Ismail El-Mokadem

Progression, interobserver agreement, and malignancy rate in complex renal cysts (≥Bosniak category IIF)

OBJECTIVE The objective of this study was to assess interobserver agreement, clinicopathologic correlation, and radiologic follow-up progression of complex cystic renal masses. PATIENTS AND METHODS The medical records of 143 patients with 154 complex cystic renal masses were retrieved. Primary outcomes were interobserver agreement between the radiologists, and malignancy rates following surgical extirpation with or without follow-up in Bosniak IIF, III, and IV categories. Secondary outcomes were correlation between histology and degree of enhancement on contrast-enhanced computed tomography scans and survival analysis of patients with or without surgical intervention using the Kaplan-Meier analysis. RESULTS The overall malignancy rate in patients who had surgery was 74.5% (29/39). Of 27 confirmed renal cell carcinoma on final histology, 9 were papillary renal cell carcinoma (incidence 33.3%). Assessment of interobserver agreement yielded a weighted kappa statistic value of 0.69 (95% confidence interval 0.56-0.82, P<0.0001). Radiologic progression rate of Bosniak IIF cysts over median follow-up of 18.5 months was 13% (10/78). There was no statistically significant difference between progression rate and regression rate of IIF cysts (13.8% vs. 11.5%) over the period of 24 months of follow-up. Most of the progression in complex cystic renal masses was seen in the first 2 years of follow-up. The malignancy rate on radiologic progression was 87.5% (8/9) and 75% (6/8) in Bosniak IIF and III cystic masses, respectively. The malignancy rate in Bosniak III cyst was 50% (4/8) without a period of initial observation or follow-up. CONCLUSIONS A good degree of agreement exists between radiologists in classifying complex renal masses. Malignancy rate is considerably high in Bosniak IIF when they exhibit radiologic progression on systematic follow-up.

Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

Background:Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC.Methods:Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival.Results:There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001).Conclusions:Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion.

Carcinoma In Situ Is Significantly Underdetected by Prenephroureterectomy Ureteroscopy in the Management of Upper Tract Urothelial Cancers

Objective. Diagnostic reliability of prenephroureterectomy ureteroscopy (PNU) for the detection of upper tract carcinoma in situ (CIS) remains unproven in particular and underreported in general. Methods. Patients who underwent radical nephroureterectomy (RNU) in a large multicentre retrospective study for upper tract transitional cell carcinoma (UT-TCC) between January 2002 and December 2013 were identified from our hospitals databases. PNU appearances, stage, and grade of ureteroscopic biopsy were compared with final histology results of RNU to assess the diagnostic reliability of PNU for carcinoma in situ (CIS). Results. Three hundred patients underwent RNU for UT-TCC. 106 (106/300; 35.3%) of the cohort had PNU using white light with biopsies taken in most (92/106; 86.7%). Postnephroureterectomy histology of the cohort showed CIS in 65 (65/300; 21.6%) patients. Thirty nine of patients with CIS (39/65; 60%) had prenephroureterectomy ureteroscopy biopsies. Out of ten patients with CIS on ureteroscopic biopsies, six did not show CIS on final histopathology (6/10; 60%). Moreover, grading and staging on PNU biopsies of obvious tumours showed a significant nonconcordance with final histopathology of RNU specimen (P = 0.02). Overall survival was also shorter in patients with CIS compared with those without; this showed strong statistical significance (P = 0.004). Conclusions. There is a high incidence of CIS in upper tract with significant underdetection and discordance rate between the histopathology of biopsy samples obtained by white light PNU and resected specimen of radical nephroureterectomy. The presence of concomitant CIS and high stage disease in the upper tract TCC carried a poor prognosis following radical nephroureterectomy.

Tumour suppressor gene (CDKNA2) status on chromosome 9p in resected renal tissue improves prognosis of localised kidney cancer

Background Genetic alterations on chromosome 9p, including inactivation of the tumour suppressor gene, CDKN2A, result in cellular proliferation and growth of tumours. Our aim was to use microsatellite analysis and fluorescence in situ hybridization (FISH) to characterise the architecture of this region. Results Seventy-five out of 77 clear cell renal cell cancers (tumour/normal pairs) were interpretable for LOH analysis on chromosome 9p (two tumours were excluded, as all five primers were uninformative). Twenty out of 75 (26.6%) tumours showed LOH in at least one of the five primers employed. Most allelic deletions were detected, telomeric to the CDKN2A region at D9S916, with 11 out of 52 informative tumours (21%) displaying LOH. The LOH in the coding region of CDKN2A, at D9S974 and D9S942, was associated with a higher pT-stage (p = 0.004) and metastasis (p = 0.006, both markers). The rate of chromosome 9p deletion in ccRCC was 44% (35/80 cases) according to FISH. Somatic copy number loss of chromosome 9p was associated with a larger tumour size (p = 0.002), higher pathological tumour stage (p = 0.021), presence of tumour necrosis (p = 0.019) and microvascular invasion (p = 0.032). The cases with copy number loss, loss of heterozygosity and copy number neutral (n = 42) were at a higher risk of cancer-specific death when compared to tumours in category D (n = 32) (Log-rank: p = 0.001). Seventeen patients with localised ccRCC developed recurrence, and fourteen of those showed either LOH or somatic copy number loss at CDKN2A (Log-rank: p = 0.005). Multivariate analysis showed that LOH or copy number loss at CDKN2A retained its independent prognostic effect, improving the predictive accuracy of stage and SSIGN score by concordance Index C from 0.823 to 0.878 (p = 0.001). Materials and Methods Cytogenetics data, microsatellite analysis and FISH were acquired for a cohort of patients undergoing resection for clinically localised renal cancer between January 2001 and December 2005. Five microsatellite markers (D9S916, D9S1814, D9S974, D9S942 and D9S171) assessed loss of heterogeneity (LOH) using DNA samples and in the same cohort FISH analysis was accomplished on tissue microarray slides. The FISH data were scored by two observers blinded to the histological data of the patients. Cytogenetic aberrations were correlated with histological and clinical outcomes by univariate and multivariate analyses using different prognostic models. Disease specific and recurrence free survival based on cytogenetic changes were assessed by Kaplan Meier methods. Conclusions A comprehensive cytogenetic analysis using microsatellite analysis and FISH of the CDKN2A region on chromosome 9p improves the predictive accuracy of known prognostic factors in clinically localised renal cell carcinoma undergoing surgical resection.

Significance of Chromosome 9p Status in Renal Cell Carcinoma: A Systematic Review and Quality of the Reported Studies

Defining the prognosis of renal cell carcinoma (RCC) using genetic tests is an evolving area. The prognostic significance of 9p status in RCC, although described in the literature, remains underutilised in clinical practice. The study explored the causes of this translational gap. A systematic review on the significance of 9p status in RCC was performed to assess its clinical applicability and impact on clinical decision-making. Medline, Embase, and other electronic searches were made for studies reporting on 9p status in RCC. We collected data on: genetic techniques, pathological parameters, clinical outcomes, and completeness of follow-up assessment. Eleven studies reporting on 1,431 patients using different genetic techniques were included. The most commonly used genetic technique for the assessment of 9p status in RCC was fluorescence in situ hybridization. Combined genomic hybridisation (CGH), microsatellite analysis, karyotyping, and sequencing were other reported techniques. Various thresholds and cut-off values were used for the diagnosis of 9p deletion in different studies. Standardization, interobserver agreement, and consensus on the interpretation of test remained poor. The studies lacked validation and had high risk of bias and poor clinical applicability as assessed by two independent reviewers using a modified quality assessment tool. Further protocol driven studies with standardised methodology including use of appropriate positive and negative controls, assessment of interobserver variations, and evidenced based follow-up protocols are needed to clarify the role of 9p status in predicting oncological outcomes in renal cell cancer.

A minimally invasive temporary cavernoso-saphenous shunt in the management of priapism after failed conservative treatment

Abstract Priapism is an urological emergency with detrimental consequences, if not managed expeditiously. Though a rare condition with an incidence between 0.3 and 1.5 per 100,000 population, its management options are limited and decision making could be challenging. We present a case of late presenting priapism for which the initial routine clinical care (aspiration, intracavernosal injection, and distal shunt) failed to relieve erection. Subsequently, the patient was successfully treated by a temporary cavernoso-saphenous shunt using carotid shunt and repeated heparin flushes. This novel surgical treatment offers an alternate method of relieving priapism, avoiding the long-term undesired effects associated with permanent proximal shunts such as cavernoso-venous grafts. Moreover, interval flushes (and/or repeated aspirations) with heparin ensures patency of this new shunt during the perioperative period. The patient recovered without any complications and the shunt was removed after one week. He has regained partial erection, however refused to have further treatment. Temporary cavernoso-saphenous shunt using carotid shunt offers an alternate option of management of priapism in patients with failed initial conservative treatment and distal shunts.