Intrahepatic bile duct (IHD) lesions are primarily diagnosed and treated using endoscopic retrograde cholangiopancreatography (ERCP).¹ Cholangioscopy can be used as an alternative for IHD lesions that cannot be successfully accessed using ERCP. Percutaneous transhepatic cholangioscopy allows visualization of IHD for diagnostic and therapeutic purposes. Nevertheless, percutaneous tract formation is both invasive and cumbersome.² Peroral cholangioscopy (POC) is another option that allows direct visualization of the bile duct through the ampulla of Vater. Direct POC using an ultraslim endoscope has the advantages of high image quality, a large working channel, and the application of image-enhanced endoscopy (IEE).³ Its limitations include loop formation, cannulation difficulties, and scope instability. A new multibending (MB) ultraslim endoscope has been introduced to overcome these limitations. It is specifically designed for direct POC and has several features that enhance access and stability, thereby improving the technical success rate for the procedure.⁴ The present study investigated the usefulness of direct POC using the MB ultraslim endoscope for the evaluation and treatment of IHD lesions.

1. Patients and study design

This retrospective study analyzed data that were prospectively collected between March 2017 and March 2020 at a single tertiary referral center. The inclusion criteria were (1) indeterminate IHD lesions on cross-sectional image and/or ERCP requiring cholangioscopic confirmation and tissue biopsy; (2) hepatolithiasis, defined as presence of calculi proximal to confluence of right and left hepatic duct; (3) dilated common bile duct (CBD; >9 mm) and IHD (>6 mm); and (4) previous sphincteroplasty such as endoscopic sphincterotomy and/or endoscopic papillary balloon dilation. Exclusion criteria were (1) the presence of extrahepatic bile duct stricture; (2) presence of periampullary or extrahepatic bile duct malignancies; (3) surgically altered anatomy; (4) bleeding tendency (international normalized ratio >1.5 or platelet count <60,000/mm³); and (5) refusal to participate. Informed consent was obtained from all participants. The study was approved by the Institutional Review Board of Soonchunhyang University Bucheon Hospital (IRB number: 2022-05-009).

2. Devices

The third-generation prototype MB ultraslim endoscope (CHF-Y0010; Olympus Medical Systems, Co., Ltd., Tokyo, Japan) exhibits an additional two-directional bending point at the distal portion of the shaft, with 200° upward and 100° downward angulations. The endoscope has a working length of 1,330 mm. The diameters at the distal end are 4.9 mm and 7.0 mm at the insertion tube, respectively. It is also equipped with two accessory channels (2.2 and 1.0 mm) for simultaneous insufflation and suctioning during the procedure (Fig. 1).⁴

Figure 1. The 3rd-generation multibending ultraslim endoscope. (A) Overall view of the multibending endoscope (CHF-Y0010), which has two bending points at the distal portion of the shaft. (B) The endoscope is equipped with additional control lever for second bending point and two accessory channels of 2.2- and 1.0-mm diameter in the control section.

3. Procedures

All patients received prophylactic intravenous antibiotics with 3rd generation cephalosporin. Each procedure was performed with the patient in the prone position under conscious midazolam and meperidine sedation by two experienced endoscopists (J.H. Moon and Y.N.L.). Sphincteroplasty such as endoscopic sphincterotomy and/or endoscopic papillary balloon dilation was performed before direct POC, if it had not been performed previously. The MB ultraslim endoscope was inserted orally and advanced through the papillary orifice, past the bifurcation, up to the target IHD lesions (Supplementary Video 1). CO₂ (Colcosense CO-3000; Mirae Medics Co., Ltd., Seoul, Korea) was insufflated in the gastrointestinal tract before entry into the bile duct. Inside the bile duct, saline irrigation and suctioning were initiated and CO₂ insufflation was discontinued to minimize the risk of air embolism. Appropriate diagnostic or therapeutic interventions were performed in the IHD under endoscopic and fluoroscopic guidance.

At least four POC-guided forceps biopsy (POC-FB) samples were obtained using 2-mm biopsy forceps (FB-39Q; Olympus Medical Systems, Co., Ltd.). Hepatolithiasis was treated using a 5-F basket (Memory basket; Cook Endoscopy Inc., Winston-Salem, NC, USA) for the direct capture and removal of residual stones. If intraductal lithotripsy was indicated, electrohydraulic lithotripsy or laser lithotripsy was conducted. Electrohydraulic lithotripsy was performed using an electrohydraulic shockwave generator (Lithotron EL-27; Olympus Optical, Hamburg, Germany), whereas laser lithotripsy was performed using the Holmium or FREDDY laser system (FREDDY U100 Plus Lithotripsy Laser; World of Medicine, Berlin, Germany).

Initially, all insertions were attempted in a free-hand manner without the use of any accessories. If free-hand insertion was not possible, an intraductal 5-F access balloon catheter (MTW Endoskopie, Wesel, Germany) was used.⁵

4. Definitions and outcome measurements

The primary outcome was technical POC success, defined as successful access to the IHD and the target lesion. Secondary outcomes were technical success of POC-guided interventions, median procedure time, and POC-related adverse events. An inability to achieve the initial objective of the procedure because of POC-related factors, such as instability or improper endoscope positioning, was regarded as technical failure. Free-hand insertion was considered successful if the MB ultraslim endoscope was advanced to the target lesion within 15 minutes without the use of accessories. The procedure time was measured from duodenal ampullary entrance of the MB ultraslim endoscope until endoscope withdrawal from the bile duct.

All patients were followed up via clinical, laboratory, and radiographic evaluations for 7 days after the procedure. POC-related adverse events (e.g., cholangitis, pancreatitis, perforation, and air embolism) were defined according to the American Society for Gastrointestinal Endoscopy criteria.⁶

In total, 22 patients (17 women; median age, 69 years [range, 32 to 82 years]) with IHD lesions documented during previous imaging studies and/or ERCP underwent direct POC. Indications for direct POC included hepatolithiasis, intraductal lesions, and indeterminate strictures in 12 (54.6%), seven (31.8%), and three (13.6%) patients, respectively (Table 1).

Table 1 . Baseline Patient Characteristics.

Characteristic	Overall (n=22)
Age, median (range), yr	69 (32–82)
Sex (male/female)	5/17
Indications of cholangioscopy, No. (%)
Hepatolithiasis	12 (54.5)
Evaluation of intrahepatic duct lesions	10 (45.5)
Intraductal superficial lesions of the bile duct	7
Indeterminate biliary stricture	3

Direct POC using the MB ultraslim endoscope was successfully performed in 21 patients (95.5%). The ultraslim endoscope could not be advanced to the target IHD lesion after CBD entry in one patient due to the instability of the ultraslim endoscope. Among the 21 patients with successful endoscopy, free-hand insertion was performed in 20 patients (95.2%), whereas one patient (4.8%) required intraductal balloon assistance due to endoscope instability within the bile duct. The median procedure time for direct POC was 29 minutes (Table 2).

Table 2 . Peroral Cholangioscopy Outcomes for Intrahepatic Duct Lesions.

Outcome	Value (n=22)
Technical success of peroral cholangioscopy, No. (%)	21 (95.5)
Free-hand insertion	20
Intraductal balloon assistance	1
Total procedure time, median (range), min	29 (9–79)
Adverse events, No. (%)	0

Diagnostic interventions, including narrow-band imaging and POC-FB, were performed in nine cases, with a technical success rate of 100% (Fig. 2, Supplementary Video 2). All targeted biopsy samples were adequate for pathologic diagnosis. Therapeutic IHD stone removal was performed in 12 patients (Fig. 3). Direct stone capture and removal using a 5-F basket was successful in eight cases. Intraductal lithotripsy was performed in four patients (33%), using electrohydraulic lithotripsy in three cases and laser lithotripsy in one case (Fig. 4, Supplementary Video 3). Intraductal lithotripsy was technically successful in all four cases (100%). The overall technical success rate for POC-guided interventions was 100%. Procedure-related adverse events were not observed in any patients (Table 3).

Figure 2. Direct peroral cholangioscopy using the multibending ultraslim endoscope in a patient with an indeterminate intrahepatic duct (IHD) lesion. (A) Magnetic resonance cholangiopancreatography showing a suspicious intraductal superficial lesion of the B3 branch of the IHD. (B) Cholangiogram showing advancement of the multibending ultraslim endoscope into the deep left IHD. (C) Cholangioscopic view and (D) narrow-band imaging of a papillary mucosal lesion in the left IHD. (E) cholangioscopic views of peroral cholangioscopy-guided forceps biopsy of the intraductal superficial lesion. (F, G) An intraductal papillary neoplasm of the bile duct was diagnosed by histology (hematoxylin and eosin stain, F: ×100 and G: ×200).

Figure 3. Direct peroral cholangioscopy using the multibending ultraslim endoscope in a patient with intrahepatic duct (IHD) stones. (A) Magnetic resonance cholangiopancreatography showing right IHD stones and bile duct dilation. (B) Cholangiogram showing advancement of the multibending ultraslim endoscope toward the right IHD. (C) Cholangioscopic and (D) fluoroscopic views of stone removal by basket using the multibending ultraslim endoscope. (E) Cholangiogram showing complete ductal clearance.

Figure 4. Direct peroral cholangioscopy-guided laser lithotripsy using the multibending ultraslim endoscope for left intrahepatic duct (IHD) stones. (A) Computed tomography showing hepatolithiasis and left IHD dilation. (B) Cholangiogram showing left IHD stones. Cholangioscopic view showing (C) laser lithotripsy for IHD stones and (D) fragmented IHD stones after laser lithotripsy. (E) Fluoroscopic view showing complete ductal clearance.

Table 3 . Outcomes of POC-Guided Interventions for Intrahepatic Duct Lesions.

Variable	Overall
Diagnostic interventions (n=9)
NBI and POC-FB	9 (100)
Final diagnosis
Benign lesions	6 (66.7)
Inflammatory changes	4
Benign strictures	2
Malignant lesions	3 (33.3)
Intrahepatic cholangiocarcinoma	2
Intraductal papillary neoplasm of the bile duct	1
Therapeutic interventions (n=12)
Direct stone removal by basket	8 (66.7)
Intraductal lithotripsy	4 (33.3)
Electrohydraulic lithotripsy	3
Laser lithotripsy	1

POC, peroral cholangioscopy; NBI, narrow-band imaging; POC-FB, POC-guided forceps biopsy..

Both anterograde and retrograde endoscopic access to the IHD is cumbersome because of narrow ducts compared with the extrahepatic duct, deep location, and branching structure. Although ERCP is the first-line approach for IHD lesions, indirect presentation of structures via fluoroscopy is a major limitation despite the aid of endoscopic ultrasonography, radiologic studies, and laboratory tests. Differentiation between benign and malignant intraductal lesions is essential for early detection of malignancy and avoidance of unnecessary surgery; however, the diagnostic yield of ERCP brush cytology and biopsy remains unsatisfactory.^7,8 Furthermore, intraductal lithotripsy cannot be performed using ERCP because of poor precision and safety.

Percutaneous transhepatic cholangioscopy was introduced in the 1980s to allow direct visualization during procedures.⁹ Nevertheless, its complexity and potential complications have prevented widespread use, particularly in Western countries. A peroral approach was suggested as another alternative for cholangioscopy. Although early iterations of POC had technical limitations, recent technological advancements, the development of accessories, improvements in image resolution and maneuverability have allowed operation by a single endoscopist thereby broadening its scope of application in biliary diseases. Digital single-operator cholangioscopy (Spyglass direct visualization system; Boston Scientific Corp., Marlborough, MA, USA) has become the standard procedure for POC. Its limitations include the small caliber of accessory channels, inferior image quality, and the lack of IEE. Furthermore, single-operator cholangioscopy for IHD lesions is challenging because of Spyscope DS catheter stiffness and limited catheter tip maneuverability.

Direct POC using the ultraslim endoscope has several unique advantages, including larger accessory channels, high-definition images, and IEE. Notably, IEE provides precise details of mucosal microvessels and surface structures, allowing clinicians to distinguish between neoplastic and benign lesions.^10-12 However, difficult intubation and instability are the main obstacles that hinder its use.¹³ The third-generation MB ultraslim endoscope has been modified to overcome these limitations. Its greater angulation facilitates endoscope insertion and positioning within the duct. Additionally, the longer working length and increased stiffness improve maneuverability and minimize loop formation.⁴

The present study investigated the usefulness of direct POC using the MB ultraslim endoscope for evaluating and treating IHD lesions in selected patients. The technical success rates of direct POC and free-hand insertion for IHD lesions were 95.5% (21/22) and 95.2% (20/21), respectively. These results were similar or superior to previously reported results achieved using an ultraslim endoscope with additional accessories for intubation.^5,14 We speculate that additional bending section with greater angulation and improved pushability have contributed to higher success rate of direct POC. POC-FB was successful in 100% (9/9) of the patients, and all specimens were adequate for pathologic diagnosis. Large biopsy forceps passage through a 2.2-mm channel, combined with precise direct visual guidance, may explain the high rate of successful tissue acquisition. The success rate for POC-FB was consistent with the findings in a recent meta-analysis, which revealed a 79% (95% confidence interval, 74% to 84%) success rate for histological diagnosis via POC-FB in indeterminate bile duct strictures.¹⁵ Therapeutic interventions using the MB ultraslim endoscope also had a technical success rate of 100% (12/12), which was significantly higher than the 64% success rate for IHD stone removal via intraductal lithotripsy and basket with the mother-baby system reported by Okugawa et al.¹⁶ These findings reflect advancements in the cholangioscopy system and lithotripsy modality. The high technical success rate of IHD stone removal highlights the importance of increased stability and maneuverability in accurate targeting of intraductal lithotripsy and subsequent stone removal. Furthermore, fatal adverse events (e.g., air embolism and cholangitis) were not observed in any patients. The risk of air embolism was reduced by using CO₂ only before CBD intubation, and by using saline irrigation to clear the endoscopic view after entering distal CBD.¹⁷

Improvements in devices and techniques have expanded the indications for direct POC. The MB ultraslim endoscope is a useful modality for various IHD lesions that occur in difficult-to-access locations. The improved technical success rate of direct POC may allow differentiation between premalignant and malignant lesions, as well as the treatment of IHD stones.

Although direct POC has several advantages, it is currently recommended only for selected patients. Direct POC may be safely performed in patients with dilated bile ducts (>9 mm)^3,18 whereas patients with non-dilated bile ducts are ineligible for direct POC. In the present study, patients with IHD >6 mm were included because the outer diameter of the distal end of the MB ultraslim endoscope is 4.9 mm. Despite high quality images and the use of IEE, there are some limitations, including the lack of standard visual criteria for intraductal lesions and the potential for interobserver variability during image interpretation.

There were some limitations in this study. First, it was a single-center, single-arm, retrospective study. To demonstrate the utility of the MB ultraslim endoscope in the evaluation of IHD lesions, it may be necessary to compare it with the most widely used disposable digital single-operator cholangioscopy, which is planned as a subsequent study. Second, our study had low statistical power because of the small number of enrolled patients. Third, direct POC was performed only in patients with bile duct dilation, which may have led to selection bias. The procedure was not performed in patients with IHD lesions who lacked bile duct dilation. Finally, the endoscopists in the present study had extensive experience in the use of direct POC. Therefore, different results may be obtained in other institutions and among operators with diverse POC experience.

In conclusion, direct POC with the MB ultraslim endoscope resulted in high technical success rates for IHD procedures without any serious adverse events. The MB ultraslim endoscope can facilitate the management of IHD lesions in selected patients by allowing procedures under direct visualization. Future studies with larger sample sizes and control groups are warranted to further validate the use of direct POC in treatment for IHD lesions.

This work was partly supported by the Soonchunhyang University Research Fund (J.H. Moon), which has no role in the design, practice, or analysis of this study.

We thank A Ri Song, RN, Song Ah Jeong, RN, Sun Hwa Cho, RN, and all the other nursing staff, for their support and assistance with the procedure.

No potential conflict of interest relevant to this article was reported.

Study conception and design: Jong Ho Moon, Y.N.L. Data analysis and interpretation: W.M.L., C.W.M. Drafting of the manuscript: W.M.L., I.S.S. Obtained funding: Jong Ho Moon, Critical revision of the manuscript for important intellectual content: Jong Ho Moon, Y.N.L., T.H.L., Jun Ho Myeong, J.K.Y., H.K.K. Approval of final manuscript: all authors.

Supplementary materials can be accessed at https://doi.org/10.5009/gnl230163.