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Walid A Farhat

Publications and source records attributed to Walid A Farhat.

13 recordsLinked to original sources

Quantifying angiogenesis in VEGF-enhanced tissue-engineered bladder constructs by dynamic contrast-enhanced MRI using contrast agents of different molecular weights.

PURPOSE: To compare Gadomer, a macromolecular magnetic resonance (MR) contrast agent, and gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) for quantifying angiogenesis in tissue-engineered bladder constructs. MATERIALS AND METHODS: Constructs enhanced with vascular endothelial growth factor (VEGF) were grafted onto the bladder of 12 rabbits (N= 3/VEGF, VEGF = 0,10,15,20 ng/g tissue). After eight days dynamic contrast-enhanced MRI (DCE-MRI) was performed in each animal using Gadomer and Gd-DTPA, separated by a one-hour interval. DCE-MRI parameters were calculated from two-compartment pharmacokinetics (plasma volume fraction, v(p); transfer constant, K(trans)) and model-free analysis, area under the concentration-time curve (AUC). Histology assessment of microvessel density (MVD) and Evans blue permeability were compared to DCE-MRI. RESULTS: MVD was elevated (P < 0.05) at the highest VEGF but not among lower levels; permeability differences were absent. Contrast enhancement increased with VEGF and was better resolved with Gadomer than Gd-DTPA. Gadomer was the better assay for estimating plasma volume: v(p) provided the best distinction (P < 0.005), but both v(p) and AUC were correlated to MVD. With Gd-DTPA, only AUC distinguished MVD differences (P< 0.05). Changes in K(trans) were insignificant. CONCLUSION: Macromolecular contrast agents are valuable for monitoring angiogenesis in tissue-engineered bladder grafts. Compared to Gd-DTPA, Gadomer provides more accurate and precise quantification of microvessel function, and is better suited to pharmacokinetic analysis for accurate physiological quantification.

Analysis of Variance↗

Dynamic contrast-enhanced MRI to quantify VEGF-enhanced tissue-engineered bladder graft neovascularization: pilot study.

Tissue engineered organs require an immediately perfused vascular tree. Currently, neovascularization assessment requires animal sacrifice and graft harvest. In this pilot study we assess whether neovascularization of an engineered urinary bladder construct is enhanced with vascular-derived endothelial growth factor (VEGF) and assessable non-invasively with dynamic contrast-enhanced MRI (DCE-MRI). Rabbit bladder acellular matrix was hybridized with hyaluronic acid (ACM-HA), fortified with one of three concentrations (0 ng, 10 ng, or 20 ng per gram of tissue) of vascular-derived endothelial growth factor (VEGF), and grafted onto bladders in nine rabbits (3 per VEGF concentration). At 1, 2 and 3 weeks, one rabbit from each VEGF group underwent DCE-MRI and graft harvest. Microvasculature was quantified with scrial optical transverse sectioning of CD31 stained whole mounts using PCl software. Masson trichrome and H&E staining were used to assess cellular proliferation and fibrosis. There was a significant difference in mean microvascular area (MVA) between the 10 and 20 ng VEGF groups (230187 vs 477894 microm2, P=0.014) but not between the 0 and 10 ng groups (210497 microm2, P=0.21). Gadolinium uptake increased with MVA and correlated with it on linear regression analysis (Pearson's correlation coefficient r=0.71). At three weeks, stromal cellularity was greatest, and fibrosis was least, in the high VEGF group. This preliminary work demonstrates improved neovascularization of bladder constructs with VEGF fortification of ACM-HA and the feasibility of MRI as a non-invasive method to assume angiogenesis in tissue engineered constructs.

Animals↗

Porcine bladder acellular matrix porosity: impact of hyaluronic acid and lyophilization.

Bladder acellular matrix (ACM) is being investigated as a urinary bladder replacement scaffold. We have demonstrated that ACM is porous and theorized that this contributes to ACM fibrosis and contracture over time in vivo and may preclude uptake and retention of molecules, which may aid cellular repopulation. We sought to determine if hyaluronic acid (HA) would decrease ACM porosity. Porcine ACM was lyophilized and rehydrated in HA (SIGMA) to form the hybrid HA-ACM construct. Three groups (n = 15/group: HA-ACM, ACM, and lyophilized/rehydrated ACM) were tested for porosity to a 10 cm column of distilled water, measuring the effluent hourly for 3 h. A porosity index was determined as the total effluent divided by time and area (cc/cm2 hr). Alcian blue staining and fluorophore-assisted carbohydrate electrophoresis qualitatively and quantitatively confirmed the uptake of HA. HA-ACM and lyophilized/rehydrated ACM were significantly less porous to water than untreated ACM [mean (+/-SE): 0.09 (+/-0.02), 0.74 (+/-0.4), and 9.8 (+/-1.6) cc/cm2 hr, respectively; Mann Whitney p < 0.0001 (HA) and p < 0.0001 (lyo)]. The difference between HA-ACM and lyophilized ACM was also statistically significant (p = 0.014). ACM hybridization with HA decreases ACM porosity, in part because of ACM lyophilization during the hybridization process. In future applications, HA may function as a carrier for smaller molecules such as growth factors, and as a bioactive molecule to improve wound healing and decrease fibrosis in tissue-engineered bladder constructs.

Animals↗

Hemodynamic and respiratory effects of pediatric urological retroperitoneal laparoscopic surgery: a prospective study.

PURPOSE: Our understanding of the effects of retroperitoneal CO(2) insufflation on cardiopulmonary variables in children remains limited. This study was designed to investigate prospectively the effect of CO(2) insufflation in a pediatric population undergoing retroperitoneal laparoscopic surgery. MATERIALS AND METHODS: We prospectively evaluated a consecutive series of patients enrolled between July 2003 and August 2004. Anesthesia was administered following a standardized protocol. Data collection included respiratory rate, PAP, O(2) saturation, ETCO(2), HR, MAP, electrocardiogram and insufflation pressure. All variables were recorded before, during and after CO(2) insufflation at regular intervals of 1 to 2 minutes, with up to 23 measurements recorded for each period. RESULTS: A total of 18 participants were recruited. Mean +/- SD for age and weight were 79.4 +/- 53.2 months and 26.7 +/- 15.5 kg, respectively. Mean retroperitoneal CO(2) insufflation pressure was kept at 12 mm Hg. Significant differences (p <0.05) in average ETCO(2), PAP and MAP were noted after CO(2) insufflation compared to baseline (pre-pneumoretroperitoneum) values. HR and temperature did not change. At completion of the laparoscopic intervention physiological variables exhibited a trend to return to baseline values. CONCLUSIONS: This prospective study documents significant changes in systemic hemodynamic variables that seem to be directly associated with the insufflation of CO(2) during pediatric retroperitoneal laparoscopic surgery. This ongoing evaluation confirms the effect of laparoscopic urological surgery and CO(2) insufflation on cardiopulmonary function in children.

Child↗

Outcome analysis of retroperitoneal laparoscopic heminephrectomy in children.

PURPOSE: Retroperitoneal laparoscopic heminephrectomy is a relatively new, well tolerated, minimally invasive alternative to open surgery for children with a nonfunctioning moiety in a duplex kidney. We collected data to assess outcomes in our experience with this procedure. MATERIALS AND METHODS: Data were retrospectively gathered on all patients operated on for retroperitoneal laparoscopic heminephrectomy at our institution between February 2001 and November 2004. Followup ultrasound was performed in all patients, and additional imaging was done only when clinically indicated. RESULTS: Retroperitoneal laparoscopic heminephrectomy was performed in 18 girls and 4 boys (18 upper and 5 lower pole moieties). Indications included ureterocele (12 patients), ectopic ureter (9) and vesicoureteral reflux (5). Mean age at surgery was 5 years (range 4 months to 18 years). Four patients required conversion to an open procedure due to inadequate exposure and were excluded from further review. Urine leaks developed postoperatively in 3 patients and were treated with Foley catheter drainage and/or stent placement. Two patients were noted to have large (more than 5 cm) asymptomatic retroperitoneal fluid collections on followup ultrasound. Functional loss of the remaining ipsilateral moiety was confirmed by DMSA scan in 2 children (ages 6 and 7 months). Doppler studies confirmed normal hilar blood flow in both cases. Clinical presentation for this subgroup included fever on postoperative day 3 in 1 patient and hypertension at 32 months postoperatively in 1. Mean followup was 33 months (range 3 to 56). CONCLUSIONS: Although retroperitoneal laparoscopic renal ablative surgery in children appears to be relatively safe and is associated with low morbidity, serious complications may occur with subtle or even late presentation.

Adolescent↗

Impact of fibrin glue and urinary bladder cell spraying on the in-vivo acellular matrix cellularization: a porcine pilot study.

PURPOSE: Urinary bladder tissue engineering utilizing autologous cell-seeded scaffolds requires enough bladder cells to populate a large surface area which may be difficult to obtain from abnormal bladders. We evaluated whether a fibrin glue spray technique enhances cell seeded acellular matrix (ACM) repopulation in a porcine bladder model. MATERIALS AND METHODS: Porcine urothelial and smooth muscle cells cultured from open bladder biopsy were sprayed with or without fibrin glue onto porcine bladder ACM. After 10 days in vitro, constructs were implanted onto porcine bladders (4/group) and harvested after 1 or 6 weeks for H&E and immunohistochemical staining. RESULTS: In vitro, fibrin glue was associated with more continuous cell growth and enhanced cellular organization, maintained particularly in the periphery in vivo, where both groups demonstrated central fibrosis. CONCLUSIONS: While fibrin glue enhanced cellular organization on ACM in vitro, central fibrosis in vivo suggests that factors supporting seeded cell survival are lacking.

Animals↗

Dynamic Gd-DTPA enhanced MRI as a surrogate marker of angiogenesis in tissue-engineered bladder constructs: a feasibility study in rabbits.

PURPOSE: To evaluate the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess angiogenesis in tissue-engineered bladder constructs in a blinded animal study, and compare different analysis approaches and their correlation with microvessel density (MVD). MATERIALS AND METHODS: Constructs fortified with vascular endothelial growth factor (VEGF) for enhanced vascularity were grafted onto the bladder in nine rabbits. DCE-MRI of Gd-DTPA uptake was performed and analyzed using Tofts' model, the area under the concentration time curve (AUC), and the uptake slope. DCE-MRI parameters were compared to MVD determined with CD31 immunohistochemistry. RESULTS: Significantly increased MVD was found in the high VEGF group (20 ng/g of tissue) but not at low VEGF (10 ng/g) (2.3x increase, P = 0.035 vs. 1.1x over control). Enhanced permeability at low VEGF was suggested by elevated K(trans), but overall correlation to MVD was poor. Significant correlation to MVD was obtained with AUC(8min) (r = 0.705, P = 0.034). Furthermore, AUC(8min) provided the most precise discrimination between different VEGF preparations and was the only parameter to show a significant increase (P = 0.0058) consistent with MVD changes at high VEGF. CONCLUSION: Findings support DCE-MRI for evaluating angiogenesis in bladder constructs and suggest vessel changes other than density. Future studies should incorporate larger contrast agents and permeability assessment to devise an optimal DCE-MRI strategy.

Animals↗

Use of buccal mucosa to simulate the coronal sulcus after traumatic penile amputation.

Traumatic penile amputation is a rare but catastrophic complication of newborn circumcision, usually involving a portion of, or the entire, glans penis. Emergent reimplantation is necessary to prevent glans loss. However, loss of the coronal sulcus might occur despite successful reimplantation, resulting in a cosmetically unacceptable appearance. We report such a case involving a newborn who suffered partial penile glans amputation and loss of the coronal sulcus after reimplantation, successfully treated with buccal mucosa grafting.

Amputation, Traumatic↗

Simplified mons plasty: a new technique to improve cosmesis in females with the exstrophy-epispadias complex.

PURPOSE: Long-term data suggest that a significant number of women with the exstrophy-epispadias complex (EEC) report dissatisfaction with the cosmetic appearance of the genitalia. We developed a new technique of mons plasty in an attempt to improve the overall cosmetic appearance of the external genitalia in females with EEC. MATERIALS AND METHODS: Nine consecutive females with a mean age of 6.4 years (range 2 days to 12.2 years) previously diagnosed with EEC underwent simplified mons plasty concomitantly with various other urological reconstructive procedures. Briefly, a simplified mons plasty was performed by approximating the bifid hemiclitoris and subsequently incising the lateral sulci between the labia majora and minora, which allowed the superomedial rotation of the labia majora and underlying peripubic adipose tissue, thus, recreating the mons. RESULTS: There were no perioperative complications. With a mean followup of 6 months (range 4 to 12) all patients had improved cosmesis with respect to a more prominent mons, more appropriately situated labia and adequately recessed introitus. CONCLUSIONS: Simplified mons plasty improves cosmesis in females with external genital abnormalities secondary to EEC. Although our followup is admittedly short, we believe that this technique should be considered in the armamentarium of the reconstructive surgeon during the operative treatment of this complex group of patients.

Abdominal Wall↗

Prospective evaluation of remote, interactive videoconferencing to enhance urology resident education: the genitourinary teleteaching initiative.

PURPOSE: Changes in referral patterns and resource allocation into Centers of Excellence affect the educational experience of urology trainees by altering resident exposure to patients and clinicians, especially at sites where subspecialty deficiencies exist. Access to educators at Centers of Excellence using interactive videoconferencing technology may facilitate residency training objectives and enhance trainees' overall educational experience. We prospectively evaluated the implementation of this technology at tertiary care teaching centers to enhance urology resident education. MATERIALS AND METHODS: Using videoconferencing technology, urology residents at the University of Western Ontario (London, Canada) participated in a series of didactic, interactive pediatric urology teleteaching seminars. These were presented by an expert pediatric urologist from the Hospital for Sick Children, Toronto, Canada. Using a 5-point Likert scale (1-strongly disagree, 5-strongly agree), participants responded to statements pertaining to seminar content, technology and ease of use at the completion of each session. The results were subsequently tabulated and evaluated to determine the effectiveness and accessibility of the program in providing expert pediatric urological education to residents at a remote urology training program. RESULTS: The entire urology resident staff from postgraduate year 1 to 5 participated in the seminar program. The overall acceptance of this medium was high (mean score 4.5). The quality of presentation, as well as picture and sound quality, all received mean scores greater than 4. Participants indicated that their ability to interact with the presenter was not inhibited by using this medium. All participants agreed that they would use this technology in the future (mean score 4.5) and that the presentation would not be improved if the presenter were on-site. Due to preexisting technology at both centers, no direct cost was incurred throughout the study. CONCLUSIONS: Our experience suggests that interactive teleteaching using readily available, existing technology, is a cost-effective and accepted method of providing trainees with an appropriate educational experience. In centers where subspecialty deficiencies exist, this medium may provide residents with the necessary education requirements of their respective programs without the need for costly teacher (or student) travel. Continual improvements in technology as well as the addition of multiple sites will increased this medium's impact in the future.

Adult↗

A multicenter evaluation of technical preferences for primary hypospadias repair.

PURPOSE: Considerable controversy exists regarding the optimal surgical technique for the repair of mid shaft and proximal hypospadias. We sought to evaluate differences in surgical preferences among an international cohort of pediatric urologists. MATERIALS AND METHODS: An anonymous questionnaire containing relevant demographic data as well as choices of technique to repair 5 representative hypospadias cases was developed and administered. RESULTS: Of 121 pediatric urologists contacted 101 completed the survey, representing an 83% response rate. The majority were full-time academic pediatric urologists who performed 6 to 10 hypospadias surgeries monthly. A total of 92 respondents (confidence interval [CI) 0.84 to 0.96) preferred the tubularized incised urethral plate (TIP) technique for the repair of distal hypospadias. Similarly, 82 (CI 0.72 to 0.88) preferred TIP for the repair of mid shaft hypospadias. The 2 most common techniques for repair of proximal hypospadias without chordee, preferred by 43 correspondents each (CI 0.33 to 0.53), were TIP and transverse island flap (TVIF) onlay. For repair of moderate (30-degree to 40-degree) chordee dorsal plication was preferred by 82 respondents, while a ventral approach was preferred by 12. When moderate chordee was associated TVIF onlay was preferred by 35 (CI 0.26 to 0.45) and TIP by 24 respondents (CI 0.16 to 0.34). For severe chordee (greater than 50 degrees) 31 respondents preferred dorsal plication, while 68 chose some form of ventral repair. Among the respondents 37 approach proximal hypospadias associated with severe chordee using a staged procedure, while 40 use a single stage procedure using a TVIF tube (CI 0.30 to 0.50). Using Spearman's rank correlation coefficient, no significant correlations were identified between respondent practice demographics and choice of repair for each hypothetical hypospadias case. CONCLUSIONS: In this cohort of pediatric urologists we observed that the majority prefers TIP to repair distal and mid shaft hypospadiac defects. Significant variability exists for preferred technique for proximal hypospadias and chordee correction. These results support the need for prospective trials comparing techniques for the repair of proximal hypospadias.

Europe↗

The development of laparoscopic surgical skills in pediatric urologists: longterm outcome of a mentorship-training model.

INTRODUCTION AND OBJECTIVES: We previously reported the successful attainment of laparoscopic skills in a group of practicing pediatric urologists without previous formal laparoscopic training. During the mentorship period, the four urologists (trainees A, B, C, and D) performed a number of renal retroperitoneal laparoscopic procedures (RRLP) under the tutelage of an expert mentor. Specifically, trainee A performed or assisted in 8 RRLP while trainees B, C, and D performed/assisted in 10, 7, or 18 RRLP, respectively. Herein we assessed the outcome of this training program and practice pattern of this same group of urologists. METHODS: Following the completion of the mentorship period, we reviewed the outcomes of all of the consecutive RRLP performed from September 2001 to March 2005 with respect to operative time, conversion rate, perioperative complications and length of hospital stay (LOS). Furthermore, we attempted to correlate the number of procedures each surgeon performed both during and subsequent to the mentorship period. RESULTS: Fifty-two ablative RRLP including nephrectomy (n=38), partial nephrectomy (n=12), or synchronous bilateral nephrectomy (n=2), were performed on 50 patients (19 males, 31 females) with a mean age of 5.5 years (range 4 months-14 years). Trainee A performed 16/40 procedures, trainees B and C each performed 2/40, while trainee D performed 20/40 procedures. Mean operative time was 2.4 hours (range 1.5-6.3 hours). Five patients required open conversion due to inability to obtain retroperitoneal access (n=3) or failure to progress (n=2). Two patients (one nephrectomy, one partial nephrectomy) developed retroperitoneal urinomas requiring temporary urinary diversion. There were no other perioperative complications and mean LOS was 1.2 days (range 1-4 days). More advanced reconstructive procedures have since been performed with the aid of laparoscopic exposure; trainee D has thus far successfully performed 12 laparoscopically assisted pyeloplasties. CONCLUSIONS: This series demonstrates the effectiveness of the mentorship-training model to introduce RRLP to a pediatric urology training program. It is evident that the post-mentorship practice is affected by the number of cases initially performed during the training period. The development of an "expert" laparoscopist is dependent not only on initial training experience, but continued education through ongoing case exposure.

Adolescent↗