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Objectives: Contrast-enhanced ultrasound (CEUS) allows excellent delineation of perfusion in septa and nodules without exposure to ionizing radiation or nephrotoxic contrast media. The aim of our study was to evaluate the role of CEUS for the assessment of cystic renal masses and compare its diagnostic performance with that of CECT., Methods: Exactly 40 patients diagnosed to have cystic renal masses on CECT scan were prospectively evaluated with CEUS and were assigned a Bosniak class. Based on results of final histopathology and clinical follow-up, internal validity of both CEUS and CECT was evaluated, including agreement between these two modalities., Results: Out of the 40 patients (mean size 3.1 ± 2.5 cm), 23 patients had benign lesions and 17 patients had malignant lesions. For CEUS, the sensitivity and negative predictive value was 100%, the specificity and positive predictive value was 73.9%. For CECT, the sensitivity and negative predictive value were 88.2 and 83.3%, respectively, whereas the specificity and positive predictive value was 87 and 90.9%, respectively. Both imaging modalities had similar accuracy with fair to good agreement with the final diagnosis (Κ = 0.71 and 0.75 for CEUS and CECT, respectively). Concordance between CEUS and CECT was seen in 29 patients (72.5%) with fair agreement between the two modalities (K = 0.66)., Conclusion: CEUS has comparable accuracy with CECT and could be used as screening modality to rule out the presence of complex cystic renal masses without exposure of nephrotoxic contrast media and ionizing radiation., (© 2023 American Institute of Ultrasound in Medicine.)

Focal renal lesions in the background of chronic kidney disease (CKD) present a diagnostic challenge. Contrast administration is usually avoided in such a setting, undermining the usefulness of computed tomography and magnetic resonance imaging. Focal regenerating nodules may occur in the background of CKD and closely mimic renal neoplasms. The aim of the present article was to highlight the salient manifestations of such CKD pseudotumors on different imaging modalities and also to depict the differentiating features from malignancy. Radiologists must be aware of the imaging appearance of this uncommonly talked about entity so as to avoid inadvertent surgery or cause undue anxiety to the patient.

Purpose: Trace elements and/or heavy metals are important for various biological activities. However, excess amount of these elements is associated with a variety of diseases, including cancer. We aimed to analyse the alterations of trace elements levels in renal cell carcinoma (RCC) patients., Materials and Methods: In this observational study, patients with biopsy proven RCC were taken as study group while age- and sex-matched healthy volunteers were taken as control. Blood and urine samples were compared for Arsenic (As), Copper (Cu), Manganese (Mn), Selenium (Se), Cadmium (Cd), Lead (Pb) and Mercury (Hg) levels measured by inductively coupled plasma mass-spectroscopy. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) antioxidant enzymes and lipid peroxidation (LPO) levels were assessed to know the redox status between 2 groups., Results: A total of 76 RCC cases and 64 controls were recruited in the study. A significantly higher concentration of As, Cu, Mn, Cd, Pb and Hg were observed in the blood of RCC patients as compared to controls. However, blood Se level was significantly lower in RCC patients. In 33 (43.4%) patients, one or more heavy metals were higher in the blood above their permitted level as compared to 10 (15.6%) subjects in control group. RCC patients had a higher urinary Mn and Se levels compared to controls. A significantly lower GSH-Px (182.08 ± 132.91 vs. 236.95 ± 132.94, P = 0.04) and a higher LPO levels (26.02 ± 20.79 vs. 14.06 ± 8.44, P = 0.003) were noted in RCC patients than controls. SOD levels were comparable between two groups., Conclusions: A significantly altered heavy metals concentration is noted in the blood and urine in RCC patients as compared to healthy controls. An associated lower levels of GSH-Px antioxidant enzyme and increased LPO in RCC patients signifies an imbalance in the redox status., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To qualitatively assess the clinical usefulness of patient-specific high-fidelity three-dimensional (3D) print model of kidney before partial nephrectomy (PN) and to identify subset domains where it may help in clinical terms. Materials and Methods: Thirteen 3D models were printed for tumors having RENAL nephrometry score of ≥8. Their usage for PN was assessed prospectively using a qualitative questionnaire to be answered on a Likert scale of 1-10. The questions focused on realistic resemblance, preoperative dry surgical run, intertest comparison, surgical impact, and overall beneficence domains as perceived by primary surgeons with respect to surgical conduct during PN. Results: Mean RENAL score was 9.15 (8-11). Models were rated high (9.07 ± 0.86) for realistic resemblance domain and were rated better than contrast-enhanced computed tomography (CECT) (8.38 ± 0.87) and intraoperative ultrasonography (8.07 ± 1.26) for orientation regarding resection margins. A further marginal improvement to 8.2 ± 0.84 was noted against ultrasound where surgeon did a dry cut preoperatively. Use of superselective arterial approach in four, precise awareness about dissection of a major vessel in four, retroperitoneoscopic approach in one, and surgical margin awareness in three were directly attributed to the model. Overall utility of having a model printed was rated high (8.23 ± 1.3). Conclusion: The 3D print models of complex renal tumors have high realistic resemblance to actual patient's anatomy. They were rated better than preoperative CECT or intraoperative ultrasonography for orientation regarding surgical resection margins. It may also help change or modify the surgical plan in a subset of patients with a potential to improve overall outcomes in these complex cases.

Purpose: Circulating tumor cells (CTC) have been demonstrated to have prognostic and predictive role in certain human cancers. However, studies exploring their role in metastatic renal cell carcinoma (mRCC) are scarce. We aimed to evaluate the prognostic and predictive role of CTC in mRCC., Materials and Methods: In this prospective study, 35 patients with mRCC were analyzed for the presence of CTC before starting tyrosine kinase inhibitors (TKI). Progression-free and overall survival rates were estimated using the Kaplan-Meier curves and log-rank test. The prediction to TKI therapy was calculated with the response to treatment determined by standard imaging techniques., Results: Outcomes were assessed according to the CTC positivity at baseline, before the patients started TKI for mRCC. At a mean follow-up of 12.4 ± 4.1 months, disease progression was noted in 17 patients (48.6%) including 8 deaths (22.9%). CTC positive patients had a significantly lower progression-free survival rate (12.5% vs. 64.1%, respectively; P = 0.009) but not in the overall survival rate (75% vs. 76.3%, respectively; P = 0.88) in the Kaplan-Meier estimation curves. CTC positivity at baseline significantly predicted a poorer response to TKI (87.5% vs. 37.1%, P = 0.01). The multivariate Cox proportional hazards analysis showed that CTC at baseline was the most significant predictor of progression-free survival (hazard ratio 4.17, 95% confidence interval 1.41-11.99, P = 0.01)., Conclusions: Baseline CTC detection can be an important prognostic factor of progression-free survival and significant predictor of poor response to TKI in patients with metastatic RCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To assess the utility of magnetic resonance texture analysis (MRTA) in differentiating renal cell carcinoma (RCC) from lipid-poor angiomyolipoma (lpAML) and oncocytoma., Methods: After ethical approval, 42 patients with 54 masses (34 RCC, 14 lpAML and six oncocytomas) who underwent MRI on a 1.5 T scanner (Avanto, Siemens, Erlangen, Germany) between January 2011 and December 2012 were retrospectively included in the study. MRTA was performed on the TexRAD research software (Feedback Plc., Cambridge, UK) using free-hand polygonal region of interest (ROI) drawn on the maximum cross-sectional area of the tumor to generate six first-order statistical parameters. The Mann-Whitney U test was used to look for any statically significant difference. The receiver operating characteristic (ROC) curve analysis was done to select the parameter with the highest class separation capacity [area under the curve (AUC)] for each MRI sequence., Results: Several texture parameters on MRI showed high-class separation capacity (AUC > 0.8) in differentiating RCC from lpAML and oncocytoma. The best performing parameter in differentiating RCC from lpAML was mean of positive pixels (MPP) at SSF 2 (AUC: 0.891) on DWI b500. In differentiating RCC from oncocytoma, the best parameter was mean at SSF 0 (AUC: 0.935) on DWI b1000., Conclusions: MRTA could potentially serve as a useful non-invasive tool for differentiating RCC from lpAML and oncocytoma., Advances in Knowledge: There is limited literature addressing the role of MRTA in differentiating RCC from lpAML and oncocytoma. Our study demonstrated several texture parameters which were useful in this regard.

Objective: The primary objective of the study was to evaluate the correlation between semi-quantitative F-18 FDG PET parameters and renal cell carcinoma (RCC) grade and its role in predicting the histopathological grade in RCC. The secondary objective was to evaluate the role of forced diuresis in improving the diagnostic accuracy of F-18 FDG for RCC., Methods: Thirty-three patients with radiologically proven RCC were included in the study. All patients underwent PET/CT on a dedicated PET/CT scanner (Biograph mCT; Siemens Medical Solutions, Erlangen, Germany) 45-60 min post-injection F-18-FDG. Patients were then injected 1 mg/kg body weight furosemide (upto 40 mg) and regional PET/CT images of abdomen were acquired after 2 h. For both baseline and post-diuretic F-18-FDG PET/CT scans, maximum standardized uptake value for tumor (SUVmax), mean SUV for tumor, metabolic tumor volume (MTV), tumor-to-liver (T/L) and tumor-to-kidney ratio (T/K) were calculated. Histopathology findings were considered as the reference standard. To assess the incremental value of diuresis in scan interpretation, visual analysis of scans was done., Results: Of 33 patients, histopathology grading was available for comparison with metabolic tumor markers in all except four. Of 29 patients (mean age = 51.89 ± 13.54 years), 20 patients had clear cell (cc) type while rest had non-cc RCC. Difference between the mean values among the categories was insignificant for all parameters except T/K. Fuhrman grading was obtained in 25 patients (17 low and eight high). SUVmax, MTV and T/L were found to be significantly different between low and high grade patients. Significantly strong positive correlation was observed between Furhman grades and tumor metabolism (r ≥ 0.5). No significant difference was observed between baseline and post-diuretic scan in any of the patients., Conclusion: Semi-quantitative F-18 FDG PET parameters (SUVmax, MTV and T/L) were found to be significantly correlated with Fuhrman grade in patients with RCC and are important markers for differentiation between low- and high-grade tumors. Furthermore, forced diuresis had no incremental value in characterization of primary RCC lesions.

The Corona Virus Disease-2019 (COVID-19), one of the most devastating pandemics ever, has left thousands of cancer patients to their fate. The future course of this pandemic is still an enigma, but health care services are expected to resume soon in a phased manner. This might be a long drawn process and we need to have policies in place, to be able to fight both, the SARS-CoV-2 virus and cancer, simultaneously, and emerge triumphant. An extensive literature search for impact of delay in management of various urological malignancies was carried out. Expert opinions were sought wherever there was paucity of evidence, in order to reach a consensus and come up with recommendations for directing uro-oncology services in the times of COVID-19. The panel recommends deferring treatment of patients with renal cell carcinoma by 3 to 6 months, except for those with ongoing hematuria and/or inferior vena cava thrombus, which warrant immediate surgery. Metastatic renal cell cancers should be started on targeted therapy. Low grade non-muscle invasive bladder cancers can be kept on active surveillance while high risk non-muscle invasive bladder cancers and muscle invasive bladder cancers should be treated within 3 months. Neoadjuvant chemotherapy should be avoided. Management of low and intermediate risk prostate cancer can be deferred for 3 to 6months while high risk prostate cancer patients can be initiated on neoadjuvant androgen deprivation therapy. Patients with testicular tumors should undergo high inguinal orchiectomy and be treated according to stage without delay, with stage I patients being offered surveillance. Penile cancers should undergo penectomy, while clinically negative groins can be kept on surveillance. Neoadjuvant chemotherapy should be avoided and adjuvant therapy should be deferred. We need to tailor our treatment strategies to the prevailing present conditions, so as to fight and defeat both, the SARS-CoV-2 virus and cancer. Protection of health care workers, judicious use of available resources, and a rational and balanced outlook towards different malignancies is the need of the hour., Competing Interests: None

Purpose: The study evaluated the usefulness of magnetic resonance imaging (MRI) texture parameters in differentiating clear cell renal carcinoma (CC-RCC) from non-clear cell carcinoma (NC-RCC) and in the histological grading of CC-RCC., Materials and Methods: After institutional ethical approval, this retrospective study analyzed 33 patients with 34 RCC masses (29 CC-RCC and five NC-RCC; 19 low-grade and 10 high-grade CC-RCC), who underwent MRI between January 2011 and December 2012 on a 1.5-T scanner (Avanto, Siemens, Erlangen, Germany). The MRI protocol included T2-weighted imaging (T2WI), diffusion-weighted imaging [DWI; at b 0, 500 and 1000 s/mm 2 with apparent diffusion coefficient (ADC) maps] and T1-weighted pre and postcontrast [corticomedullary (CM) and nephrographic (NG) phase] acquisition. MR texture analysis (MRTA) was performed using the TexRAD research software (Feedback Medical Ltd., Cambridge, UK) by a single reader who placed free-hand polygonal region of interest (ROI) on the slice showing the maximum viable tumor. Filtration histogram-based texture analysis was used to generate six first-order statistical parameters [mean intensity, standard deviation (SD), mean of positive pixels (MPP), entropy, skewness and kurtosis] at five spatial scaling factors (SSF) as well as on the unfiltered image. Mann-Whitney test was used to compare the texture parameters of CC-RCC versus NC-RCC, and high-grade versus low-grade CC-RCC. P value < 0.05 was considered significant. A 3-step feature selection was used to obtain the best texture metrics for each MRI sequence and included the receiver-operating characteristic (ROC) curve analysis and Pearson's correlation test., Results: The best performing texture parameters in differentiating CC-RCC from NC-RCC for each sequence included (area under the curve in parentheses): entropy at SSF 4 (0.807) on T2WI, SD at SSF 4 (0.814) on DWI b500, SD at SSF 6 (0.879) on DWI b1000, mean at SSF 0 (0.848) on ADC, skewness at SSF 2 (0.854) on T1WI and skewness at SSF 3 (0.908) on CM phase. In differentiating high from low-grade CC-RCC, the best parameters were: entropy at SSF 6 (0.823) on DWI b1000, mean at SSF 3 (0.889) on CM phase and MPP at SSF 5 (0.870) on NG phase., Conclusion: Several MR texture parameters showed excellent diagnostic performance (AUC > 0.8) in differentiating CC-RCC from NC-RCC, and high-grade from low-grade CC-RCC. MRTA could serve as a useful non-invasive tool for this purpose.

Background: Recurrence of renal cell cancer (RCC) affects approximately one-third of patients after curative nephrectomy. However, studies from the Indian subcontinent have been scarce. We here ddetermine relapse rates and patterns in an Indian cohort. Methods: This study included all patients with RCC who underwent nephrectomy from 2004 to 2013 at our centre. Recurrence-free survival (RFS) was calculated from the date of surgery to date of recurrence or death. The Cox regression model was applied to identify significant prognostic factors. Results: Overall a total of 292 patients were included. Median age was 50 years (range 19-84 years), with a male:female ratio of 3:1. Radical and partial nephrectomy were performed for 276 (94.5%) and 16 (5.5%) patients, respectively. Clear cell was most common histological subtype (71.2%) and T1, T2, T3 and T4 stages accounted for 89 (30.5%), 86 (29.5%), 105 (36%) and 12 (4.1%) patients, respectively. One hundred and thirty-six patients (46.6%) demonstrated recurrence. Eighty-six (63.2%) relapsed at distant sites, 14 (10.3%) and at locoregional sites whereas 36(26.5%) had both distant and locoregional recurrence. Median time to recurrence was 18 months. Approximately 17.7% of cases had disease reappearance after five years. Factors predicting shorter RFS on multivariate analysis were patient reported weight loss (p=0.004), Fuhrman grade 3 or 4 (p<0.0001), presence of necrosis (p<0.0001) and higher tumour stage (p=0.005). Conclusion: Compared to previous studies, our patients had higher rates of recurrence in general and locoregional recurrence in particular. However, except for weight loss, other predictive factors remain similar. Finding weight loss as the marker of recurrence emphasises the importance of the simple task of history taking., (Creative Commons Attribution License)

Objective: To study the expression profiles of 5 microRNAs in tissue and serum of patients with clear cell renal cell cancer (ccRCC) and evaluate their diagnostic and prognostic potential., Materials and Methods: We prospectively analyzed 30 patients of histologically proven ccRCC and collected 3 mL of serum preoperatively and small pieces of tumor and adjacent non-tumor renal tissue intraoperatively. Control serum samples were obtained from 15 patients of non-renal benign diseases. We analyzed 5 miRNAs-miR-34a, miR-141, miR-200c, miR-1233, and miR-21-2. Freshly collected samples were immediately frozen in liquid nitrogen and total RNA was extracted. cDNA was synthesized by reverse transcription, and quantitative polymerase chain reaction was performed to determine relative miRNA expression., Results: In the renal tissue and serum samples, 3 out of 5 miRNAs were differentially expressed; that is, the expression levels of miR-34a and miR-141 were significantly decreased, whereas that of miR-1233 was significantly increased. Serum miR-34a, miR-141, and miR-1233 were able to diagnose ccRCC with a sensitivity of 80.76%, 75%, and 93.33%, and specificity of 80%, 73.33%, and 100%, respectively, as compared to histopathology. Using a panel of 2 serum miRNAs (miR-141 and miR-1233) ccRCC can be diagnosed with 100% sensitivity and 73.3% specificity., Conclusion: miRNAs are differentially expressed in serum of patients with ccRCC and can be used to diagnose ccRCC with high sensitivity and specificity. Diagnostic sensitivity can be further improved by using a panel of miRNAs and has the potential to serve as novel diagnostic markers of ccRCC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Angiomyolipomas (AMLs) are benign hamartomatous tumours of the kidney that occur sporadically or in association with tuberous sclerosis. Although they are benign lesions, larger tumours can, rarely, behave aggressively and have extrarenal extension. Extension of an AML into the renal veins and inferior vena cava (IVC) is rare. We report a rare case of an AML with extension into the renal vein and IVC up to the right atrium that was successfully managed surgically., (2016 BMJ Publishing Group Ltd.)

Purpose: The aim of this study was to evaluate the role of F-fluoride PET/computed tomography (CT) in the detection of bone metastasis in patients with renal cell carcinoma (RCC) and compare the results with fluorine-18 fluorodeoxyglucose (F-FDG) PET/CT and technetium-99m methylene diphosphonate bone scintigraphy (BS) when available., Materials and Methods: The data of 36 patients (mean age: 52.5±14.1 years; male/female: 27/9) with RCC who prospectively underwent F-fluoride PET/CT were analyzed. PET/CT images were analyzed by two nuclear medicine physicians in consensus, visually and semiquantitatively [maximum standardized uptake value (SUVmax)]. Results of F-fluoride PET/CT were compared with those of F-FDG PET/CT (n=16) and BS (n=22). Histopathology or clinical or imaging follow-up (minimum 6 months) were used as the reference standard., Results: Overall, F-fluoride PET/CT showed a sensitivity of 100%, specificity of 94.4%, positive predictive value of 94.7%, negative predictive value of 100%, and accuracy of 97.2%. It demonstrated a total of 134 skeletal lesions, of which 101 were characterized as metastasis and 33 as benign. Corresponding CT changes were seen for 129/134 lesions. The mean SUVmax of the lesions was 30.3±48.4. F-Fluoride PET/CT and F-FDG PET/CT showed similar accuracy for visualization of bone metastasis (93.7 vs. 100%; P=0.993). However, F-FDG PET/CT additionally demonstrated extraskeletal metastasis in 6/16 patients. No significant difference was seen between the accuracies of BS and F-fluoride PET/CT for visualization of bone metastasis (93.7 vs. 100%; P=0.115), but the former showed significantly more skeletal lesions (91 vs. 44; P<0.0001). In 4/22 patients (18%) with negative BS, F-fluoride PET/CT demonstrated skeletal metastasis., Conclusion: F-Fluoride PET/CT shows high diagnostic accuracy for the detection of bone metastasis in patients with RCC. It shows comparable results to F-FDG PET/CT and detects more skeletal lesions compared to BS.

Background: Hypoglycemia secondary to ectopic insulin secretion of non-pancreatic tumors is rare., Case Presentation: We describe a middle aged woman with recurrent hypoglycemia. On evaluation, she was detected to have hyperinsulinemic hypoglycemia and right sided renal mass lesion. 68Ga-Dotanoc and 99mTc-HYNICTOC scans confirmed the intrarenal mass to be of neuroendocrine origin. Right nephrectomy was done and it turned out to be an insulin secreting neuroendocrine tumour. Neuroendocrine nature of this tumour was further confirmed by ultra-structural examination. Her hypoglycemia did not recur after resection of this tumour., Conclusion: Few cases of ectopic insulin secretion have been reported though some are not proven convincingly. This case addresses all the issues raised in previous case reports and proves by clinical, laboratory, functional imaging and immunohistochemical analysis that ectopic origin of insulin by non-pancreatic tumors does occur. To our knowledge, this is the first reported case of ectopic insulinoma arising from the kidney.

Objectives: To evaluate whether diffusion-weighted MRI (DW-MRI) can distinguish pseudotumours in chronic kidney disease (CKD pseudotumours) from renal-cell-carcinomas (RCCs) (with or without CKD) and whether it offers additional benefit over conventional MRI., Methods: One-hundred patients underwent MDCT, MRI and DW-MRI (at b-values of 0 and 500s/mm(2)) for evaluation of focal renal lesions. Of these, 20 patients with 40 CKD pseudotumours and 36 patients with 40 RCCs were retrospectively analyzed. T1-weighted, T2-weighted, diffusion-weighted images were evaluated, apparent-diffusion-coefficient (ADC) values were compared and receiver-operating-characteristic (ROC) curves were drawn to establish cut-off ADC-values., Results: 92.5% of CKD pseudotumours remained indeterminate after conventional MRI. On DW-MRI, none of them showed restricted diffusion and thus malignancy could be ruled out in 100% of the lesions. In contrast, all the solid RCCs showed diffusion restriction. Mean ADC-value for CKD pseudotumours was significantly higher than RCCs and surrounding diseased parenchyma [2.50 vs 1.56 (×10(-3)mm(2)/s) (P<0.0001) and 2.05 (×10(-3)mm(2)/s) (P=0.0001) respectively]. ROC analysis for differentiating CKD pseudotumours and RCC yielded high sensitivity (91.7%) and specificity (100%) for cut-off ADC-value of 2.04 (×10(-3)mm(2)/s)., Conclusions: CKD pseudotumors usually remain indeterminate on conventional non-contrast MRI. DW-MRI can distinguish CKD pseudotumors from RCCs and offers a non-contrast non-invasive alternative for ruling out malignancy., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The progressive increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the opinion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence and progression of this disease in developing countries like India. The polymorphism of the enzymes involved in metabolism of such environmental factors may, therefore, confer variable propensity to RCC. The possible association between RCC and a polymorphism of the CYP1A1 and CYP2D6 genes specific to the Indian population was examined using peripheral blood DNA from 196 RCC cases and 250 population controls with detailed data of clinicopathologic characteristics for the disease. The CYP1A1 (val) "variant" genotype, which contains at least 1 copy of the CYP1A1 variant alleles, was found to be associated with a 2.03-fold [GG ver. AA/AG, unadjusted OR = 2.03; 95%CI = 1.233-3.342; P = 0.005] increase in the risk of RCC. There was also a significant association (p(trend) = 0.034) between higher frequency of RCC subjects containing at least of copy of the CYP1A1 (val) "variant" genotype with III or IV Fuhrman's grade. Whereas, the CYP2D6 polymorphism did not show any association with RCC risk [TT ver. CT/CC, unadjusted OR = 95%CI = 1.233-3.342; P = 0.005]. There was a significant association (p(trend) = 0.001) between the poor metabolizer CYP2D6 (TT) and progression towards higher pathological stage of RCC. Our data demonstrate for the first time a significant association between pharmacogenetic polymorphisms of CYP1A1 and risk of RCC development in the Indian population. The findings suggest that inter-individual variation in the phase I metabolic enzymes involved in the fictionalization and detoxification of specific xenobiotics is an important susceptibility factor for development and progression of RCC in Indians., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: Heterotrimeric G protein α-subunit Gαs is required for activation of adenylyl cyclase and generation of cyclic adenosine monophosphate (cAMP) in cells and plays a key role in multiple signal transduction pathways, linked to proapoptotic processes in cancer cells. This study investigated whether Gαs gene polymorphism was associated with increased renal cell carcinoma (RCC) risk in the North Indian population. In the present study, genotyping of GNAS1 gene in 196 RCC cases and 250 healthy controls was performed via polymerase chain reaction-restriction fragment length polymorphism., Results: The frequency of homozygous genotype CC was 29.6%, heterozygous TC was 51.5%, and homozygous TT was 18.9% in cases, whereas in controls it was 16.8%, 50.8%, and 32.4%, respectively; thus, there was a significant difference between the two groups (p=0.0001) in the univariate model. Further, multivariate analysis also demonstrated significant association of CC genotype with RCC risk (p=0.002). The high-risk genotype CC of GNAS1 gene showed threefold increase in risk to RCC relative to the TT genotype (unadjusted odds ratio [OR]=3.023, 95% confidence interval [CI]: 1.734-5.270). Whereas multivariate analysis showed a twofold increase in RCC risk among the CC genotype compared with the TT genotype (adjusted OR=2.181, 95% CI: 1.344-3.538). The C allele frequency was found to be significantly higher in RCC patients (55.3%) than in controls (42.2%) as compared with the T allele frequency that was 44.64% in RCC cases and 57.8% in controls. Moreover, patients with the CC genotype showed the worst prognosis in terms of the highest frequency of individuals having higher stages of RCC, but did not show any association with histological grade., Conclusion: Our results suggest that a T393C SNP could be considered as a genetic marker implicated in the pathogenesis of RCC.

In this study, we investigated the association of GSTP1, GSTM1, and GSTP1 genetic variants with renal cell carcinoma (RCC) among North Indian patients. The difference in frequency of the GSTT1 null genotype between cases and control subjects was statistically significant (active ver. null, odds ratio [OR]=0.368; confidence intervals [CI] 95%=0.243-0.557, p=0.001). The differences in the frequency of GSTP1 genotypes were statistically significant (AA ver. AG/GG, OR=1.879; CI 95%=0.355-0.797, p=0.002). Higher allelic frequency of the GSTP1 G allele was associated with RCC cases (G ver. A allele, OR=1.534; 95% CI=1.159-2.030, p=0.003). The gene-gene interaction in terms of three-way combination of GSTM1 null, GSTT1 null, and GSTP1 (AG/GG) resulted in 4.5-fold increase in RCC risk (OR=4.452; 95% CI=2.220-9.294). Similarly, our study revealed that GST polymorphism might be a vital determinant of advancement to higher pathological stages and histological grades of RCC. Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to RCC and its progression.

Background: Though previous investigators have attempted to evaluate its utility in characterization of focal renal lesions, diffusion-weighted MR imaging (DW MRI) in renal diseases is still an evolving field and its role in predicting the aggressiveness of renal cell carcinoma (RCC) is yet to be established., Purpose: To assess whether apparent diffusion coefficient (ADC) values can be used to determine the nuclear grade and histological subtype of RCCs and to identify the tumor attributes contributing to variation in ADC values., Material and Methods: The institutional ethics committee waived the requirement of informed consent for this retrospective study. The study cohort consisted of 33 patients who underwent MRI (with diffusion-weighted imaging at b values of 0 and 500 s/mm(2)) and were found to have 36 pathologically-proven RCCs. ADC values were determined for solid portions of RCC, cystic/hemorrhagic areas, and normal renal parenchyma. Histological subtype, nuclear grade, and cell count were determined for each lesion. ADC values were compared between different grades and subtypes and correlation with cell count was investigated. Receiver operating characteristic curves were drawn to establish cut-off ADC values., Results: There were 23 low grade (grades I and II) and 13 high grade tumors (grades III and IV). There were 32 clear-cell and four non-clear-cell RCCs. A decreasing trend of ADC values was seen with increasing grade and mean ADC of high grade RCC was significantly lower than low grade (1.3145 vs 1.6982 × 10(-3) mm(2)/s) (P = 0.005). Mean ADC for clear-cell RCC was significantly higher than non-clear-cell RCC (1.6245 vs. 1.0412 × 10(-3) mm(2)/s) (P = 0.005). ADC values higher than 1.7960 × 10(-3) mm(2)/s were seen only with low grade and values greater than 1.4904 × 10(-3) mm(2)/s were seen only with clear-cell RCC., Conclusion: ADC values provide a non-invasive means to predict the nuclear grade and histological subtype of RCC. Cellularity and morphology are other tumor attributes contributing to the variation in ADC values of RCCs.

Aberrant promoter hypermethylation of cancer associated genes occur frequently during carcinogenesis and may serve as a cancer biomarker. The aim of this study was to investigate the occurrence and relevance of promoter methylation of the tumor suppressor DAPK-1, APAF-1 () and SPARC in relation to different pathological stages and histological grades of tumor progression that might act as possible independent prognostic factor in the susceptibility towards renal cell carcinoma (RCC) in North Indian population. Three tumor suppressor gene promoters namely APAF-1, DAPK-1 and SPARC were assessed by methylation-specific PCR (MS-PCR) in 196 primarily resected renal cell tumors paired with the corresponding normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters, pathological stage and Fuhrman nuclear grade of RCC. Significant differences in methylation frequency among the four subtypes of renal tumors were found for APAF-1 (p < 0.001), DAPK-1 (p < 0.001) and SPARC (p = 0.182), when compared with the corresponding normal tissue. Male subjects showed stronger association of methylation frequency of all the three genes with RCC than the female subjects. Additionally, higher frequency of APAF-1, DAPK-1 and SPARC promoter methylation were directly correlated with higher tumor stage (p (trend) < 0.001). Higher frequency of promoter methylation of APAF-1 and SPARC were also associated with higher nuclear grade (p < 0.001 and p = 0.036, respectively). This gene panel might contribute to a more optimal diagnostic coverage and information, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

Vitamin D exerts its activity through binding to the high-affinity nuclear vitamin D receptor (VDR), and majority of genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology in our study population. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of RCC in the North Indian population. Genotyping of two polymorphic sites (FokI and BsmI) in the VDR gene of 196 RCC cases and 250 healthy controls was performed via PCR-RFLP. The frequency of homozygous genotype FF was 31.6%, heterozygous Ff was 48.0%, and homozygous ff was 20.4% in cases, whereas in controls it was 45.6%, 39.2%, and 15.2%, respectively; thus, there was a significant difference between the two groups (p (Trend) = 0.011) in the univariate model. The frequencies of the BB, Bb, and bb genotypes were 25.5%, 44.9% and 29.6% in cases, respectively, while in controls it was 33.2%, 52.0% and 14.8%, respectively; thus, there was a significant difference between the two groups (p (Trend) = 0.001) in the univariate model. The two high-risk genotype ff of FokI and bb of BsmI of VDR showed a cumulative 1.87-fold increase in risk to RCC. Moreover, the FF genotype was associated with lower pathological stage and histological grade. Our results suggest that the FokI and BsmI genotypes of VDR gene may be implicated in the pathogenesis of RCC.

In the present study, we have evaluated the chemopreventive potential of geraniol (GOH), an acyclic monoterpene alcohol against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. The chemopreventive efficacy of GOH was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers and the expression of putative nephrotoxicity biomarker Kim-1, tumor suppressor gene P53, inflammation, cell proliferation and apoptosis related genes in the kidney tissue. Oral administration of GOH at doses of 100 and 200mg/kg b wt effectively suppressed renal oxidative stress and tumor incidence. Chemopreventive effects of GOH were associated with upregulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. GOH was able to down regulate expression of Kim-1, NFκB, PCNA, P53 along with induction of apoptosis. However, higher dose of GOH was more effective in modulating these multiple molecular targets both at transcriptional and protein level. These results provide a powerful evidence for the chemopreventive efficacy of GOH against renal carcinogenesis possibly by modulation of multiple molecular pathways., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. Our recent studies have suggested an association of sperm-associated antigen 9 (SPAG9) with ovarian carcinomas. In the present study, we investigated the clinical relevance of SPAG9 in RCC patients. RT-PCR analysis showed expression of SPAG9 transcript in RCC tissues and RCC cell lines. In situ RNA hybridization and immunohistochemistry analyses confirmed the expression of SPAG9 in 88% of cancer patients, suggesting that SPAG9 participates in renal cancer. In addition, immunoblotting and ELISA analyses revealed a humoral immune response against SPAG9 in the sera of RCC patients but not in healthy individuals. Consistent with the clinical findings, knockdown of SPAG9 expression in RCC cells with specific siRNA significantly reduced cell growth and colony formation. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a SPAG9 siRNA plasmid significantly inhibited tumor growth. In conclusion, SPAG9 expression is associated with clinicopathologic features of tumors, suggesting that SPAG9 could contribute to the early spread of cancer. These results indicate that SPAG9 may have a role in tumor development and metastasis and thus could serve as a novel target for early detection and treatment of RCC.

Background: Radical nephrectomy with tumor thrombectomy in patients with renal cell carcinoma and level I to III thrombus extension is directly associated with an improved prognosis. However, radical surgery in patients with level IV thrombus extension is associated with high perioperative mortality, even if long-term survival is possible. In this report, we describe an alternative technique of vena caval and intraatrial tumor thrombectomy to decrease perioperative mortality and morbidity., Methods: A cohort of 6 patients aged 46, 50, 53, 56, 54, and 52 years underwent radical nephrectomy with tumor thrombectomy from the vena cava and right atrium under mild hypothermic cardiopulmonary bypass and intermittent cross-clamping of the supraceliac abdominal aorta. Intraatrial tumor thrombectomy was performed on a beating, perfused heart in 4 patients and a hypothermic, cardioplegia-perfused heart in 2 patients., Results: There were no early or late deaths. The aortic cross-clamp time was 12 and 15 minutes for patients 5 and 6, respectively. The cumulative hepatic and renal ischemic time was 16 minutes (range, 14 to 22 minutes) at 32 degrees C. The mean cardiopulmonary bypass time was 53.3 +/- 8.9 minutes (range, 40 to 65 minutes). At a mean follow-up of 43 +/- 24.6 months (range, 10 to 70 months), all patients are active and remain disease-free., Conclusions: We conclude that radical nephrectomy and tumor thrombectomy in patients with level IV thrombi can be safely performed with cardiopulmonary bypass, mild hypothermia. and intermittent supraceliac abdominal aortic occlusion, avoiding potential hematologic, hepatic, renal, neurologic, and septic complications associated with circulatory arrest.

Background: Increasing numbers of patients with renal cell carcinoma (RCC) are incidentally detected and can be potentially cured by surgery alone. In treating metastatic RCC, worthwhile survival rates are achieved in cases of low burden recurrences. This necessitates a rational follow up protocol, which picks up early recurrences and avoids costly surveillance for those with a favorable prognosis., Aims: We studied the patterns of metastases occurring in patients operated for localized or locally advanced renal cell carcinoma in the Indian setting and try to evolve a suitable follow up protocol., Setting and Design: Institution based, retrospective data., Method and Materials: Records of patients from January 1988 to December 2003, operated for initially localized RCC were reviewed. Follow up was performed using an established protocol. Occurrence of metastases and their patterns were studied., Statistical Analysis Used: Comparison of the different survival times was performed using the one-way analysis method. Multiple comparisons (post hoc test) were performed using the Bonferroni method., Result: Follow up was available on 209 patients. Mean survival was 43.75 months (SD +/- 28.72). Thirty-nine patients developed 59 metastases. Lungs were the commonest site of metastases (37%), followed by bone (22%), liver (19%) and brain (8%). Relapse and survival showed significant correlation with pathological stage (p, Conclusions: Occurrence of metastases correlate with the pathological stage of the disease at primary presentation. Tailored, stage-based follow up protocols allow adequate surveillance for disease activity and progression without escalating the overall costs.

Squamous cell carcinoma of the renal pelvis is a rare neoplasm and is usually associated with long standing stone disease. The disease is aggressive in nature and usually has a poor prognosis. We report a case of renal lithiasis who underwent successful percutaneous nephrolithotomy (PCNL) for renal pelvic calculus, and eight months later presented with a large invasive squamous cell carcinoma in the same location.

Objectives: To determine the necessity of pelvic computed tomography (CT) in patients of renal cell carcinoma (RCC)., Materials and Methods: We reviewed the records of 400 patients of RCC, who underwent treatment at our institution between January 1988 and February 2001. These patients were evaluated pre-operatively with ultrasonograms (USG) and contrast enhanced CT scan of the abdomen and pelvis. USG or CT scans of these cases were reviewed for presence of pathology in the pelvis, which were classified into 3 categories viz; benign and likely to be insignificant, benign and likely to be significant; and malignant., Results: Of the 400 cases, 114 were stage I, 68 were stage II, 99 were stage III and 119 were stage IV. In all patients, tumour was identified in the kidney on preoperative CT scan. Fourteen patients (3.5%) had an abnormality on pelvic CT. Five (1.25%) had category 1, three (0.75%) had category 2 and six (1.5%) had category 3 abnormality on pelvic CT. However, all these abnormalities in pelvis were detected prior to CT by other investigations (USG or plain x-ray). Of the six cases with malignant findings, two had superficial bladder cancer, one had RCC in a pelvic kidney and three had bone metastases in the pelvis., Conclusions: Pelvic CT does not offer additional information in the vast majority of cases with RCC and should be performed selectively. Thus the cost of diagnostic imaging in RCC can be reduced.