sirolimus and Pleural-Effusion

BACKGROUND Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor, which is used in immunosuppressive treatment regimens in organ transplant recipients. Although mTOR inhibitors are well tolerated, their adverse effects have been reported. Sirolimus treatment in transplant recipients has been reported to be associated with lymphedema of the skin and subcutaneous tissues, and with pleural effusion, but edema of internal organs and organomegaly have not been previously reported. A case is presented lymphedema of the transplanted kidney and abdominal wall with ipsilateral pleural effusion following kidney biopsy in a patient treated with sirolimus. CASE REPORT A 32-year-old woman with a history of end-stage renal disease of unknown etiology had undergone right renal transplantation from an unrelated living donor, eight years previously. She was referred to our hospital with dyspnea, localized abdominal pain, and swelling of the transplanted kidney. The symptoms appeared following a kidney biopsy and the replacement of cyclosporin with sirolimus four months previously. On examination, she had localized swelling of the abdominal wall overlying the transplanted kidney, and a right pleural effusion. Hydronephrosis and nephrotic syndrome were excluded as causes of kidney enlargement. Following the withdrawal of sirolimus therapy her symptoms resolved within three months. CONCLUSIONS A case is described of lymphedema of the transplanted kidney and abdominal wall with ipsilateral pleural effusion following kidney biopsy attributed to her change in anti-rejection therapy to sirolimus. This case report should raise awareness of this unusual complication of sirolimus anti-rejection therapy and its possible effects on the lymphatic system.

Topics: Abdominal Wall; Adult; Biopsy; Female; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Lymphedema; Pleural Effusion; Sirolimus

Chylothorax can be a presenting symptom of complex lymphatic anomaly in children and is associated with significant respiratory morbidity. Historically, the traditional pharmacological treatment has been octreotide. There are several treatments that have been utilized in the past few years including sirolimus; however, data regarding their efficacy and outcomes is limited. Furthermore, sirolimus has proven efficacy in complex vascular malformations, and hence, its utility/efficacy in infantile primary chylous effusions warrants further investigation.. In this retrospective study at Texas Children's Hospital, data were extracted for all infants with chylothorax who were treated with sirolimus between 2009 and 2020. Details regarding underlying diagnosis, comorbidities, and number of days from sirolimus initiation to resolution of effusion were collected.. Initially a total of 12 infants were identified. Among them, seven patients had complete data and were included in the study. Reasons for chylous effusions include presumed complex lymphatic anomaly, generalized lymphatic anomaly, and complex congenital lymphatic anomaly. The mean duration of sirolimus treatment needed for chest tube removal was 16 days, with a median of 19 days and range of 7-22 days. No patients had progression of effusions while on sirolimus.. With close monitoring, sirolimus appears to be an effective therapy for pediatric lymphatic effusions even in critically ill infants. The study also demonstrates shorter duration of chest tube requirement after initiation of sirolimus compared to previous studies. Larger multi-institutional studies are needed to further support our findings.

Topics: Child; Chylothorax; Critical Illness; Humans; Infant; Lymphatic Abnormalities; Octreotide; Pleural Effusion; Retrospective Studies; Sirolimus

Topics: Adolescent; Biopsy; Bone Density Conservation Agents; Dyspnea; Exudates and Transudates; Humans; Imaging, Three-Dimensional; Male; Membrane Glycoproteins; Osteolysis, Essential; Pleural Effusion; Ribs; Sirolimus; Tomography, X-Ray Computed; Zoledronic Acid

A 34-year-old man presented to a community hospital with sudden-onset pleuritic chest pain on a background of a 12-month indolent history of progressive exertional dyspnea. He denied cough, fevers, night sweats, or weight loss. He reported some low back pain and ache. He had a history of gastroesophageal reflux and was a current smoker with a 20-pack year history. There were no known occupational or environmental exposures and there was no family history of any lung disease.

Topics: Adult; Antibiotics, Antineoplastic; Biopsy; Bone and Bones; Chest Pain; Chylothorax; Diagnosis, Differential; Humans; Immunohistochemistry; Lung Diseases; Lymphangiectasis; Male; Musculoskeletal Pain; Pleura; Pleural Effusion; Sirolimus; Thoracentesis; Tomography, X-Ray Computed; Treatment Outcome

Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women caused by proliferation of neoplastic-like LAM cells, with mutations in the TSC1/2 tumor suppressor genes. Based on case reports, levels of cancer antigen 125 (CA-125), an ovarian cancer biomarker, can be elevated in patients with LAM. We hypothesized that elevated serum CA-125 levels seen in some patients with LAM were due to LAM, not other malignancies, and might respond to sirolimus treatment.. Serum CA-125 levels were measured for 241 patients at each visit. Medical records were reviewed for co-morbidities, disease progression, and response to sirolimus treatment. CA-125 expression in LAM cells was determined by using immunohistochemical analysis.. Almost 25% of patients with LAM had at least one elevated serum CA-125 measurement. Higher serum CA-125 levels correlated with lower FEV. Higher serum CA-125 levels were associated with pleural effusions and reduced pulmonary function and were decreased with sirolimus therapy. LAM cells express CA-125. Some elevated serum CA-125 levels may reflect serosal membrane involvement.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; CA-125 Antigen; Disease Progression; Female; Humans; Immunohistochemistry; Immunosuppressive Agents; Lymphangioleiomyomatosis; Middle Aged; Pleural Effusion; Respiratory Function Tests; Sirolimus; Young Adult

Topics: Child, Preschool; Dyspnea; Female; Humans; Osteolysis; Osteolysis, Essential; Pleural Effusion; Radiography, Thoracic; Respiration; Respiratory Rate; Sirolimus; Skin

Lymphangioleiomyomatosis (LAM), a rare, multisystem disorder primarily affecting women of reproductive age, is characterized by cystic-appearing lung lesions, progressive loss of lung function, chylous effusions and renal angiomyolipomas. Sirolimus, an mammalian target of rapamycin inhibitor, has been shown to stabilize lung function, reduce symptoms and resolve chylous effusions in the short term for patients with LAM. Herein, we report a premenopausal female with LAM who experienced complete and durable resolution of her chylothoraces with significant and sustained improvement in lung function on sirolimus.

Topics: Adult; Antibiotics, Antineoplastic; Female; Humans; Lung Neoplasms; Lymphangioleiomyomatosis; Magnetic Resonance Imaging; Pleural Effusion; Sirolimus; Tomography, X-Ray Computed

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

Gorham-Stout disease (GSD) is a rare disease of unknown etiology characterized by vascular proliferation that produces destruction of bone matrix.. This case is about 43 year old woman who begins with pain in sternum, dyspnea, abdominal mass and, serous-hematic pleural effusion. Imaging tests were performed showing lesions on 6. treatment was initiated with sirolimus achieving remission of the disease after the first month; however, because the presence of metrorrhagia the treatment was discontinued, reappearing symptoms afterwards. For that reason the treatment was restarted getting disappearance of the symptoms again, 4 weeks later.. we present the first clinical cases of EGS with pleural effusion with response to sirolimus treatment that could be an alternative to the current therapy.. La enfermedad de Gorham-Stout (EGS), es una enfermedad poco común, de etiología desconocida, caracterizada por la proliferación vascular que produce destrucción de la matriz ósea.. Se presenta el caso de mujer de 43 años que comienza con dolor en el esternón, disnea y tumoración abdominal junto con derrame pleural izquierdo de características serohemáticas como forma de presentación de una EGS. En pruebas de imagen que mostraron lesiones líticas en el 6º y 10º arcos costales izquierdos. Posteriormente se realizó toracotomía con biopsia pulmonar, pleural y costal observándose ausencia del extremo de la 6ª costilla. En el estudio histopatológico se describe proliferación vascular linfática en tejido óseo de pared costal. Se excluyeron otras patologías y se diagnosticó EGS.. Se inició tratamiento con sirolimus consiguiendo remisión completa desde el primer mes. Sin embargo, tras la suspensión del tratamiento por metrorragias, presentó reaparición de los síntomas. Se decide entonces reiniciar el tratamiento, consiguiendo nuevamente desaparición de los síntomas, tras 4 semanas de tratamiento.. Se presenta el primer caso clínico de EGS en edad adulta con derrame pleural asociado y con respuesta clínica a sirolimus, fármaco que podría ser una alternativa a la terapéutica actual.

Topics: Adult; Female; Humans; Immunosuppressive Agents; Osteolysis, Essential; Pleural Effusion; Sirolimus; Treatment Outcome

The aim of this study was to report on sirolimus activity in a series of patients with hemangioendothelioma (HE) treated at the National Cancer Institute, Milan (Istituto Nazionale Tumori; INT) and within the Italian Rare Cancer Network ("Rete Tumori Rari"; RTR).. We retrospectively reviewed patients with advanced and progressing epithelioid hemangioendothelioma (EHE) treated with sirolimus at the INT and/or within the RTR. Pathologic review and molecular analysis for WWTR1 rearrangement were performed. Sirolimus was administered until unacceptable toxicity or progression, with the dose being adjusted to reach target plasma levels of 15-20 ng/dL. Responses were assessed using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria.. Since 2005, 18 patients (17 EHE, 1 retiform HE; 1 locally advanced, 17 metastatic; WWTR1 rearrangement: 16) have been identified, with 17/18 patients being evaluable for response. Mean sirolimus daily dose was 4.5 mg. According to RECIST, best responses in EHE were 1 partial response (PR), 12 stable disease (SD), and 3 progressive disease (PD); the patient with retiform HE also achieved a PR, lasting >2 years. Four patients with a reversed interval progression on interruption were observed. Median overall survival was 16 months, and median progression-free survival was 12 months (range 1-45), with four patients progression-free at 24 months. The clinical benefit (complete response [CR] + PR + SD >6 months) was 56 %. Seven patients receiving sirolimus experienced an increase in pleural/peritoneal effusion plus worsening of tumor-related symptoms; six of these patients died within 1-8 months from evidence of effusion progression, while a RECIST PD was assessed in two of seven patients.. A clinical benefit was achieved in 56 % of patients receiving sirolimus, which lasted >24 months in four patients. Most patients with pleural effusion did not benefit from sirolimus and had a poor outcome.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Ascitic Fluid; Databases, Factual; Disease Progression; Disease-Free Survival; Gene Rearrangement; Hemangioendothelioma, Epithelioid; Humans; Intracellular Signaling Peptides and Proteins; Italy; Male; Middle Aged; Pleural Effusion; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Sirolimus; Survival Rate; Trans-Activators; Transcription Factors; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Treatment Outcome; Young Adult

Generalized lymphatic anomaly (GLA) is a rare and often fatal congenital lymphatic disorder that also commonly affects bone. Kaposiform lymphangiomatosis (KLA) is a novel subtype of GLA with poor prognosis and no proper treatment guidelines. A 9-year-old male with recurrent pleural effusion was clinically diagnosed as KLA. Following sirolimus therapy at a dose of 0.8 mg/m(2) twice daily, pleural effusion was significantly decreased and the general status of the patient markedly improved. The clinical course indicates that sirolimus may present an effective therapeutic option in KLA. Moreover, KLA should be considered in differential diagnosis for cases of GLA with coagulopathy.

Topics: Antibiotics, Antineoplastic; Child; Hemangioendothelioma; Humans; Kasabach-Merritt Syndrome; Male; Pleural Effusion; Prognosis; Sarcoma, Kaposi; Sirolimus

Topics: Adult; Antibiotics, Antineoplastic; Cell Proliferation; Chyle; Female; Humans; Immunosuppressive Agents; Lung; Lung Neoplasms; Lymphangioleiomyomatosis; Middle Aged; Muscle, Smooth; Pleural Effusion; Radiography; Sirolimus

Lymphangioleiomyomatosis (LAM) is a disorder that affects women and is characterized by cystic lung destruction, chylous effusions, lymphangioleiomyomas, and angiomyolipomas. It is caused by proliferation of abnormal smooth muscle-like cells. Sirolimus is a mammalian target of rapamycin inhibitor that has been reported to decrease the size of neoplastic growths in animal models of tuberous sclerosis complex and to reduce the size of angiomyolipomas and stabilize lung function in humans.. To assess whether sirolimus therapy is associated with improvement in lung function and a decrease in the size of chylous effusions and lymphangioleiomyomas in patients with LAM.. Observational study.. The National Institutes of Health Clinical Center.. 19 patients with rapidly progressing LAM or chylous effusions.. Treatment with sirolimus.. Lung function and the size of chylous effusions and lymphangioleiomyomas before and during sirolimus therapy.. Over a mean of 2.5 years before beginning sirolimus therapy, the mean (±SE) FEV1 decreased by 2.8%±0.8% predicted and diffusing capacity of the lung for carbon monoxide (Dlco) decreased by 4.8%±0.9% predicted per year. In contrast, over a mean of 2.6 years of sirolimus therapy, the mean (±SE) FEV1 increased by 1.8%±0.5% predicted and Dlco increased by 0.8%±0.5% predicted per year (P<0.001). After beginning sirolimus therapy, 12 patients with chylous effusions and 11 patients with lymphangioleiomyomas experienced almost complete resolution of these conditions. In 2 of the 12 patients, sirolimus therapy enabled discontinuation of pleural fluid drainage.. This was an observational study. The resolution of effusions may have affected improvements in lung function.. Sirolimus therapy is associated with improvement or stabilization of lung function and reduction in the size of chylous effusions and lymphangioleiomyomas in patients with LAM.. Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health.

Topics: Adult; Angiomyolipoma; Antibiotics, Antineoplastic; Cell Proliferation; Chyle; Female; Humans; Immunosuppressive Agents; Lung; Lung Neoplasms; Lymphangioleiomyomatosis; Lymphangiomyoma; Middle Aged; Muscle, Smooth; Observation; Pleural Effusion; Respiratory Function Tests; Sirolimus; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases

Topics: Airway Obstruction; C-Reactive Protein; Calcineurin Inhibitors; Dose-Response Relationship, Drug; Female; Humans; Hypoproteinemia; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Pleural Effusion; Sirolimus; Tomography, X-Ray Computed; Treatment Outcome