Efficacy and safety of sirolimus treatment for intractable lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)

Ozeki, Michio; Asada, Ryuta; Saito, Akiko; Hashimoto, Hiroya; Fujimura, Takumi; Kuroda, Takeshi; Ueno, Shinji; Watanabe, Shôji; Nosaka, Shunsuke; Miyasaka, Mikiko; Umezawa, Akihiro; Matsuoka, Katsuyoshi; Maekawa, Takanobu; Yamada, Yasuaki; Fujino, Akihiro; Hirakawa, Satoshi; Furukawa, Taiji; Tajiri, Tatsuro; Kinoshita, Yoshiaki; Souzaki, Ryota; Fukao, Toshiyuki

doi:10.1016/j.reth.2018.12.001

Cited by 31 publications

(27 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Before administering sirolimus, zoledronic acid, interferon, or propranolol were given, indicating that the current therapeutic protocols are not uniform (Table 2). In addition to cases listed in Table 1, Ricci et al [23] and Ozeki et al [24] reported eight cases treated with sirolimus but did not provide clinical histories of these cases. Six of the eight cases responded well to sirolimus.…”

Section: Discussionmentioning

confidence: 99%

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature

Tian

Wang

et al. 2020

BMC Musculoskelet Disord

View full text Add to dashboard Cite

Background: Gorham-Stout disease (GSD) is a rare disease characterized by bone lesions and osteolysis. Therapy usually involves surgical resection. Sirolimus (Rapamycin) is used in some patients with GSD but the efficacy and safety of Sirolimus remains unclear. We propose that Sirolimus may be a novel therapeutic for GSD and present a case and review of literature that supports this. Case presentation: We presented a 1-year-old boy with GSD involving osteolysis of the right humerus with fracture of the left femur complicated by an effusion in the right pleural cavity. X-rays showed osteolysis in the right clavicle. A large pleural effusion was observed on the right-side, and the left lung was significantly compressed. Xrays also showed a fracture of the left femur. A femoral biopsy was performed that showed necrotic tissue in the cortical bone and a large number of irregularly shaped capillaries that proliferated within the necrotic tissue. Dilated lymphatic vessels were seen adjacent to the cortex, with fibrous tissue hyperplasia. We prescribed sirolimus, which is an oral mTOR inhibitor, for two consecutive years. The boy recovered well without other progressive bone lesions and participates in normal daily activities. His growth and development are the same as that of his peers. Discussion and conclusion: Gorham-Stout disease is a rare and enigmatic disease characterized by the presentation of an intraosseous lymphatic anomaly (LM), which results in progressive bone resorption. Based on this case report and a literature review, we conclude that sirolimus may be an effective alternative medication for GSD.

show abstract

Section: Discussionmentioning

confidence: 99%

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature

Tian

Wang

et al. 2020

BMC Musculoskelet Disord

View full text Add to dashboard Cite

show abstract

“…1) Localized macrocystic LMs are effectively treated with sclerotherapy with sclerosing agents (doxycycline, OK432, ethanol, bleomycin, sodium tetradecyl sulfate), those involving the skin and mucosa may be treated with PDL, and those that are complicated or extensive can be treated with sirolimus alone or in combination with sclerotherapy. 3,5,8,27,[55][56][57] AVMs are direct connections of arteries to veins that bypass the capillary bed. [2][3][4][5]7,8) AVMs of the skin are very rare, present as reddish-pink patches progressing to a deep red color with skin thickening, and can be diagnosed by arterial palpation.…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

Update on infantile hemangioma

Jung

2021

Clin Exp Pediatr

View full text Add to dashboard Cite

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5-10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age.High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a non-selective betaadrenergic antagonist, is the first-line treatment for IHs at a dosage of 2-3 mg/kg/day divided into two daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical non-selective beta-blocker, may be used for small superficial type IHs at a dosage of 1-2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.

show abstract

“…mTOR is an important kinase in the progression of the cell cycle. The net result is immune suppression by inhibition of lymphocytes and decreased lymphangiomatous invasion by inhibition of lymphangiogenic growth factors (33,34). The betablocking agent propranolol has also been reported as therapeutic option for Gorham-Stout disease, possibly through lowering of VEGF-A levels (35).…”

Section: Treatmentmentioning

confidence: 99%

A Large Skull Defect Due to Gorham-Stout Disease: Case Report and Literature Review on Pathogenesis, Diagnosis, and Treatment

et al. 2020

View full text Add to dashboard Cite

A 24-year old man was referred to the Erasmus MC Bone Center because of an asymptomatic increasing skull defect of the left parietal bone. The defect was first noticed at the age of six, and gradually increased over the years. His medical history was unremarkable, without any known trauma and a negative family history for bone diseases. Laboratory tests showed a low vitamin D level without other abnormalities. Particularly, there was no increase in markers of inflammation or bone turnover. CT-scans of the skull showed an osteolytic region of the parietal skull bone, with a two-centimeter increase in diameter over 9 years. Contrast enhanced MRI showed lymphangiogenic invasion, which was compatible with our suspicion of Gorham-Stout disease. The patient was referred to the neurosurgeon for treatment with a bone graft while considering additional drug treatment. Gorham-Stout or vanishing bone disease is a rare entity characterized by progressive osteolysis with lymphangiogenic bone invasion. Although already reported in 1838, currently the diagnosis and treatment of Gorham-Stout disease is still challenging. The underlying pathophysiology is not clarified yet and several theories exist. The disease usually affects persons younger than 40 years and the majority present with bone disease of the maxillofacial region, the upper extremities or the torso. The clinical presentation includes most frequently pain, swelling, and functional impairment of the affected region, but the disease can also be asymptomatic. Laboratory investigations are usually normal, and diagnosis is based upon imaging and sometimes pathology examination of affected bone tissue. Treatment is experimental and there is no general consensus about the best option due to lack of randomized controlled trials. Case reports showed patients treated with bisphosphonates, interferon-alpha, anti-VEGF therapy, mTOR inhibitors, and radiotherapy. There are some reports of surgery with prosthetic or bone grafts but no long-term follow-up data exist. This paper describes a unique case of Gorham-Stout disease of the parietal skull bone and discusses the current state of knowledge about this rare bone disease.

show abstract

Efficacy and safety of sirolimus treatment for intractable lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA)

Cited by 31 publications

References 15 publications

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature

Update on infantile hemangioma

A Large Skull Defect Due to Gorham-Stout Disease: Case Report and Literature Review on Pathogenesis, Diagnosis, and Treatment

Contact Info

Product

Resources

About