Molecular test doubles detection of bile duct cancer, suggests study

When patients develop a narrowing or blockage in the bile ducts - the tubes connecting the liver, gallbladder and intestines - physicians must determine whether the cause is cancer or a benign condition. The location of these blockages adds challenges to the diagnosis, and this uncertainty can delay treatment decisions for patients in the event they have this rare type of cancer.

Scientists at UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine developed BiliSeq, a molecular test that detected bile duct cancer with twice the sensitivity of the standard test, giving physicians a more accurate picture of the patient’s diagnosis.

Published today in Gastroenterology, the flagship journal of the American Gastroenterological Association, the study evaluated BiliSeq’s real-world performance over six years in more than 2,000 patients across the United States, analyzing nearly 3,000 bile duct specimens. BiliSeq detected approximately 82% of bile duct cancers, compared to 44% with pathology alone. More importantly, when combined with pathology, BiliSeq increased cancer detection to nearly 90% while rarely misclassifying benign disease as malignant.

Because bile duct tumors are often small, difficult to reach and surrounded by inflammation or scar tissue, standard biopsy and cytology methods often fail to give doctors a clear diagnosis.

“For decades, in bile duct cancer we’ve known that a negative biopsy doesn’t always rule out cancer,” said Adam Slivka, M.D., Ph.D., professor of medicine in the Division of Gastroenterology, Hepatology and Nutrition at Pitt. “That uncertainty drives repeat testing and sometimes surgery without clear answers.”

BiliSeq addresses this limitation by detecting genetic mutations associated with cancer in bile duct tissue. The test functions even when tumor cells are sparse, damaged or indistinguishable from inflammation under the microscope — a key limitation of traditional pathology, which can miss cancers and produce false-negative results.

BiliSeq is not a screening test for the general population. Instead, it is used for patients with bile duct narrowing or obstructions that need a clearer diagnosis.

One of the most important advantages of BiliSeq is that it provided more than a simple yes-or-no answer to patients waiting for a diagnosis. In the study, BiliSeq identified treatment-relevant genetic information in about one out of every five patients. In nearly one-third of those cases, that information led doctors to change how care was managed. “That’s where this really becomes personalized medicine,” said Slivka, who directs the gastroenterology service line at UPMC. In addition, BiliSeq results are already being used alongside standard clinical evaluation to help inform liver transplant decision-making in select patients at UPMC.

The study also reported on BiliSeq’s detection performance across high-risk patient groups, including patients with primary sclerosing cholangitis (PSC) and Hispanic patients. In these populations, pathology alone could miss up to half of cancers. However, when combined with BiliSeq, clinicians were able to identify up to 86% of cancer cases.

This work extends a broader effort by Pitt and UPMC researchers to develop molecular tools that improve cancer diagnosis and treatment decisions, including prior work in pancreatic cancer and pre-cancerous cysts, developed by Aatur Singhi, M.D., Ph.D, associate professor of pathology at Pitt, Director of the UPMC Developmental Laboratory, who is a co-author of the study.

The large, prospective, multi-institutional design makes the findings representative of real-world clinical practice. “We receive and analyze samples from patients at medical centers across the country,” Slivka said, “For these patients, BiliSeq means less testing, less waiting and more options.”

Reference:

Das R, Kleinberger J, Sawas T, Wald AI, Bubar R, Singh H, Chennat J, Khalid A, Romutis SL, Rabinovitz M, Tavakkoli A, Fairley KJ, Boone BA, Sarkaria S, Nasr J, Thiruvengadam NR, Gabbert C, Mahmood S, Messallam AA, Gjeorgjievski M, Goldschmiedt M, Thakkar S, Tielleman T, Dugum M, Reich J, Singh S, Brand RE, McGrath K; Molecular test doubles detection of bile duct cancer; Journal: Gastroenterology; DOI: 10.1053/j.gastro.2026.02.040