In this relatively large series of patients with hepatic cavernous hemangioma, we found that in most cases the disease had a benign course. The pain at presentation seemed to be more common in those with accompanying GI disease, especially IBS, but large tumors were more likely to cause persistent pain later during follow-up.
Among our patients 58% had abdominal pain at baseline, and in 50% of cases this pain was the reason for referral which led to the diagnosis of liver hemangioma. However, in only 12.6% of the cases could the pain be attributed to the hemangioma; in the other patients, other GI diseases, especially IBS and peptic ulcer disease, were also present. IBS was also a determinant of persistent abdominal pain in our patients. Other studies of hepatic cavernous hemangioma have also reported that the majority of patients have other causes for abdominal pain.[1
] In a study by Farges and colleagues [14
], pain disappeared in 54% of patients after treatment of associated disorders, and in 4 out of 11 patients, pain persisted even after tumor resection. In this series, pain also diminished in many patients even in the absence of any specific treatment. When no other reason is found for symptoms in patients with hepatic hemangiomas, pain is thought to be present as a result of infarct and necrosis of the tumor[22
] or the result of the tumor pressing on the liver capsule or adjacent organs.[10
] The latter is especially important in large tumors and left-lobe lesions.[14
] In our study, although lesion size was not associated with pain at the start of the study, patients who experienced continued pain during follow-up had larger lesions. It is also interesting to notice that the main determinant of continued pain was the baseline size of the tumor, and not an increase in tumor size during follow-up. We think that at baseline most of the abdominal pain in our patients was caused by other GI diseases, and this masked any pain caused by the hemangioma. With the exception of IBS, pain from these other diseases was relieved by appropriate treatment, and then the effect of hemangioma size on pain became more evident.
Similar to previous studies, our patients showed a female predominance. The 2:1 female:male ratio in our study is lower than those reported in most earlier series, which were usually in the range of 5-6:1.[6
] However, a few other studies have also reported a 2:1 sex ratio.[8
] While some studies show that female sex hormones may play an important role in the pathogenesis of these tumors, the literature is inconclusive in this regard.[3
] Gemer et al., in a case-control study of 40 women with liver hemangiomas, reported that the disease was not associated with menstrual or reproductive history or oral contraception use.[23
] However, this study may have been underpowered to show such associations. In a larger study by Glinkova and colleagues, 94 women with 181 hemangiomas were followed for an average of 7.3 years.[4
] They concluded that both exogenous and endogenous sex hormones may influence hepatic hemangimatosis, although significant enlargement was relatively uncommon even in patients receiving hormone therapy. In our patients, pregnancy history or estrogen use had no significant effect on lesion progression or symptoms during follow-up.
Cavernous hemangiomas of the liver usually follow a benign and non-progressive course.[1
] In most studies, these tumors show little change in size during follow–up, and are rarely complicated.[24
] In our patients the average size of their lesions did not change significantly during their 3.2 year follow-up period. On the other hand, 35% of the lesions with more than one sonography did show some degrees of size increase which is higher than the 10-13% enlargement rates reported in other series [14
]. It is believed that dilatation or ectasia of the vascular channels, and not than proliferation of endothelial cells, is the main reason for the enlargement of these lesions.[25
] Glinkova and colleagues[4
] reported a 12.7% increase in size. Similar to our study, they found an inverse association between hemangioma number and the likelihood of progression (OR=0.27; p=0.006). We didn’t find any association between size increase and symptoms.
We found a resection rate of 7% in our series. Different studies have reported resection rates from 3.2% to 45% for cavernous hemangioma.[14
] Many previous series have come from surgical centers, where patients had been referred because of progressive disease, and this may have led to results biased in favor of more advanced, symptomatic disease and treatment by surgical resection.[14
] In contrast, our study was conducted in the setting of a general hepatology clinic, thus giving a better insight into the natural history of patients seen in non-surgical settings. It is also important to note that our study was not conducted in hospital setting, so its findings should be closer to that of the everyday experience of most internists and hepatologists.
One limitation of our study was that many of our patients could not be followed or had incomplete information, due to the retrospective nature of the study. Most of the other studies published about cavernous hemangimatosis of the liver have this same limitation.
The usual approach for cavernous hemangiomatosis of the liver is conservative management, and there are only a few indications for surgery, such as complicated or symptomatic lesions or diagnostic uncertainty.[1
] Previous series have reported that symptoms persist post-operatively in many of patients, irrespective of the exact surgical methods.[19
] Also, in three of our patients, we observed recurrence of the hemangioma following tumor resection. Risk of surgical complications appears to be related to the hemangioma size and not the technique used, and thus the indications for surgery must be carefully weighed for each individual.[16
In conclusion, our study confirms previous findings about the benign and non-progressive nature of hepatic cavernous hemangiomas. It also shows that many of the symptoms in patients with these tumors, especially abdominal pain, are attributable to accompanying GI diseases, especially IBS, and lesion growth alone does not often cause symptoms. Later during the course of the disease, patients with a single giant hemangioma are more likely to have persistent pain, and single lesions are more likely to grow in size, so they must be followed up for any remarkable change in disease course. Neither abdominal pain nor lesion size alone warrant surgical intervention.