3.1. Patient’s Characteristics and Baseline Evaluation
Table 1 showed the characteristics of patients with biliary disease. In this study, the malignant group included 12 patients with perihilar cholangiocarcinoma, 14 patients with distal cholangiocarcinoma, one patient with intrahepatic cholangiocarcinoma and one patient with cystic ductal carcinoma. Macroscopic types of BTC included four papillary-type, 16 nodular-type, and eight flat-type. The benign group included nine patients with benign biliary strictures, three patients with IgG4-associated sclerosing cholangitis, three patients with primary sclerosing cholangitis, two patients with drug-induced cholangitis, one with intraductal papillary neoplasm of the bile duct (IPNB), and one with a peribiliary cyst. This study group included 24 patients with perihilar bile duct stricture, 19 patients with distal bile duct stricture, two patients with cystic duct stricture, and one patient with intrahepatic bile duct stricture. One patient did not have any biliary stricture, and he received POCS-guided forceps biopsy for distal bile duct near the ampulla of Vater in order to evaluate the hypertrophic extrahepatic bile duct. The median length of stricture in this study group was 16.6 mm (range, 0–46.0 mm). The median levels of serum total bilirubin (T-Bil), carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19–9) were 1.3 mg/dl (range, 0.3–14.8 mg/dl), 2.4 ng/ml (range, 0.8–10.1 ng/ml), and 34.6 U/ml (range, 0.8–4430.0 U/ml), respectively (Table 1). The median procedure time of POCS-guided forceps biopsy was 77 minutes (range, 26–170 minutes). The final clinical diagnosis was derived from surgical pathology in 15 patients. There were 18 patients with a final diagnosis based on clinical and radiological follow-up data (median follow up period, 7 months; range, 1–22 months). We performed both the POCS-guided forceps biopsy for biliary lesions and the POCS-guided forceps mapping biopsy for 29 patients with biliary disease. Eleven patients received only the POCS-guided forceps biopsy for indeterminate biliary lesions, and Seven patients received only the POCS-guided forceps mapping biopsy for non-stenotic bile duct to determine the longitudinal extension of BTC. Therefore, Cohort 1 and Cohort 2 included 40 and 36 patients, respectively (Figure 3).
3.2. Diagnostic Performance and Tissue Acquisition Rate of POCS-guided Forceps Biopsy for Biliary Tract Cancer.
The total and the median number of biopsies for indeterminate biliary lesions were 140 and 3 (range, 2–8) in Cohort 1, respectively. The total number of POCS-guided forceps mapping biopsies was 196 in Cohort 2. By the location in the bile duct, 93 specimens were obtained from the perihilar bile ducts of 25 patients (41 specimens from the confluence of the hepatic ducts of 23 patients), 31 specimens from the distal bile ducts of 15 patients, 22 specimens from the junction of the cystic ducts of 11 patients, 27 specimens from the first order branch of the intrahepatic ducts of 12 patients, and 23 specimens from the second order branch of the intrahepatic ducts of 12 patients. Eleven patients received biliary stenting before POCS-guided forceps biopsy. In Cohort 1, 21 patients were with BTC, and 19 patients were with benign. Cohort 1 included 22 patients with perihilar bile duct stricture, 15 patients with distal bile duct stricture, 2 patients with cystic duct stricture, and 1 patient with extrahepatic bile duct hypertrophy. Table 2 summarizes the diagnostic performance of POCS-guided forceps biopsy to differentiate BTC from benign biliary disease. The values for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of POCS-guided forceps biopsy were 76.2%, 94.7%, 94.1%, 78.3%, and 85.0%, respectively (Table 2). The sufficient tissue acquisition rate of POCS-guided forceps biopsy for biliary lesions was 86.4% (121/140).
3.3. Factors Affecting the Sufficient Tissue Acquisition of POCS-guided Forceps Biopsy for Biliary Lesion.
Table 3 summarizes the result of analyses for the sufficient tissue acquisition in POCS-guided forceps biopsy for biliary lesions. In the univariate analyses, age, sex, the location of the biliary lesion, and previous biliary stenting before POCS were factors with P < 0.1 and were included in the multivariate logistic regression analyses. Age <65 years old (odds ratio 0.170, 95% confidence interval [CI] 0.044–0.649, P = 0.004) and previous biliary stenting before POCS (odds ratio 0.199, 95% CI 0.053–0.756, P = 0.017) were the significant factors affecting the sufficient tissue acquisition rate in the multivariate analysis.
3.4. Tissue Acquisition Rate of POCS-guided Forceps Biopsy for Non-Stenotic Bile Duct.
Cohort 2 included 17 patients with perihilar bile duct stricture, 16 patients with distal bile duct stricture, two patients with cystic duct stricture, and one patient with intrahepatic bile duct lesion. The sufficient tissue acquisition rate of POCS-guided forceps mapping biopsy for non-stenotic bile duct was 68.9% (135/196), which was significantly lower than that of POCS-guided forceps biopsy for biliary lesion (P < 0.001). The sufficient tissue acquisition rates of POCS-guided forceps mapping biopsy were calculated by the location in the bile duct: the distal bile duct (58.1%), the junction of the cystic duct (86.4%), the perihilar bile duct (77.4%; including the confluence of the hepatic duct 82.9%), the first order branch of the intrahepatic bile duct (37.0%), and the second order branch of the intrahepatic bile duct (69.6%) (Table 4).
3.5. Factors Affecting the Sufficient Tissue Acquisition of POCS-guided Forceps Biopsy for Non-Stenotic Bile Duct.
Table 5 summarizes the results of the analyses for the sufficient tissue acquisition in POCS-guided forceps mapping biopsy for a non-stenotic bile duct. In the univariate analyses, age, malignant lesion, the location of the biliary lesion, the length of stricture, the biopsy site in the intrahepatic bile duct, procedure time, and EST were factors with P < 0.1, and were included in the multivariate logistic regression analyses. The biliary lesion in the distal bile duct (odds ratio 0.322, 95% CI 0.139–0.744, P = 0.008), procedure time of 75 min or less (odds ratio 3.012, 95% CI 1.092–8.312, P = 0.033), and EST (odds ratio 7.041, 95% CI 2.117–23.421, P = 0.002) were the significant factors affecting the sufficient tissue acquisition rate in the multivariate analyses.
3.6. Adverse Events
Adverse events following POCS-guided forceps biopsy occurred in eight patients (17.0%), with four patients (8.5%) developing acute pancreatitis, including one case of severe pancreatitis; and three patients (6.4%) developing cholangitis. Severe hemorrhage related to the precut papillotomy occurred in one patient (2.1%). No perforations were observed, all cases were resolved with conservative treatment, and there was no procedure-related mortality (Table 6).