A tissue attached to self-expandable metal stents for biliary stricture could be useful to find malignancy


Our prospectively collected database of SEMS removal procedures performed from August 2016 to December 2019 at Kyungpook National University Hospital in Daegu was analyzed. During this period, 55 patients underwent endobiliary biopsy and SEMS insertion and removal. Based on the clinical history and imaging studies, those who underwent SEMS placement at the stricture were suspected to have malignant biliary strictures. Patients with incomplete data were excluded from this study. This study was approved and the informed consent was waived by the Institutional Review Board of Kyungpook National University Hospital. All methods were performed in accordance with the Declaration of Helsinki.

All patients underwent endobiliary biopsy at least once, during which SEMS were placed for the biliary stricture. The SEMS were removed when the patient was treated for obstructive jaundice or acute cholangitis due to stent malfunction. The removed SEMS were prepared for cytology in the same manner as a tissue specimen. Demographic data, CA 19–9 levels, endobiliary biopsy and SEMS cytology results, and final diagnoses were determined by reviewing the medical records.

ERCP procedures

All procedures were performed at a single academic referral center. ERCP was performed by a dedicated therapeutic endoscopist (M.K. Jung) who performs over 1000 ERCP procedures annually using standard techniques. Endobiliary biopsies with or without brush cytology were routinely performed in all cases. After endobiliary biopsy, the therapeutic endoscopist placed the SEMS to dilate the biliary stricture. Follow-up ERCP was then performed for SEMS removal, reevaluation, or exchange if malignancy was confirmed. The follow-up ERCP was usually performed 3 months later. Upon follow-up ERCP, the removed biliary stent was sent for cytology analysis.

Preparation of SEMS for cytology

Upon arrival at the cytology laboratory, the stent was removed after which the attached material was rinsed into a fixative (CytoLyt, Hologic Inc., MA, USA). The tissue, attached to self-expandable metal stents, was spontaneously separated from the SEMS (Fig. 1). The sample was centrifuged at 2000 rpm for 10 min and affixed to the CytoLyt for 30 min. The supernatant was discarded, and the cell pellet was placed into the ThinPrep 5000 automated slide processor (Hologic Inc., MA, USA) for liquid-based cytology. A single ThinPrep monolayer cytology slide was prepared and stained using the Papanicolaou method. This cytology slide was come from the tissue from SEMS. So in this study I used the term “SEMS cytology” to clearly discriminate from bile cytology or brush cytology.

Figure 1

The removed self-expandable metal stents.

Diagnostic reporting of these specimens followed standard cytology categorization as follows: non-diagnostic (i.e. a cytology specimen that provides no diagnostic or useful information about the lesion sampled), negative for malignant cells, atypical (i.e. cytologic changes that are more likely than not to be benign), suspicious for malignant cells (i.e. cytologic changes that are more likely than not to be malignant), and positive for malignant cells. In this study, malignant disease was considered when the cytologic category was atypical, suspicious for malignant cells, or positive for malignant cells.

Endobiliary biopsy

Two specimens were obtained from the biliary stricture during endobiliary biopsy. For biopsies diagnosed as category 1, which indicates negativity for neoplasia/dysplasia (including normal, reactive, regenerative, hyperplastic, atrophic and metaplastic epithelium), further follow-up of the lesion may or may not be necessary, as clinically indicated. In the case of category 2, which is indefinite for neoplasia/dysplasia, follow-up is needed due to uncertainty regarding the true nature of the lesion. For category 3, which indicates non-invasive low-grade neoplasia (low-grade adenoma/dysplasia), neoplasia is present, but the risk for developing invasive carcinoma is low. For category 4, which indicates non-invasive high-grade neoplasia, the risk for invasion and development of metastases is increased. In the case of category 5, which indicates invasive neoplasia, the risk of subsequent deeper invasion and metastases is so high that treatment is urgently needed and should only be withheld in cases with clinical contraindications. Generally, before a treatment is selected, the possibility of sampling errors should always be considered, which may cause underestimation of the grade of neoplastic change or depth of invasion. We followed the Vienna classification of gastrointestinal epithelial neoplasia13. In this study, malignant disease was considered when the biopsy showed category 3, 4, or 5 disease.

Final diagnosis

The final diagnosis was established using (1) cytologic and/or histologic evidence obtained by tissue sampling during ERCP, endoscopic or percutaneous fine needle biopsy, surgery, or autopsy or (2) clinical data obtained during follow-up of at least a year. Definitely malignant and severely suspicious cytological or histopathological findings were classified as positive. Nearly all tissue samples acquired by brush cytology or forceps biopsy were examined by two local pathologists with appropriate expertise. When brush cytology and forceps biopsy were performed during ERCP, tissue samples obtained by both modalities were examined by the same pathologists. A stricture was considered benign when no evidence of malignancy was observed after follow-up for at least 1 year (i.e. absence of radiological tumor progression including infiltration and/or metastatic dissemination).

Statistical analysis

Results were expressed as means ± standard deviations or as percentages. Statistical analysis was performed using the chi-square test, Student’s t test, or Fisher’s exact test. Test characteristics for endobiliary biopsy, SEMS cytology, and endobiliary biopsy with SEMS cytology, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Moreover, we compared receiver operating characteristic curve values for (1) biopsy, (2) biopsy and SEMS cytology, (3) biopsy and CA 19–9, and (4) biopsy, CA 19–9, and SEMS cytology. All statistical analyses were performed with SAS 9.4 (SAS Institute Inc., Cary, NC, USA), and p values < 0.05 indicated statistical significance.

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