Diagnosing bile duct strictures can be difficult because it is often unclear whether a narrowing is benign or caused by cancer. A team led by researchers at the University of Pittsburgh Medical Center evaluated how next-generation sequencing using both DNA and RNA could improve diagnostic accuracy in real clinical settings.

Traditionally, doctors collect samples during a procedure called ERCP and examine them under a microscope. While this approach is highly specific, meaning positive results are usually correct, it often misses cancers because of low sensitivity. This is especially problematic in patients with conditions like primary sclerosing cholangitis, where inflammation can obscure early tumor signals.

To address this challenge, the research team used advanced sequencing panels, called BiliSeq, to analyze genetic material from bile duct samples collected across 28 medical centers over six years. By combining DNA and RNA sequencing, they were able to detect cancer-associated mutations and gene fusions that are not always visible through standard pathology.

The results showed a clear improvement. RNA sequencing and DNA analysis together significantly increased the ability to detect cancer, with sensitivity rising from 44 percent using traditional methods to over 80 percent with sequencing. When both approaches were combined, sensitivity increased even further while maintaining high specificity.

Importantly, the sequencing approach also identified actionable genetic changes in a subset of patients. These findings helped guide treatment decisions in about 30 percent of cases where such alterations were detected. This highlights the growing role of molecular diagnostics in not only identifying disease earlier but also informing personalized treatment strategies.

Overall, the findings show that RNA sequencing, combined with DNA analysis, provides a more accurate and informative way to evaluate bile duct strictures. This approach could lead to earlier diagnoses, better patient management, and improved outcomes, particularly in high-risk populations.