Diagnosis of biliary strictures remains challenging because of the low sensitivity of conventional transpapillary sampling using endoscopic retrograde cholangiopancreatography. New devices and tips have been developed to increase the diagnostic yield of conventional transpapillary sampling. However, additional endoscopic procedures are often necessary for indeterminate biliary strictures. Two major approaches for indeterminate biliary strictures are endoscopic ultrasonography-guided sampling and peroral cholangioscopy (POCS)-guided biopsy. The selection of modalities should be considered based on the stricture location. Although endoscopic ultrasound is the preferred approach for distal biliary strictures, POCS is preferred for perihilar biliary strictures. Endoscopic ultrasonography-guided sampling is highly sensitive in cases with a mass, but the sensitivity of POCS-guided biopsies is unsatisfactory, and discrepancy with the visual diagnosis of POCS is common. Whether these advanced techniques should be performed as the initial procedure or as a rescue after a failed diagnosis by conventional transpapillary sampling needs to be clarified in terms of diagnostic yield and cost-effectiveness.

Objective: Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). Methods: In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. Results: We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. Conclusion These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.