sirolimus and Lymphangioma

Lymphatic malformations (LMs) are low-flow lesions resulting from abnormalities in the development of lymphatics. The management of these lesions is complex and involve the collaboration of many specialties. The purpose of this review is to summarize current knowledge regarding the different therapeutic options used in complex lymphatic malformations, analyzing their indications, efficacy and complications.. A search was made using the algorithm: "(lymphatic abnormality OR lymphatic malformation OR lymphangioma OR cystic hygroma) AND (extensive OR giant OR complex) AND (therapeutics OR treatment) AND (child OR children)". Of the 120 articles found, 53 were included.. Historically, surgery was the treatment of choice for this type of lesions. However, excision was often incomplete, associated with high rates of recurrence and severe complications. The use of sclerotherapy emerged as a minimal invasive option appropriate in selected cases as a single or adjuvant therapy. Inhibitors of the mammalian target of rapamycin, such as sirolimus, now play a central role in the treatment of complex malformations resistant to sclerotherapy, recurrent after surgery or more extensive malformations that affect vital structures. Other therapeutic options as sildenafil and laser ablation are also recognized as effective in selected cases.. Looking through the literature over the last decade authors realize that surgery had gradually been replaced by less invasive options such as sirolimus with or without adjuvant sclerotherapy. In conclusion, each treatment option seems to have its own indications and characteristics, which must be considered in therapeutic decision and individualized for each patient.

Topics: Child; Humans; Lymphangioma; Lymphatic Abnormalities; Pediatrics; Sclerotherapy; Sirolimus

Currently, there is no ideal management for orbital lymphatic malformations. Significant advances have been made since the discovery of new agents in the treatment. The purpose of this manuscript is to review the recent evidence on new sclerotherapy agents and systemic medications.. Traditional sclerosants are OK-432, sodium tetradecyl sulphate and ethanol. More recent developments are the use of doxycycline, bleomycin, and pingyangmycin. Sirolimus as a systemic medication has revolutionized the medical management of lymphatic malformations. Other oral drugs such as propranolol and sildenafil are controversial. Future treatment involves targeting lymphangiogenic pathways including inhibition of vascular endothelial growth factors and the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit.. The development of new agents allows multimodal management either as monotherapy or combined therapy to achieve better outcomes in this difficult to manage disease.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Bevacizumab; Bleomycin; Doxycycline; Humans; Immunosuppressive Agents; Lymphangioma; Orbital Neoplasms; Picibanil; Sclerosing Solutions; Sclerotherapy; Sirolimus

Lymphatic malformations (LMs) occur in 2.8 to 5 per 100,000 live births. Most involve the head and neck and they are equally common in men and women. They are developmental anomalies of unknown cause, although recent evidence suggests that an upregulation of the mammalian target of rapamycin (mTOR) pathway may be a causal factor leading to the overproduction of abnormal lymph vessels. These vessels are likely dilated lymphatic sacs sequestered from the lymphatic and venous systems. This overproduction results in the accumulation of lymph in dilated cystic spaces, which in turn results in the clinical features of an LM.

Topics: Combined Modality Therapy; Head and Neck Neoplasms; Humans; Lymphangioma; Magnetic Resonance Imaging; Sclerotherapy; Sildenafil Citrate; Sirolimus; Surgical Procedures, Operative; Treatment Outcome

Topics: Child; Humans; Immunosuppressive Agents; Lymphangioma; Lymphatic Abnormalities; Sirolimus

Lymphangioma is a known, but rare manifestation of Noonan syndrome. We present the case of disseminated and circumscribed cutaneous lymphangiomas in the context of Noonan syndrome. Oral rapamycin is a promising treatment in these extensive and morbidity-causing cases.

Topics: Administration, Oral; Adolescent; Antibiotics, Antineoplastic; Humans; Lymphangioma; Male; Noonan Syndrome; Penis; Scrotum; Sirolimus; Skin Neoplasms; Treatment Outcome

Topics: Administration, Cutaneous; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Endometrial Neoplasms; Female; Humans; Lymphangioma; Middle Aged; Radiotherapy; Sirolimus; Skin Neoplasms; Thoracic Wall; Vulvar Neoplasms

Topics: Humans; Lymphangioma; Lymphangiomyoma; Sirolimus; TOR Serine-Threonine Kinases

Microcystic lymphatic malformations are difficult to treat surgically, especially when located in the orbital apex. Recently, pharmacologic inhibition of the mTOR pathway by sirolimus was reported as a safe and efficacious treatment option for lymphatic malformations (also known as lymphangiomas). We report the case of a young male patient in which a unilateral, retrobulbar lymphatic malformation regressed to a large extent under treatment with 1 mg sirolimus given orally twice a day over a period of six months.

Topics: Administration, Oral; Antibiotics, Antineoplastic; Humans; Lymphangioma; Magnetic Resonance Imaging; Male; Orbital Neoplasms; Sirolimus; Treatment Outcome; Young Adult

Acquired progressive lymphangioma (benign lymphangioendothelioma) is a rare lymphatic anomaly of unclear pathogenesis. Excision is generally advised for local disease, although other therapies have been tried. This report describes a unique case of extensive acquired progressive lymphangioma involving the abdomen, genitalia, and lower extremity of a 1-year-old boy. Rapid progression and multisite involvement required exploration of nonsurgical options for management.

Topics: Diagnosis, Differential; Humans; Immunosuppressive Agents; Infant; Lymphangioma; Male; Sirolimus; Skin

Microcystic lymphatic malformation (MLM), also known as "lymphangioma circumscriptum," is a lymphatic malformation which may involve the skin and subcutaneous tissues. Progressive growth of lesions may cause pressure to the surrounding organs. Lesions frequently reoccur after treatment with surgery, sclerotherapy, radiotherapy, and laser therapy. In the last decades, oral sirolimus has been successfully used in lymphatic malformations. Since systemic treatment with sirolimus is associated with various side effects, topical form of the drug has been used with satisfying results, especially for the angiofibromas. Promisingly, few case studies indicate topical sirolimus as a potential treatment for the lymphatic malformations. Here, we report an 8-year-old girl with MLM on left trunk whose lesions recurred after the surgery that has been performed at 1 year of age. We administered twice daily topical sirolimus at 0.75 mg/ml concentration. After 2 weeks, a local irritation occurred and the dose was decreased to once daily. The treatment was stopped at the end of 3 months as the lesions were almost cleared and the patient did not want to continue to therapy. There were no new lesions after 8 months of follow up.

Topics: Administration, Cutaneous; Antibiotics, Antineoplastic; Child; Female; Humans; Lymphangioma; Sirolimus; Skin Neoplasms; Torso

Diffuse lymphangiomatosis is a rare disorder characterized by abnormal proliferation of lymphatic channels. It can involve just one organ or multiple organs, such as liver, spleen, lungs, and bone. This disorder generally presents in children and young adults, but in rare cases, patients first present with symptoms in adulthood. Here, we describe a 48-year-old HIV-positive man who presented with shortness of breath. Computed tomography scan revealed a large right-sided pleural effusion and a heterogeneously enhancing liver. Thoracentesis demonstrated a chylous effusion and subsequent liver biopsy revealed a proliferation of dilated lymphatics to establish a diagnosis of lymphangiomatosis.

Topics: Antirheumatic Agents; Bevacizumab; Cell Proliferation; HIV Infections; Humans; Lung; Lymphangioma; Lymphatic Vessels; Male; Middle Aged; Pleural Effusion; Propranolol; Sirolimus; Tomography, X-Ray Computed

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disease characterized by congenital and progressive vascular lesions of the skin and gastrointestinal tract that may be associated with thrombocytopenia and possibly life-threatening gastrointestinal bleeding. Reports published on the disease and treatment strategies are scarce. We present two cases of MLT treated with sirolimus.

Topics: Antibiotics, Antineoplastic; Female; Gastrointestinal Hemorrhage; Humans; Infant; Lymphangioma; Sirolimus; Skin; Skin Neoplasms; Thrombocytopenia

Lymphangiomas of the tongue are rare, and their treatment is problematic. A 10 year-old patient with tongue lymphangioma who was previously treated with surgery and propranolol with no response was treated with sirolimus in our department. We used sirolimus with a dose of 1.6 mg/m(2)/day. After 3 months of treatment, the mass had decreased by more than 60%. We continued the treatment for 1 year with a maximum response of 70% decrease in mass. Disease remained stable 6 months after stopping therapy, the latest time of follow-up. Sirolimus appears to be effective in lymphangioma but requires further study.

Topics: Adrenergic beta-Antagonists; Antibiotics, Antineoplastic; Child; Combined Modality Therapy; Humans; Lymphangioma; Male; Postoperative Complications; Propranolol; Sirolimus; Tongue Neoplasms; Treatment Outcome

Topics: Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphangioma; Male; Middle Aged; Sirolimus; Skin Neoplasms; Thigh

Topics: Adolescent; Antibiotics, Antineoplastic; Humans; Lymphangioma; Male; Sirolimus; Soft Tissue Neoplasms

Lymphangiomatosis is a rare and fatal congenital lymphatic malformation. Because the natural course of the disease affects multiple body systems, the management can be challenging. This article presents a novel approach to the treatment of diffuse lymphangiomatosis using sirolimus. The reported case involves a 4-month-old male with a known lymphatic malformation who presented to the emergency department with respiratory difficulties. Sirolimus was successful at significantly reducing our patient's mass at a relatively low target level of 5 to 10 μg/L. The use of sirolimus for the treatment of lymphangiomatosis should be studied further in the setting of a formal trial.

Topics: Antibiotics, Antineoplastic; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Infant; Lymphangioma; Lymphoma; Magnetic Resonance Imaging; Male; Sirolimus; Ultrasonography

Lymphatic complications are common side effects of mammalian target of rapamycin (mTOR) inhibitor-based immunosuppression in kidney transplantation. Therefore, we investigated whether the mTOR inhibitor rapamycin, besides its known antihemangiogenic effect, also impedes regenerative lymphangiogenesis. In a murine skin flap model, rapamycin impaired recovery of lymphatic flow across surgical incisions resulting in prolonged wound edema in these animals. Importantly, the antilymphangiogenic effect of rapamycin was not related to a general inhibition of wound healing as demonstrated an in vivo Matrigeltrade mark lymphangiogenesis assay and a model of lymphangioma. Rapamycin concentrations as low as 1 ng/ml potently inhibited vascular endothelial growth factor (VEGF)-C driven proliferation and migration, respectively, of isolated human lymphatic endothelial cells (LECs) in vitro. Mechanistically, mTOR inhibition impairs downstream signaling of VEGF-A as well as VEGF-C via mTOR to the p70S6 kinase in LECs. In conclusion, we provide extensive experimental evidence for an antilymphangiogenic activity of mTOR inhibition suggesting that the early use of mTOR inhibitor following tissue injury should be avoided. Conversely, the antilymphangiogenic properties of rapamycin and its derivates may provide therapeutic value for the prevention and treatment of malignancies, respectively.

Topics: Animals; Cell Movement; Cell Proliferation; Collagen; Drug Combinations; Endothelial Cells; Endothelium, Lymphatic; Immunosuppressive Agents; Laminin; Lymphangiogenesis; Lymphangioma; Mice; Mice, Inbred C57BL; Peritoneal Neoplasms; Phosphorylation; Protein Kinases; Proteoglycans; Ribosomal Protein S6 Kinases, 70-kDa; Sirolimus; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C