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Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex.

ABSTRACT: Renal angiomyolipomas are found in up to 80% of tuberous sclerosis complex (TSC) patients. Although these tumours are usually asymptomatic, lesions >3?cm in diameter are prone to bleeding and up to 10% of TSC patients may experience a massive and potentially fatal retroperitoneal haemorrhage. Diagnosis can be complicated because of the initial lack of symptoms and the fat-poor content of atypical renal angiomyolipomas. After diagnosis, tumour growth and the emergence of new tumours must be monitored. Treatment with mammalian target of rapamycin (mTOR) inhibitors can reduce tumour size and is indicated in patients with TSC-associated renal angiomyolipomas >3?cm in diameter. Imaging-based assessment of kidney disease is essential to the diagnosis and management of patients with TSC. The aims of imaging studies in this context are to detect and characterize tumours, assess and detect the risk of complications and evaluate the response to treatment, especially in patients treated with mTOR inhibitors. A multidisciplinary expert panel developed a series of recommendations based on current evidence and professional experience for imaging studies in adults and children with TSC-associated renal angiomyolipoma. The recommendations cover radiological diagnosis and follow-up of the classic and atypical or fat-poor TSC-associated renal angiomyolipomas, biopsy indications, minimal requirements for radiological requests and reports and recommended technical features and protocols for computed tomography and magnetic resonance imaging.

SUBMITTER: Buj Pradilla MJ

PROVIDER: S-EPMC5716090 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex.

Buj Pradilla María José MJ Martí Ballesté Teresa T Torra Roser R Villacampa Aubá Felipe F

Clinical kidney journal 20170911 6

Renal angiomyolipomas are found in up to 80% of tuberous sclerosis complex (TSC) patients. Although these tumours are usually asymptomatic, lesions >3 cm in diameter are prone to bleeding and up to 10% of TSC patients may experience a massive and potentially fatal retroperitoneal haemorrhage. Diagnosis can be complicated because of the initial lack of symptoms and the fat-poor content of atypical renal angiomyolipomas. After diagnosis, tumour growth and the emergence of new tumours must be monit ...[more]

PMID: 29225800

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Project description:BACKGROUND:Renal angiomyolipoma occurs at a high frequency in patients with tuberous sclerosis complex (TSC) and is associated with potentially life-threatening complications. Despite this frequency and severity, there are no large population-based cohort studies. Here we present baseline and follow-up data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with an aim to provide detailed clinical characteristics of renal angiomyolipoma among patients with TSC. METHODS:Patients of any age with a documented clinic visit for TSC within 12 months or who were newly diagnosed with TSC before participation in the registry were eligible. Data specific to renal angiomyolipoma included physical tumour characteristics (multiple, bilateral, lesion size and growing lesions), clinical signs and symptoms, and management. The effects of age, gender and genotype on the prevalence of renal angiomyolipoma were also evaluated. RESULTS:Renal angiomyolipoma was reported in 51.8% of patients at baseline, with higher frequency in female patients (57.8% versus 42.2%). The median age at diagnosis was 12 years. Prevalence of angiomyolipoma was higher in patients with TSC2 compared with TSC1 mutations (59.2% versus 33.3%, P?<?0.01). Of the 1031 patients with angiomyolipoma at baseline, multiple lesions were reported in 88.4% and bilateral in 83.9% of patients, while the size of angiomyolipoma was >3 cm in 34.3% of patients. Most patients were asymptomatic (82%). Frequently reported angiomyolipoma-related symptoms included bleeding, pain, elevated blood pressure and impaired renal function. Embolization and mammalian target of rapamycin inhibitors were the two most common treatment modalities. CONCLUSIONS:The TOSCA registry highlights the burden of renal angiomyolipoma in patients with TSC and shows that renal manifestations are initially asymptomatic and are influenced by gender and genotype. Furthermore, the occurrence of significant problems from angiomyolipoma in a minority of younger patients suggests that surveillance should begin in infancy or at initial diagnosis.

Project description:Angiomyolipomas in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis are associated with mutations in tuberous sclerosis genes resulting in constitutive activation of the mammalian target of rapamycin (mTOR). The drug sirolimus suppresses mTOR signaling.We conducted a 24-month, nonrandomized, open-label trial to determine whether sirolimus reduces the angiomyolipoma volume in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Sirolimus was administered for the first 12 months only. Serial magnetic resonance imaging of angiomyolipomas and brain lesions, computed tomography of lung cysts, and pulmonary-function tests were performed.Of the 25 patients enrolled, 20 completed the 12-month evaluation, and 18 completed the 24-month evaluation. The mean (+/-SD) angiomyolipoma volume at 12 months was 53.2+/-26.6% of the baseline value (P<0.001) and at 24 months was 85.9+/-28.5% of the baseline value (P=0.005). At 24 months, five patients had a persistent reduction in the angiomyolipoma volume of 30% or more. During the period of sirolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 second (FEV1) increased by 118+/-330 ml (P=0.06), the forced vital capacity (FVC) increased by 390+/-570 ml (P<0.001), and the residual volume decreased by 439+/-493 ml (P=0.02), as compared with baseline values. One year after sirolimus was discontinued, the FEV1 was 62+/-411 ml above the baseline value, the FVC was 346+/-712 ml above the baseline value, and the residual volume was 333+/-570 ml below the baseline value; cerebral lesions were unchanged. Five patients had six serious adverse events while receiving sirolimus, including diarrhea, pyelonephritis, stomatitis, and respiratory infections.Angiomyolipomas regressed somewhat during sirolimus therapy but tended to increase in volume after the therapy was stopped. Some patients with lymphangioleiomyomatosis had improvement in spirometric measurements and gas trapping that persisted after treatment. Suppression of mTOR signaling might constitute an ameliorative treatment in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. (ClinicalTrials.gov number, NCT00457808.)

Project description:Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder characterized by the development of numerous benign tumors. Renal angiomyolipoma (RAML) occur in up to 80% of TSC patients, which is a leading cause of TSC-related death in adult patients. The aim of the study was to evaluate the efficacy and safety profiles of everolimus in Chinese patients of TSC associated with RAML(TSC-RAML).In this 2-years, nonrandomized, open-label trial, 18 patients of TSC-RAML, with at least one RAML 3 cm or larger in its longest diameter, were enrolled to assess the efficacy and safety of everolimus therapy in Chinese patients. Everolimus was administered for the first 12 months only. The primary endpoint was a reduction of 50% or more relative in RAML volume to the baseline in the absence of new RAML ?1 cm and no RAML-related bleeding of grade???2. The secondary endpoints included: safety, lung function and skin lesions response rate. Serial computed tomography of RAML, magnetic resonance imaging of brain lesions and pulmonary-function tests were performed. Adverse events were investigated using CTCAE v4.0. All analyses used a significance level of 0.05 and were generated in SPSS19.0 software.The proportion of patients who achieved ?50% reduction from baseline in the sum of volumes of target lesions increased from 52.94% at 3 months, to 58.82% and 66.67% at months 6 and 12, respectively. During the period of everolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 s (FEV1) increased by 276?±?78 ml (P?<?0.001), the forced vital capacity (FVC) increased by 433?±?170 ml (P?<?0.001), and the residual volume decreased by 408?±?243 ml (P?=?0.009), as compared with baseline values. The angiomyolipoma volume and the lung function approached, but did not completely return to, the baseline values. The skin lesions response rate was 37.5% after 12 months of therapy falling to 21.4% at 12 months after stopping everolimus. The most common adverse events were mucositis oral, irregular menstruation, abdominal pain, hypertriglyceridemia and headache. The most common grade 3 adverse events were irregular menstruation and mucositis oral. In addition, one patient died from RAML spontaneous haemorrhage during treatment with everolimus, even with reduction in RAML volume of 60.68% at 3 months. A second death was due to epithelioid RAML progression, with metastasis to multiple retroperitoneal lymph node, who died from severe infection one month after surgery.Angiomyolipomas regressed somewhat during everolimus therapy but tended to increase in volume after the therapy was stopped. Everolimus was well tolerated and showed promising activity in Chinese patients with TSC-RAML, however, we should alert the life-threatening hemorrhage of large RAML in the early period and the lymph node metastasis of epithelioid RAML.ChiCTR-OPC-14005488 . Registered November 17, 2014.

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Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex.

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Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex.

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