1139 Everolimus for renal angiomyolipoma associated with tuberous sclerosis complex (TSC): EXIST-2 3-year follow-up

Tuberous sclerosis complex (TSC) is a rare disease that causes multisystem benign neoplasm, induced by dysregulation of the mammalian target of the rapamycin pathway (mTOR). This study aimed to examine the effects of continuous low-dose everolimus, a potent and selective inhibitor of mTOR, on the treatment of TSC-associated renal angiomyolipoma (AML). Between July 2013 and August 2017, 11 patients with TSC-AML were enrolled for an everolimus therapy protocol. An oral everolimus dose starting at 2.5 mg daily was gradually increased to 5.0 mg daily. All patients were evaluated using MRI or CT scanning at baseline, 12, 24, 36 and 48 months after the start of treatment for measuring changes of renal AML mass volume. Everolimus therapy resulted in significant shrinkage of TSC-AML volume after 48 months follow-up. Serum levels of everolimus were subdivided into group I (<8 ng/mL, n=6) and group II (>8 ng/mL, n=5). The volume reduction rates were 10.6%–65.2% in group I and 42.5%–70.6% in group II. To evaluate the response to treatment, three of six (50%) were responders in group I, and all the patients in group II (5/5, 100%) were responders. The differences in AML volume reduction between the groups were statistically significant at 12 months (p=0.011), 24 months (p=0006), 36 months (p=0.014) and 48 months (p=0.05). These results suggest that continuous low-dose everolimus therapy (2.5–5 mg daily) might be effective in shrinking TSC-AML volume and minimizes adverse effects and subsequent reducing medical costs.

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Rare variant of genetically confirmed tuberous sclerosis complex presenting with bilateral renal angiomyolipoma in Wünderlich syndrome

BMJ Case Reports ◽

10.1136/bcr-2021-243380 ◽

2021 ◽

Vol 14 (8) ◽

pp. e243380

Author(s):

Ramon Jr Bagaporo Larrazabal ◽

Harold Henrison Chang Chiu ◽

Dennis L Sacdalan

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Fluid Collection ◽

Well Being ◽

Renal Angiomyolipoma ◽

Abdominal Ct ◽

Once Daily ◽

Mass Size ◽

The Right

A 28-year-old woman came for non-traumatic right flank pain with hypotension and right flank mass. She had multiple hyperpigmented skin papules located on the centre area of her face, and angiomas on her toes. She was anaemic and had a blood transfusion on top of aggressive fluid resuscitation. Abdominal CT showed bilaterally enlarged kidneys and fluid collection in the right perirenal space (haemorrhage). The consideration was an angiomyolipoma in spontaneous perinephric haemorrhage. We considered tuberous sclerosis complex (TSC) and did genetic testing. Results revealed mutations in the TSC2 gene, consistent with the diagnosis of TSC. No immediate surgical plans were considered at that time. She opted to be discharged against medical advice and was scheduled for a close outpatient follow-up. The patient followed up after 2 weeks, already on sirolimus 2 mg once daily. She reported improved overall well-being and a decrease in the flank mass size.

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Long-term Follow-up Assessing Renal Angiomyolipoma Treatment Patterns, Morbidity, and Mortality: An Observational Study in Tuberous Sclerosis Complex Patients in the Netherlands

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2015.05.016 ◽

2015 ◽

Vol 66 (4) ◽

pp. 638-645 ◽

Cited By ~ 53

Author(s):

Marinus J.C. Eijkemans ◽

Willem van der Wal ◽

Leida J. Reijnders ◽

Kit C.B. Roes ◽

Sahar Barjesteh van Waalwijk van Doorn-Khosrovani ◽

...

Keyword(s):

The Netherlands ◽

Observational Study ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Treatment Patterns ◽

Renal Angiomyolipoma ◽

Complex Patients ◽

Long Term Follow Up

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

Human Genomics ◽

10.1186/s40246-021-00344-1 ◽

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.

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Efficacy and Safety of Sirolimus for Renal Angiomyolipoma in Patients with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis: A Systematic Review

The Journal of Urology ◽

10.1016/j.juro.2014.04.096 ◽

2014 ◽

Vol 192 (5) ◽

pp. 1424-1430 ◽

Cited By ~ 23

Author(s):

Zhu-feng Peng ◽

Lu Yang ◽

Ting-ting Wang ◽

Ping Han ◽

Zhen-hua Liu ◽

...

Keyword(s):

Systematic Review ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Renal Angiomyolipoma ◽

Efficacy And Safety

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

Neuro-Oncology ◽

10.1093/neuonc/noaa222.736 ◽

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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Renal angiomyolipoma in Birt-Hogg-Dube syndrome: A case study supporting overlap with tuberous sclerosis complex

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.37952 ◽

2016 ◽

Vol 170 (12) ◽

pp. 3323-3326 ◽

Cited By ~ 4

Author(s):

Eryn Dow ◽

Ingrid Winship

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Renal Angiomyolipoma

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Malignancy of renal angiomyolipoma from tuberous sclerosis complex with TSC2 mutation

Chinese Medical Journal ◽

10.1097/cm9.0000000000000026 ◽

2019 ◽

Vol 132 (1) ◽

pp. 103-105

Author(s):

Yu-Jing Huang ◽

Zong-Pei Jiang ◽

Yu-Ping Chen ◽

Jin-Quan Wu ◽

Jia-Li Huang ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Renal Angiomyolipoma

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Nephron Sparing Surgery for Renal Angiomyolipoma with Inferior Vena Cava Thrombus in Tuberous Sclerosis

Case Reports in Urology ◽

10.1155/2014/285613 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Adrien Riviere ◽

Thomas Bessede ◽

Jean-Jacques Patard

Keyword(s):

Inferior Vena Cava ◽

Tuberous Sclerosis ◽

Inferior Vena ◽

Vena Cava ◽

Nephron Sparing Surgery ◽

Renal Angiomyolipoma ◽

Nephron Sparing ◽

Mean Size ◽

The Mean

Introduction. Angiomyolipoma is a common benign renal tumor. It is associated with Tuberous Sclerosis Complex (TSC) in 20% of patients. Angiomyolipomas are classically multiple, bilateral, and growing; they may lead to complications such as Wunderlich syndrome or, in rare cases, to venous extension.Observation. a 74-year-old woman with TSC presented with an angiomyolipoma of the right kidney with inferior vena cava (IVC) fatty thrombus. She underwent partial nephrectomy and thrombectomy. After a 7-year follow-up there was no evidence of recurrence or metastasis and her renal function was preserved.Review of Literature. It is the 44th reported angiomyolipoma associated with IVC thrombus. The mean size of angiomyolipomas was 86.1 mm and 67.4% of patients were symptomatic. Pulmonary embolism was found in 6 patients. There were 2 cases of recurrence/metastatic outcome after radical nephrectomy and thrombectomy. They were associated with epithelioid form. The mean size of epithelioid tumors was significantly bigger than in classical angiomyolipomas (127.1 mm versus 82.6 mm,P=0.037). With a median follow-up of 12 months, 91.3% of patients were recurrence and metastasis free, with 3 cases of nephron sparing surgery.Conclusion. Nephron sparing surgery for angiomyolipoma with IVC fatty thrombus can be safely performed in TSC, even in sporadic angiomyolipoma.

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