Exploring serum metabolic markers for the discrimination of ccRCC from renal angiomyolipoma by metabolomics.

Aim: The discrimination of renal cell carcinoma from renal angiomyolipoma (RAML) is crucial for the effective treatment of each. Materials & methods: Serum samples were analyzed by nuclear magnetic resonance spectroscopy-based metabolomics and a number of metabolites were further quantified by HPLC-UV. Results: Clear-cell renal carcinoma (ccRCC) was characterized by drastic disruptions in energy, amino acids, creatinine and uric acid metabolic pathways. A logistic model for the differential diagnosis of RAML from ccRCC was established using the combination of serum levels of uric acid, the ratio of uric acid to hypoxanthine and the ratio of hypoxanthine to creatinine as variables with area under the curve of the receiver operating characteristic curve value of 0.907. Conclusion: Alterations in serum purine metabolites may be used as potential metabolic markers for the differential diagnosis of ccRCC and RAML.

Evaluation of ABO blood groups and blood-based biomarkers as a predictor of growth kinetics of renal angiomyolipoma.

PURPOSE: The aim of our study was to investigate the impact of the ABO blood groups and blood-based biomarkers on the growth kinetics of renal angiomyolipoma (AML). METHODS: A total of 124 patients with AML who were followed-up between 2010 and 2018 were retrospectively reviewed. The patients' characteristics were recorded, including age, body mass index (BMI), blood pressure, smoking history, and ABO blood group. Baseline laboratory test results, including serum creatinine, AST, ALT, platelet, neutrophil and lymphocyte count, were used to calculate the estimated glomerular filtration rate (eGFR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and De Ritis ratio. The Cox regression analysis was used to evaluate the relationship between variables and tumor growth. RESULTS: The study population comprised 71 women and 44 men with a median age of 47.3 (28-65) years. Among patients classified according to the blood groups, no significant differences were observed regarding age, BMI, smoking history, co-morbidities, NLR, PLR, De Ritis ratio, eGFR, or tumor size and localisation. The mean growth rate from baseline to the last scan was 0.36 ± 0.27 cm, 0.21 ± 0.21 cm, 0.14 ± 0.11 cm, and 0.19 ± 0.17 cm for blood type O, A, B, and AB, respectively. In multivariate analysis, eGFR < 60 (p = 0.044), central tumor localisation (p = 0.030), presence of blood group-0 (p = 0.038), and De Ritis ratio ≥ 1.24 (p = 0.047) were statistically associated with tumor growth. CONCLUSION: Our study demonstrates that both the ABO blood groups and the De Ritis ratio might represent independent predictors of tumor growth rate in patients with renal AML.

Retroperitoneal laparoscopic nephron sparing surgery for large renal angiomyolipoma: Our technique and experience. A case series of 41 patients.

OBJECTIVES: To introduce a 'kidney priority' strategy in treating large renal angiomyolipoma (RAML) with retroperitoneal laparoscopic nephron sparing surgery (RLNSS). PATIENTS AND METHODS: From 2010 to 2017, 41 patients with large RAML underwent RLNSS. Distinguished from the standard practice, the kidney was preferentially mobilized and separated from the RAML. Subsequently, it was reconstructed. Finally, the RAML was resected from the perinephric fat. The perioperative variables, surgical technique and complications were reviewed. Patients were followed up with ultrasonography and computed tomography. RESULTS: RLNSS was successfully performed in 35 patients with four conversions to open surgery and two conversions to nephrectomy, respectively. Eight patients required an intraoperative blood transfusion. Seven patients experienced postoperative complications, including one wound infection, one urinary tract infection, one pneumonia, one urinary fistula and three hemorrhage. The median operation time was 167min (range, 95-285min), the median warm ischemia time was 21 min (range, 0-40 min), and the median estimated blood loss was 200 ml (range, 30-2500 ml). The median postoperative stay was 6.5 days (range, 3-11 days). Angiomyolipoma was confirmed pathologically in all patients. Median serum creatine increased after surgery, from 0.7 mg/dl (range, 0.4-1.1 mg/dl) preoperatively to 0.8 mg/dL (range, 0.5-1.4 mg/dl) postoperatively (P = 0.016). No patient required dialysis, and no recurrence was observed after a median follow-up of 35 months (range, 3-85 months). CONCLUSIONS: RLNSS is a safe, feasible, effective and minimally invasive procedure to manage large RAML in selected patients.

Partial Nephrectomy for Presumed Renal-Cell Carcinoma: Incidence, Predictors, and Perioperative Outcomes of Benign Lesions.

BACKGROUND: The aim of this study was to investigate the incidence of benign histology after partial nephrectomy (PN) in patients with presumed malignancy from preoperative imaging. Furthermore, preoperative predictors of benign lesions and perioperative outcomes were also assessed. METHODS: A series of patients undergoing PN for renal masses was identified using a prospectively maintained database. Patients were excluded for known genetic conditions, if more than one renal mass was resected, or if standard preoperative imaging was not suspicious for renal-cell carcinoma (RCC). Differences in characteristics between patients with benign and malignant pathology were assessed. RESULTS: A total of 916 patients were identified who underwent PN between 2007 and 2015, including 129 (14.1%) patients with a final diagnosis of benign disease. The most common types of benign pathology were oncocytoma (n = 66, 51.2%), angiomyolipoma (n = 37, 28.7%), and complex cysts (n = 10, 7.8%). Low body mass index (BMI) [0.96 (0.92-0.99) p = 0.02], low R.E.N.A.L. score [0.86 (0.76-0.96) p = 0.007], and low preoperative creatinine [0.37 (0.14-0.91) p = 0.04] predicted benign histology in multivariate analysis. Tumor size was a significant predictor in additional modeling [0.81 (0.69-0.94) p = 0.008]. Patients with benign histology had significantly shorter operative times (p < 0.001) and less estimated blood loss (p < 0.001), and there was no difference in complication (p = 0.93) or blood transfusion (0.24) rates. CONCLUSIONS: In this study, the rate of benign pathology after PN for presumed RCC is 14.1%. BMI, R.E.N.A.L. score, and preoperative creatinine are predictive of benign histology, but the ability of different variables to predict benign lesions may be influenced by the distribution of benign tumor subtypes, reflecting potential unidentified selection bias.

miR-144-3p as a novel plasma diagnostic biomarker for clear cell renal cell carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal subtype of renal cell carcinoma, whose most effective measure of curing remains diagnosis and nephrectomy in its early phase. However, there is no feasible and recognized plasma biomarker for the clinical diagnosis of ccRCC. The objective of this study is to identify a novel plasma microRNA (miRNA) acting as an efficient diagnostic plasma biomarker in ccRCC. METHODS AND MATERIALS: The plasma miRNA expression profile was quantified by miRNA microarray. Validation of miRNA levels of plasmas and tissues were performed by quantitative reverse transcription polymerase chain reaction in 106 ccRCC, 28 renal angiomyolipomas (AML), and 123 healthy control plasmas and in 110 ccRCC tissues. RESULTS: We found that plasma miR-144-3p levels in 106 ccRCC plasmas were remarkably up-regulated compared with that in healthy individuals and in patients with AML. miR-144-3p served as a promising plasma biomarker for yielding an area under the receiver operating characteristic curve of 0.91 with 87.10% sensitivity and 83.02% specificity in discriminating ccRCC from healthy individuals, and an area under the curve of 0.82 with 75.00% sensitivity and 71.70% specificity in discriminating ccRCC from patients with AML. In addition, plasma miR-144-3p levels were significantly decreased after surgery in 106 patients with ccRCC. Next, we examined miR-144-3p levels in 110 human ccRCC tissues, and found that miR-144-3p levels in ccRCC tissues were increased compared with adjacent normal tissues. Pearson correlation analysis revealed that miR-144-3p levels in tumor tissues were positively correlated with preoperative plasma miR-144-3p levels in the matched samples from patients with ccRCC. In addition, the miR-144-3p levels in ccRCC plasmas and tissues were increased in patients with advanced pT stage. CONCLUSIONS: Our data indicate that miR-144-3p, which is significantly up-regulated in ccRCC plasmas and tissues, particularly with advanced pT stage, is a novel and excellent plasma biomarker for the diagnosis of ccRCC.

Hemorragia retroperitoneal espontánea por rotura de angiomiolipoma renal. Presentación de caso / Spontaneous retroperitoneal hemorrhage due to renal angiomyolipoma rupture. Case presentation

Introducción: El angiomiolipoma renal es un tumor benigno y poco común que, al romperse, origina hemorragia retroperitoneal que puede poner en riesgo la vida. Objetivos: Presentar un nuevo caso de hemorragia retroperitoneal por rotura espontánea de un angiomolipoma renal, con énfasis en los elementos del diagnóstico y la terapéutica. Presentación del caso: Paciente masculino de 53 años de edad, con antecedentes de crisis convulsivas desde la infancia e hipertensión arterial, quien asistió al Cuerpo de Guardia de la Clínica Multiperfil de Luanda, por dolor en el hemiabdomen derecho, vómitos y febrícula de dos días de evolución. Al examen físico, presentaba contractura abdominal en flanco y fosa ilíaca derechos y taquicardia. La analítica sanguínea reveló leucocitosis ligera, por lo que se sospechó abdomen agudo de origen inflamatorio visceral, y se decidió realizar laparoscopía diagnóstica, en la que fue identificado un hematoma retroperitoneal extenso, con predominio hacia la derecha. Ante la estabilidad hemodinámica del paciente, se dispuso realizar tomografía axial computarizada abdominal contrastada, que evidenció una masa tumoral compleja en la cara anterior del riñón derecho, con discontinuidad de la corteza y colección hemática circundante. En la laparotomía de urgencia fue hallado un tumor renal derecho roto que precisó de la nefrectomía total. El paciente evolucionó satisfactoriamente. El informe histopatológico de la pieza quirúrgica fue angiomiolipoma renal roto. Conclusiones: Aunque es infrecuente, debe tenerse en cuenta la posibilidad del debut clínico de un angiomiolipoma renal roto, con hemorragia retroperitoneal, dentro de los diagnósticos diferenciales del abdomen agudo quirúrgico(AU)

Introduction: The renal angiomyolipoma is a benign and rare tumor that when breaking, cause a retroperitoneal hemorrhage. Objective: To present a new case of spontaneous retroperitoneal hemorrhage due to renal angiomyolipoma rupture, with emphasis in the diagnostic elements and therapeutics. Case presentation: Male patient, 53 years old, with antecedents of convulsive crises since infancy and high blood pressure, that arrives to Luanda´s Multiprofile Clinic, showing pain in the right side of abdomen, vomits and low-grade fever of two days of evolution. On physical examination revealed abdominal contracture in rights flank and iliac fossa and tachycardia. Blood analysis revealed a light leucocytosis, and form that which was suspected an acute abdomen of inflammatory visceral origin, deciding a performance of a diagnostic laparoscopy, in which was identified an extensive retroperitoneal hematoma, with right side predominance. Taking in account the patient hemodynamic stability, was determinate to make an abdominal contrasted computerized axial tomography, which shows a complex tumoral mass in the anterior surface of the right kidney, with cortex discontinuity and hematic collection in the surrounding area. An urgency laparotomy was performed; was found a broken tumor in the renal right side that required a total nephrectomy without complications. The patient evolved satisfactorily. A broken renal angiomyolipoma was point by the histopathology report. Conclusions: Although it is infrequent, has to take into account the possibility of the clinical debut of a renal angiomyolipoma with retroperitoneal bleeding, as part of the differential diagnostics of the acute surgical abdomen(AU)

Correlation of serum vascular endothelial growth factor-D concentration with clinical presentation and course of lymphangioleiomyomatosis.

BACKGROUND: Increased serum vascular endothelial growth factor D (VEGF-D) concentration has been accepted as a diagnostic marker in lymphangioleiomyomatosis (LAM). The study was performed to evaluate the correlation of VEGF-D with clinical presentation and course of LAM. MATERIAL: The study group comprised of 48 women with LAM (27 with sLAM, 9 with sLAM and lymphangioma (sLAM-LYM) and 12 patients with TSC/LAM). Patients were assessed at the time of VEGF-D examination, and pulmonary function parameters were compared with those, obtained one year before. VEGF-D serum concentration was measured by ELISA method. RESULTS: Patients with TSC/LAM and sLAM-LYM displayed higher concentrations of VEGF-D than patients with sLAM (2682 ± 1347 pg/mL and 2223 ± 1184 pg/mL vs.1281 ± 791 pg/mL; p = 0.0002, p = 0.009) respectively. Patients with sLAM and VEGF-D concentration <800 pg/mL (sLAM-L) had better lung function as assessed by FEV1 (2.38 ± 0.88 L vs. 1.75 ± 0.8 L; p < 0.015) and DL,CO (5.8 ± 2.25 vs. 3.93 ± 1.74 mL/min/mmHg; p < 0.028), had higher blood oxygenation, then those with VEGF-D >800 pg/mL (sLAM-H). Significant yearly increase of TLC (390 ± 700 mL; p < 0.021) and RV (340 ± 790 mL; p < 0.03), and decrease of distance in 6MWT (-30 ± 50 m; p = 0.04) were observed in sLAM-H group. Lung function parameters remained constant in sLAM-L patients. Patients with sLAM-H displayed higher yearly decline of FVC (120 vs. 50 mL; p = 0.035) and increase of TLC (390 vs. -80 mL; p = 0.038) and RV (340 vs. 90 mL; p = 0.045) than sLAM-L patients. Negative correlations between VEGF-D concentration and DL,CO, PaO2, PaCO2, and positive with HRCT grading, and desaturation in 6MWT were noticed in sLAM patients without lymphangioma. CONCLUSIONS: Serum VEGF-D is the useful biomarker of LAM extension, and might also prove predictive towards therapeutic decision.

Similar trends in serum VEGF-D levels and kidney angiomyolipoma responses with longer duration sirolimus treatment in adults with tuberous sclerosis.

CONTEXT: We have previously shown that serum VEGF-D is elevated at baseline, correlates with kidney angiomyolipoma size at baseline and 12 months, and decreases with sirolimus treatment in adults with tuberous sclerosis complex (TSC). To further investigate the utility of serum VEGF-D for longer term monitoring of TSC kidney disease, we present VEGF-D level results with 24 month follow-up. OBJECTIVE: To compare 24 month VEGF-D levels in two subgroups of sirolimus treated patients (OFF SIROLIMUS AFTER 12 MONTHS or ON SIROLIMUS AFTER 12 MONTHS). DESIGN AND INTERVENTION(S): Serum VEGF-D was measured in samples collected from subjects enrolled in a phase 2 multicenter trial evaluating sirolimus for the treatment of kidney angiomyolipomas associated with TSC or TSC/LAM. All participants were treated with sirolimus from 0-12 months. During months 12-24, sirolimus was discontinued in one subgroup. The other subgroup was treated with additional sirolimus. SETTING: Adult TSC participants were recruited from six clinical sites in the United States (comprehensive TSC clinics, 5; urology clinic, 1). PATIENTS: There were 28 TSC patients who completed all 24 months of the study and serum samples were available at 24 months from 18/28 patients. MAIN OUTCOME MEASURE(S): We compared the percent change in VEGF-D levels (baseline to 24 months) in patients from the two treatment subgroups. RESULTS: At 24 months, VEGF-D levels decreased by 67% compared with baseline (to 787 ± 426 pg/ml) in the ON SIROLIMUS AFTER 12 MONTHS group versus a 13% decrease (to 2971 ± 4014 pg/ml) in the OFF SIROLIMUS AFTER 12 MONTHS group (p=0.013, Mann-Whitney test). A similar trend was observed in kidney angiomyolipoma size but not in pulmonary function tests. Conclusions Serum VEGF-D may be useful for monitoring response to treatment with sirolimus and kidney angiomyolipoma size in patients with TSC, but confirmation is needed. TRIAL REGISTRATION: Clinical trials.gov NCT00126672.

In vivo partial nephrectomy of angiomyolipoma with concurrent transplantation.

INTRODUCTION/OBJECTIVE: To describe a novel management approach to patients presenting for living renal donation who have a suspicious renal mass or cyst and review the current literature for the management of renal allografts containing masses. MATERIALS AND METHODS: We retrospectively reviewed the preoperative, intraoperative, and postoperative records of both the donor and recipient for pertinent imaging, laboratory results, and complications. We also performed a Medline search to review the world literature of such cases, using the key words that we have listed for this article. RESULTS: In our reported case, an angiomyolipoma (AML) was confirmed intraoperatively in the donor, the donor nephrectomy was completed, and the graft was successfully transplanted. There were no postoperative complications. The recipient remains off dialysis with a serum creatinine of 2.4 mg/dl at 18 months of follow-up. Review of the current literature supports using a similar strategy for both renal masses and suspicious cysts. Furthermore, it confirms the safety and benefits of using a laparoscopic surgical approach to similar patients in the future. CONCLUSIONS: Intraoperative pathologic analysis of small renal lesions in a renal allograft is a feasible procedure for potential kidney donors. In the future modifying this approach with a combined laparoscopic partial and donor nephrectomy will minimize the morbidity to the donor. Applying this technique may have a positive effect on organ supply.

Detection of carbonic anhydrase-9 gene expression in peripheral blood cells predicts risk of disease recurrence in patients with renal cortical tumors.

OBJECTIVES: To present extended follow-up on a cohort of patients with renal cortical tumors treated with partial or radical nephrectomy and preoperatively assess for carbonic anhydrase 9 tumor marker expression in the peripheral blood. METHODS: All patients were originally enrolled in an institutional review board-approved study assessing the role of a reverse-transcriptase polymerase chain reaction peripheral blood assay designed to detect the tumor-specific gene carbonic anhydrase-9 (CA9). A total of 41 patients with renal cortical tumors confined to the kidney were enrolled at a single institution and assessed preoperatively with peripheral blood test for CA9 expression before undergoing partial or radical nephrectomy. A Kaplan-Meier estimated survival analysis and log-rank test were performed to determine whether detection of peripheral blood cells expressing the CA9 gene influences disease-free and disease-specific survival. RESULTS: The median follow-up was 4.3 years. The median age was 71 years. Of the 41 patients, 26 were men and 15 were women. The estimated 5-year disease-free survival for patients with detectible expression of the CA9 gene in the peripheral blood was 39.5% compared with 88.1% for patients without detection of the CA9 gene (P = 0.048). On bivariate analysis, disease-free survival correlated with histologic type, tumor diameter, and tumor grade. CONCLUSIONS: The expression of the tumor-specific marker CA9 in the peripheral blood is associated with decreased disease-free survival in patients with renal cortical tumors. This is the first study reporting on the prognostic value of this peripheral blood-based tumor marker for kidney tumors.

[Incidental detection of a rare liver tumor: angiomyolipoma]. / Une rare lésion hépatique de découverte fortuite: l'angiomyolipome.

We report the case of a woman who presented a single liver lesion with no evidence of specific findings at Doppler US, CT, nuclear studies and MRI to suggest angiomyolipoma. The final diagnosis was confirmed at anatomopathology and immunohistochemistry which demonstrated positive anti-HMB 45 aspect.

Detection of prostate-specific membrane antigen expressing cells in blood obtained from renal cancer patients: a potential biomarker of vascular invasion.

Originally, prostate-specific membrane antigen (PSMA) was described in benign and malignant prostate cells. On the basis of recent reports that this antigen also is expressed in normal renal proximal tubular cells and in the neovascular endothelium associated with renal carcinoma, we used a nested reverse transcriptase-polymerase chain reaction assay to evaluate whether PSMA-expressing cells might be present in specimens of peripheral blood obtained from renal cancer patients, benign renal tumor patients, and healthy volunteers. Our reverse transcriptase-polymerase chain reaction PSMA assay had a sensitivity of detecting 1 lymph node prostate cancer (LNCaP) per 10(7) lymphocytes. None of the 20 non-renal cancer controls were positive for PSMA mRNA, whereas 11 of 50 patients (22%) with diagnosed renal cancer were positive. Despite a comparative increase of PSMA positivity with stage, no statistical correlation was found. However, 44% of PSMA-positive patients had tumor size greater than 12 cm, versus only 9% in patients negative for PSMA (P = .03), and 67% of positive PSMA patients were found to have vascular invasion versus only 16% of patients negative for PSMA (P = .006; odds ratio, 10.8). This preliminary study suggests the possibility that PSMA expression in peripheral blood might be a useful biomarker for detecting or monitoring the progression of renal cancer in patients.

Giant hepatic angiomyolipoma associated with disseminated intravascular coagulation.

We report a case of giant hepatic angiomyolipoma in a 68-year-old woman who had an increase in the fibrinolytic activity concomitant with disseminated intravascular coagulation (DIC). The presence of the tumor was confirmed by ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen and the selective arteriography of the liver via the superior mesenteric artery. Following treatment with heparin and gabexate mesilate, abnormal hemostatic values were corrected. Furthermore, the surgical removal of the huge hepatic angiomyolipoma completely normalized the alternations of the clotting system. These findings suggest that giant hepatic angiomyolipoma was profoundly associated with DIC.