Pancreatic duct brush cytology and fluorescence in situ hybridization during endoscopic retrograde cholangiopancreatography were shown to be safe and have moderate accuracy for diagnosing pancreatic cancer in a retrospective cohort study of patients at a single tertiary center.

Patients who had undergone pancreatic duct (PD) brushing via brush cytology (BC) or fluorescence in situ hybridization (FISH) between 2004 and 2023 were included in the study, led by Shuji Mitsuhashi, MBBS, a gastroenterology fellow at Mayo Clinic, in Rochester, Minn. The investigators assessed the incidence of adverse events and diagnostic accuracy of BC and FISH relative to endoscopic ultrasound–guided tissue sampling or surgical histology findings.

The criteria for a positive BC were evidence of malignancy or suspicious findings. The criteria for a positive FISH were polysomy (=3 copies of =2 probes), tetrasomy (4 copies of each probe), single locus gain with concurrent 9p21 loss (=3 copies of 1q21, 7p12, or 8q24 and 0-1 copy of 9p21 in the same cell), single locus gain (=3 copies of a single probe with 2 copies of the other 3 probes), or homozygous 9p21 loss (0 copies of 9p21 probe and 2 copies of the other 3 probes).

Presenting the findings at ACG 2024 (abstract P1727), Dr. Mitsuhashi reported that of the 205 patients who underwent ERCP PD brushing, 35 were diagnosed with a malignancy. Those with malignancy were, on average, older (66.2 vs. 57.5 years of age) and more often were male (74.3% vs. 58.2%), had pancreatic cysts (65.7% vs. 37.7%), and had a mass seen on imaging (54.3% vs. 10.6%) than those without malignancy. Those with malignancy had chronic pancreatitis less often (34.3% vs. 78.7%).

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The sensitivity and specificity of BC for diagnosing pancreatic cancer were 31.4% and 95.8%, respectively. For FISH, sensitivity and specificity were 45.7% and 89.4%, respectively, and for combined BC and FISH, they were 54.3% and 87.7%, respectively.

Interpreting these results, Dr. Mitsuhashi told Gastroenterology & Endoscopy News that “the diagnostic utility of PD brushing, particularly when combined with FISH, lies in its ability to provide moderate diagnostic accuracy for pancreatic malignancy. With a combined sensitivity of 54.3% and specificity of 87.7% (AUC [area under the curve], 0.71), these techniques significantly enhance diagnostic confidence when imaging and serum markers are inconclusive.” In addition, he said, polysomy FISH is “particularly valuable for confirming malignancy in ambiguous cases,” given its high specificity.

Among patients without a mass detected on imaging, 16 had malignancy. In these 16 patients, BC was positive in one, FISH was positive in six, both BC and FISH were positive in two, and both tests were negative in seven.

Overall, 7.8% of patients who underwent ERCP PD brushing had post-ERCP pancreatitis, 1.0% had bleeding and 0.5% had perforation. There were no instances of sepsis or death.

Gregory Coté, MD, MS, a professor of medicine and the head of the Division of Gastroenterology and Hepatology at Oregon Health & Science University, in Portland, who was not involved in the study, told Gastroenterology & Endoscopy News that the study “is a reminder that intraductal sampling of pancreatic strictures can be helpful in challenging cases of chronic pancreatitis with suspected cancer.” He added that “endoscopic ultrasound–guided fine-needle aspiration—and now biopsy—has largely addressed the problem of the ‘indeterminate pancreatic duct stricture.’ The sensitivity of EUS-based sampling is greater than 80% and cytopathology maintains specificity greater than 98%, which is why cytopathology is considered diagnostic for cancer: False-positive cytopathology should be very rare.”

According to Dr. Mitsuhashi, “the best candidates for PD brushing are patients with indeterminate PD strictures or those exhibiting high-risk features for pancreatic malignancy where imaging, including endoscopic ultrasound, and serum markers, such as CA 19-9, provide inconclusive results.” He explained that “these patients may benefit from PD brushing, as it complements other diagnostic modalities, enhancing sensitivity, particularly in cases where more invasive approaches, like surgical resection, are not immediately feasible.”

Dr. Coté outlined three specific scenarios in which he said “it’s worth considering pancreatic intraductal brushing: 1) cancer is suspected despite two consecutive EUS-based samplings (separate procedures) [being] inconclusive; 2) the patient has an indication for ERCP, which is usually symptoms related to the stricture; [and] 3) empiric surgical resection of the stricture is not considered a good option.”

Ultimately, given that “FISH is somewhat resource-intense,” Dr. Coté said he does not “foresee an expanding role in pancreatobiliary diagnostics. I think broader quantitative molecular testing such as next-generation sequencing is more likely to become part of our standard workflows.”

While acknowledging “the need for … the development of advanced molecular diagnostics to further enhance sensitivity while maintaining the high specificity of these [PD brushing] techniques,” Dr. Mitsuhashi said “PD brushing, with or without FISH, should be considered as part of the diagnostic workup in high-risk patients with inconclusive results from standard imaging and serum markers, especially in patients with prior PD stents in place.” He added that “incorporating PD brushings into a multidisciplinary diagnostic strategy helps refine patient selection for invasive procedures or surgeries, reducing unnecessary interventions in benign conditions.”

—Natasha Albaneze, MPH

Drs. Coté and Mitsuhashi reported no relevant disclosures.

This article is from the April 2025 print issue.