Mohamed Badawy

Single-step renal dilatation in percutaneous nephrolithotomy: A prospective randomised study

Abstract Objective: To perform an economical single-step renal dilatation (RD) during percutaneous nephrolithotomy (PCNL), using directly a 30-F Amplatz dilator over the central Alken dilator, in a trial to reduce the operative duration and radiation exposure during RD while avoiding an exchange of dilators that might increase the risk of blood loss. Patients and methods: In a prospective randomised study including 49 patients divided into two groups, the first had RD before PCNL using the standard metallic telescopic dilators (Alken), and the second had RD using the 30-F Amplatz dilator over the central Alken dilator. The operative duration, with X-ray exposure, was calculated. The procedure outcome in terms of complications, stone-free rates and hospital stay was evaluated statistically. Results: The tract was dilated correctly in all cases. The operative duration and X-ray exposure was shorter in patients undergoing single-step RD (P < 0.05). There were perioperative complications, according to the Clavien grading system, in 17 (34%) patients but there was no statistically significant difference between the groups. The stone-free rates were comparable in both groups. Conclusion: A single-step RD during PCNL is feasible, with a shorter operative duration and X-ray exposure. The outcomes were comparable with those of a standard metallic telescopic RD.

Expression of MDM2 mRNA, MDM2, P53 and P16 Proteins in Urothelial Lesions in the View of the WHO 4th Edition Guidelines as A Molecular Insight towards Personalized Medicine

AIM: Here we imposed a multimarker molecular panel composed of P53, MDM2 protein & mRNA & P16 with the identification of sensitive and specific cut offs among the Egyptian urothelial carcinomas bilharzial or not emphasize the pathological and molecular classifications, pathways and prognosis as a privilege for adjuvant therapy. METHODS: Three hundred and ten urothelial lesions were pathologically evaluated and grouped as follows: 50 chronic cystitis as benign, 240 urothelial carcinomas and 20 normal bladder tissue as a control. Immunohistochemistry for MDM Protein, P16 & p53 and In Situ Hybridization for MDM2mRNA were done. RESULTS: MDM2mRNA overexpression correlated with low grade low stage non invasive tumors, while P53 > 40% & p16 < 10% cut offs correlated with high grade high stage invasive carcinomas & bilharzial tumors (P=0.000). CONCLUSION: MDM2mRNA overexpression vs. P53 > 40% & P16 < 10% constitutes a multimarker molecular panel with significant cut offs, proved to distinguish low grade, low stage non invasive urothelial carcinomas (MDM2mRNA overexpression, P53 < 40%, P16 > 10%) from high grade, high stage invasive urothelial carcinomas (with p53 > 40, p16 < 10% & absent MDM2mRNA overexpression). Combined P53 > 40 & p16 < 10%, together with the histopathological features can distinguish in situ urothelial lesions from dysplastic and atypical lesions.

Upregulation of Twist2 in Non-Muscle Invasive Urothelial Carcinoma of the Bladder Correlate with Response to Treatment and Progression

BACKGROUND: Twist2 is a transcription factor and an epithelial-to-mesenchymal transition that plays an important role in cell polarity, cell adhesion, and has a role in tumour invasion and metastases. AIM: In this study, we examined the expression of Twist2 in non-muscle invasive bladder carcinoma (NMIBC) and correlated the expression with response to treatment and tumour progression. METHODS: Data of 305 patients with NMIBC of Ta, T1 were retrieved from hospitals archives. Twist2 expression was examined in tissue samples by immunohistochemistry at initial diagnosis and final follow-up, normal control was 10 normal urothelium, 10 patients with muscle-invasive bladder cancer (MIBC) were a positive control. Treatment of NMIBC was implemented according to the European Association of Urology guidelines on NMIBC. The descriptive statistical analysis included means, standard deviation, p-value; Univariate and multivariate Cox regression analyses. RESULTS: Twist2 expression score was identified as negative, low (1-15%); medium (15-40%); and high (40-100%). Patients who had low or low medium scores at the initial diagnosis had a good response and a favourable prognosis. Expression of a high score of Twist2 in patients having high-grade T1 tumours showed non-responsiveness to repeated courses of intravesical bacillus Calmette Guerin (BCG) therapy and was upstaged to MIBC. CONCLUSION: Twist2 expression in tissue samples of NMIBC would indicate the tumour response to therapy, upgrading and upstaging in the follow up after intravesical BCG therapy.

Expression of FGFR3 Protein and Gene Amplification in Urinary Bladder Lesions in Relation to Schistosomiasis

BACKGROUND: Bladder cancer represents the fifth most common malignancy worldwide and a major cause of cancer-related morbidity and death. Incidence and mortality rates have remained relatively constant over the past four decades. Urothelial bladder cancers have identified multiple risk factors. AIM: We aimed at evaluating the expression of the FGFR3 protein and gene amplification in the urothelial cells of neoplastic and non-neoplastic urothelial lesions of the urinary bladder, and correlation with tumour grade, stage and associated bilharziasis. MATERIAL AND METHODS: One hundred and five different urinary bladder lesions were studied, including 15 cystitis cases (9 bilharzial and 6 non-bilharzial cystitides), 75 urothelial carcinoma cases (18 bilharzial associated and 57 non-bilharzial associated) and 15 squamous cell carcinoma associated with bilharziasis, beside 5 control cases. Data concerning age, sex, tumour grade, stage, and associated bilharziasis were obtained. Each case was studied for FGFR3 expression, and FISH technique was applied on forty malignant cases that show high protein expression. RESULTS: The highest incidence of cystitis was in the fourth decade while of bladder cancer was in the seventh decade. Tumour grade was correlated significantly with tumour stage. FGFR3 correlates significantly with tumour grade, stage and with a bilharzial infestation. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours. CONCLUSIONS: FGFR3 overexpression in malignant cases was significantly higher than in chronic cystitis. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours. FGFR3 may be further studied as a subject for target therapy of bladder cancer.

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

AIM: Prostate cancer (PCa) is the second most common cancers in men worldwide. Its incidence can be influenced by several risk factors including genetic susceptibility. Therefore the search for the expression of a certain gene (ERG) and its rearrangement could give us clues for proper identification of PCa. And the study of ERG expression and its comparison to FISH in Egyptian patients can show whether ERG immunophenotype could be used instead of FISH, as it is cheaper. MATERIALS AND METHODS: This study was performed on 85 cases of PCa, showing 30 cases with HGPIN and 30 cases of prostatic hyperplasia. All were immunohistochemistry stained using ERG monoclonal rabbit antihuman antibody was used (clone: EP111). FISH analysis was performed in 38 biopsies of PCa cases to detect TMRPSS2-ERG rearrangement using the FISH ZytoLight TriCheck Probe (SPEC TMRPSS2-ERG). RESULTS: ERG expression was found in 26% of PCa cases and 20% of HGPIN cases. FISH analysis showed fusion of 21 cases of PCa (out of 22 cases showing ERG immunoexpression). CONCLUSION: Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.

Evaluation of cellular transformation and tumor aggressiveness factor expression in urinary bladder lesions and transitional cell carcinoma special variants in relation to bilharziasis

Background Identification of molecular factors as diagnostic and prognostic indicators, as well as targets, for better therapy is a high priority. Human epidermal receptors constitute a family of receptor tyrosine kinases, which appear to be implicated in cellular transformation and can be overexpressed in a variety of solid tumors. Moreover, there has been a progressive interest in the expression of CD44 as a marker of tumor aggressiveness and metastatic potential in some human cancers. Hypothesis A variety of urinary bladder lesions and urothelial neoplasms are associated with alterations in epithelial growth factor receptor (EGFR) and CD44 gene and protein expression. Studying these factors using immunohistochemical methods and selectively using fluorescent in-situ hybridization (FISH) technique may give an idea of the influence of bilharziasis upon induction and progression of these lesions. Patients and methods Biopsies from 150 patients with urinary bladder lesions were subjected to histopathological examination, immunohistochemical detection of EEGF and CD44, and gene expression of EGFR using the FISH technique. Results Malignant urothelial lesions showed a higher percentage of cellular positivity and scores for both markers compared with control and cystitis cases (P<0.01). Cases of bilharzial cystitis showed significantly higher percentages and higher scores of CD44 expression compared with nonbilharzial cystitis cases (P<0.01). Bilharzial [transitional cell carcinoma (TCC)+squamous cell carcinoma (SCC)] cases showed significantly higher scores of both EGFR and CD44 expression, compared with nonbilharzial (TCC+SCC) cases. EGFR protein and gene were upregulated in malignant urothelial lesions – namely, TCC and SCC – with significant correlation with grade of neoplasia. CD44 expression was also upregulated in urothelial bladder lesions, especially SCC, and was correlated positively with both the grade and the stage of malignancy. All examined control, cystitis, and adenocarcinoma cases showed negative results for EGFR gene activation using FISH technique. All cases of bilharzial TCC showed positive gene expression, which is considered significant when compared with other nonbilharzial TCC (P<0.01). No significant difference in gene expression was detected between bilharzial and nonbilharzial cases of SCC (P>0.05). Conclusion In our study we found that grouping cases of TCC+SCC showed significantly higher scores for both EGFR and CD44 expression in bilharzial patients compared with nonbilharzial patients, pointing to the possible role of bilharzial infection in progression of cancer. TCC subgroups, although small in number, showed variable expression of EGFR and CD44, denoting possibly different molecular backgrounds. FISH results confirmed EGFR upregulation in TCC and SCC but not in adenocarcinoma.

Clinical versus Pathologic staging of Renal Tumors: Role of Multi-Detector CT Urography.

Introduction Our ability to diagnose renal cell carcinoma (RCC) has increased in the past 30 years as a result of the extensive application of imaging techniques, such as ultrasonography, computed tomography, and magnetic resonance imaging. Multi-detector computed tomography (MDCT) remains the most appropriate imaging modality for the diagnosis and staging of RCC. The aim of this work was to compare the findings of MDCT with surgical pathology to determine the accuracy of delineating tumor size, localization, organ confinement, lymph node metastases, and the extent of tumor thrombus in the renal vein and inferior vena cava. Methods The clinical, surgical, and anatomo-pathologic records of 99 patients treated by nephrectomy (radical or partial) for solid renal tumors at Theodor Bilharz Research Institute and Nasser Institute from 2005 to 2011 were reviewed retrospectively. All cases were staged pre-operatively with abdominal MDCT (pre- and post-contrast enhancement) in addition to the routine biochemical, hematological, and radiological work-up. The tumors’ histologic types were determined according to the WHO classification of renal tumors in adults in 2004, and staging was updated to the TNM 2010 system. Data were analyzed using the t-test. Results The mean age was 52 (range 21–73). Seventy-eight patients were males, and 21 patients were females (Male/Female ratio: 3.7:1). There were no significant differences in the mean tumor size between radiographic and pathologic assessments in different tumor stages. The overall incidence of lymph node invasion in surgical specimens was 76%, whereas MDCT showed a positive incidence in 68.4% of cases (false negative result in 7 cases, 7.6%). Conclusion Our findings indicated that MDCT urography is an accurate method to estimate renal tumor size, lymph node, vascular and visceral metastases preoperatively. Also, preoperative staging of renal tumors with MDCT represents a valuable and accurate tool.

Superiority of Flourescent in Situ Hybridization over Immunohistochemistry in Detection of her2 Gene in Carcinoma of the Urinary Bladder Associated with and without Schistosomiasis

HER2 is an oncogene encoding a type 1 tyrosine kinase growth factor receptor and the role of HER2 in the development of numerous types of human cancer is still understood and correlates with clinical outcome, poor prognosis, it is a predictor factor for poor response to chemotherapy. HER2 overexpression is associated with reduced disease free and overall survival. Patients who have HER2 negative expression have a poor prognosis. The aim of the present study is to explore the accuracy of detection of expression of HER2 protein by two different techniques of immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). The two techniques were applied to sixty two patients that included different cell types of carcinoma of the bladder, benign bilharzial lesions and control. Characteristics of the 62 patients are: 10 chronic cystitis, 19 squamous cell carcinoma (SCC) with schistosomiasis, 33 urothelial carcinoma (UC) schistosomal and non-schistosomal, ten healthy individuals without schistosomiasis served as controls. Gene amplification of HER2 was done using FISH and protein expression of HER2 by IHC. The study was applied on archival data of formalin-fixed paraffin embedded tissues and patient clinical data and follow up for 5 years. Overexpression of HER2 protein was found in 30/52 (57.7%). Fourteen cases had score of 2+, and sixteen cases had score of 3+. Using FISH technique it showed more accurate detection of HER2 gene as those fourteen cases who had score of 2+ had been found to be 5 out of 14 were positive for gene over expression, the other sixteen who had score of 3+ all were positive for gene amplification. HER2 protein and gene was found to be significantly overexpressed in carcinoma of the bladder in both cell types SCC and UC with or without schistosomiasis compared to the benign lesions and control groups (P <0.01) by both techniques. There is significant increase in expression of HER2 protein and gene in SCC compared to UC (P< 0.01). In UC overexpression of HER2 protein and gene was evident in all stages Ta, T1, T2-4. HER2 protein and gene overexpressed in different grades of UC. In SCC HER2 protein and gene had overexpression in different stages and grades.

Squamous Cell Carcinoma and Squamous Differentiation Histologic Variant of Urothelialcarcinoma of Urinary Bladder: Oncological Outcome Following Definitive Surgical Treatment

Objectives: To investigate the impact of variant histologic patterns of urothelialcarcinoma of the bladder on oncological outcomes of patients treated with Radical Cystectomy (RC). Three histologic patterns were evaluated: Urothelial Carcinoma (UC), Squamous Cell Carcinoma (SCC), and urothelial carcinoma with Squamous Differentiation (SqD). Materials and methods: Retrospective archival study included 258 patients treated with RCfor muscle-invasive carcinoma. Data were reviewed in demographic and clinicopathological parameters that included histopathological variant, tumor stage, and nodal status. Overall survival and cancer-specific survival were evaluated. Histologic patterns of these 258 patients were: 90 patients with UC, 112 patients with SCC, and 56 patients with UC with SqD. Archival data were retrieved from 1995 to 2012. Results: Median followup was 44 months. There were statistically significant differences between survivals in the three groups. Overall survival decreased in UC with SqD. Patients with SCC had a higher risk of local recurrence, while patients with pure UC had a higher risk of metastases. Conclusion: Squamous differentiation of UC was associated with high tumor stage and high tumor grade. Patients with this histologic variant had less favorable prognosis compared to pure UC and pure SCC. Diagnosis of divert histologic patterns in RC is valuable forplanning a treatment strategy.