Renal angiomyolipoma rupture in the immediate postoperative period following caesarean section.

Renal angiomyolipoma (rAML) is a rare benign tumour primarily affecting women due to hormonal influences, with accelerated growth observed during pregnancy. This case report presents a multigravida woman in her mid-20s at 37 weeks of gestation with stable vital signs and normal physical examination findings, except for swelling in the lower extremities. Following caesarean section delivery, she developed flank pain and haematuria in the immediate postoperative period. Emergency surgery revealed a ruptured rAML, resulting in unstable haemodynamics and significant blood loss. A multidisciplinary team performed a left radical nephrectomy to control bleeding. The patient required transfusions, ventilation and postoperative antibiotic therapy. This case underscores the importance of considering rAML rupture in the immediate postoperative period following caesarean section, highlighting the need for prompt evaluation in pregnant women with a history of urologic disorders.

CT and MRI Findings of Renal Angiomyolipoma With Lung Metastasis: A Case Report and Literature Review.

Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).

Tuberous Sclerosis Complex and the kidneys: what nephrologists need to know.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives.

[Clinical diagnosis and treatment of renal angiomyolipoma with inferior vena cava tumor thrombus].

OBJECTIVE: To summarize the clinical characteristics of patients with renal angiomyolipoma (RAML) combined with inferior vena cava (IVC) tumor thrombus, and to explore the feasibility of partial nephrectomy and thrombectomy in this series of patients. METHODS: The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed, and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Electronic Medical Record System, including age, gender, surgical methods, and follow-up time, etc. The clinical characteristics between classic angiomyolipoma (CAML) patients with IVC tumor thrombus and epithelioid angiomyolipoma (EAML) patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients. RESULTS: A total of 11 patients were included in this study, including 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus. There were 9 females (9/11, 81.8%) and 2 males (2/11, 18.2%), with an average age of (44.0±17.1) years. 9 patients (9/11, 81.8%) experienced clinical symptoms, including local symptoms including abdominal pain, hematuria, abdominal masses, and systemic symptoms including weight loss and fever; 2 patients (2/11, 18.2%) with RAML and IVC tumor thrombus did not show clinical symptoms, which were discovered by physical examination. Among the 11 patients, 10 underwent radical nephrectomy with thrombectomy, of whom, 3 underwent open surgery (3/10, 30.0%), 2 underwent laparoscopic surgery (2/10, 20.0%), and 5 underwent robot-assisted laparoscopic surgery (5/10, 50.0%). In addition, 1 patient underwent open partial nephrectomy and thrombectomy. The patients with EAML combined with IVC tumor thrombus had a higher proportion of systemic clinical symptoms (100% vs. 0%, P=0.003), more intraoperative bleeding [400 (240, 3 050) mL vs. 50 (50, 300) mL, P =0.036], and a higher proportion of tumor necrosis (75% vs. 0%, P=0.024) compared to the patients with CAML combined with IVC tumor thrombus. However, there was no statistically significant difference in operation time [(415.8±201.2) min vs. (226.0±87.3) min, P=0.053] between the two groups. CONCLUSION: Compared with the patients with CAML and IVC tumor thrombus, the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis. In addition, in the selected patients with CAML with IVC tumor thrombus, partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.

Management of renal sinus angiomyolipoma: modified robotic nephron-sparing surgery in a single center.

BACKGROUND: Renal sinus angiomyolipoma (RSAML) is a rare and typically complex renal tumor. The objective is to present our single-center experience with a modified technique of robotic nephron-sparing surgery (NSS) for treating RSAML. METHODS: We retrospectively evaluated 15 patients with RSAMLs who were treated with robotic NSS at the Department of Urology of Tongji hospital, ranging from November 2018 to September 2022. Renal vessels and ureter were dissected. The outer part of RSAML was resected. The rest of tumor was removed by bluntly grasp, curettage and suction. Absorbable gelatin sponges were filled in the renal sinus. The preoperative parameters, operative measures and postoperative outcomes were all collected. Follow-up was performed by ultrasonography and estimated glomerular filtration rate (eGFR). RESULTS: Robotic NSS was successfully performed in all the patients, without any conversion to open surgery or nephrectomy. The mean operation time was 134.13 ± 40.56 min. The mean warm ischemia time was 25.73 ± 3.28 min. The median estimated blood loss was 100 [50, 270] ml and 1 patient required blood transfusion. The mean drainage duration was 5.77 ± 1.98 days. The median postoperative hospital stay was 6.90 [5.80, 8.70] days. Two patients experienced postoperative urinary tract infection (Clavien-Dindo Grade II). During the median follow-up of 25.53 ± 15.28 months, patients received 91.18% renal function preservation. No local recurrence occurred in all the patients. CONCLUSIONS: Robotic NSS for RSAML is a complicated procedure that demands technical expertise and a well-designed strategy is critical in the operation. Treating RSAML with modified robotic NSS is safe, effective and feasible.

Utility of Chemical Shift Imaging and Diffusion-weighted Images/Apparent Diffusion Coefficient Maps as a Tool for Evaluation of Solid Renal Tumors.

OBJECTIVES: To study the utility of chemical shift imaging (CSI) and diffusion-weighted images (DWI)/apparent diffusion coefficient (ADC) maps for the evaluation of solid renal tumors. METHODS: Magnetic resonance imaging (MRI) has an equivalent application as computerized tomography (CT) in the characterization of renal masses. It offers a radiation-free imaging technique and has a better soft tissue contrast than CT. Also, MRI is favored in patients with chronic kidney disease. MRI is useful when findings on CT are equivocal. The role of DWI in characterizing solid renal lesions as malignant is encouraging, and DWI can be particularly useful when gadolinium is contraindicated. CSI is useful in differentiating angiomyolipoma (AML) from clear cell (cc) renal cell carcinoma (RCC). We did a cross-sectional study on 24 patients with solid renal masses. MRI of the upper abdomen (from the dome of the diaphragm to the iliac crest) will be done on an MRI machine in our department (1.5T, ACHIEVA, Phillips medical system) using the torso coil. RESULT: There was no significant association seen in terms of ADC values and histological subtypes (χ2 = 11.222, p = 0.082). In our study, 50% (one out of two) of AML showed a signal drop, whereas 40% of cases (6 out of 15) of ccRCC and 66% (two out of three) of papillary RCC showed a signal drop. CONCLUSION: In this article, we concluded CSI, although a useful tool to look for microscopic fat, can't be used as a reliable marker to rule in cc-carcinoma as both AML and papillary cell carcinoma have microscopic fat. Further, no histological classification can be done on the basis of DWI/ADC images.

Evolving horizons in renal angiomyolipoma: two decades of management strategies and clinical perspectives in a single institutional study.

OBJECTIVE: To assess various management options for renal angiomyolipoma (AML) to guide clinical practice. METHODS: A single center retrospectively reviewed an AML series from 2002 to 2022. The image reports and chart reviews of patients who received two abdominal scans at least 6 months between the first and last scans were assessed. RESULTS: A total of 203 patients with 209 tumors were identified and followed up for a median of 42.6 months. Active surveillance (AS) was the most frequently selected option (70.9% of cases). Interventions were required for 59 AMLs, of which 20 were treated with embolization, 29 with partial nephrectomy, 9 with radical nephrectomy, and 1 with radiofrequency (RF) ablation. The median size of the lesions at intervention was 5 cm. The average growth rate of the lesions was 0.12 cm/year, and there was a significant difference in the average growth rate of lesions ≤4 cm and those >4 cm (0.11 vs. 0.24 cm/year; p = 0.0046). CONCLUSION: This series on AMLs confirms that lesions >4 cm do not require early intervention based on size alone. Appropriately selected cases of renal AML can be managed by AS.KEYWORDS: Angiomyolipoma; active surveillance; embolization; nephrectomy; nephron-sparing surgery.

High-frame-rate contrast-enhanced ultrasound to differentiate between clear cell renal cell carcinoma and angiomyolipoma.

BACKGROUND: To investigate the diagnostic efficacy of high-frame-rate contrast-enhanced ultrasound (H-CEUS) in differentiating between clear cell renal cell carcinoma (CCRCC) and angiomyolipoma (AML). METHODS: A retrospective study was performed on the clinical data of 79 patients diagnosed with CCRCC and 31 patients diagnosed with AML at the First Affiliated Hospital of Nanchang University between October 2022 and December 2023. Conventional ultrasound (US) and H-CEUS examinations were conducted on all patients prior to surgery, dynamic images were recorded from the US, and the qualitative and quantitative parameters of H-CEUS were collected. The t-test, χ² test and non-parametric Mann-Whitney test were employed to assess differences in clinical data, US characteristics, and qualitative and quantitative parameters of H-CEUS between the CCRCC and AML groups. The independent risk factors of CCRCC were identified using binary logistic regression. The receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic effectiveness of clinical + US and H-CEUS in differentiating between CCRCC and AML. RESULTS: The CCRCC group and the AML group exhibited significant differences in patient gender, operation mode, nodular echo, and nodule blood flow (χ²=11.698, -, -,=10.582; P<0.001, <0.001, <0.001, and = 0.014, respectively). In addition, the H-CEUS qualitative analysis demonstrated significant differences between the AML group and the CCRCC group with respect to enhancement mode, regression mode, peak intensity, enhancement uniformity, no enhancement, and presence or absence of pseudocapsule (χ²=41.614, -, -, = 2.758, = 42.099, -; P<0.001, <0.001, <0.001, 0.097, <0.001, and <0.001, respectively). The Arrival time (AT) in the CCRCC group was significantly shorter than that in the AML group, as determined by quantitative analysis of H-CEUS (Z=-3.266, P = 0.001). Furthermore, the Peak intensity (PI), Ascent slope (AS), and The area under the curve (AUC) exhibited significantly higher values in the CCRCC group compared to the AML group (Z=-2.043,=-2.545,=-3.565; P = 0.041, = 0.011, and <0.001, respectively). Logistic regression analysis indicated that only gender, nodule echo, the pseudocapsule, AS, and AUC of H-CEUS were independent risk factors of CCRCC. The ROC curve revealed that combining gender and nodule echo yielded a sensitivity of 92.4%, specificity of 64.5%, and an AUC of 0.847 in distinguishing between CCRCC and AML. When combining the H-CEUS parameters of pseudocapsule, AS, and AUC, the sensitivity, specificity, and AUC for distinguishing between CCRCC and AML were 84.8%, 96.8%, and 0.918, respectively. No statistically significant difference was observed in the diagnostic effectiveness of the two methods (Z=-1.286, P = 0.198). However, H-CEUS demonstrated better AUC and specificity. CONCLUSIONS: H-CEUS enhances the sensitivity and specificity of differentiating between CCRCC and AML by improving the temporal resolution, offering a more precise diagnostic foundation for identifying the most appropriate therapy for patients.

[Discussion on the surgical timing of rupture and hemorrhage of renal angiomyolipoma].

OBJECTIVE: To investigate the effect of different surgical timing on the surgical treatment of renal angiomyolipoma (RAML) with rupture and hemorrhage. METHODS: The demographic data and perioperative data of 31 patients with rupture and hemorrhage of RAML admitted to our medical center from June 2013 to February 2023 were collected. The surgery within 7 days after hemorrhage was defined as a short-term surgery group, the surgery between 7 days and 6 months after hemorrhage was defined as a medium-term surgery group, and the surgery beyond 6 months after hemorrhage was defined as a long-term surgery group. The perioperative related indicators among the three groups were compared. RESULTS: This study collected 31 patients who underwent surgical treatment for RAML rupture and hemorrhage, of whom 13 were males and 18 were females, with an average age of (46.2±11.3) years. The short-term surgery group included 7 patients, the medium-term surgery group included 12 patients and the long-term surgery group included 12 patients. In terms of tumor diameter, the patients in the long-term surgery group were significantly lower than those in the recent surgery group [(6.6±2.4) cm vs. (10.0±3.0) cm, P=0.039]. In terms of operation time, the long-term surgery group was significantly shorter than the mid-term surgery group [(157.5±56.8) min vs. (254.8±80.1) min, P=0.006], and there was no significant difference between other groups. In terms of estimated blood loss during surgery, the long-term surgery group was significantly lower than the mid-term surgery group [35 (10, 100) mL vs. 650 (300, 1 200) mL, P < 0.001], and there was no significant difference between other groups. In terms of intraoperative blood transfusion, the long-term surgery group was significantly lower than the mid-term surgery group [0 (0, 0) mL vs. 200 (0, 700) mL, P=0.014], and there was no significant difference between other groups. In terms of postoperative hospitalization days, the long-term surgery group was significantly lower than the mid-term surgery group [5 (4, 7) d vs. 7 (6, 10) d, P=0.011], and there was no significant difference between other groups. CONCLUSION: We believe that for patients with RAML rupture and hemorrhage, reoperation for more than 6 months is a relatively safe time range, with minimal intraoperative bleeding. Therefore, it is more recommended to undergo surgical treatment after the hematoma is systematized through conservative treatment.

Management of Nontraumatic Spontaneous Renal Hemorrhage (Wünderlich Syndrome) through Robotic-Assisted Laparoscopic Nephrectomy: A Case Series.

BACKGROUND Wünderlich syndrome (WS) is a rare diagnosis of nontraumatic spontaneous renal hemorrhage into the subcapsular, perirenal, or pararenal spaces. Prompt and effective intervention is necessary for an accurate pathological diagnosis and preservation of life. In the current literature, open surgery is the primary option when conservative treatment fails, but there can be serious trauma and corresponding consequences. Herein, we present 3 cases of Wünderlich syndrome managed by robot-assisted laparoscopic nephrectomy via a retroperitoneal approach. CASE REPORT Patient 1 was a 44-year-old woman with right flank pain for 6 h. Patient 2 was a 53-year-old woman with a history of diabetes who had pain in her right flank pain and nausea for 1 day. Patient 3 was a 45-year-old man with left flank pain for 1 day. All cases of WS were confirmed by CT. All 3 patients were treated with retroperitoneal robot-assisted nephrectomy after conservative treatment failed. Pathological examination confirmed that patient 1 had angiomyolipoma, and patients 2 and 3 had renal clear cell carcinoma. At the 9-month follow-up, renal function was good and no evidence of recurrence or metastasis has been detected. CONCLUSIONS These cases have highlighted the importance of the clinical history and imaging findings in the diagnosis of Wünderlich syndrome, and show that rapid management can be achieved using robot-assisted laparoscopic nephrectomy. However, it is crucial to have a skilled surgical team and adequate preoperative preparation.

Stepwise algorithm using computed tomography and magnetic resonance imaging for differential diagnosis of fat-poor angiomyolipoma in small renal masses: A prospective validation study.

OBJECTIVES: To validate the diagnostic accuracy of a stepwise algorithm to differentiate fat-poor angiomyolipoma (fp-AML) from renal cancer in small renal masses (SRMs). METHODS: We prospectively enrolled 223 patients with solid renal masses <4 cm and no visible fat on unenhanced computed tomography (CT). Patients were assessed using an algorithm that utilized the dynamic CT and MRI findings in a stepwise manner. The diagnostic accuracy of the algorithm was evaluated in patients whose histology was confirmed through surgery or biopsy. The clinical course of the patients was further analyzed. RESULTS: The algorithm classified 151 (68%)/42 (19%)/30 (13%) patients into low/intermediate/high AML probability groups, respectively. Pathological diagnosis was made for 183 patients, including 10 (5.5%) with fp-AML. Of these, 135 (74%)/36 (20%)/12 (6.6%) were classified into the low/intermediate/high AML probability groups, and each group included 1 (0.7%)/3 (8.3%)/6 (50%) fp-AMLs, respectively, leading to the area under the curve for predicting AML of 0.889. Surgery was commonly opted in the low and intermediate AML probability groups (84% and 64%, respectively) for initial management, while surveillance was selected in the high AML probability group (63%). During the 56-month follow-up, 36 (82%) of 44 patients initially surveyed, including 13 of 18 (72%), 6 of 7 (86%), and 17 of 19 (89%) in the low/intermediate/high AML probability groups, respectively, continued surveillance without any progression. CONCLUSIONS: This study confirmed the high diagnostic accuracy for differentiating fp-AMLs. These findings may help in the management of patients with SRMs.

The effect of pregnancy on renal angiomyolipoma; a world of knowledge to gain, specifically in women with TSC.

BACKGROUND: Women are counseled preconceptionally about the potential risks of rAML progression and chance of complications during and due to pregnancy. However, a systematic search investigating the evidence on which this advice is based does not exist. The aim of this systematic review is to determine the effect of pregnancy on renal angiomyolipoma (rAML) size and risk of haemorrhage in patients with tuberous sclerosis complex (TSC). METHODS: We searched PubMed, EMBASE, Medline and ClinicalTrials.gov using terms for "renal angiomyolipoma" and "pregnancy". English-language articles published between January 1st 2000, and December 31st 2020 of which full-text was available were included. The initial search resulted in 176 articles. After the screening process we included 45 case reports and 1 retrospective study. For the retrospective study we assessed the risk of bias using the Newcastle-Ottawa Scale. We included articles about renal AML and pregnancy with and without an established diagnosis of TSC. From these articles we recorded the rAML sizes and rAML complications. RESULTS: Seven case reports, from a total of 45 case reports, provided follow-up data on renal AML size (these were all cases of renal AML without a known diagnosis of TSC). Of these cases, renal AML size decreased in one patient, was stable in one patient, increased in three patients and fluctuated in two others. Renal AML size of women who suffered a haemorrhage were significantly larger (12.1 ± 4.6 cm) than rAMLs of women who did not suffer a haemorrhage (8.3 ± 3.2 cm). Data from the retrospective study showed no difference in renal complications between the women with and without a history of pregnancy. Haemorrhage occurred in 30% of the women with a history of pregnancy (n = 20) and in 11% in the patients without a history of pregnancy (n = 2), however this retrospective study had methodological limitations. CONCLUSION: The effect of pregnancy on renal AML size and complications in patients with TSC is unclear. More research is needed to determine the risk of pregnancy on TSC-associated kidney disease in TSC patient.

Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: a consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the presence of proliferative lesions throughout the body. Management of TSC is challenging because patients have a multifaceted systemic illness with prominent neurological and developmental impact as well as potentially severe kidney, heart and lung phenotypes; however, every organ system can be involved. Adequate care for patients with TSC requires a coordinated effort involving a multidisciplinary team of clinicians and support staff. This clinical practice recommendation was developed by nephrologists, urologists, paediatric radiologists, interventional radiologists, geneticists, pathologists, and patient and family group representatives, with a focus on TSC-associated kidney manifestations. Careful monitoring of kidney function and assessment of kidney structural lesions by imaging enable early interventions that can preserve kidney function through targeted approaches. Here, we summarize the current evidence and present recommendations for the multidisciplinary management of kidney involvement in TSC.

Nutritional status as a predictive factor for paediatric tuberous sclerosis complex-associated kidney angiomyolipomas: a retrospective analysis.

The purpose of this study is to determine the predictive factors of tuberous sclerosis complex (TSC)-associated kidney disease and its progression in children. Retrospective review of children with TSC in a tertiary children's hospital was performed. Relevant data were extracted, and Cox proportional hazards regression was used to establish predictors of kidney lesions. Logistic regression was conducted to identify factors predicting chronic kidney disease (CKD) and high-risk angiomyolipomas (above 3 cm). Kidney imaging data were available in 145 children with TSC; of these, 79% (114/145) had abnormal findings. The only significant predictive factor for cyst development was being female (HR = 0.503, 95% CI 0.264-0.956). Being female (HR = 0.505, 95% CI 0.272-0.937) and underweight (HR = 0.092, 95% CI 0.011-0.800) both lowers the risk of having angiomyolipomas, but TSC2 mutations (HR = 2.568, 95% CI 1.101-5.989) and being obese (HR = 2.555, 95%CI 1.243-5.255) increases risks. Ten (12%) of 81 children with kidney function tested demonstrate CKD stages II-V, and only angiomyolipomas above 3 cm predict CKD. Additionally, 13/145 (9%) children had high-risk angiomyolipomas, whereby current age (adjusted odds ratio (aOR) 1.015, 95% CI 1.004-1.026) and being overweight/obese (aOR 7.129, 95% CI 1.940-26.202) were significantly associated with angiomyolipomas above 3 cm. CONCLUSIONS: While gender and genotype are known predictors, this study includes the novel finding of nutritional status as a predictor of TSC-associated kidney disease. This study sheds light on a possible complex interplay of hormonal influences, obesity, and kidney angiomyolipomas growth, and further investigations focusing on the impact of nutritional status on TSC-associated kidney disease are warranted. WHAT IS KNOWN: • Gender and genotype are well-studied predictive factors in TSC kidney disease. WHAT IS NEW: • Nutritional status may influence the development and the progression of kidney lesions in children with TSC and should not be overlooked. • Management guidelines of TSC-associated kidney disease can address nutritional aspects.

Patients' and physicians' awareness of clinical symptoms and disease severity in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare inherited disease with the potential to affect virtually every organ system. Clinical presentation is age- and partly sex-dependent and varies broadly with respect to disease manifestations including treatment-refractory epilepsy, intellectual disability and TSC-associated neuropsychiatric disorders, chronic kidney disease or progressive lung function decline. Given the complexity of this disease, multidisciplinary care in specialized TSC centres is recommended. We aimed to elucidate the state of knowledge of patients/caregivers and physicians on individual disease manifestations. We further examined whether the association to a TSC centre has an impact on the comprehensive consideration of potential disease manifestations. Therefore, a survey was performed in a cohort of German TSC patients and their physicians. Complete information was available for 94 patients with a median age of 18 years [range 1-55] and a sex distribution of 53.2% (male): 48.8% (female). Using almost identical questionnaires for patients/caregivers and their respective physician, there was a good correlation for disease assessments associated with relevant morbidity and mortality like epilepsy, renal angiomyolipoma, cardiac rhabdomyomas or intellectual disability. Correlation was moderate for several neuropsychiatric disorders and only poor for hypomelanotic macules, dental pits or retinal achromic patches. Estimation of overall disease severity using a numeric rating scale correlated highly significantly (Pearson correlation coefficient = 0.767; p < 0.001) between patients/caregivers and physicians. In general, physicians more likely quoted items as 'unknown' than patients (822 answers vs. 435 answers in the respective groups). Questionnaires completed by physicians who were associated with a specialized TSC centre declared a significantly lower proportion of items as unknown (mean 8.7% vs. 20.5%; p < 0.001). These findings indicate that patients treated by specialized TSC centres seem to obtain a more comprehensive surveillance. Furthermore, it shows that there were reasonable surveillance strategies in general and sufficient patient/caregiver interaction and education in the examined cohort. However, for the most prominent disease characteristics there was a good awareness within both the patients/caregivers and the physicians group.