Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques.

BACKGROUND: Her2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients' clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients' in Saudi Arabia, and to explore its prognostic value in BC. METHODS: A total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures. RESULTS: IHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient's cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort. CONCLUSION: The study showed that 25 % of our patients' cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.

Novel augmentation ileocystoplasty technique to manage non-compliant bladders in the presence of obstructed megaureters: the "fez procedure".

OBJECTIVES: To show the efficacy and safety of a novel modification of Studer's neobladder, herein defined as the "fez procedure." METHODS: The medical records of 21 children (mean age 9.4 ± 1.3 years) who underwent the "fez procedure" at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, to manage refractory poorly-compliant bladders and concomitantly obstructed megaureters were retrospectively reviewed. The patients had been previously managed by either preliminary cutaneous ureterostomy (17 patients) or temporary nephrostomy (four patients) to improve and stabilize the renal functions. The "fez procedure" entailed augmentation ileocystoplasty and the use of an afferent tubularized ileal loop for direct ureteroileal anastomosis. The augmented bladder together with the tubularized loop were fashioned as a "fez" with its tassel. The outcome measures were changes in cystometric capacity, bladder compliance, glomerular filtration rate, serum creatinine, technetium 99m-diethylene triamine pentaacetic acid diuretic renography (T1/2), ureteral diameter, vesicoureteral reflux, febrile urinary tract infections, continence and complications. RESULTS: The mean study follow-up period was 52.5 ± 12.8 months. Means of changes of cystometric capacity (273.2 ± 60.9 mL) and bladder compliance (15.6 ± 4.2 mL/cm H2 O) were significant (P < 0.0001). Resolution of ureteral obstruction was documented with improved T1/2 and ureteral diameter (P < 0.0001, each) of all patients. The initially improved renal functions after ureterostomies or nephrostomies were maintained after "fez surgery," with non-significant changes in the improved glomerular filtration rate (P = 0.22) and serum creatinine (P = 0.18). None of the patients experienced ureteral restenosis, vesicoureteral reflux, febrile urinary tract infections, incontinence or significant complications. CONCLUSIONS: The "fez procedure" represents a versatile and successful surgical option for these selected patients, as it offers improved bladder capacity/compliance, resolution of ureteral obstruction and vesicoureteral reflux, preservation of the renal function, control of urinary tract infections and urinary continence, and acceptable morbidity.

Circulating proteomic signature for detection of biomarkers in bladder cancer patients.

The identification of clinically-relevant early diagnostic and prognostic protein biomarkers is essential to maximize therapeutic efficacy and prevent cancer progression. The aim of the current study is to determine whether aberrant plasma protein profile can be applied as a surrogate tool for early diagnosis of bladder carcinoma. Plasma samples from patients with low grade non-muscle invasive bladder cancer and healthy controls were analyzed using combined 2D-DIGE and mass-spectrometry to identify differentially expressed proteins. Validation was performed using western blotting analysis in an independent cohort of cancer patients and controls. Fifteen differentially-expressed proteins were identified of which 12 were significantly up-regulated and three were significantly down-regulated in tumors compared to controls. The Ingenuity Pathways Analysis revealed functional connection between the differentially-expressed proteins and immunological disease, inflammatory disease and cancer mediated through chemokine and cytokine signaling pathway and NF-kB transcription factor. Among the three validated proteins, haptoglobin was able to distinguish between patients with low grade bladder cancer and the controls with high sensitivity and specificity (AUC > 0.87). In conclusion, several biomarker proteins were identified in bladder cancer. Haptoglobin is a potential candidate that merit further investigation to validate its usefulness and functional significance as potential biomarkers for early detection of bladder cancer.

Sonic Hedgehog Expression is Associated with Lymph Node Invasion in Urothelial Bladder Cancer.

Bladder cancer (BC) is a deadly disease characterized by high recurrence rates and frequent progression to an aggressive phenotype. Dysregulation of various signaling pathways have been implicated in BC tumorigenesis, however, the clinical relevance of sonic hedgehog pathway (Shh) remains under investigated. The aim of the current study was to analyze the prognostic value of Shh expression in patients with bladder carcinoma. Immunohistochemical expression of Shh was performed using tissue microarray with 128 specimens from bladder cancer patients. Kaplan-meier survival was analysed and correlation between Shh protein expression and patients' clinicopathological parameters wasexamined using Fisher's exact test. The immuno-staining results revealed that Shh protein exhibits cytoplasmic localization and is expressed in 49% of the analyzed bladder cancer cohort. Our data indicated that high Shh expression significantly correlated with increased lymph node metastasis (p = 0.02), however no association was reported between Shh expression and other clinicopatholigical parameters. High expression of sonic hedgehog was associated with lymph node invasion which may indicate that Shh might play an important role in progression and metastasis of bladder cancer.

Laparoscopic transperitoneal ureterolithotomy for large ureteric stones.

OBJECTIVES: To evaluate the efficacy and safety of laparoscopic transperitoneal ureterolithotomy for management of large proximal ureteric stones. MATERIALS AND METHODS: Medical records of patients who underwent laparoscopic transperitoneal ureterolithotomy for proximal ureteral stones ≥2 cm were reviewed retrospectively. Patients' characteristics, stone characteristics, perioperative and follow-up data were studied. Patients with stones <2 cm in size, previous transperitoneal surgical procedure, or follow-up duration <6 months were excluded from the study. RESULTS: Twelve patients (mean age = 52.9 ± 12 years) with large upper ureteric stones (mean stone largest diameter = 39 ± 13 mm) were included. Nine patients had single stone, 2 patients had two stones, and 1 patient had large impacted stone with 2 small stones floating above. Mean operative time was 107 ± 49.5 min with mean blood loss of 60.5 ± 19.2 cc. Mean total pain score was 38.4 ± 5.5 (100 point scale) and mean time till resuming oral intake was 3.6 ± 0.5 h. Mean duration of hospital stay was 2.6 ± 1.4 days and mean duration of stenting was 7.3 ± 2 weeks. Throughout a mean duration of follow-up of 14.8 ± 7.6 months, 100% stone clearance rate was achieved with no recurrence. One patient developed a ureteric stricture treated by laser endoureterotomy and stenting for 6 weeks and responded without re-stricture formation. CONCLUSION: Laparoscopic transperitoneal ureterolithotomy is a safe and effective approach for selected patients with large proximal ureteric stones with reduced postoperative pain and short hospital stay, and should be considered as a treatment option for such stones.

Renal primitive neuroectodermal tumour in childhood: Case report and review of literature.

Primitive neuroectodermal tumour (PNET) is presumed to be of neural crest origin, mostly presenting as bone or soft tissue masses. It usually occurs in the trunk or axial skeleton; while renal PNET is considered an extremely rare tumour. We report a case of 11-year-old male who presented with right flank pain and gross hematuria after suffering blunt trauma. During investigations, he was found to have a large renal mass on computed tomography. He underwent a right radical nephrectomy where the pathology report showed PNET of the kidney. The patient received chemotherapy afterwards. Despite the chemotherapy, he had a local tumour recurrence 3 months after and continued to deteriorate and developed distant metastasis. Primitive neuroectodermal tumour of the kidney is a distinct and rare entity. It is very aggressive, with a poor survival despite combined modality treatment.

Redo hypospadias repair: experience at a tertiary care children's hospital.

OBJECTIVE: Treatment of patients with failed hypospadias repairs can be challenging. Our study aimed to determine the best type of redo repair depending on the location and size of the urethral meatus, the status of the urethral plate and genital skin, the severity of residual chordee and the amount of scar tissue. METHODS: The Institutional Review Board approved our retrospective chart review of patients who had a redo hypospadias repair at our institution over the past 6 years. We recorded the type and number of previous repair(s), the type and number of redo procedure(s),as well as the complications and functional outcomes. RESULTS: There were 28 patients, aged 1-12 (mean 3.8) years, with failed hypospadias repairs. The initial severity of the hypospadias were as follows: perineal (1), penoscrotal (9), proximal shaft (1), mid-shaft (9), distal shaft (4), coronal (3) and mega-meatus (1). Of all the patients, 24 had 1 repair, 3 had 2 repairs and 1 had 3 repairs. The initial repairs comprised 11 tubularized island flaps (TIFs), 8 Snodgrass tubularized incised plate (TIP) techniques, 5 Mathieu repairs, 1 Meatal Advancement and GlanuloPlasty Incorporated (MAGPI) technique, 1 Pyramid, 1 Arap technique and 1 Thiersch-Duplay repair. Twenty-one of 28 patients had 1 redo operation, 5 had 2 redo operations, 1 had 3 redo operations and 1 had 4 redo operations, for a total of 38 redo operations. Of these, 26 were TIP techniques (68.4%), 3 were Mathieu (7.9%), 3 were TIF repairs (7.9%), 2 were onlay island flaps (5.3%) and 4 were buccal mucosal grafts (10.5%). Follow-up was 1-5 years (mean 3.5 yr). The final locations of urethral meatus included glans (18), corona (6), mid-shaft (3) and penoscrotal (1). Complications after redo surgery comprised 4 urethrocutaneous fistulae, 2 meatal stenoses, 1 urethral stricture and 3 dehiscences. Sixteen patients were followed with yearly uroflow with a Q-mean (mean uroflow) range of 3-14 mL/s (mean 8.1 mL/s). CONCLUSION: The majority of hypospadias failures can be salvaged with one operation. The TIP repair is our procedure of choice in most cases. In the setting of a poor urethral plate, TIF or buccal mucosa may be necessary. Complications are not infrequent in redo procedures.

Can prophylactic antibiotics safely be discontinued in children with vesicoureteral reflux?

PURPOSE: We review the outcome of stopping prophylactic antibiotics in children with persistent vesicoureteral reflux (VUR). MATERIALS AND METHODS: We performed a retrospective chart review of patients with VUR followed off antibiotics during the last 12 years. Selection criteria included children 4 years old or older who were toilet trained, could verbalize and had a normal voiding pattern. Exclusion criteria were posterior urethral valves, ectopic ureter, neurogenic bladder and severe voiding dysfunction. Outcome measures were age at stopping antibiotics, duration on and off antibiotics, grade of reflux at the time of stopping antibiotics, the occurrence of urinary tract infections (UTI) and new renal scarring on followup. All patients had upper tract assessment performed with renal ultrasound. RESULTS: A total of 67 girls (85.9%) and 11 boys (14.1%) were included in the analysis. VUR was bilateral in 36 patients (46.2%), on the left side in 29 (37.2%) and on the right side in 13 (16.7%). Reflux was grade I in 16.7% of the cases, II in 75.6% and III in 7.7%. Mean patient age when taken off antibiotics was 5.74 years. The period on prophylactic antibiotics ranged from 0 to 84 months (mean 26.2) and the period off antibiotics ranged from 5 to 138 months (37.7). UTI developed in 9 girls (11.5%), of whom 8 had cystitis (10.2%) and 1 had clinically presumptive pyelonephritis (1.3%). These 9 girls were off antibiotics 5 to 60 months (mean 21.1). None of our patients, including those with UTI, had new renal scarring on followup renal ultrasound. CONCLUSIONS: Discontinuing prophylactic antibiotics in selected school age children is safe practice. The risk of significant upper tract infection is low and the development of new renal scars unlikely. However, we fully acknowledge that renal ultrasound is not the most accurate investigation for detection of renal scars. Therefore, continuing medical surveillance of these children is important.