bleeding (Fig. 2F) [2,4,20-22]. Additional microvascular and pit-pattern findings have been proposed, and the Monaco (Table 1) and Mendoza classifications are used for differentiation [23,24]. A systematic review and meta-analysis of POCS-based visual diagnosis for malignant biliary strictures demonstrated high diagnostic performance, with a sensitivity of 93% (95% confidence interval [CI], 88%–96%) and a specificity of 86% (95% CI, 75%–92%) [25]. In contrast, benign strictures are typically characterized by flat and smooth mucosa, uniform granularity, and paucity of neovascularization, and the interobserver agreement for non-neoplastic diagnoses based on the Mendoza classification was as high as 0.90 [26]. Although high diagnostic accuracy has been reported for visual diagnosis alone, inflammation can lead to falsepositive judgments, and histopathological confirmation remains the standard. POCS is also useful for diagnosing skip lesions and early cholangiocarcinoma. It can detect early lesions that cannot be identified by ERCP cholangiography and is therefore valuable in preoperative assessment [27].
3. Preoperative mapping of cholangiocarcinoma
While the diagnostic utility of POCS for IBS has been established, its application has expanded to more strategic purposes, such as preoperative mapping in cholangiocarcinoma. One of the most important diagnostic roles of POCS is the accurate preoperative assessment of the longitudinal spread of intraepithelial tumor spread (ITS) in cholangiocarcinoma [22,28]. Precise evaluation of ITS is essential for achieving R0 resection (resection with negative margins) [29]. Cholangiocarcinoma is broadly classified into localized biliary duct carcinoma (LBDC) and diffuse sclerosing biliary duct carcinoma (DSBDC). The incidence of extensive ITS is markedly higher in LBDC, at approximately 20%–30%, whereas in DSBDC it is very low, at approximately 3%–4% [22]. In a study by Kawakami et al. [22], the diagnostic accuracy for the presence or absence of ITS was 79.5% with ERC alone, whereas the combination of POCS and biopsy (excluding cases in which scope passage was not possible) allowed 100% accurate diagnosis of ITS. Similarly, in a multicenter study by Osanai et al. [4], the diagnostic accuracy for ITS improved from 73.5% with ERC alone to 92.9% with ERC plus POCS and mapping biopsy. POCS-guided mapping biopsy is thus utilized to evaluate the longitudinal extent of tumors in preoperative assessment, and in a pilot study of SpyGlass DS-guided mapping biopsy, the overall success rate was 88% [28]. More recently, neoadjuvant chemotherapy has been increasingly administered for extensive cholangiocarcinoma, and POCS has made it possible to clearly visualize the therapeutic response [30]. In the future, POCSbased evaluation is expected to contribute to decisions regarding the optimal timing of surgery.
4. Utility of POCS in primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tract and is recognized as a major risk factor for cholangiocarcinoma. Because POCS findings may vary according to disease activity and stage, cholangioscopy has the potential to provide real-time information on the current inflammatory and fibrotic status. In the active phase, intense inflammation of the biliary epithelium predominates, whereas the chronic phase is characterized by fibrosis and stricture formation due to repeated inflammatory insults. During the active phase, mass-forming inflammatory lesions may mimic malignancy, making differentiation from cholangiocarcinoma particularly difficult and requiring careful interpretation [31]. Conversely, in the chronic phase, characteristic morphologic features such as longitudinal scarring—formed by several intertwined fibrotic bands—and punched-out lesions with multiple pseudodiverticula have been reported to be distinctive for PSC and useful for its diagnosis. Nevertheless, the risk of cholangiocarcinoma development in PSC remains remarkably high, with cumulative incidences of 6%, 14%, and 20% at 10, 20, and 30 years after diagnosis, respectively, according to the American Association for the Study of Liver Diseases guidelines [32]. Despite these advances, the accurate diagnosis of cholangiocarcinoma complicating PSC continues to be challenging in clinical practice.
ACCURACY AND LIMITATIONS OF POCSGUIDED SAMPLING
1. Diagnostic accuracy
POCS-guided forceps biopsy has higher sensitivity for IBS than conventional ERCP-guided fluoroscopic biopsy (sensitivity 45%– 48%). SpyBite biopsy has been shown to achieve a sensitivity of 77% and a specificity of 100% [5]. In a randomized multicenter trial, digital SOC-guided biopsy achieved a sensitivity of 91.3%, whereas in another study the sensitivity was 77.8%, which was not significantly different from that of brush cytology (75.9%), indicating variability in performance across studies [17]. Deeplearning– based analysis of POCS images has demonstrated higher accuracy than conventional sampling in differentiating benign from malignant strictures and may help to reduce diagnostic delays, thereby potentially improving patient outcomes [33].
2. Optimization of specimen size and number of biopsies
One of the main limitations of POCS-guided forceps biopsy is that the specimens are often small, restricting histopathological evaluation. This problem is exacerbated by the fact that the biliary epithelium is frequently inflamed because of prior stenting or cholangitis, making it difficult to distinguish benign from malignant changes on tiny samples. To address this, newer POCS systems have improved the biopsy port; for example, the eyeMAX system, with its 2.0-mm channel, allows the use of forceps with a cup length of 1.6 mm and an opening width of 4.5 mm. This results in a larger mean specimen area than with SpyGlass DS II and reduces the number of biopsies required to achieve material sufficient for histological evaluation (MOSE positivity) [15].
While the usefulness of POCS-guided sampling has been demonstrated, it is also important to consider the optimal allocation of other diagnostic modalities, such as EUS-guided tissue acquisition (EUS-TA), according to tumor location and resectability.
POSITIONING OF POCS AMONG OTHER TECHNOLOGIES
1. Role sharing with EUS-TA
For distal biliary strictures, EUS-TA is often considered more sensitive than ERCP-based sampling [34]. However, in small lesions (<10 mm) or in cases with mural thickening, tissue acquisition may be difficult, and ERCP / POCS may be more suitable. Given that the utility of EUS-TA is limited for proximal or hilar strictures, and percutaneous transhepatic biopsy carries a risk of peritoneal seeding, POCS-guided biopsy represents a valuable alternative. ERCP-guided intraductal biopsy or EUS-fine needle aspiration may be more sensitive diagnostic tools than biliary brush cytology for the diagnosis of perihilar and distal cholangiocarcinoma. Either modality can be selected as an initial or rescue approach depending on expertise and clinical circumstances [35]. Therefore, the optimal modality for pathological sampling should be selected based on tumor location, resectability, and oncological safety.
2. Integration with artificial intelligence
Recently, artificial intelligence (AI), particularly deep-learning models such as convolutional neural networks (CNNs), has begun to be applied to the automatic diagnosis of biliary strictures using POCS images [36]. In a pilot study, a CNN model trained solely on visual POCS data achieved an overall diagnostic accuracy of 90.6% for malignancy classification, which was superior to conventional ERCP-based sampling methods (62.5% for brush cytology and 60.9% for forceps biopsy) [33]. AI models can identify visual features of malignant strictures—such as tumor vessels, papillary projections, nodules, and masses—and are expected to improve the accuracy of malignant diagnosis. In the latest studies, multimodal CNN models have achieved higher sensitivity (87.8% or 89.0%) than image-only models for the diagnosis of malignant biliary strictures, demonstrating superior performance [37]. AI-based tools may also enable automatic identification of high-risk lesions and further increase the diagnostic yield of targeted biopsies [21].
CHALLENGES IN POCS-BASED MANAGEMENT
Despite its growing diagnostic utility, several practical challenges remain for the widespread implementation of POCS. One major concern is the economic burden associated with dedicated cholangioscopy platforms and disposable accessories. However, economic analyses suggest that the use of SOC may reduce overall healthcare expenditures by decreasing the number of repeat procedures and improving diagnostic accuracy. In a decision-tree model evaluating difficult bile duct stones and indeterminate strictures, SOC reduced both the number of procedures and total hospital costs compared with conventional ERCP-based strategies [38]. Similarly, a cost-utility analysis demonstrated that SOC-guided biopsy represents the most cost-effective diagnostic strategy for cholangiocarcinoma in patients with PSC, yielding favorable incremental cost-effectiveness ratios within accepted willingness-to-pay thresholds [39].
Another practical challenge is the procedural learning curve. Early studies of D-POCS demonstrated a recognizable learning phase, with cumulative sum analysis showing stabilization of technical performance after approximately nine procedures, even among experienced endoscopists [40]. In addition, procedural factors such as biopsy technique, specimen handling, and operator experience significantly influence diagnostic yield, highlighting the need for procedural standardization and structured training programs for optimal clinical implementation [19].
THERAPEUTIC APPLICATIONS, SAFETY, AND TECHNICAL LIMITATIONS
1. Therapeutic applications
In recent years, POCS has expanded from purely diagnostic use to therapeutic applications in combination with EUS techniques. In particular, POCS-assisted approaches through the transendosonographically/guided created route (trans-ESCR) procedure have emerged as new options for accessing lesions that were previously difficult to reach, such as those in patients with surgically altered anatomy. POCS insertion and evaluation through the trans-ESCR procedure was also useful for diagnosing recurrence at the choledochojejunostomy anastomotic site after surgery (Fig. 3).
POCS provides effective visual guidance for electrohydraulic lithotripsy (EHL) or laser lithotripsy in the treatment of difficult bile duct stones, with complete clearance rates of 91%–94% [41]. In patients with biliary–enteric anastomotic strictures after reconstructive surgery, insertion of POCS via EUS-guided biliary drainage (EUS-BD) and ESCR allows simultaneous exclusion of malignancy and treatment of concomitant stones. Candidates for EUS-BD are those with biliary strictures that cannot be reached by duodenoscopy. The main indications include: (1) chronic pancreatitis with duodenal stenosis (including groove pancreatitis) or walled-off necrosis; (2) cases in which biliary cannulation is difficult; and (3) biliary strictures in patients with surgically altered anatomy (e.g., Roux-en-Y hepaticojejunostomy, pancreatoduodenectomy). In an international multicenter retrospective comparative study of 98 post-surgical cases, EUS-BD achieved a higher technical success rate than balloon-assisted ERCP (98% vs. 65.3%). Although the adverse event rate was higher with EUS-BD (20% vs. 4%), most of the events were not severe [42]. Through the trans-ESCR, POCS enabled direct evaluation of the hepaticojejunostomy stricture, biopsy sampling, and EHL for concomitant intrahepatic stones, facilitating both diagnosis and therapeutic management [43]. For benign biliary strictures, placement of fully covered self-expandable metal stents (SEMS) via various approaches has been shown to be safe and effective, and SEMS placement through ESCR is also feasible [44]. In addition, laser stricturoplasty using both the shaving-off and bridge-formation methods for benign strictures has recently been reported (Fig. 4, 5), although long-term outcomes remain to be elucidated [45].
2. Safety
POCS may be associated with a higher incidence of adverse events than ERCP alone. The main POCS-related adverse events are pancreatitis and cholangitis. In a prospective multicenter study conducted at 20 centers in Japan on SOC-based POCS (SpyGlass system), the overall adverse event rate was 18.6%, with pancreatitis (11.6%) and cholangitis (7%) being the most common [46]. Continuous irrigation of normal saline into the bile duct during observation increases intraductal pressure and can potentially increase the risk of liver abscess. Periodic suction and control of the irrigation volume, as well as the use of CO2 insufflation, may help reduce adverse events.
3. Technical limitations
Conventional mother–baby systems often require two operators. The image quality of the first-generation SpyGlass was inferior to that of video endoscopes [41]. Biopsy specimens obtained with forceps such as SpyBite are small, which may limit definitive histological diagnosis. In cases with severe strictures, scope passage can be difficult, and D-POCS can be challenging if the bile duct is not sufficiently dilated.
CONCLUSION
POCS has become a central modality that complements and overcomes the limitations of conventional ERCP-based techniques in the etiological diagnosis of IBS and in preoperative mapping of cholangiocarcinoma. The advent of DSOC and POCS has enabled detailed assessment of characteristic findings such as tumor vessels, irregular granularity, and papillary projections, and has improved diagnostic sensitivity through visually guided targeted biopsy. In particular, accurate evaluation of ITS is indispensable for planning R0 resection.
Future advances in IEE, AI-assisted diagnosis, and the clinical implementation of new large-channel scopes such as eyeMAX are expected to further improve specimen quality and procedural efficiency. Nevertheless, procedure-related risks and technical constraints remain, and careful patient selection and institutional preparedness are essential.










