title: Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations.
abstract: OBJECTIVE
  Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).
  
  
  METHODS
  We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus.
  
  
  RESULTS
  After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma.
  
  
  CONCLUSIONS
  Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.
authors.affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Carolina Salim Gonçalves
authors.initials: CS
authors.lastname: Freitas
authors.affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Bruno Guedes
authors.initials: BG
authors.lastname: Baldi
authors.affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Mariana Sponholz
authors.initials: MS
authors.lastname: Araújo
authors.affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Glaucia Itamaro
authors.initials: GI
authors.lastname: Heiden
authors.affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Ronaldo Adib
authors.initials: RA
authors.lastname: Kairalla
authors.affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Carlos Roberto Ribeiro
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018192:Lymphangioleiomyomatosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus