Azadeh Elmi

Transurethral Autologous Myoblast Injection for Treatment of Urinary Incontinence in Children With Classic Bladder Exstrophy

PURPOSE The application of autologous myoblasts is an area of active research that may represent an improved alternative for the treatment of urinary incontinence. In this study we investigated the effectiveness of autologous myoblast injection for the treatment of urinary incontinence in children with classic bladder exstrophy. MATERIALS AND METHODS Seven boys and 1 girl with persistent urinary incontinence were entered in the study. All children had undergone staged bladder repair and bladder neck reconstruction, and 5 patients had received 1 to 3 transurethral injections of bulking agent. Autologous myoblasts were isolated from abdominal muscle biopsy and cultured before endourethral injection. After the procedure patients underwent pelvic floor electrical stimulation and continued pelvic floor exercises that had been started at least 1 year before injection. The clinical outcomes (based on a 24-hour voiding diary), and cystometric and urodynamic studies were evaluated. Followup ranged from 12 to 18 months (average 15.3). RESULTS There was a significant, time dependent improvement in urinary continence. At final followup all 7 boys (88% of patients) were socially dry (daytime dryness more than 3 hours), including 3 (38%) who were completely dry. Urodynamic studies revealed an increase in mean bladder capacity (p <0.001), detrusor leak point pressure (p <0.001) and average maximum urinary flow (p <0.01). All 7 boys (vs only 2 patients preoperatively) achieved normal voiding with demonstrable voiding detrusor contraction in the presence of a compliant stable bladder (p <0.05). CONCLUSIONS Our results suggest that transurethral autologous myoblast injection is a valid option for the treatment of structural urinary incontinence in children with classic bladder exstrophy. However, favorable preoperative urodynamic profiles and postoperative pelvic floor electrical stimulation may have contributed to the outcome in this series.

Functional external anal sphincter reconstruction for treatment of anal incontinence using muscle progenitor cell auto grafting.

PURPOSE: This study aimed to investigate the feasibility of autologous muscle progenitor cell transplantation for anal sphincter regeneration in a rabbit model of anal incontinence. We examined the serial changes in structure, with particular emphasis on histology and functional properties of the anal sphincter. METHODS: External anal sphincterotomy was performed in 21 rabbits; these rabbits were randomly assigned to 2 groups. In group I (n = 9), autologous muscle progenitor cells were isolated from quadriceps myofiber explants, labeled with PKH-26, and injected into sphincter 3 weeks after sphincterotomy. In group II (n = 12), saline buffer was injected at the site of damage. Sphincter electromyography and manometry were performed immediately before sphincterotomy and 14, 28, and 60 days after injection in 3 animals in each group at every interval and the findings were correlated with histomorphological studies. In addition, electromyography and manometry were performed in the remaining 3 rabbits in group II after 6 months. RESULTS: In group II, a flaccid sphincter persisted during the 6 months of follow-up. In group I, muscle progenitor autografting accelerated sphincter myofiber repair and improvement in functional capacity of the damaged sphincter. Fluorescently labeled cells were detected in all of the grafted sphincters; regenerated myotubes were detectable at the injection site as evidenced by the presence of desmin. We also observed a significant decrease in interstitial fibrosis in the 4th week and strikingly higher amounts of Ki-67-positive cells in group I. Manometry and electromyography showed a significant improvement in the mean resting anal canal pressure and sphincteric electrical activity 4 weeks after cell injection, respectively. CONCLUSION: Transplanting muscle progenitor cells showed the potential for recapitulation of a myogenic program when injected into deficient rabbit anal sphincter. Objective anal measures of resting and stimulated pressures and electromyographic profile improved. Stem cell-mediated anal myoplasty warrants additional investigation as a new method to treat anal incontinence before attempting this modality in the clinical setting.

Apparent diffusion coefficient as a non-invasive predictor of treatment response and recurrence in locally advanced rectal cancer

AIM To evaluate the role of pretreatment apparent diffusion coefficient (ADC) as a predictor of treatment response and local recurrence in patients with locally advanced rectal cancer who underwent neoadjuvant therapy. MATERIALS AND METHODS Forty-nine patients who underwent preoperative diffusion-weighted magnetic resonance imaging (MRI) followed by neoadjuvant chemoradiation and surgery were enrolled in the study. The mean tumour ADC was measured independently from multiple, non-overlapping regions of interest (ROIs) to cover the entire tumour area on a single section by two radiologists and patients were followed postoperatively for a median of 16.4 months. Diagnostic accuracy of ADC for predicting treatment response and recurrence was evaluated using the area under the receiver-operating characteristic (ROC) curve, sensitivity, specificity, and predictive values. Univariate and multivariate analyses including clinical tumour (cT) staging, carcinoembryonic antigen (CEA) level, lymph-node involvement, tumour grade, surgical margin, vascular involvement, and ADC were performed with respect to recurrence. Interobserver agreement of ADC values was assessed. RESULTS Twenty patients showed response to neoadjuvant therapy and recurrence was noted in 17 patients. Low pretreatment ADC, MRI findings of cT4 staging, and node involvement were significantly related to poor treatment response. Sensitivity and specificity of ADC = 0.833 × 10(-3) mm(2)/s for prediction of treatment response was 75 and 48% for reader 1 and 65 and 52% for reader 2, respectively. Univariate and multivariate analyses identified pretreatment tumour ADC as the only predictive factor for recurrence. Sensitivity and specificity of ADC = 0.833 × 10(-3) mm(2)/s for prediction of recurrence was 86 and 77% for reader 1 and 80 and 69% for reader 2, respectively. Interobserver agreement for measuring ADC was good with a kappa value of 0.70. CONCLUSION Pretreatment rectal tumour ADC values may be an early biomarker for predicting treatment response and local recurrence in patients who underwent neoadjuvant chemoradiation.

Predictive Value of Chemical-Shift MRI in Distinguishing Clear Cell Renal Cell Carcinoma From Non-Clear Cell Renal Cell Carcinoma and Minimal-Fat Angiomyolipoma

OBJECTIVE The purpose of this study was to evaluate the diagnostic performance of chemical-shift MRI in the differentiation of clear cell renal cell carcinoma (RCC) from minimal-fat angiomyolipoma (AML) and non-clear cell RCC. MATERIALS AND METHODS In this retrospective study, 97 patients with solid renal tumors without macroscopic fat and with a pathologic diagnosis of clear cell RCC (n = 40), non-clear cell RCC (n = 31), or minimal-fat AML (n = 26) who had undergone renal chemical-shift MRI were included. Size, location, morphology, and signal intensity (SI) of the tumors and the contralateral normal kidneys on T2-weighted and in-phase and opposed-phase images were recorded by readers blinded to the pathology. Percentage tumor-to-renal parenchymal SI drop (percentage SI drop) was calculated and correlated to tumor histology. The statistical analysis was done using Kruskal-Wallis, one-way ANOVA, chi-square, and Fisher exact tests. RESULTS The percentage SI drop was significantly higher in clear cell RCC compared with non-clear cell RCC and minimal-fat AML (p < 0.001). Percentage SI drop of greater than 20% had 57.5% sensitivity, 96.5% specificity, and 92% positive predictive value (PPV); and percentage SI drop greater than 29% had 40% sensitivity and 100% specificity for diagnosis of clear cell RCC within the cohort of clear cell RCC, minimal-fat AML, and non-clear cell RCC. A significant proportion of minimal-fat AML (46.2%) displayed homogeneous low T2-weighted SI as opposed to clear cell RCC (5%) and non-clear cell RCC (29%) (p < 0.001). CONCLUSION The percentage SI drop on chemical-shift MRI had high specificity and moderate sensitivity in predicting clear cell RCC over non-clear cell RCC and minimal-fat AML. A percentage SI drop greater than 20% in a renal mass without macroscopically visible fat has high PPV for clear cell RCC over minimal-fat AML and non-clear cell RCC. Among morphologic features, homogeneous low T2 SI favors minimal-fat AML over RCC.

Cystic renal cell carcinomas: do they grow, metastasize, or recur?

OBJECTIVE The purpose of this study is to evaluate the interval growth, tumor recurrence, and metastatic disease occurrence of cystic renal cell carcinoma (RCC). MATERIALS AND METHODS Pre-and posttreatment imaging of 47 histologically proven cystic RCCs, with at least 6 months of pretreatment imaging monitoring or at least 2 years of posttreatment imaging follow-up, or both, was retrospectively reviewed. Tumor morphologic features, preoperative growth, histologic typing and grading, and the incidence of tumor recurrence or metastasis were evaluated. Growth rate of tumors were compared among various histologic subtypes and Fuhrman grades. RESULTS Of 47 tumors, 27 (57.5%) were clear cell RCCs, 12 (25.5%) were multilocular RCCs, and eight (17%) were papillary cystic RCCs. Overall, 26 (55.3%) tumors were graded as Fuhrman grade 2, 17 (36.1%) were Fuhrman grade 1, and one tumor was Fuhrman grade 3. Of the 26 tumors with a minimum of 6 months of pretreatment imaging monitoring, 19 (73%) did not show a significant increase in tumor size. The differences in mean growth among the Fuhrman grades and different subtypes were not statistically significant. The average duration of posttreatment follow-up was 51 months. There were no local recurrences among the 43 patients who underwent posttreatment imaging, except for one patient who had metastasis at preoperative clinical presentation. CONCLUSION Cystic RCCs exhibit slow indolent growth, if any, and show no significant metastatic or recurrence potential, with excellent clinical outcomes. We raise the need for revisiting current imaging protocols that may involve frequent pre-and posttreatment imaging in cystic RCCs.

Is Early Colonoscopy Beneficial in Patients With CT-Diagnosed Diverticulitis?

OBJECTIVE The purpose of this study was to establish CT criteria as an indication for colonoscopy in patients with acute diverticulitis. MATERIALS AND METHODS The study was composed of patients diagnosed with acute diverticulitis on contrast-enhanced CT (CECT) from January 2000 to December 2004. Patients without subsequent colonoscopy were excluded. Findings on CT were correlated with patient outcomes over follow-up. Sensitivity, specificity, and predictive values of the imaging parameters for prediction of colon cancer were calculated. Outcomes were also compared between men and women. RESULTS Of 1034 patients with a CT diagnosis of diverticulitis, 402 (235 women and 167 men; mean age, 63.3 years) had available endoscopic colonic evaluation after CECT. The mean follow-up was 5.3 years. Seventy-eight patients had polyps (71% adenomatous) and nine patients (2.2%) were diagnosed with colon cancer (seven women, two men). The odds ratio for diagnosis of colon cancer was 23.35 in patients with mesenteric or retroperitoneal lymphnodes, 4.67 for abscess, and 24.43 in patients with obstruction and localized mass reported on CT. A significant correlation was found between the location of diverticulitis and cancer (p < 0.001). The diagnosis of cancer was made within 6 months from the date of CECT in eight patients. The odds of cancer were 2.5 times higher in women. CONCLUSION On the basis of the significant correlation of complicated diverticulitis or presence of lymph nodes with new diagnoses of colon cancer, we recommend early colonoscopy in patients with wall thickness more than 6 mm, abscess, obstruction, or lymph nodes seen on CECT.

Comparison of magnetic resonance urography with ultrasound studies in detection of fetal urogenital anomalies

PURPOSE Prenatal ultrasonography detects the vast majority of urogenital anomalies, but in some cases the diagnosis remains in doubt. We assessed the potential of magnetic resonance urography (MRU) in the evaluation of different urogenital anomalies in fetuses when ultrasound study was equivocal. PATIENTS AND METHODS We retrospectively reviewed the medical records of 46 fetuses in whom the presence of urogenital anomalies was suspected at ultrasound studies, but remained inconclusive. Fetal MRU was performed within the same week as ultrasound studies. All patients underwent MRU, comprising overview, fast, thick-slab, heavily T2-weighted sequences, followed by focused, high-resolution T2-weighted sequences obtained in sagittal, axial and coronal planes. T1-weighted sequences were obtained in selected cases for assessment of the gastrointestinal tract. All MRU results were compared with ultrasound findings. Sensitivity of each imaging modality was estimated based on definite diagnoses made after birth or abortion. RESULTS The mean (range) gestational age was 27 (18-36)weeks. The final diagnosis was ureteropelvic junction obstruction in 12, ureteral dilation (due to vesicoureteral junction obstruction) in five, ureterocele in five, posterior urethral valve in 16, multicystic dysplastic kidney in six, mesenteric cyst in one and abdominoscrotal hydrocele in one. Overall diagnostic sensitivity of fetal MRU was 96% compared to sonography with 58% sensitivity (p<0.05). Fetal MRU studies provided additional information to sonography in 17 (37%) cases, and were especially more sensitive in evaluation of ureteral anatomy. CONCLUSIONS Fetal MRU can accurately diagnose a wide variety of urinary tract disorders and must be regarded as a valuable complementary tool to ultrasound in the assessment of the urinary system, particularly in cases of inconclusive ultrasound findings. The present study had a selection bias, as only fetuses with possible anomalies proposed by sonography were referred for MRU; however, this is the population that probably benefits most from MRU studies.

Prostate Cancer Imaging: What the Urologist Wants to Know

No consensus exists at present regarding the use of imaging for the evaluation of prostate cancer. Ultrasonography is mainly used for biopsy guidance and magnetic resonance imaging is the mainstay in evaluating the extent of local tumor. Computed tomography and radionuclide bone scanning are mainly reserved for assessment of advanced disease. Positron emission tomography is gaining acceptance in the evaluation of treatment response and recurrence. The combination of anatomic, functional, and metabolic imaging modalities has promise to improve treatment. This article reviews current imaging techniques and touches on the evolving technologies being used for detection and follow-up of prostate cancer.

Urinary and Serum Carbohydrate Antigen 19-9 as a Biomarker in Ureteropelvic Junction Obstruction in Children

PURPOSE We evaluated the predictive role of serum and urinary carbohydrate antigen 19-9 in the diagnosis and followup of pediatric ureteropelvic junction obstruction. MATERIALS AND METHODS The study included 27 children with ureteropelvic junction obstruction who underwent pyeloplasty (group 1), and 41 controls consisting of 27 healthy children (group 2) and 14 children with hydrocele/renal cyst (group 3). Serum and voided urine were evaluated for carbohydrate antigen 19-9 in each group. Additionally urine from the affected pelvis and fluid in hydrocele/renal cyst were collected at surgery in groups 1 and 3. Serum and voided urine samples were obtained at 3, 6 and 9 months after pyeloplasty for carbohydrate antigen 19-9 assessment, and were correlated with clinical factors. RESULTS Preoperative carbohydrate antigen 19-9 level was significantly greater in group 1 than in controls. The best cutoff values for serum and urinary carbohydrate antigen 19-9 were 13.21 U/ml and 30.6 U/ml, respectively, with significantly higher sensitivity and specificity for urinary values. Obstruction release was followed by improvement of renal function together with significant reduction in urinary and serum carbohydrate antigen 19-9 at 3 months. Initial pelvis diameter and renographic function significantly correlated with urinary carbohydrate antigen 19-9. No significant correlation was found regarding serum carbohydrate antigen 19-9. CONCLUSIONS Voided urine carbohydrate antigen 19-9 is a noninvasive, clinically applicable marker in congenital obstructive nephropathy. The practical implications of these data for diagnosis and long-term followup in ureteropelvic junction obstruction are significant. Our findings suggest that proper decrease in urinary carbohydrate antigen 19-9 after pyeloplasty is predictive of excellent surgical outcomes and resolution of renal damage.

Safety, Efficacy and Health Related Quality of Life of Autologous Myoblast Transplantation for Treatment of Urinary Incontinence in Children With Bladder Exstrophy-Epispadias Complex

PURPOSE Children with bladder exstrophy-epispadias complex undergoing endourethral autologous myoblast transplantation to treat urinary incontinence were evaluated at 4 years of followup regarding the safety, efficacy and durability of the procedure, and health related quality of life. MATERIALS AND METHODS Seven boys underwent autologous myoblast transplantation between May and December 2006. All patients had persistent urinary incontinence after bladder neck reconstruction and bulking agent injection. Patients were followed for 4 years after autologous myoblast transplantation regarding clinical outcomes and cystometric, urodynamic, uroflowmetric and urethrocystoscopic evaluations. Health related quality of life was also measured before treatment and at final followup. RESULTS No evidence of urinary obstruction was observed. Five children (71%) were completely continent and 2 (29%) were socially dry with complete daytime dryness at final followup. Health related quality of life was improved significantly. Urodynamic studies revealed a progressive increase in bladder capacity (p <0.001). Mean detrusor leak point pressure showed a 27 cm H(2)O (158%) increase during 4-year followup. Uroflowmetry parameters of voided volume and average maximum flow rate were improved significantly (p <0.001). CONCLUSIONS The 4-year outcomes demonstrate that autologous myoblast transplantation for urinary incontinence in children with bladder exstrophy-epispadias complex is relatively reliable, reproducible, safe and effective with minimal morbidity. This novel treatment represents a promising therapeutic approach in patients with urinary incontinence. Further randomized trials with larger numbers of patients and longer followup are needed.