Evaluation of percutaneous endobiliary punch biopsy in suspected malignant biliary strictures: Five-year experience from a tertiary center

Abstract

Background and Aim

To evaluate the diagnostic performance, technical feasibility, and safety of percutaneous endobiliary punch biopsy (PEPB) in patients with suspected malignant biliary strictures, particularly when endoscopic approaches are not feasible.

Materials and Methods

This retrospective, single-center study included 23 patients with radiologically confirmed biliary strictures who underwent PEPB between January 2020 and January 2025. All procedures were conducted under fluoroscopic guidance following percutaneous biliary drainage. Clinical, laboratory, and procedural data were reviewed.

Results

Biopsy samples were adequate for histopathological analysis in all cases. The technical success rate was 100%. Malignancy was detected by PEPB in 17 patients, while 3 cases were confirmed as benign and 3 were false-negative results later proven malignant. PEPB demonstrated a sensitivity of 85%, specificity of 100%, and an overall accuracy of 86.96%. Fisher’s exact test showed a significant association between biopsy results and final diagnosis (p=0.011). Two minor complications (8.7%)—cholangitis and hemobilia—occurred and were managed conservatively.

Conclusion

PEPB is a safe, technically viable, and diagnostically accurate method for tissue sampling in biliary strictures. It offers a valuable alternative when endoscopic biopsy fails or is not feasible.

Highlights & Insights

• Scientific Gap: Evidence regarding the diagnostic performance of percutaneous endobiliary punch biopsy (PEPB) in biliary strictures remains limited.

• Key Finding: In this single-center study, PEPB demonstrated high specificity and moderate sensitivity for detecting malignancy, with no false-positive results. False-negative findings were mainly associated with subepithelial growth and limited tissue sampling due to fibrosis or necrosis.

• Clinical Impact: PEPB is a safe and effective diagnostic option, particularly when sampling via endoscopic retrograde cholangiopancreatography (ERCP) is not feasible or yields inconclusive results.

Introduction

Biliary system diseases are significant clinical conditions that may develop due to benign or malignant causes and can lead to severe complications if not diagnosed early. Among these diseases, biliary obstruction holds a special place in terms of both diagnosis and treatment. Although various imaging and laboratory methods are used to determine the etiology of the obstruction, interventional procedures are often required for definitive diagnosis and treatment. These include Endoscopic Retrograde Cholangiopancreatography (ERCP), percutaneous transhepatic intervention, and surgical approaches.

Percutaneous transhepatic intervention serves as an alternative method in patients for whom endoscopic procedures are unsuitable or unsuccessful. Through percutaneous transhepatic access, not only can biliary drainage be established via catheter or stent placement, but therapeutic interventions such as stone removal and endobiliary ablation can also be performed. Recently, the introduction of endobiliary punch biopsy has expanded the diagnostic capabilities of percutaneous transhepatic procedures.

This study aims to evaluate the effectiveness and safety of percutaneous endobiliary punch biopsy (PEPB).

Materials and Methods

This retrospective, single-center, single-arm study included 23 patients over the age of 18 with biliary stenosis. The cohort consisted of 14 males and 9 females, with a mean age of 67.

The study covers patients who underwent PEPB between January 2020 and January 2025 after imaging and laboratory results indicated obstructive jaundice. Prior to the procedure, clinical, laboratory, and imaging results of the patients were reviewed. All patients underwent imaging with CT, MRI, or ultrasound. Retrospective analysis confirmed biliary obstruction in all 23 patients before the intervention. The procedures were performed by two interventional radiologists experienced in biliary interventions, either during or after biliary decompression via percutaneous transhepatic access. Data obtained through histopathological analysis were recorded in a Microsoft Excel spreadsheet.

Ethical Approval

This study was approved by the Clinical Research Ethics Committee of Ondokuz Mayıs University (Application No: 2024/544; Date: March 28, 2025). The research was conducted in accordance with the principles of the Declaration of Helsinki.

Patient Selection

The indication for biopsy was suspicion of malignant obstruction. Medical records, histopathology reports, diagnostic imaging, surgical reports (if applicable), and patient prognoses were retrospectively reviewed. Collected data included age, gender, technical success of the biopsy, lesion location, stricture length, complications, number of samples taken, laboratory values (ALP, GGT, direct and indirect bilirubin), imaging findings, pathology results, and surgical reports if available.

Clinical features included varying degrees of jaundice observed in mucous membranes and sclera, dark urine, epigastric pain, fatigue, abdominal distension, anorexia, pruritus, and acholic stool. Laboratory tests showed signs of liver injury with elevated total and direct bilirubin levels.

Some patients had pre-existing conditions. Five patients (21.7%) had a history of malignancy, including three with gastric cancer (13%), one with pancreatic cancer (4%), and one with colon cancer (4%). Informed consent was obtained from all patients before the procedure.

Histopathological diagnosis was established in all patients using PEPB. A pathological diagnosis was considered positive when compatible with radiological, clinical, surgical, or prognostic findings. If no tumor was found in pathology but imaging, clinical evidence, surgical report, or prognosis suggested malignancy, the pathology was considered negative.

Technique

PEPB procedures were conducted in our hospital’s Interventional Radiology Unit using a Digital Subtraction Angiography system (Innova, General Electric). Biopsies were performed under sedoanalgesia using midazolam and tramadol, along with local anesthesia via prilocaine at the skin entry site.

Biopsies were conducted in sessions following the placement of internal-external biliary drainage catheters. In cases with hilar strictures, two catheters were placed along the right and left intrahepatic bile ducts. For extrahepatic obstructions distal to the hilum, a single catheter was usually placed via the right intrahepatic duct. During biopsy, existing catheters were removed over guidewires. A 7 Fr, 45 cm long introducer sheath was inserted via the planned biopsy route, and a shorter sheath was placed on the alternate route if applicable. Cholangiography confirmed the stricture site. Biopsy forceps were advanced through the long sheath to the proximal side of the stricture (Fig. 1). In cases where re-accessing the stricture post-biopsy might be challenging due to bleeding or edema, a guidewire was positioned through the sheath extending to the jejunum. Multiple tissue samples were obtained using endoscopic biopsy forceps through the stricture (Fig. 2). After sampling, double or single internal-external drainage catheters were re-inserted depending on stricture location. For some inoperable patients, metallic stents were placed upon request. Tissue samples were fixed in formalin. Specimens measuring at least 1–2 mm and structurally intact were considered suitable for histopathological examination.

Figure 1.

Confirmation of the distal choledochal obstruction by cholangiography.

Figure 2.

(a) Collection of multiple tissue samples from the obstruction site using endoscopic biopsy forceps. (b) Placement of internal and external drainage catheters.

Primary endpoints were technical success and complication rates. Additional metrics included the average number of biopsy samples, total procedure time (from start to obtaining suitable tissue), mean fluoroscopy time, and mean radiation exposure (in mSv).

Complications were classified according to SIR standards for percutaneous biliary interventions: minor complications included those requiring no treatment (class A) or minimal treatment with overnight observation (class B). Major complications were those requiring short hospital stays under 48 hours (class C), major treatment or hospitalization over 48 hours (class D), permanent adverse sequelae (class E), or death.^[1]

Statistics

Statistical analysis was performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Categorical variables were expressed as counts and percentages. Due to the small sample size and expected cell counts below five, associations between PEPB pathology results and final diagnosis were analyzed using Fisher’s Exact Test. A two-tailed p value <0.05 was considered statistically significant.

Results

PEPB was technically successful in all 23 patients. Each patient yielded at least two and up to eleven samples. The localization of the biliary obstructions was determined to be in the intrahepatic bile ducts in 2 patients and at the hepatic hilum or distal bile ducts in 21 patients. The detailed information for the biliary obstruction according to Bismuth–Corlette Classification is given in Table 1. The mean fluoroscopy time was 18.2±5.2 minutes, and the mean radiation dose (air kerma) was 680±210 mGy.

Table 1.

Radiological classification of the biliary strictures and status of the prior ERCP attempts

Bismuth type	n	ERCP not attempted (n)	ERCP attempted but failed (n)
Type I	2	1	1
Type II	9	6	3
Type IIIa	2	2	0
Type IIIb	1	1	0
Type IV	9	7	2
Total	23	17	6

ERCP: Endoscopic retrograde cholangiopancreatography.

Laboratory values prior to PEPB showed: mean age 67.4±10.2 years, total bilirubin 6.9±4.6 mg/dL, direct bilirubin 6.1±4.5 mg/dL, GGT 287.0±217.5 IU/L, and ALP 443.1±264.0 IU/L.

All biopsy specimens were adequate for histopathological evaluation. Malignancy was detected by PEPB in 17 patients, including 16 cases of cholangiocarcinoma and one case of metastatic colon cancer. Three patients were reported as benign by PEPB but were later confirmed to have malignancy based on surgical, radiological, or clinical follow-up findings, constituting false-negative results.

Accordingly, PEPB demonstrated a sensitivity of 85%, specificity of 100%, accuracy of 86.96%, positive predictive value of 100%, and negative predictive value of 50%. Fisher’s exact test showed a statistically significant association between PEPB pathology results and final diagnosis (p=0.011).

Detailed evaluation of the three false-negative cases revealed potential procedural and pathological limitations. In two patients, histopathological examination showed fibrotic or necrotic tissue without viable tumor cells, suggesting sampling from non-representative areas of the stricture. In the remaining case, the tumor demonstrated predominantly submucosal growth with intact biliary epithelium, which may have limited the diagnostic yield of superficial forceps biopsy. These findings highlight that false-negative results are more likely in tumors with subepithelial growth patterns or extensive necrosis.

Two complications (8.7%) were observed: the first was post-procedural cholangitis, which was treated successfully with antibiotics. The second was a hemobilia that regressed spontaneously without the need for surgical or other intervention, as confirmed through multiple follow-up CT scans.

Discussion

The location of bile duct obstruction can be rapidly and accurately identified using non-invasive imaging modalities such as ultrasound, CT, or MRI. However, tumors originating from the biliary epithelium are often very small and lack specific imaging characteristics.^[2] Obtaining tissue samples for histological and pathological evaluation remains a cornerstone in the diagnosis of neoplasms.^[3,4] While a lesion may be benign, the lower the differentiation of a malignant tumor, the higher its grade of malignancy, with increased potential for local invasion and metastasis.^[5,6] Therefore, pathological diagnosis is crucial for accurate identification of neoplasms and for guiding subsequent management.^[7-9]

Nevertheless, obtaining biopsy samples in biliary system neoplasms continues to pose challenges. In cases where pathological diagnosis cannot be established through ERCP in biliary strictures, percutaneous transhepatic biopsy using forceps is employed. Percutaneous endobiliary punch biopsy (PEPB) not only provides diagnostic information for cancer but also offers a therapeutic approach for obstructive disease.^[10] This technique, involving biopsy forceps via a percutaneous approach, was first reported in 1980^[11] and has since undergone continuous development.^[12-16] Studies have suggested that histological diagnosis with forceps biopsy is more successful than bile cytology or fine-needle aspiration, with reported sensitivity ranging from 71% to 93%.^[7,8,17-19] Accordingly, PEPB is a technically simple, minimally invasive procedure with low complication rates and high diagnostic yield compared to other established techniques.^[2,10,19,20]

Although diagnostic and technical success rates of PEPB vary across the literature, in our study, the technical success rate was 100% and the diagnostic success rate was 86.96%. In three cases (13%), false-negative results were obtained, though malignancy was confirmed by clinical, radiological, or surgical findings. In our cohort, complications were observed in 2/23= %8.7: one case of post-procedural cholangitis and one case of hemobilia. Theoretically, bile leakage or severe bleeding due to injury to adjacent vascular structures can occur as complications of PEPB.^[21] However, such complications have not been reported in the literature. A recent meta-analysis including 14 studies and 1,762 patients reported a sensitivity of 81%, specificity of 100%, and a major complication rate of 3.1% for PEPB.^[22] In a single-center retrospective study by Zhang et al.^[23] involving 194 patients, the sensitivity, specificity, and false-positive rate of PEPB were reported as 81.8%, 100%, and 0%, respectively. In a retrospective case series by Ozdemir et al.,^[24] a 100% technical success rate, 87.5% diagnostic success rate, and 12.5% complication rate were reported.

Although the study period spanned five years, the number of included patients was relatively limited. This reflects the highly selective indication for percutaneous endobiliary punch biopsy (PEPB) in our institution. The procedure was reserved for patients with suspected malignant biliary strictures in whom ERCP-based tissue acquisition was unsuccessful or not feasible due to anatomical constraints, prior interventions, or technical failure. Consequently, PEPB represents a niche diagnostic approach rather than a routinely performed procedure, explaining the low annual case volume. Given the descriptive nature of this case series, the primary objective of the study was to report the diagnostic performance of PEPB rather than to establish comparative superiority over ERCP-based tissue acquisition techniques.

One important limitation inherent to forceps-based biopsy techniques is the limited depth of tissue acquisition. Tumors exhibiting predominantly subepithelial growth patterns, extensive fibrosis, or central necrosis may not be adequately sampled despite technically successful biopsy procedures. This limitation was also evident in our cohort, where false-negative results were primarily attributed to histopathological characteristics rather than procedural failure.

Several additional limitations should be acknowledged. This study has a retrospective design and lacks a direct control group using endoscopic sampling techniques, precluding direct comparative analysis. Furthermore, the relatively small sample size limits the statistical power of subgroup analyses. Despite these limitations, our findings provide clinically relevant real-world data on the diagnostic performance and safety of PEPB in a carefully selected patient population.

Conclusion

From a technical perspective, PEPB is a simple, minimally invasive procedure with low complication rates and high diagnostic accuracy compared to other techniques. It has broadened the scope of biliary diagnostics and proved to be a reliable and accurate method for histopathological diagnosis of biliary neoplasms. PEPB is a safe, feasible, and effective technique that yields a high rate of true-positive results in diagnosing obstructive jaundice.

Ethics Committee Approval

This study was approved by the Clinical Research Ethics Committee of Ondokuz Mayıs University (Application No: 2024/544; Date: March 28, 2025).

Informed Consent

Informed consent was obtained from all patients before the procedure.

Conflict of Interest

The authors declare that they have no conflict of interest.

Financial Disclosure

No funding was received for this study.

Use of AI for Writing Assistance

The authors declare that no artificial intelligence (AI)–assisted technologies (including but not limited to Large Language Models [LLMs], chatbots, or image creators) were used in the preparation of this manuscript. All content was solely generated by the authors.

Author Contributions

Concept: UA, HD, IG; Design: AS, AB, HA; Supervision: FU, IG; Funding: TA, MU; Materials: TA, MU; Data Collection and/or Processing: UA, FU; Analysis and/or Interpretation: AS, MU, IG; Literature Review: TA, HA, FU; Writing: MU, HD, HA; Critical Review: UA, AS, AB.

Peer-review

Externally peer-reviewed.