UNASSIGNED: The aim of this study is to summarize the surgical experience of renal artery cold perfusion combined with laparoscopic nephron preserving surgery for the treatment of complex renal angiomyolipoma and to evaluate the safety and feasibility of this surgical protocol.
UNASSIGNED: Clinical data of nine patients who received renal artery cold perfusion combined with laparoscopic nephron preserving surgery for complex renal angiomyolipoma in our hospital from February 2017 to August 2020 were retrospectively analyzed. The study parameters included imaging findings, total renal function before and after surgery, glomerular filtration rate (GFR) of affected kidney before and after surgery, and related complications.
UNASSIGNED: Eight of the nine patients successfully completed the operation, one patient was intolerant to renal artery balloon implantation, and the success rate of the operation was 88.89%. The mean maximum tumor diameter was 6.8 cm, and RENAL score was 7 points. Postoperative total renal function and GFR of the affected kidney had no significant changes compared with that before surgery, and imaging examination showed no tumor residue or recurrence.
UNASSIGNED: This surgical procedure is safe and feasible for complex renal angiomyolipoma and can be used as a surgical option for renal hamartoma. The long-term effect needs to be confirmed by further studies.

UNASSIGNED: Postembolization syndrome (PES) after renal arterial embolization (RAE) can reduce the patient\'s tolerance of the procedure and extend the length of hospital stay. We aimed to assess the efficacy of steroid administration in preventing PES in patients undergoing RAE for angiomyolipoma (AML).
UNASSIGNED: Between May 2004 and March 2020, 29 RAE procedures in 26 patients with AML were performed. Patient information, including age, sex, tumor size, tuberous sclerosis complex-associated/sporadic AML, hemorrhagic/nonhemorrhagic AML, embolic material, steroid use, medication type, some blood laboratory parameters, hospital stay, and PES occurrence were retrospectively obtained. The prophylactic steroid protocol used in the study was as follows: 250 mg of intravenous methylprednisolone (Solu-Medrol) 2 h before the RAE procedure, followed by 2 days of intravenous prednisolone (Predonine; 2 mg/kg/day), which was tapered by halving the dose every 2 days within the course of 2 weeks. After the discharge, intravenous prednisolone was changed to oral prednisolone (Predonine). PES was defined as the presence of fever, pain, nausea, or vomiting. Data were compared between the steroid and non-steroid groups and between PES and non-PES groups.
UNASSIGNED: The PES incidence rate was 76%, and a comparison between the steroid and non-steroid groups revealed that steroid use significantly decreased the incidence of PES (P < 0.001), including fever (P < 0.001), pain (P = 0.005), and nausea (P = 0.028). The use of anti-inflammatory drugs during the hospital stay was significantly lower in the steroid group (P = 0.019). Moreover, in the steroid group, C-reactive protein level was significantly lower (P = 0.006), whereas white blood cell count was significantly higher (P = 0.004). Conversely, the median length of hospital stay was not significantly shorter in the steroid group (P = 0.292).
UNASSIGNED: The prophylactic use of steroids before and after embolization of renal AML may be effective in preventing PES in this small retrospective study.

UNASSIGNED: To clarify the utility of microballoon catheter in renal arterial ethanol embolization of renal angiomyolipoma (AML).
UNASSIGNED: A total of 20 patients (15 women, 5 men) with median age of 45 years (39-60 years) underwent embolization to treat 22 AMLs. A mixture of ethanol and iodized oil was injected into the feeding arteries of 13 tumors using balloon occlusion (the balloon embolization group) with a microballoon catheter and 9 tumors without using balloon occlusion (the non-balloon embolization group). Changes in the maximum tumor diameter, tumor volume, and adverse events were evaluated.
UNASSIGNED: The median baseline maximum tumor diameters and volumes were 6.3 cm and 61.4 cm3 in the balloon embolization group, and 4.6 cm and 40.1 cm3 in the non-balloon embolization group, respectively. Tumor enhancement disappeared on postembolization angiography in all cases. All tumors shrunk after embolization. There were no statistically significant differences in the percent decrease in the maximum tumor diameter and volume at 10-12 month between balloon occlusion group (31.5% and 67.9%) and control group (34.8% and 62.6%). Fever was significantly more frequent when balloon occlusion was used: 38% vs. 0% (p = 0.03). No major complication was observed in either patient group.
UNASSIGNED: Balloon occlusion may not affect tumor shrinkage when embolizing AMLs with a mixture of ethanol and lipiodol.

Tuberous Sclerosis Complex (TSC) is a genetic disorder, with renal manifestations like angiomyolipoma (AML) occurring in 70-80% of patients. AML usually cause more complications in TCS patients than in non-TSC patients. However, AML patients are not routinely investigated for TSC. Our aim was to retrospectively assess the correlation between radiologically diagnosed AML and TSC.
All patients were stratified into AML related vs. unrelated to TSC. Correlations were calculated to determine the association between age, AML, and TSC.
Complete data were available for 521 patients with renal AML, in 7 of which the concurrent diagnosis of TSC was found. Younger age significantly positively correlated with the prevalence of TSC in AML patients (p <  0.01). 37 (7%) of the 521 patients were within the age-range of 18-40 years, in which TSC occurred in 6 cases, 4 (66.7%) of which presented with multiple, bilateral renal AML (p <  0.05), and 2 (33.3%) of which with a single, unilateral AML (p <  0.05). In patients with AML but without TSC, unilateral AML was found in 83.9% and bilateral AML in 16.1% (p <  0.05). Simple binary logistic regression analysis revealed bilateral AML (OR 33.0; 95% CI 3.2-344.0; p = 0.003) (but not unilateral AML (OR 0.09; 95% CI 0.01-0.88; p = 0.04)) to be a risk factor for TSC.
The presence of bilateral AML in patients within the age-range of 18-40 years should raise suspicion for TSC as the underlying cause. Therefore, our advice is to refer patients with multiple bilateral renal AML for further investigations regarding TSC.

Renal angiomyolipomas are one of the most common renal manifestations in patients with tuberous sclerosis complex (TSC), with potentially life-threatening complications and a poor prognosis. Despite the considerable progress in understanding TSC-associated renal angiomyolipomas, there are no large scale real-world data. The aim of our present study was to describe in detail the prevalence and outcome of renal angiomyolipomas in patients with TSC, enrolled into the TuberOus SClerosis registry to increase disease Awareness (TOSCA) from 170 sites across 31 countries worldwide. We also sought to evaluate the relationship of TSC-associated renal angiomyolipomas with age, gender and genotype. The potential risk factors for renal angiomyolipoma-related bleeding and chronic kidney disease (CKD) were studied in patients who participated in the TOSCA renal angiomyolipoma substudy. Of the 2,211 eligible patients, 1,062 (48%) reported a history of renal angiomyolipomas. The median age of TSC diagnosis for the all subjects (n = 2,211) was 1 year. The median age of diagnosis of renal angiomyolipoma in the 1,062 patients was 13 years. Renal angiomyolipomas were significantly more prevalent in female patients (p < 0.0001). Rates of angiomyolipomas >3 cm (p = 0.0119), growing lesions (p = 0.0439), and interventions for angiomyolipomas (p = 0.0058) were also higher in females than males. Pre-emptive intervention for renal angiomyolipomas with embolisation, surgery, or mammalian target of rapamycin (mTOR) inhibitor may have abolished the gender difference in impaired renal function, hypertension, and other complications. The rate of interventions for angiomyolipomas was less common in children than in adults, but interventions were reported in all age groups. In the substudy of 76 patients the complication rate was too low to be useful in predicting risk for more severe CKD. In addition, in this substudy no patient had a renal hemorrhage after commencing on an mTOR inhibitor. Our findings confirmed that renal angiomyolipomas in subjects with TSC1 mutations develop on average at the later age, are relatively smaller in size and less likely to be growing; however, by age 40 years, no difference was observed in the percentage of patients with TSC1 and TSC2 mutations needing intervention. The peak of appearance of new renal angiomyolipomas was observed in patients aged between 18 and 40 years, but, given that angiomyolipomas can occur later, lifelong surveillance is necessary. We found that pre-emptive intervention was dramatically successful in altering the outcome compared to historical controls; with high pre-emptive intervention rates but low rates of bleeding and other complications. This validates the policy of surveillance and pre-emptive intervention recommended by clinical guidelines.

TSC2 gene mutation was repeatedly reported to be associated with a more severe phenotype in patients with tuberous sclerosis complex (TSC). Our current study aims to further explore whether there is such a correlation in patients with TSC-associated renal angiomyolipoma (TSC-RAML). TSC1/TSC2 gene mutation was screened by high-throughput sequencing in 25 TSC-RAML patients from 2 medical centers. Clinical data were also carefully collected. Linear regression analysis and Student t-test were conducted by IBM SPSS Statistics Version 21.0 to analyze the genotypic-phenotypic relationship. The results indicated a high level of TSC gene mutation (80%; 20/25) in TSC-RAML patients, with higher frequency of TSC2 mutation (68%; 17/25) than TSC1 mutation (12%; 3/25). Seven novel mutation sites were detected in this study. In general, there were no significant correlations between tumor size and age (r = 0.134, P = .522), hemoglobin (r = 0.255, P = .219), and serum creatinine (r = 0.043, P = .839). Patients with larger tumor size have higher risk of bleeding. Specially, it was higher hemoglobin level in patients with TSC1 mutation than ones with TSC2 mutation and without TSC mutation (P < .05). However, no difference was found in either tumor size or serum creatinine by TSC mutation genes (P > .05). Furthermore, no difference was found in tumor size, hemoglobin, and serum creatinine by TSC mutation types (P > .05). In conclusion, TSC-RAML is TSC2 mutation dominant, with the individual differences varying greatly. No definite genotype-phenotype correlation exists in patients with TSC-RAML, and it needs to be further explored.

To examine outcomes of clinical procedures for renal angiomyolipoma associated with tuberous sclerosis complex (TSC) based on US national health claims databases.
This retrospective cohort study selected two cohorts of TSC patients, who underwent either embolization or nephrectomy (either partial or complete) for renal angiomyolipoma in the years from 2000 through 2011. Based on claims diagnosis codes, we estimated the prevalence rates of 10 angiomyolipoma-related conditions and 50 embolization- or nephrectomy-related conditions in the pre- and post-baseline periods respectively, and made cross-year and cross-period comparison of these rates with repeated measures analysis methods.
The embolization cohort (N = 4280) and the nephrectomy cohort (N = 3842) had mean baseline ages of 50.7 and 51.7 years with 52.5% and 51.3% males, respectively. After the intervention, the embolization cohort had statistically significant reductions (all p < .05) in gross hematuria (-27.7%), retroperitoneal hemorrhage (-8.4%), and abdominal mass (-6.9%), and increases in hypertension (15.5%), renal mass or unspecified disorder of kidney and ureter (13.8%), anemia (5.1%), and renal insufficiency (3.3%). Similarly, the nephrectomy cohort saw statistically significant reductions (all p < .05) in gross hematuria (-30.6%), flank pain (-7.5%), and abdominal mass (-6.4%), but increases in hypertension (11.9%), renal insufficiency (10.4%), and anemia (7.6%). Embolization was associated with post-procedure increases in renal mass or unspecified kidney/ureter disorder (13.9%), other disorders of kidney and ureter (3.4%), non-acute renal insufficiency (3.1%), flank pain (3.7%), renal insufficiency (3.2%), etc. (all p < .05). Nephrectomy was associated with post-procedure increases in postoperative ileus (5.3%), pain and headache (4.8%), paralytic ileus (3.6%), etc. (all p < .05).
Both embolization and nephrectomy were effective, but associated with increases in certain angiomyolipoma-related conditions. Further, the embolization effect on gross hematuria, retroperitoneal hemorrhage, and abdominal mass might subside after the intervention year.

Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant disease characterised by benign cutaneous lesions, pulmonary cysts, and an increased risk of renal tumors. This rare condition is due to a mutation in the folliculin (FLCN) gene on chromosome 17q11.2, which has a role in the mechanistic/mammalian target of rapamycin (mTOR) signaling pathway of tumorigenesis. This case illustrates a patient with BHD and a renal angiomyolipoma, a neoplastic lesion not usually associated with BHD but common in Tuberous Sclerosis Complex (TSC). There is both clinical and molecular overlap between BHD and TSC, which may arise from similarities in function of the TSC and FLCN proteins in the mTOR pathway; this case further demonstrates this potential correlation. © 2016 Wiley Periodicals, Inc.

BACKGROUND: Long-term data from patients with tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (angiomyolipoma) are limited.
METHODS: Retrospective observational study.
METHODS: Adult patients with TSC treated at the University Medical Center Utrecht (the Netherlands) from January 1990 through April 2012.
METHODS: Patient age and angiomyolipoma stage, based on computed tomography lesion count, size, and impact on renal anatomy, with higher stage representing higher angiomyolipoma burden. Patients in stages 3 or higher were considered at high risk for hemorrhage and candidates for selective arterial embolization.
RESULTS: Kidney-related outcomes included hypertension, anemia, decreased kidney function, dialysis, kidney transplantation, nephrectomy, kidney-related blood transfusions, and mortality. Observed mortality was compared to the Dutch National Bureau of Statistics using standardized mortality ratio.
RESULTS: Median follow-up was 15.8 years, of which staging was available for 5.4 years. Of 351 patients with TSC, 244 (69.5%) had confirmed angiomyolipoma; 144 (59.0%) reached stage 3 or higher. Age and angiomyolipoma stage were positively correlated: median age in the none-detected stage was 36.8 years, increasing to 43.6 years for stage 6. Embolization was performed in 117 patients; 57 had 2 or more embolization procedures. Higher stage was associated with hypertension, anemia, decreased kidney function, and transfusion. Hypertension, anemia, and decreased kidney function were more common in patients who underwent selective arterial embolization. 7 patients required dialysis, 7 received a kidney transplant, and 16 underwent nephrectomy. 29 deaths were recorded, most commonly related to renal complications (n=9[31%]). Mortality was significantly higher in the study cohort versus the general population (standardized mortality ratio, 4.8; 95% CI, 3.4-6.9).
CONCLUSIONS: Duration of follow-up with staging was too short to observe stage progression in most patients.
CONCLUSIONS: Despite the use of preventive selective arterial embolization, patients with TSC exhibit clinically significant kidney disease and excess mortality, largely because of kidney-related complications.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial are presented.
METHODS: Following favorable results from the primary analysis (data cutoff 30 June 2011) of the EXIST-2 trial, patients still receiving study treatment were allowed to enter an open-label extension. Everolimus was initiated at 10 mg once daily and titrated based on tolerability. The primary outcome was angiomyolipoma response rate (≥ 50% reduction from baseline in target lesion volumes). Safety was a secondary endpoint.
RESULTS: As of the cutoff date (1 May 2013), 112 patients had received everolimus, and the response rate in 107 patients with angiomyolipoma (median duration of medication exposure of 28.9 months) was 54%. The proportion of patients achieving angiomyolipoma reductions of ≥ 30% and ≥ 50% increased over time, reaching 81.6% (62/76) and 64.5% (49/76), respectively, by Week 96. No everolimus-treated patients experienced renal bleeding. The long-term safety profile was consistent with previous reports; adverse events (AEs) were mostly Grade 1/2, and there were no new safety issues. The frequency of emerging AEs and severe AEs lessened over time.
CONCLUSIONS: Longer term everolimus treatment appeared safe and effective in patients with TSC- or sporadic LAM-associated renal angiomyolipoma not requiring surgical intervention. Continued reduction in angiomyolipoma volume was demonstrated, and there was no angiomyolipoma-related bleeding; AEs were predictable and generally manageable.
BACKGROUND: clinicaltrialsgov identifier: NCT00790400 (http://clinicaltrials.gov/ct2/show/NCT00790400).