scholarly journals Management of adult tuberous sclerosis complex-related angiomyolipoma: A single-center experience

2021 ◽  
Vol 16 (5) ◽  
Author(s):  
Terry Li ◽  
Meghna Siddoji ◽  
Jen Hoogenes ◽  
Camilla Tajzler ◽  
Nikhita Singhal ◽  
...  
Keyword(s):  
Side Effects ◽  
High Risk ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Local Therapy ◽  
Mtor Inhibitors ◽  
Low Risk ◽  
Renal Angiomyolipoma ◽  
Single Center ◽  
Asymptomatic Patients

Introduction: Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disease. A significant cause of TSC-related morbidity is potential bleeding from renal angiomyolipoma (AML). To pre-emptively decrease AML bleeding, mTOR inhibitors can be used; however, thresholds for initiating and maintaining everolimus therapy remain uncertain. Recent literature suggests not triggering active treatment of AMLs based on size thresholds alone. We evaluated the appropriateness of initiating everolimus therapy in asymptomatic patients after considering AML size, rate of growth, and other factors. Methods: Diagnostic criteria developed by the 2012 International TSC Consensus Group and presence of AML were used as inclusion criteria. Medical and imaging reports of 20 TSC patients from a single center were reviewed. Results: Mean age was 40.55 (±16.27) and 11 patients were female. Eight asymptomatic patients at high risk for complications underwent everolimus therapy, of which seven (88%) demonstrated decreased AML size but multiple side effects were reported. Four high-risk asymptomatic patients did not undergo therapy due to side effect concerns, while four low-risk asymptomatic patients had stable AMLs under active surveillance. Four patients had reduced AMLs through local therapy. Conclusions: Everolimus treatment was effective for managing AML size in most high-risk asymptomatic patients with tolerable side effects. AML size can remain relatively stable for asymptomatic low-risk patients despite not receiving intervention(s). Patients with TSC-related AML can be safely managed with mTOR inhibitors like everolimus, with shared decision-making including factors such as bleeding risk, AML growth rate, and number and absolute size of AMLs.

Everolimus-induced near-resolution of giant cardiac rhabdomyomas and large renal angiomyolipoma in a newborn with tuberous sclerosis complex

2016 ◽  
Vol 26 (5) ◽  
pp. 1025-1028 ◽  
Author(s):  
Massimo Colaneri ◽  
Andrea Quarti ◽  
Marco Pozzi
Keyword(s):  
Side Effects ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Renal Angiomyolipoma ◽  
Cardiac Rhabdomyoma

AbstractWe report a case of a newborn, affected by tuberous sclerosis complex, with a prenatally diagnosed giant cardiac rhabdomyoma associated with a large renal angiomyolipoma presenting as a duct-depending lesion not treatable by surgery. After receiving everolimus, a mammalian target of rapamycin inhibitor, we observed a rapid, significant, and durable reduction of both lesions without remarkable side effects.

scholarly journals Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Janina Grau ◽  
Johann Philipp Zöllner ◽  
Susanne Schubert-Bast ◽  
Gerhard Kurlemann ◽  
Christoph Hertzberg ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Direct Cost ◽  
Nursing Care ◽  
Tuberous Sclerosis Complex ◽  
Indirect Costs ◽  
Mtor Inhibitors ◽  
Direct Costs ◽  
Driving Factors ◽  
Care Level ◽  
Organ Manifestations

Abstract Background Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. Methods A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany. Results The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7–21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088–5863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027–1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221–3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193–586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs. Conclusions This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

scholarly journals High-throughput screening of circRNAs reveals novel mechanisms of tuberous sclerosis complex-related renal angiomyolipoma

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Yang Zhao ◽  
Hao Guo ◽  
Wenda Wang ◽  
Guoyang Zheng ◽  
Zhan Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Regulatory Network ◽  
High Throughput Screening ◽  
Kidney Tissue ◽  
Cell Types ◽  
The Body ◽  
Differentially Expressed ◽  
Renal Angiomyolipoma

Abstract Objective Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. Methods Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. Results We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. Conclusion circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.

scholarly journals The effect of sirolimus on angiomyolipoma is determined by decrease of fat-poor compartments and includes striking reduction of vascular structures

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elieser Hitoshi Watanabe ◽  
Fernando Morbeck Almeida Coelho ◽  
Hilton Leão Filho ◽  
Bruno Eduardo Pedroso Balbo ◽  
Precil Diego Miranda de Menezes Neves ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Blood Vessels ◽  
Tuberous Sclerosis Complex ◽  
Hounsfield Unit ◽  
Mtor Inhibitors ◽  
Volume Reduction ◽  
Tumor Reduction ◽  
Vascular Structures ◽  
Remarkable Reduction

AbstractRenal angiomyolipomas hemorrhage is associated with their size and vascular constitution. The effects of sirolimus on different components of angiomyolipomas was analyzed in patients with tuberous sclerosis complex, sporadic lymphangioleiomyomatosis and multiple sporadic angiomyolipomas. Thirty angiomyolipomas from 14 patients treated with sirolimus were retrospectively evaluated. A Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. A median reduction of 100% (75 to 100) in the diameter of aneurysmatic/ectatic vascular structures was observed. Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels, revealing the likely mechanism responsible for the risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. These findings support the role of mTOR in the development of angiomyolipoma blood vessels.

scholarly journals RARE-25. RETINAL ASTROCYTOMA mTOR INHIBITOR THERAPY IN TUBEROUS SCLEROSIS MOSAICISM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii447-iii447
Author(s):  
Naomi Evans ◽  
Katherine Paton ◽  
Harinder Kaur Gill ◽  
Juliette Hukin
Keyword(s):  
Optic Nerve ◽  
Retinal Detachment ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Neovascular Glaucoma ◽  
Renal Angiomyolipoma ◽  
Gradual Reduction ◽  
Health Canada

Abstract INTRODUCTION Everolimus is an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), it is Health Canada and FDA approved for SEGA and renal angiomyolipoma in the setting of tuberous sclerosis complex (TSC). There is little data available in regards to this treatment of TSC associated retinal astrocytoma (RA). Although the behaviour of RA is often indolent or slowly progressive, aggressive behaviour with retinal detachment and neovascular glaucoma requiring enucleation has been reported in several patients. Definite TSC diagnosis is established when either two major features or one major and two minor features are present. Probable TSC diagnosis is established when one major plus one minor feature is present. METHODS We report a child with probable TSC mosaicism, with negative serum NGS for TSC but RA and retinal achromic patch on the left. A left retinal peripapillary astrocytoma around optic nerve and very close to fovea was noted. There was concern that if it grew or there were to be any leakage it would cause visual impairment. This lead to therapy with everolimus 4.5 mg/m2/d aiming for level between 5 and 10 mcg/L. RESULTS This boy has had a gradual reduction of the RA over the last 29 months, with healthy retina in the region no longer occupied by the lesion and preserved vision. He has tolerated therapy well with occasional mouth ulcers. CONCLUSION mTORC1 inhibition is effective therapy to preserve vision in the setting of retinal astrocytoma and tuberous sclerosis mosaicism.

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