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Radiology Case Reports Mar 2024Angiomyolipomas are benign renal hamartomas with - fat, smooth muscle, and abnormal blood vessel (tortuous, dysmorphic) components. The risk of hemorrhage is related to...
Angiomyolipomas are benign renal hamartomas with - fat, smooth muscle, and abnormal blood vessel (tortuous, dysmorphic) components. The risk of hemorrhage is related to size of the tumor, presence of aneurysm, associations with tuberous sclerosis. In this case report we review the case of a 42-year-old woman presenting with acute flank pain and decreased hemoglobin, who was diagnosed with AML with right renal artery pseudo aneurysm on CT. Subsequent coil embolization of feeding vessels and using PVA particles was successfully done. Selective embolization remains a minimally invasive, attractive option, and a nephron sparing approach.
PubMed: 38226046
DOI: 10.1016/j.radcr.2023.11.077 -
Nature Communications Jan 2024Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in...
Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in TSC. Here, we generated two mouse models of TSC in which kidney pathology is the primary phenotype. Knockout of TFEB rescues kidney pathology and overall survival, indicating that TFEB is the primary driver of renal disease in TSC. Importantly, increased mTORC1 activity in the TSC2 knockout kidneys is normalized by TFEB knockout. In TSC2-deficient cells, Rheb knockdown or Rapamycin treatment paradoxically increases TFEB phosphorylation at the mTORC1-sites and relocalizes TFEB from nucleus to cytoplasm. In mice, Rapamycin treatment normalizes lysosomal gene expression, similar to TFEB knockout, suggesting that Rapamycin's benefit in TSC is TFEB-dependent. These results change the view of the mechanisms of mTORC1 hyperactivation in TSC and may lead to therapeutic avenues.
Topics: Animals; Mice; Kidney Neoplasms; Mechanistic Target of Rapamycin Complex 1; Mice, Knockout; Sirolimus; Tuberous Sclerosis
PubMed: 38195686
DOI: 10.1038/s41467-023-44229-4 -
Frontiers in Surgery 2023Hepatic angiomyolipoma is a rare and possibly cancerous mesenchymal tumor that consists of three components: blood vessels, smooth muscle cells, and adipose tissue. In...
Hepatic angiomyolipoma is a rare and possibly cancerous mesenchymal tumor that consists of three components: blood vessels, smooth muscle cells, and adipose tissue. In this paper, we reported a case of a 36-year-old man who had a giant hepatic angiomyolipoma with spontaneous rupture and hemorrhage. The patient was admitted to our hospital with sudden upper abdominal pain for 3 h. A giant tumor was found in the left and caudate lobes of the liver, as well as significant blood collection around the liver and in the pelvis. Hemoglobin, liver function test results, and serum tumor maker levels were all within normal ranges. To prevent bleeding, emergency angiography and embolization were performed. During angiography, it was discovered that the tumor was supplied by the left hepatic artery and had a very rich internal blood supply. A massive left hepatic mass of about 11 cm in diameter was found bulging from the surface of the liver and rupturing there during laparoscopic exploration a week later. The rupture was strongly adhered to the smaller curvature of the stomach. The patient underwent laparoscopic left hemihepatectomy and caudate lobectomy, and the tumor specimen was brown, with clear boundaries with the surrounding normal liver parenchyma, and there were a large number of necrotic lesions inside the tumor. Histopathological results confirmed the mass as hepatic angiomyolipoma with negative resection margins. Immunohistochemical staining indicated that the tumor had positive homatropine methylbromide-45. After 13 months of follow-up, no tumor recurrence or metastasis occurred in the patient.
PubMed: 38186388
DOI: 10.3389/fsurg.2023.1329535 -
Sultan Qaboos University Medical Journal Dec 2023Angiomyolipoma is a common benign solid tumour that accounts for up to 3% of all renal tumours; most of the cases are sporadic. However, it can be part of other...
Angiomyolipoma is a common benign solid tumour that accounts for up to 3% of all renal tumours; most of the cases are sporadic. However, it can be part of other diseases. Angiomyolipomas are usually found incidentally through unrelated clinically indicated images but also, they can be diagnosed after complications have occurred. We report the case of retroperitoneal haemorrhage following the rupture of renal angiomyolipoma post-fibrinolysis, we are highlighting such a rare condition, the management options and the follow-up plan. The management of angiomyolipomas ranges from conservative treatment to surgical intervention depending on the patient's condition and the tumour's radiological features. Following-up on patients with angiomyolipomas depends on the symptoms and the tumour size. Till date, there is no reported cases of renal angiomyolipoma rupture post-fibrinolysis therapy as a treatment for myocardial infarction in non-percutaneous intervention capable facility.
Topics: Humans; Kidney Neoplasms; Angiomyolipoma; Fibrinolysis; Hamartoma; Thrombolytic Therapy
PubMed: 38161759
DOI: 10.18295/squmj.12.2023.074 -
Asian Journal of Surgery Mar 2024
Topics: Humans; Tuberous Sclerosis; Angiomyolipoma; Kidney Neoplasms; Hamartoma; Hemorrhage; Embolization, Therapeutic
PubMed: 38145913
DOI: 10.1016/j.asjsur.2023.12.080 -
Cureus Dec 2023Wunderlich syndrome, a rare manifestation of spontaneous renal hemorrhage often attributed to renal angiomyolipomas, presents a complex clinical scenario demanding...
Wunderlich syndrome, a rare manifestation of spontaneous renal hemorrhage often attributed to renal angiomyolipomas, presents a complex clinical scenario demanding nuanced management. This article delves into the multifaceted dimensions of this syndrome, dissecting its clinical, diagnostic, and therapeutic intricacies. Illustrating this complexity is the case of a 26-year-old female with Wunderlich syndrome and comorbid type 1 diabetes mellitus, revealing challenges at the intersection of these conditions. While initial intervention via laparoscopic drainage and antibiotic therapy yielded symptomatic relief, the subsequent recurrence of a renal abscess prompted a re-evaluation of the treatment strategy, culminating in a second surgical intervention. The intricate interplay between Wunderlich syndrome and diabetes introduces unique challenges, with fluctuations in hemoglobin and recurrent leukocytosis mirroring the underlying complexities of this clinical dyad. This case underscores the indispensability of a multidisciplinary approach, seamlessly integrating medical and surgical modalities, coupled with vigilant postoperative monitoring. Swift identification of complications and adaptability of the treatment plan emerged as pivotal in addressing recurrent manifestations and averting long-term sequelae. The necessity for continuous surveillance and personalized management strategies becomes evident, emphasizing Wunderlich syndrome as a clinical entity requiring bespoke attention. In conclusion, this case serves as an example, highlighting the intricate nature of Wunderlich syndrome, accentuated by the presence of type 1 diabetes mellitus. The initial therapeutic success, followed by a recurrence, underscores the need for ongoing research, paving the way for refined diagnostic and treatment paradigms. The synthesis of clinical complexities in this scenario elucidates the imperative for a comprehensive understanding, guiding future endeavors aimed at optimizing the prognosis of patients affected by this uncommon syndrome.
PubMed: 38098738
DOI: 10.7759/cureus.50481 -
Asian Journal of Surgery Mar 2024
Topics: Humans; Carcinoma, Renal Cell; Angiomyolipoma; Kidney Neoplasms; Epidermal Cyst; Hamartoma; Diagnostic Errors; Diagnosis, Differential
PubMed: 38087691
DOI: 10.1016/j.asjsur.2023.12.016 -
Orphanet Journal of Rare Diseases Dec 2023The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms... (Clinical Trial)
Clinical Trial
BACKGROUND
The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC.
RESULTS
The study included 64 patients with TSC (median age: 19, range 0.9-54 years) receiving everolimus treatment (Norway: n = 35; Denmark: n = 29). Among 45 patients with epilepsy, 14 (31%) were responders experiencing ≥ 50% reduction in seizure frequency in the last 3 months of treatment compared with the last 3 months before treatment. Nineteen (42%) patients changed their anti-seizure medications (ASMs). Responders were more common among patients < 18 years (46%) than among patients ≥ 18 years (14%, p = 0.03). In 29 patients with rAML, everolimus reduced (≥ 30% decrease) and stabilized (< 20% increase, ≤ 30% decrease) longest diameter of rAML in 38% and 59%, respectively, after a mean treatment duration of 37 months. SEGA volume was reduced in three patients by 71%, 43%, and 48% after 39, 34, and 82 months. Adverse effects were reported in 61 of 64 patients (95%) after a median treatment duration of 31 months (range 0-106), with oral ulceration/stomatitis (63%) and upper respiratory tract infections (38%) being the most common. The most common laboratory abnormalities were increased cholesterol (41%), anaemia (30%), and leucopoenia (25%). Grade 3-4 adverse effects were reported in 36% of cases, and life-threatening conditions were reported in two patients. Nine patients discontinued everolimus treatment.
CONCLUSIONS
Seizure reduction in this study sample was consistent with results from EXIST, but might be lower than expected, given that changes in concomitant ASMs are part of clinical practice. Seizure reduction was associated with younger age. As with EXIST, everolimus reduced or stabilised rAML size in most patients. SEGA volume was reduced in all three patients. Close follow-up is needed for this group, especially for children and patients who may not be able to report adverse effects.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Middle Aged; Young Adult; Angiomyolipoma; Antineoplastic Agents; Astrocytoma; Epilepsy; Everolimus; Kidney Neoplasms; Seizures; Tuberous Sclerosis
PubMed: 38042867
DOI: 10.1186/s13023-023-02982-1 -
Frontiers in Physiology 2023Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disease caused by mutations in either or genes. Approximately, two million individuals suffer from... (Review)
Review
Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disease caused by mutations in either or genes. Approximately, two million individuals suffer from this disorder worldwide. TSC1 and TSC2 code for the proteins harmartin and tuberin, respectively, which form a complex that regulates the mechanistic target of rapamycin complex 1 (mTORC1) and prevents uncontrollable cell growth. In the kidney, TSC presents with the enlargement of benign tumors (angiomyolipomas) and cysts whose presence eventually causes kidney failure. The factors promoting cyst formation and tumor growth in TSC are poorly understood. Recent studies on kidney cysts in various mouse models of TSC, including mice with principal cell- or pericyte-specific inactivation of TSC1 or TSC2, have identified a unique cystogenic mechanism. These studies demonstrate the development of numerous cortical cysts that are predominantly comprised of hyperproliferating A-intercalated (A-IC) cells that express both TSC1 and TSC2. An analogous cellular phenotype in cystic epithelium is observed in both humans with TSC and in TSC2 mice, confirming a similar kidney cystogenesis mechanism in TSC. This cellular phenotype profoundly contrasts with kidney cysts found in Autosomal Dominant Polycystic Kidney Disease (ADPKD), which do not show any notable evidence of A-IC cells participating in the cyst lining or expansion. RNA sequencing (RNA-Seq) and confirmatory expression studies demonstrate robust expression of Forkhead Box I1 (FOXI1) transcription factor and its downstream targets, including apical H-ATPase and cytoplasmic carbonic anhydrase 2 (CAII), in the cyst epithelia of (or ) knockout (KO) mice, but not in Polycystic Kidney Disease () mutant mice. Deletion of FOXI1, which is vital to H-ATPase expression and intercalated (IC) cell viability, completely inhibited mTORC1 activation and abrogated the cyst burden in the kidneys of KO mice. These results unequivocally demonstrate the critical role that FOXI1 and A-IC cells, along with H-ATPase, play in TSC kidney cystogenesis. This review article will discuss the latest research into the causes of kidney cystogenesis in TSC with a focus on possible therapeutic options for this devastating disease.
PubMed: 38028758
DOI: 10.3389/fphys.2023.1289388 -
Cureus Oct 2023Hemangioblastoma, also known as capillary hemangioblastoma, is a rare benign mesenchymal tumor commonly found in the central nervous system (CNS). It can also manifest...
Hemangioblastoma, also known as capillary hemangioblastoma, is a rare benign mesenchymal tumor commonly found in the central nervous system (CNS). It can also manifest in various organs, including the kidney. Renal hemangioblastoma (RH) is often associated with Von Hippel-Lindau (VHL) disease, but sporadic occurrences are observed infrequently. While RH is usually asymptomatic, it can also cause abdominal pain and hematuria. In this study, we present a case of an elderly patient without history of VHL but complaining of abdominal pain for three days. Serological evaluations were unremarkable, and a CT scan identified a 2.4 cm mixed solid-cystic mass lesion on the left kidney's superior aspect. The patient subsequently underwent a biopsy followed by lesion ablation. Microscopic analysis revealed sheets of eosinophilic cells with ovoid nuclei, showing focal rhabdoid and spindle cell features, with an intricate capillary network. Focal nuclear atypia without necrosis or mitosis was noted. Immunohistochemistry (IHC) demonstrated positive staining for inhibin, S100, PAX8, and vimentin, along with patchy positivity for CD10 and RCC. Negative staining was observed for cytokeratin AE1/AE3, CK7, EMA, CK8/18, desmin, and HMB-45. The overall morphological characteristics and distinct IHC markers were consistent with RH. Although its pathogenesis remains unclear because of its rarity, distinguishing RH from renal cell carcinoma is crucial. IHC markers facilitate differentiation among lesions. The preferred treatment involves ablation or partial nephrectomy. Further assessment for possible VHL syndrome is essential, considering the distinct management approaches for sporadic and VHL-linked RH.
PubMed: 38022288
DOI: 10.7759/cureus.47102