The value of DNA image cytometry combined with brush routine cytology in diagnosing indeterminate biliary strictures: A large sample size retrospective study

Abstract

Background and Aim:Brush cytology is widely applied to diagnosis indeterminate biliary stricture but suffer from low sensitivity. Changes in DNA content are a character of malignant cell and can be detected by DNA image cytometry (DNA-ICM). The study aimed to estimate the value of routine cytology (RC), DNA-ICM, and their combination in diagnosing indeterminate biliary strictures. Methods: A total of 362 patients who underwent both RC and DNA-ICM tests were analysed. Their results were retrospectively applied to final diagnoses. Diagnostic values were compared among RC, DNA-ICM, and their combination based on the location of strictures. Results: The DNA-ICM and combination of two methods had higher diagnostic accuracy than RC in all strictures (63.3% vs 42.3%, P < 0.001, 64.36% vs 42.3%, P < 0.001) and in distal strictures (65.36% vs 42.81%, P < 0.001, 66.01% vs 42.81%, P < 0.001). But in proximal strictures, DNA-ICM showed no superior (51.8% vs 42.81%, P = 0.184). Combination of two methods was not fully significant superior to RC in proximal strictures (55.36% vs 39.29%, P = 0.089). After classification of "suspicious for malignancy" as positive for malignancy, the diagnostic accuracy of DNA-ICM was still higher than that of RC in all strictures (63.3% vs 51.9%, P = 0.002) and in distal strictures (65.36% vs 52.29%, P = 0.001). Combination of two methods was no superior to DNA-ICM alone (64.36% vs 63.3%, P = 0.757). The utilization of DNA-ICM was more accurate in distal strictures than in proximal strictures (65.36% vs 51.8%, P = 0.017). Conclusion: DNA-ICM is an objective and effective addition tool with RC, especially in distal strictures. The combination of DNA-ICM and RC showed no superior to DNA-ICM alone but could improve diagnostic accuracy to RC in proximal strictures although not fully significant. ) 0.738 (0.625-0.853) † Suspicious cytology findings were considered indications of malignancy.AUC, area under curve; DNA-ICM, DNA image cytometry; NPV, negative predictive value; PPV, positive predictive value; SE, sensitivity; SP, specificity.

Digital Image Analysis has an Additive Beneficial Role to Conventional Cytology in Diagnosing the Nature of Biliary Ducts Stricture

“…Centrifugation was done for 30 min, and the sediment was directly smeared onto one or more glass slides, fixed using an alcoholbased fixative, and stained with Papanicolaou stain. 11 Slides were examined with an Olympus inverted microscope (CKX41, Olympus, Hamburg, Germany) and were photographed with a mounted digital color camera (XC30, Soft Imaging System; Olympus).…”

“…Aneuploid, tetraploid, and hypertetraploid results were considered positive for malignancy. 11 Follow-up Patients were followed for 9 months, and results of DIA and CCE were compared with one of the following reference methods of diagnosis 11 : (1) histopathological diagnosis by surgical excision; (2) radiological infiltration of adjacent organs or metastases by MRCP; and (3) death secondary to disease deterioration.…”

“…Also, in a recent published study, distal biliary stricture was observed in 306/362 (84.5%) patients. 11 The higher frequency of distal CBD stricture could be explained by exposure of distal CBD to different and frequent etiologies of stricture either malignant or benign as chronic pancreatitis, pancreatic and ampullary carcinoma, external compression by lymph node, inflammatory stenosis, edema, and pancreatic-biliary surgery.…”

“…In line with the current study, many previous studies reported high frequency of malignant stricture up to 76%. 11,14,15 And yet, some published studies showed higher frequency of benign biliary stricture. This was explained by the authors because of referral bias and enrollment of high number of patients with primary sclerosing cholangitis.…”

“…Similarly, Yang et al revealed that CCE had low sensitivity (6.28%) that was increased to 21.97% when cells that were "suspicious for malignancy" were included. 11 In a review of the literature from 2002 until 2012, including 16 studies and 1556 patients, biliary brushing cytology was found to be associated with an overall sensitivity of 41.6% and a negative predictive value of 58%. Low diagnostic yield of cytology may be attributed mainly to desmoplastic reaction in biliary malignancies, inadequate sampling, paucicellular cytologic specimens, and/ or pathologic misinterpretation caused by subtle changes between malignant and nonmalignant cells.…”