[The biliary ecosystem: a holistic perspective on critical scientific issues regarding biliary tract surgeries and...

The establishment of modern biliary surgery system, alongside pivotal scientific paradigm shifts, has heralded a new era featured by precision, personalization, life-cycle care, and multidisciplinary management in the treatment of both benign and malignant biliary diseases. However, two formidable challenges persist in haunting the treatment of biliary diseases: (1) The refinement of surgical techniques has reached a plateau in reducing the disability associated with benign biliary conditions and in improving survival outcomes in biliary tract cancers; (2) Traditional evidence-based clinical studies have shown limited power in addressing complex dilemmas, such as determining whether to excise or preserve pathological gallbladders or selecting the optimal biliary drainage strategy. Consequently, the authors propose the conceptual framework of "biliary ecosystem". In this model, diverse and abundant cholangiocytes represent forest, while blood vessels, nerves, and lymphatic vessels serve as nurturing soil, biliary stem cells function as seeds, bile flows like river network, and hepatocytes mark the river's origins. Both benign and malignant biliary diseases exhibit significant spatiotemporal dynamics. The bile ducts form the "macro" environment, bile constitutes the "sub-macro" environment, and diverse cellular niches create the microenvironment. Specific pathological biliary conditions are shaped by intricate regulatory mechanisms that operate across these three tiers. Within the biliary ecosystem, cellular subpopulations exist remarkable diversity with states of homeostasis, oscillation, perturbation, or imbalance, underpinned by complex signaling networks. This holistic approach allows us to reframe and critically examine the pressing scientific issues confronting biliary tract diseases. Based on this framework, the authors distill key scientific questions and offer preliminary recommendations for embracing the paradigm shift. The authors anticipate that this conceptual model will promote interdisciplinary integration and accelerate clinical and translational researches.