Tuberous Sclerosis Complex Lymphangioleiomyomatosis Research Articles

Metabolic signatures of lymphangioleiomyomatosis in biofluids: nuclear magnetic resonance (NMR)-based metabonomics of blood plasma: a case-control study.

Our aim was to analyze and compare the characteristics and differences of blood metabolites between lymphangioleiomyomatosis (LAM) patients and healthy controls, in order to find biomarkers that can be used for the diagnosis and classification of LAM. Between January 2020 to January 2022, 61 eligible LAM patients [51 sporadic LAM (S-LAM) and 10 tuberous sclerosis complex LAM (TSC-LAM)] from the First Affiliated Hospital of Guangzhou Medical University and 30 healthy controls were enrolled. Blood samples were taken for nuclear magnetic resonance (NMR) detection. Data analysis was performed by the umbrella program, and Wilcoxon analysis was used for comparisons between groups. The difference indicators were modeled by logistic regression. Diagnostic accuracy of the best predictive parameters was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), and the sensitivity and specificity were calculated. The indexes differed between LAM patients and healthy controls, S-LAM patients and healthy controls, and between TSC-LAM patients and healthy controls. There were two different metabolic indexes between S-LAM and TSC-LAM patients. After logistic regression modeling and ROC analysis, methionine (AUC =0.929, sensitivity =73.8%, specificity =100%, cut-off value =0.011 mmol/L) and acetic acid (AUC =0.966, sensitivity =95.1%, specificity =90%, cut-off value =0.006 mmol/L) had the highest diagnostic efficiency in LAM patients, and could be used to distinguish between affected and healthy people. Methionine was significantly associated with pneumothorax (P<0.05), and creatinine was significantly correlated with hysteromyoma (P<0.05). Methionine and acetic acid in the plasma of LAM patients are potential biomarkers. Methionine was also associated with pneumothorax in LAM patients. Also, acetone and creatinine were promising metabolic markers to distinguish S-LAM from TSC-LAM. NMR as a new non-invasive diagnostic method had a good discriminatory power for LAM.

Clinical features and outcomes of male patients with lymphangioleiomyomatosis: A review.

Lymphangioleiomyomatosis (LAM) is a rare disease involving multiple systems, which is divided into sporadic LAM (S-LAM) and tuberous sclerosis complex-LAM, mostly affecting women who are in childbearing age stage. Data on male patients are limited and scattered. Therefore, it is necessary to conduct a systematic review to investigate the clinical features, diagnosis, treatment, and outcomes of LAM in male. We performed a literature review by searching for all the published reported cases of LAM in male during the past 35 years (April 1986-October 2021). 36 male patients described in 26 references were included in this article. The median age of onset was 34 years (interquartile range: 1-79). The most common initial manifestations were cough, dyspnea, respite, and hemoptysis, with pulmonary complications such as pneumothorax and chylothorax. Five patients (13.9%) were asymptomatic at admission. Nearly half of the 36 male patients had thin-walled air-filled cysts that were visible throughout both lungs. Considering the abovementioned atypical clinical features, misdiagnosis was committed in 8 patients (22.2%). In addition, patients with tuberous sclerosis complex lymphangioleiomyomatosis often have no pulmonary manifestations at onset but present multiple extrapulmonary manifestations and have higher rates of renal angiomyolipomas than patients with S-LAM (P < 0.01). Eventually, 4 patients with S-LAM eventually died. Physicians should increase the awareness of LAM in male. Early monitoring of various systems should be recommended to ensure early management and active follow-up. Tuberous sclerosis complex patients should immediately be tracked for the onset of LAM disease to improve prognosis.

Total pleural coverage followed by lung transplantation in patient with lymphangioleiomyomatosis

Tuberous sclerosis complex lymphangioleiomyomatosis (TSC-LAM) is a rare disease, which may develop an intractable pneumothorax. Chemical or mechanical pleurodesis is a general management to prevent recurrence of pneumothorax, rendering it difficult to later dissect the pleura and control intraoperative bleeding. Since total pleural coverage (TPC) alternative to pleurodesis has been firstly reported by Kurihara et al. (Jpn J Thorac Cardiovasc Surg 54:274, 2006), TPC was performed in case of a 46-year-old female with a secondary spontaneous pneumothorax caused by TSC-LAM and followed by lung transplantation. Final pathological report showed the reinforced visceral pleura in the absence of dense adhesions.

PD17-01 EVEROLIMUS FOR RENAL ANGIOMYOLIPOMA ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX: EXIST-2 LONG-TERM EFFICACY AND SAFETY

You have accessJournal of UrologyKidney Cancer: Localized II1 Apr 2014PD17-01 EVEROLIMUS FOR RENAL ANGIOMYOLIPOMA ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX: EXIST-2 LONG-TERM EFFICACY AND SAFETY John Bissler, J. Christopher Kingswood, Elzbieta Radzikowska, Bernard A. Zonnenberg, Michael Frost, Matthias Sauter, Norio Nonomura, Susanne Brakemeier, Petrus J. de Vries, Scott Segal, Oezlem Anak, Severine Peyard, and Klemens Budde John BisslerJohn Bissler More articles by this author , J. Christopher KingswoodJ. Christopher Kingswood More articles by this author , Elzbieta RadzikowskaElzbieta Radzikowska More articles by this author , Bernard A. ZonnenbergBernard A. Zonnenberg More articles by this author , Michael FrostMichael Frost More articles by this author , Matthias SauterMatthias Sauter More articles by this author , Norio NonomuraNorio Nonomura More articles by this author , Susanne BrakemeierSusanne Brakemeier More articles by this author , Petrus J. de VriesPetrus J. de Vries More articles by this author , Scott SegalScott Segal More articles by this author , Oezlem AnakOezlem Anak More articles by this author , Severine PeyardSeverine Peyard More articles by this author , and Klemens BuddeKlemens Budde More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1508AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives To assess the long-term efficacy and safety of everolimus, an oral mTOR inhibitor, for the treatment of renal angiomyolipoma associated with either tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). Methods EXIST-2 (NCT00790400), a randomized, double-blind, phase 3 trial, assessed the efficacy and safety of everolimus for the treatment of renal angiomyolipoma associated with either TSC or sporadic LAM. A total of 118 patients (median age, 31 years [range, 18-61]) who had renal angiomyolipoma associated with TSC (n=113) or sporadic LAM (n=5) were randomly assigned (2:1) to 10 mg/day everolimus (n=79) or placebo (n=39). Angiomyolipoma response rate (primary end point) was defined as the proportion of patients with confirmed ≥50% reduction in the sum of volumes of all target angiomyolipoma relative to baseline in the absence of kidney increase (>20% from nadir), no new angiomyolipoma lesions, and no angiomyolipoma-related bleeding of ≥ grade 2. Adverse events (AEs) were monitored at every visit. Results Everolimus was superior to placebo for the primary end point, renal angiomyolipoma response rate (42% vs 0%; P<0.0001; original data cutoff, 6/30/2011). Following positive results for the original cutoff, placebo patients were offered open-label everolimus in the study extension phase. As of 5/1/2013, 112 patients received ≥1 dose of everolimus, and the median duration of exposure was 29 months (range, 0.5-46). The angiomyolipoma response rate was 54% (95% confidence interval, 44-63). AEs were similar to those at the original cutoff and continued to be grade 1 or 2. The most frequent grade 3 AEs were blood phosphorus decreased (4%) and amenorrhea (3%). Individual grade 4 AEs occurred in <2% of patients; they were blood uric acid increase (n=2), convulsion, hydrocephalus, hypertensive crisis, neutropenia, pancreatic carcinoma, and rhabdomyolysis (n=1 each). The most common AEs reported in ≥20% of patients were nasopharyngitis and stomatitis (43% each), headache, acne and hypercholesterolemia (30% each), urinary tract infection (28%), aphthous stomatitis (26%), and cough (21%). Hemorrhages were seen in 34 patients (30%), with the most frequently (≥5%) reported AEs being epistaxis (10%), menorrhagia (8%), and vaginal hemorrhage unrelated to normal menstruation (7%). Of note, there were no renal hemorrhages in patients taking everolimus. Conclusions Everolimus continued to reduce angiomyolipoma volume with no new safety concerns. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e540 Advertisement Copyright & Permissions© 2014MetricsAuthor Information John Bissler More articles by this author J. Christopher Kingswood More articles by this author Elzbieta Radzikowska More articles by this author Bernard A. Zonnenberg More articles by this author Michael Frost More articles by this author Matthias Sauter More articles by this author Norio Nonomura More articles by this author Susanne Brakemeier More articles by this author Petrus J. de Vries More articles by this author Scott Segal More articles by this author Oezlem Anak More articles by this author Severine Peyard More articles by this author Klemens Budde More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Unilateral Lymphangioleiomyomatosis

Pulmonary involvement in tuberous sclerosis complex (TSC) resembles lymphangioleiomyomatosis (LAM) in its clinical, radiologic, and histopathological features. Typical high-resolution computed tomography (HRCT) findings are of bilateral thin-walled cysts symmetrically throughout both lungs, with associated increase in lung volumes. Atypical cases have been described; and we report a case of biopsy proven, focal unilateral disease. The presence of nodules has been reported in association with TSC that histologically are composed of proliferated type II pneumocytes. We discuss other atypical cases of TSC and sporadic LAM and review current concepts of the pathogenesis of the 2 diseases, with reference to our case.

Extrapulmonary Lymphangioleiomyomatosis and Lymphangiomatous Cysts in Tuberous Sclerosis Complex

To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LAM) in the tuberous sclerosis complex (TSC). We retrospectively reviewed institutional medical records since 1940 to identify patients with TSC and extrapulmonary LAM. Of 403 patients with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitoneal lymphangiomatous cysts. The clinical, imaging, and histologic features of these three patients were summarized, including analysis of biopsy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. The three young women had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent history of contraceptive use. All three patients had intra-abdominal lymphangiomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and uterine biopsy specimens demonstrated positive immunostaining for melanoma-related antigens and expression of estrogen and progesterone receptors by ligand-binding assay and immunohistology. Cells cultured from LAM tissue of one of the patients exhibited a mitogenic response to estradiol. Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this disease who also have pulmonary LAM. The clinical features of these patients confirm the importance of sex steroids in the development of these lesions. Immunohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction.