title: Sirolimus Therapy for Patients With Lymphangioleiomyomatosis Leads to Loss of Chylous Ascites and Circulating LAM Cells.
abstract: A young woman received a diagnosis of abdominal, sporadic lymphangioleiomyomatosis (LAM) and multiple abdominal lymphangioleiomyomas and was referred for recurrent chylous ascites responding only to a fat-free diet. On admission, pulmonary function test (PFT) results showed a moderate reduction in the transfer factor for carbon monoxide with normal exercise performance. The serum vascular endothelial growth factor D (VEGF-D) level was 2,209 pg/mL. DNA sequences, amplified at loci kg8, D16S3395, D16S3024, D16S521, and D16S291 on chromosome 16p13.3, showed a loss of heterozygosity (LOH) only for kg8. Fat-free total parenteral nutrition in association with sirolimus (2 mg po daily) was initiated. Serum sirolimus levels were maintained at concentrations between 5 and 15 ng/mL. After 1 month, reintroduction of a low-fat oral feeding was achieved without recurrence of ascites. PFT results were stable. Interestingly, clinical improvement was associated with a reduction in the VEGF-D serum level (1,558 pg/mL). LOH at the kg8 biomarker in blood LAM cells was no longer detected.
authors: Unità di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors: Sergio
authors: S
authors: Harari
authors: Unità di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy. Electronic address: davide.elia@multimedica.it.
authors: Davide
authors: D
authors: Elia
authors: Unità di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors: Olga
authors: O
authors: Torre
authors: Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
authors: Elisabetta
authors: E
authors: Bulgheroni
authors: Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
authors: Elena
authors: E
authors: Provasi
authors: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors: Joel
authors: J
authors: Moss
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002915:Chylous Ascites / Q000178:diet therapy* / Q000209:etiology; D018752:Diet, Fat-Restricted; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D018192:Lymphangioleiomyomatosis / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D009360:Neoplastic Cells, Circulating; D010289:Parenteral Nutrition, Total; D011653:Pulmonary Diffusing Capacity; D012129:Respiratory Function Tests; D012186:Retroperitoneal Neoplasms / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017422:Sequence Analysis, DNA; D020123:Sirolimus / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D042643:Vascular Endothelial Growth Factor D / Q000097:blood
chemical_list: D000903:Antibiotics, Antineoplastic; C579459:VEGFD protein, human; D042643:Vascular Endothelial Growth Factor D; D020123:Sirolimus