Outcome of probe-based confocal laser endomicroscopy (pCLE) during endoscopic retrograde cholangiopancreatography: A single-center prospective study in 45 patients

Abstract

Background: Diagnosis of pre-malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC).

Aims: To evaluate in a prospective cohort study the sensitivity and specificity of probe-based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP).

Methods: We performed pCLE together with mother-baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically-resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year.

Results: We were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagnosis of malignancy. Sensitivity was 91% and specificity 52%. The positive (PPV) and negative predictive value (NPV) was 82% and 100%, respectively. Apart from mild post-ERCP pancreatitis in two patients, no complications occurred.

Conclusions: Our study showed that pCLE is a safe, expert endoscopic method with high technical feasibility, high sensitivity and high NPV. It provided diagnostic information that can be helpful for decisions on patient management, especially in the case of IPMN and unclear pancreatic lesions, in individuals whom are at increased risk for pancreatic cancer.

Keywords: Bile ducts; SpyGlass; cytology; diagnostics; endoscopic retrograde cholangiopancreatography; endoscopy methods; histology; intraductal papillary mucinous neoplasia; pancreatic cancer; pancreatic neoplasia; probe-based confocal laser endomicroscopy.

Figures

Figure 1.

Algorithm of initial diagnosis (clinical and imaging), findings during pCLE, and the final diagnosis based on the tissue pathology (from surgical observation, biopsy, cytology and FISH) and clinical follow-up. (a) Biliary pCLE investigations. (b) Pancreatic pCLE investigations. Individual patients were color-coded for better tracking throughout the three diagnostic levels, referring to the initial imaging diagnosis. Cases in bold had changed in more than one category. Patient #1 and #12 did receive two pCLE; and patient #17 underwent three pCLE. In all cases, the results were identical (Miami +). In the grey-shaded cases (#8, #35 and #40), both the biopsy and cytology/FISH were normal, thus non-malignant. FISH: fluorescence in-situ hybridization; HGD: high-grade dysplasia; IPMN: intraductal papillary mucinous neoplasia; PanIN: pancreatic intra-epithelial neoplasia; pCLE: probe-based confocal laser endomicroscopy.

Figure 3.

Patient #17 with a 50 pack-year history of smoking, who had chronic hereditary pancreatitis and a positive family history for pancreatic cancer. (a) and (b) Broad, papillary structures with blunt, exaggerated tips and contrast pooling in the tips. We performed the pCLE in a first-degree side branch of the main pancreatic duct that was not accessible with SpyGlass. pCLE: probe-based confocal laser endomicroscopy; PY: patient-years.

Figure 2.

Examples of pCLE with the Cholangioflex probe in several patients, demonstrating the principal findings according to the Miami criteria. (a) Papillary structures with contrast enhancement along the tips. (b) Broad white bands within papillary structures. (c) Rather waisted tips, with contrast enhancement. (d) Broad dark bands. pCLE: probe-based confocal laser endomicroscopy.

Figure 4.

Diagnostic algorithm for the work-up of suspicious lesions of the bile ducts and the pancreas. Bx: biopsy; ERCP: endoscopic retrograde cholangiopancreatography; EUS: endoscopic ultrasound; HBP: hepatobiliopancreatic; MDCT: multi-detector computer tomography; MPD: main pancreatic duct; MRCP: magnetic resonance cholangiopancreatogram; MRI: magnetic resonance imaging; pCLE: probe-based confocal laser endomicroscopy; ROI: region of interest.