Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria

Table 1 Expanded morphometric criteria for hepatocellular carcinoma-liver transplantation

Ref.	Year	Description	Donor type	n	Survival
Yao et al[13]	2001	1 lesion ≤ 6.5 cm, or 2-3 lesions ≤ 4.5 cm each. Total tumor diameter ≤ 8 cm	Cadaveric	70	5 yr OS: 72.4%
Herrero et al[16]	2001	1 lesion ≤ 6 cm, or 2-3 lesions ≤ 5 cm each	Cadaveric	47	5 yr OS: 79%
Roayaie et al[19]	2002	Any number of lesions, 5-7 cm each	Cadaveric	43	5 yr RFS: 55%
Keneteman et al[20]	2004	1 lesion < 7.5 cm, or multiple lesions < 5 cm each	Cadaveric	40	4 yr OS: 82.9%
					4 yr RFS: 76.8%
Onaca et al[18]	2007	1 lesion ≤ 6 cm, or 2-4 lesions ≤ 5 cm each	Cadaveric	1206	5 yr RFS: 1 lesion ≤ 6 cm: 63.9%/or 2-4 lesions 3.1 cm-5 cm each: 64.6%
Soejima et al[23]	2007	Any number lesions ≤ 5 cm each	Living	67	3 yr OS: 68.6%
Jonas et al[24]	2007	Single lesion and diameter, or any number of lesions ≤ 6 cm each. Total tumor diameter ≤ 15 cm	Living	21	3 yr OS: 53%
Sugawara et al[25]	2007	Up to 5 lesions ≤ 5 cm each	Living	78	3 yr RFS: 94%
Silva et al[17]	2008	1-3 lesions ≤ 5 cm each. Total tumor diameter ≤ 10 cm	Cadaveric	257	5 yr OS: 67%
Mazzaferro et al[21]	2009	The sum of the size and number of tumors not exceeding 7 in the absence of microvascular invasion	Both	1556	5 yr OS: 71.2%

RFS: Recurrence free survival; OS: Overall survival.

Table 2 Expanded criteria that incorporate tumor biomarkers for hepatocellular carcinoma-liver transplantation

Ref.	Year	Morphometric criteria	Biomarker criteria	Donor type	n	Survival
Kwon et al[34]	2007	Any number of lesions ≤ 5 cm each	AFP ≤ 400 ng/mL	Living	139	5 yr OS: 79.9%
Takada et al[38]	2007	Up to 10 lesions ≤ 5 cm each	PIVKA-II ≤ 400 mAU/mL	Living	136	5 yr OS: 87%
Zheng et al[29]	2008	Total tumor diameter ≤ 8 cm or total	If total	Cadaveric	195	5 yr OS: 70.7%, 5 yr DFS: 62.4%
		tumor diameter > 8 cm with histopathologic grade I or II	tumor diameter > 8 cm: AFP ≤ 400 ng/mL
Fujiki et al[37]	2009	Up to 10 lesions ≤ 5 cm each	DCP ≤ 400 mAU/mL	Living	144	5 yr OS: 89%
Lai et al[31]	2012	Total tumor diameter ≤ 8 cm	AFP ≤ 400 ng/mL	Cadaveric	158	5 yr DFS: 74.4%
Grąt et al[36]	2014	UCSF or Up-to-7 criteria	AFP < 100 ng/mL	Cadaveric	121	5 yr OS: 100%
Toso et al[35]	2015	Total tumor volume ≤ 115 cm3	AFP ≤ 400 ng/mL	Cadaveric	166	4 yr OS: 74.6%
Lee et al[39]	2015	Total tumor diameter ≤ 10 cm	PET/CT negative uptake	Living	280	5 yr OS: 73.4%,
						5 yr DFS: 80.4%

AFP: Alpha fetal protein; UCSF: University of California, San Francisco; DFS: Disease free survival; PIVKA-II: Protein induced by vitamin K absence or antagonism factor II; OS: Overall survival.