April 2020 HSC Section 4 - Plastic and Reconstructive Problems

Management of Lymphatic Malformations

Surgery Up until the advent of sclerotherapy, surgery formed the mainstay of treatment. High recurrence rates led to the search for alternative treatments as well as a better under- standing of the nature of the disease. It is now known that macrocystic cervical lesions respond well to surgery and in most cases can be completely excised, whereas the likelihood of complete excision of a microcystic cervicofacial lesion is extremely low and therefore the risk of recurrence is high. 25,26 A meta-analysis found that surgical recurrence rates are around 30%, whereas the morbidity is between 2% and 6%. 27,28 Note that, to compare the results of surgery with sclerotherapy is in essence to compare the results of a single round of surgery with the results of multiple (up to 5) rounds of sclerotherapy. Despite this, there does not seem to be an appreciable difference in recurrence rates between the two modalities. Medical management Sildenafil After an initial encouraging report of a coincidental response in a patient and 2 subsequent patients, several studies were conducted, including a prospective cohort study. 29–32 However, the results of these studies have been mixed, with some showing improvement and some worsening. The use of sildenafil is currently still under investigation and, until further evidence warrants its use, the authors do not encourage its use in patients with LMs. Rapamycin (sirolimus) Sirolimus is an mTOR inhibitor and is commonly used as an immunosuppressive drug in transplant patients. 33 The mTOR pathway forms the basis for cell growth and proliferation. It increases the expression of vascular endothelial growth factor, thereby playing a part in the regulation of angiogenesis and lymphan- giogenesis. mTOR inhibitors block downstream protein synthesis and thereby have antitumoral as well as antiangiogenic activity. 34 Early reports using sirolimus for LMs have been encouraging. 6,35,36 More recently, Triana and colleagues 33 published a retrospective review of patients treated with sirolimus for vascular malformations. Eleven patients with LM were included in their series. All but 1 responded to treatment. Response was defined as shrinkage of the lesion and/or improvement of the symp- toms. No patients had a complete response. There are several issues that remain unresolved. Dosage of the drug has not been established. The duration of treatment is another issue. It seems that the duration of treatment is center specific. 33 Because many patients have been placed on “long- term sirolimus, the exact rebound rate is not known. The risk of lymphoma and skin cancer with long-term therapy in solid organ transplant patients is significant. 37 Will this also be a problem in children treated for LMs? Combined treatment Because no single modality provides a satisfactory result, most patients should be treated with multiple modalities. Surgical resection as a primary treatment can adequately dispense with large macrocystic lesions as well as significantly debulk large microcystic lesions. Any remaining disease can be treated with sclerotherapy. Bleomycin is currently being used to treat residual microcystic disease with some success. 38 Several rounds of sclerotherapy may be necessary to treat any persis- tent disease. The authors prefer surgery as a primary modality in order to reduce the volume of disease. Initial medical treatment can reduce the volume of disease and it can then be surgically removed. Once again, any residuum can be treated with sclerotherapy. However, no published data evaluating multimodal therapy exist.

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