Nuclear Localization of COX-2 in relation to the Expression of Stemness Markers in Urinary Bladder Cancer

Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of stemness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and without Schistosoma haematobium infections. Immunoreactivity to Oct3/4 was significantly higher in S. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer without S. haematobium than in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6 in bladder cancer tissues with and without S. haematobium infection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis

Genital-Sparing Cystectomy versus Standard Urethral-Sparing Cystectomy Followed with Orthotopic Neobladder in Women with Bladder Cancer: Incidence and Causes of Hypercontinence with an Ultrastructure Study of Urethral Smooth Muscles

BACKGROUND: Bladder cancer in women is an indication for radical cystectomy (RC) when the tumour is confined muscle-invasive bladder cancer (MIBC) of T2 N0M0, or high risk progressive non-muscle invasive bladder cancer (NMIBC). Radical cystectomy is either genital-sparing cystectomy (GSC) or standard urethra-sparing cystectomy (USC) that is followed with orthotopic ileal neobladder (ONB). Post-operative chronic retention “Hypercontinence†had been reported in different series following URS or GSC and ONB. In long-term follow-up, we evaluated the functional outcome of women who developed hypercontinence after USC or GSC and ONB. AIM: An ultrastructure study of female urethral smooth muscle was done to elucidate the underlying causes of hypercontinence. MATERIAL AND METHODS: Retrospective study was conducted on 71 women who underwent RC and ONB, 45women had undergone USC, and 26 women had GSC, follow-up ranged from 5 to 15 years. Ultrastructure studies were done on 5 urethral biopsy specimens from 5 women who had hypercontinence, and 4 biopsies were from a normal control. RESULTS: Follow-up showed that women who had undergone USC and ONB, 28.88% developed hypercontinence, where in the series of GSC and ONB three women out of 26 developed hypercontinence (7.80%). Three women who had hypercontinence following USC and ONB, they developed stones in the ileal pouch. Ultrastructure study of urethral smooth muscles in women who had hypercontinence showed organized collagen fibrils, absent myelin sheath, and non-detected lymphatic vessels. Normal urethra showed collagen fibrils within the interstitial matrix, preserved myelin sheath of nerve fibres, the presence of lymphatic vessels in the matrix. CONCLUSION: The present study shoes that GSC with ONB leads to the minimal incidence of hypercontinence (7.80%), while standard USC lead to higher incidence (28.88%). Ultrastructure changes of the female urethra who had hypercontinence were fibrotic changes, loss of myelin sheath and minimal vascularity, their findings explains the underlying cause of hypercontinence and support the technique of GSC rather than the standard USC

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

Detour technique, Dipping technique, or IIeal bladder flap technique for surgical correction of uretero-ileal anastomotic stricture in orthotopic ileal neobladder

ABSTRACTBackground:Uretero-ileal anastomotic stricture (UIAS) is a urological complication after ileal neobladder, the initial management being endourological intervention. If this fails or stricture recurs, surgical intervention will be indicated.Design and Participants:From 1994 to 2013, 129 patients were treated for UIAS after unsuccessful endourological intervention. Unilateral UIAS was present in 101 patients, and bilateral in 28 patients; total procedures were 157. The previous ileal neobladder techniques were Hautmann neobladder, detubularized U shape, or spherical shape neobladder.Surgical procedures:Dipping technique was performed in 74 UIAS. Detour technique was done in 60 renal units. Ileal Bladder flap was indicated in 23 renal units. Each procedure ended with insertion of double J, abdominal drain, and indwelling catheter.Results:Follow-up was done for 12 to 36 months. Patency of the anastomosis was found in 91.7 % of cases. Thirteen patients (8.3%) underwent antegrade dilatation and insertion of double J.Conclusion:After endourological treatment for uretero-ileal anastomotic failure, basically three techniques may be indicated: dipping technique, detour technique, and ileal bladder flap. The indications are dependent on the length of the stenotic/dilated ureteral segment. Better results for long length of stenotic ureter are obtained with detour technique; for short length stenotic ureter dipping technique; when the stenotic segment is 5 cm or more with a short ureter, the ileal tube flap is indicated. The use of double J stent is mandatory in the majority of cases. Early intervention is the rule for protecting renal units from progressive loss of function