In transplantation medicine, the Milan criteria are set of criteria applied in consideration of patients with cirrhosis and hepatocellular carcinoma (HCC) for liver transplantation with intent to cure their disease. Their significance derives from a landmark 1996 study in 48 patients by Mazzaferro et al which showed that selecting cases for transplantation according to specific strict criteria led to improved overall and disease-free survival at a 4-year time point. These same criteria have since been adopted by the Organ Procurement and Transplantation Network (OPTN) in the evaluation of patients for potential transplantation.
The threshold Milan criteria are as follows:
- one lesion smaller than 5 cm; alternatively, up to 3 lesions, each smaller than 3 cm
- no extrahepatic manifestations
- no evidence of gross vascular invasion
Under current OPTN/ONUS guidelines, patients with cirrhosis and HCC who meet these criteria may be considered for transplantation. Depending on the treatment algorithm, additional factors such as advanced liver disease (as classified by Child-Pugh score) or evidence of portal hypertension may also affect suitability for transplantation.
Controversy and Research
Given the limitations of the original Mazzaferro study, including the small number of patients and limited inclusion criteria, there is ongoing discussion and controversy regarding the appropriate criteria for transplant. Additional studies attempting to replicate outcomes of the Mazzaferro study using Milan criteria thresholds have reported slightly less favorable 5-year survival statistics, ranging from 50% to 70%.
Some have advocated for the use of expanded guidelines for liver transplantation in the setting of HCC. In 2003, Yao et al. reported experience at the University of California San Francisco 5-year post-transplantation survival of 75% in patients with tumors as large as 6.5 cm, or up to 3 lesions each less than 4.5 cm with cumulative tumor burden ≤8 cm. Additional studies using these so-called "UCSF criteria" have shown favorable post transplant outcomes, although also higher rates of post transplant recurrence and higher rates of disease progression while waiting for transplant.
- Mazzaferro, Vincenzo; Regalia, Enrico; Doci, Roberto; Andreola, Salvatore; Pulvirenti, Andrea; Bozzetti, Federico; Montalto, Fabrizio; Ammatuna, Mario; Morabito, Alberto (1996-03-14). "Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis". New England Journal of Medicine. 334 (11): 693–700. doi:10.1056/nejm199603143341104. ISSN 0028-4793. PMID 8594428.
- Wald, Christoph; Russo, Mark W.; Heimbach, Julie K.; Hussain, Hero K.; Pomfret, Elizabeth A.; Bruix, Jordi (2013-02-01). "New OPTN/UNOS Policy for Liver Transplant Allocation: Standardization of Liver Imaging, Diagnosis, Classification, and Reporting of Hepatocellular Carcinoma". Radiology. 266 (2): 376–382. doi:10.1148/radiol.12121698. ISSN 0033-8419. PMID 23362092.
- Yao, F. Y. (October 2008). "Liver transplantation for hepatocellular carcinoma: beyond the Milan criteria". American Journal of Transplantation. 8 (10): 1982–1989. doi:10.1111/j.1600-6143.2008.02351.x. ISSN 1600-6143. PMC 4893115. PMID 18727702.
- Yao, Francis Y.; Ferrell, Linda; Bass, Nathan M.; Watson, Jessica J.; Bacchetti, Peter; Venook, Alan; Ascher, Nancy L.; Roberts, John P. (2001-06-01). "Liver transplantation for hepatocellular carcinoma: Expansion of the tumor size limits does not adversely impact survival". Hepatology. 33 (6): 1394–1403. doi:10.1053/jhep.2001.24563. ISSN 1527-3350. PMID 11391528.
- Duffy, John P.; Vardanian, Andrew; Benjamin, Elizabeth; Watson, Melissa; Farmer, Douglas G.; Ghobrial, Rafik M.; Lipshutz, Gerald; Yersiz, Hasan; Lu, David S. K. (2007). "Liver Transplantation Criteria For Hepatocellular Carcinoma Should Be Expanded". Annals of Surgery. 246 (3): 502–511. doi:10.1097/sla.0b013e318148c704. PMC 1959350. PMID 17717454.
- Tang, An; Fowler, Kathryn J.; Chernyak, Victoria; Chapman, William C.; Sirlin, Claude B. (2017-06-13). "LI-RADS and transplantation for hepatocellular carcinoma". Abdominal Radiology. 43 (1): 193–202. doi:10.1007/s00261-017-1210-8. ISSN 2366-004X. PMID 28612162.