Liver transplantation (LT) for unresectable colorectal liver metastases has long been abandoned because of dismal prognoses. After the dark ages, advances in chemotherapy and diagnostic imaging have enabled strict patient selection, and the pioneering study from the Oslo group has contributed to the substantial progress in this field. For unresectable neuroendocrine liver metastases, LT for patients who met the Milan criteria was able to achieve excellent long-term outcomes. The guidelines further adopted in the United States and Europe were based on these criteria. For hepatoblastoma, patients with unresectable and borderline-resectable disease are considered good candidates for LT; however, the indications are yet to be defined. In the budding era of transplant oncology, it is critically important to recognize the current status and unsolved questions for each disease entity. These guidelines were developed to serve as a beacon of light for optimal patient selection for LT and set the stage for future basic and clinical studies.

Objective: To define the current status of “difficult” LLR, a global database was created and investigated. Background: In the Second International Consensus Conference in 2014, minor LLR was considered as a standard practice and major LLR remained an innovative procedure. Since then, no updates on worldwide trends have been available. Methods: A questionnaire on all consecutive patients who underwent difficult LLR (major hepatectomy, posterosuperior segmentectomy, sectionec-tomy, living donor hepatectomy, tumor size ≥10 cm, Child-Pugh grade ≥B, combined with biliary reconstruction, and Iwate criteria difficulty score ≥7) in 2014–2018 was distributed via email to 65 high-volume LLR centers worldwide. individual data on patient and tumor demographics, surgical information, and short-term outcomes were obtained to create a large-scale international registry for analyses. Results: Overall, 58 centers in 19 countries performed 4478 difficult LLR (median, 58.5; range, 5–418) during the study period. Hepatocellular carcinoma accounted for ≥ 40% of all indications. Half of the patients underwent major hepatectomy, followed by sectionectomy, posterosuperior segmentectomy, and living donor hepatectomy. in the vast majority of procedures, Clavien-Dindo grade ≥IIIa complication rates of ≈10% and 90-day mortality rates of ≈1% were achieved. Left or right trisectionectomy had the worst Clavien-Dindo grade ≥IIIa complication rate of ≥10% and 90-day mortality rate of 5%–10%. No significant correlation was observed between center volume and short-term outcomes. Conclusions: Total 4478 patients underwent difficult LLR worldwide in 2014–2018. Most procedures are safe and feasible when conducted in specialized centers.