Hepatic Hemangioendothelioma: An update

Table 1 Summaries of medical management studies for hepatic hemangioepithelioma

Study	Year	Country	Patients	Medical management	Dose	Outcome	Duration of follow up
Salech et al[78]	2010	Chile	1	Thalidomide	300 mg daily	Partial response	109 mo
Raphael et al[79]	2010	United Kingdom	1	Thalidomide	400 mg daily	Stable disease	84 mo
Kassam and Mandel[80]	2008	Canada	1	Thalidomide	400 mg twice daily	Progressive disease	Not available
Bolke et al[81]	2006	Germany	1	Thalidomide	Unknown	Progressive disease/death	Not available
Mascarenhas et al[49]	2005	United States	1	Thalidomide	Unknown	Partial response	Not available
Soape et al[60]	2015	United States	1	Thalidomide	200 mg nightly	Progressive disease	12 mo

Table 2 Summaries of chemotherapeutics management studies for hepatic hemangioepithelioma

Study	Year	Country	Patients	Chemotherapy agent	Dose	Outcome	Duration of follow up
Emad et al[55]	2019	Egypt	9/28	Propranolol, prednisolone, vincristine, cyclophos-phamide	First line therapy: 0.6–1.2 mg/kg/d propranolol and/or 0.5-2 mg/kg/d prednisolone	Regression on propranolol, propranolol/prednisolone, propranolol/prednisolone/ vincristine, propranolol/prednisolone/cyclophosphamide, propranolol/prednisolone/vincristine/cyclophosphamide, prednisolone/interferon (1/2)1	Minimum of 12 mo
					Salvage therapy: 1 million units/m2/wk interferon, 1.5 mg/m2/wk vincristine	Progression on prednisolone/interferon (1/2)1, prednisolone/vincristine/cyclophosphamide, Prednisolone/embolization/cyclophosphamide
Kim et al[82]	2010	Japan	1	Carboplatin, paclitaxel, and bevacizumab	15 mg/kg, every 21 d (bevacizumab)	Progression	Not available
Mizota et al[83]	2011	Japan	1	Carboplatin, paclitaxel, and bevacizumab	15 mg/kg, every 21 d (bevacizumab)	Progression	3 mo
Calabro et al[74]	2007	Italy	1	Interferon α-2a	Not available	Stable disease	Not available
Kayler et al[84]	2002	United States	1	Interferon α-2a	3 million units daily	Partial response	4 mo
Marsh R et al[85]	2005	United States	1	Interferon α	3 million units, 5 d/wk for 1 yr	Complete response	84 mo
Galvão et al[50]	2005	Brazil	1	Interferon alpha 2b	3 million units daily 9 weeks before and 1 week after liver resection	Complete response	36 mo
Agulnik et al[64]	2013	United States	1	Bevacizumab	15 mg/kg, every 21 d	Partial response	Not available
Lau et al[63]	2015	United States	1	Capecitabine and bevacizumab	Not available	Partial response	6 mo
Lakkis et al[86]	2013	France	2	Cyclophos-phamide	50 mg daily continuous	Complete response (1/2) and Partial response (1/2)	6 and 24 mo
Sangro et al[87]	2012	Spain	1	Sorafenib	200 mg every 36 hours	Partial response	6 mo
Kobayashi et al[62]	2016	Japan	1	Sorafenib	400-800 mg twice daily	Partial response	60 mo

¹On prednisolone/interferon treatment, regression was reported in 1 patient and progression in the other patient.

Table 3 Summary of surgical management studies for hepatic hemangioepithelioma

Study	Year	Country	Patients	Study Design	Surgical management	Outcome	Duration of follow up
Bachman et al[68]	2003	Switzerland	1	Case report	Selective hepatic artery ligation	Stable, asymptomatic, heart failure signs disappeared	48 mo
Bostancı et al[65]	2014	Turkey	1	Case report	Selective internal radiotherapy	Partial response	12 mo
Grotz et al[57]	2010	United States	11/30	Retrospective	Hepatic resection	A 1-, 3- and 5-year overall survival of 100%, 86% and 86% and a disease free survival of 78%, 62% and 62%, respectively	60 mo
Wang et al[88]	2012	China	17/33	Retrospective	Hepatic resection	No significant difference in overall survival between the 17 patients who underwent liver resection alone 3-year survival rate 74.1%	1 patient underwent liver transplant and died 12 mo post-transplant

Table 4 Summary of liver transplant studies for hepatic hemangioepithelioma

Study	Year	Country	Liver transplant patients	Study Design	Reason for liver transplant	Outcome
Emamaullee et al[75]	2010	Canada	5/6 (1 patient did chemotherapy and surgical resection)	Retrospective	EHL (5/5), Recurrence (1/5)	1 patient had recurrence twice after two transplants but 2nd transplant resulted in stable disease. 1 patient had recurrence in less than 6 mo post-transplant and passed away less than 1 year post-transplant. 4 patients have stable disease post-transplant
Nudo et al[89]	2008	Canada	11/11	Retrospective	EHL	3/11 patients died (2 had recurrence while 1 died due to hepatic artery thrombosis). 4/11 patients had recurrence. 2/5 did surgical resection (both failed and 1/2 patients died at 61 mo post-resection while other patient did a second transplant and patient is still alive). 1/11 patients did radiotherapy. 1/11 patients assigned pegylated interferon and died 11 mo later
Rodriguez et al[69]	2007	United States	110/110	Retrospective	EHL	1/110 had operative death and 2/110 patients died within 30 d post-transplant. 1-year, 3-year, and 5-year overall survivals were 80%, 68%, and 64%, respectively. 31/110 were 5-year survivors. 38/110 patients died during follow-up. 12/38 patients died of recurrent EHL with distant involvement. 12/110 required re-transplantation including four patients who did a third transplant. For re-transplantation patients: 1-year, 3-year, and 5-year allograft survivals were 70%, 60%, and 55%, respectively
Mosoia et al[90]	2008	France	6/9	Retrospective	EHL	2/6 had recurrence and died (1 patient had recurrence and died at 56 mo while other patient had liver recurrence and died at 6 mo)
Lerut et al[58]	2007	France	59/59	Retrospective	EHL	Early (< 3 mo) and late (> 3 mo) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). 14 (23.7%) patients with recurrence after a median time of 49 mo (range, 6-98). 9 (15.3%) patients died of recurrence and 5 survived with recurrent disease. Disease-free survival rates at 1, 5, and 10 yr post-liver transplant are 90%, 82%, and 64%
Mehrabi et al[2]	2006	Germany	128/286	Review	EHL	The most common management has been liver transplantation (44.8% of patients), followed by no treatment (24.8%), chemotherapy or radiotherapy (21%), and liver resection (9.4%). The 1-year and 5-year patient survival rates were 96% and 54.5%, respectively, after liver transplant; 39.3% and 4.5%, respectively, after no treatment, 73.3% and 30%, respectively, after chemotherapy or radiotherapy; and 100% and 75%, respectively, after liver resection
Jung et al[70]	2016	Korea	2/8	Retrospective	EHL	One patient died from tumor recurrence at 9 mo and the other is alive after 5 years without recurrence
Cardinal et al[91]	2009	United States	17/25	Retrospective	EHL	Mean survival of 172 (124-220) mo in the liver transplant group
Abdoh et al[71]	2017	Finland	1	Retrospective	EHL	Recurrence after 1 month and died 1 month later
Grotz et al[57]	2010	United States	11/30	Retrospective	EHL	1-, 3- and 5-year overall survival of 91%, 73% and 73% and a disease free survival of 64%, 46% and 46% respectively

EHL: Hepatic hemangioepithelioma.