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Biomedical subjects

William Carlos Nahas

Publications and source records attributed to William Carlos Nahas.

8 recordsLinked to original sources

Neoplasms in prune belly syndrome: A novel case of early-onset metastatic bladder carcinoma and systematic review of reported tumors.

PURPOSE: Prune Belly Syndrome (PBS) is a rare congenital malformation complex characterized by cryptorchidism, urinary tract abnormalities and deficiency of the abdominal wall musculature. Although advances in neonatal and reconstructive care have substantially improved survival, the long-term risk of malignancy in this population remains poorly defined. We report a novel case of early-onset metastatic bladder carcinoma in a patient with PBS and perform a systematic review of all tumors described in association with the syndrome. METHODS: A systematic literature review was performed according to PRISMA guidelines and registered in PROSPERO (CRD420251072086). Databases searched through April 2025 included PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane, and SciELO. Reported tumor cases in PBS patients were identified and classified as either PBS-associated or not. We additionally describe a new case of invasive bladder carcinoma. RESULTS: Seventeen studies comprising 20 patients met inclusion criteria. Tumors directly related to the genitourinary tract accounted for half of the cases. Bladder carcinoma was the most frequent neoplasm (35%), followed by hepatoblastoma (25%). Bladder tumors occurred at markedly younger ages and often presented as advanced diseases. Our index case involved a 33-year-old man with PBS who developed metastatic muscle-invasive urothelial carcinoma and died shortly after diagnosis. DISCUSSION: Improved survival in PBS has led to recognition of new late complications, including malignancy. Tumorigenesis may be influenced by chronic urinary stasis, infection, catheterization, cryptorchidism, and underlying genitourinary developmental abnormalities. These findings should be interpreted as hypothesis-generating given the limited number of reported cases. CONCLUSION: Although uncommon, malignancies in PBS may occur earlier and behave more aggressively than in the general population. Given the current level of evidence, careful long-term follow-up with clinical awareness is warranted, rather than routine invasive screening for all patients.

Humans↗

Surgical aspects of third and subsequent renal transplants performed by the extraperitoneal access.

BACKGROUND: We reviewed our experience with third, fourth, and fifth renal transplants performed by the extraperitoneal access. METHODS: The charts of 21 third and subsequent transplants performed extraperitoneally were reviewed. Surgical aspects, the occurrence of rejection episodes, delayed graft function (DGF), graft and patient survival were evaluated and compared with 1560 first transplants in adults with nonmanipulated fossa performed in the same period. RESULTS: Transfusion was necessary in 52% of the retransplants and in 5.7% of the first transplants (P<0.0001). Mean operative time was 327 min for retransplants and 212 min for first transplants (P<0.0001). Surgical complications occurred in 4 patients (19%): two arterial thrombosis and two ureteral obstructions. DGF occurred in 11 patients (52%) among retransplants and in 453 (29%) among first transplants (P=0.028). Acute rejection occurred in 7 (33.3%) retransplants and in 530 first transplant patients (33.9%). The mean serum creatinine among retransplant patients 30 days and one year after transplantation was 2.5 mg/dl and 1.8 mg/dl. One-year graft survival was 57.1% (75% for live and 46% for cadaver donors) for retransplants and 86% for first transplant patients (P<0.0001). CONCLUSION: Third and subsequent transplants performed extraperitoneally are more time-consuming and require more transfusions in the perioperative period. A higher but acceptable incidence of arterial thrombosis and urinary obstruction were observed. One-year graft survival was better with live donor grafts, but was still lower when compared with first transplants using the same surgical technique.

Adolescent↗

Is polypropylene mesh safe and effective for repairing infected incisional hernia in renal transplant recipients?

INTRODUCTION: Infected incisional hernias are common in kidney transplant patients. Treating them in immunosuppressed patients can take months, increasing costs and implying loss of working productivity. Abdominal wall prostheses have not been used in infected immunosuppressed patients because of poor infection control. We evaluated the outcome of the surgical treatment of these patients with polypropylene mesh to shorten the hospitalization time and patient recovery. The records of 462 consecutive kidney transplant patients (March 2000 to February 2004) were reviewed. Of these 462 patients, 13 (2.8%) had infected or contaminated herniations at the transplant incision. They developed between 2 and 60 days (mean 14) after transplantation. The racial distribution was not significant, but herniations were more common in patients from cadaveric donors (4.5% versus 0%, P = 0.005). Predisposing factors were found in 6 patients (46.2%) and included complications from transplant surgery in 2, obesity in 1, leukopenia in 3, sepsis in 1, diabetes mellitus in 1, and wall weakness in 1 patient (3 had more than one risk factor). TECHNICAL CONSIDERATIONS: A prospective protocol of surgical correction with polypropylene mesh was established. After wound cleansing with normal saline, repair was done by primary fascial approximation and polypropylene mesh reinforcement. Broad-spectrum antibiotics and large-bore drains were used. Follow-up ranged from 1 to 40 months (mean 14.5). All patients did well except for one recurrence, 14 months after correction. CONCLUSIONS: Surgical repair with polypropylene mesh is safe and effective in treating infected or contaminated herniations in kidney transplant patients, with an acceptable (9.1%) incidence of recurrence.

Adolescent↗

Bioequivalence of a new cyclosporine a formulation to Neoral.

New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 +/- 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean +/- SD of area under the curve (AUC), maximum concentration (C(max)), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 +/- 1466 vs 3971 +/- 1325 ng x h/mL, 998 +/- 376 vs 1021 +/- 356 ng/mL, and 707 +/- 254 vs 734 +/- 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C(max) (-123, +77 ng/mL) or AUC (-214, +311 ng.mL/h) were within the Neoral bioequivalence interval for the same parameters (+/-204 ng/mL and +/-794 ng x mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.

Administration, Oral↗

Mycophenolic acid pharmacokinetics in stable pediatric renal transplantation.

Mycophenolate mofetil (MMF) is given to children in fixed doses based either on body weight or body surface area. There are data indicating mycophenolic acid (MPA) blood levels should be monitored in the early period of transplantation. However, there is little information regarding MPA pharmacokinetics (PK) in stable pediatric recipients. We evaluated MPA-PK in 20 stable renal transplant children (11.7+/-1.9 years) under long-term (46+/-31 months) MMF (26.1+/-7 mg/kg per day or 785+/-183 mg/m(2) per day) therapy plus prednisone and cyclosporin A (n=16), tacrolimus (n=3), or MMF/prednisone (n=1). Total MPA levels were measured using the EMIT-MPA assay at 0, 1, 2, 3, 4, 6, and 8 h after an oral dose of MMF. The level at 12 h was considered equal to the trough level for AUC(0-12) calculation. Mean C(0), C(max), AUC (0-12), and T(max )were 3.46+/-1.32, 13.5+/-0.58 microg/ml, 63.2+/-24.4 microg x h/ml, and 1.3+/-0.6 h, respectively. Six (30%) children were considered to have an adequate exposure (36-54 microg x h/ml) to MPA, 11 (55%) showed an AUC(0-12 )>54 microg.h/ml, and 3 (15%) showed an AUC(0-12 )<36 microg x h/ml. A C(max )>/=10 microg/ml was seen in 13 (65%) children. MMF dose did not correlate with AUC(0-12) or C(max). The combination of variables C(0), C(1), and C(4 )provided an equation to predict exposure (r(2)=0.75) where AUC(0-12)=12.62+(7.78 x C(0))+(0.90 x C(1))+(1.30 x C(2)) (P<0.001). The use of MMF without monitoring MPA blood levels may cause unnecessary overexposure to the drug in stable pediatric recipients.

Adolescent↗

Augmentation cystoplasty in renal transplantation: a good and safe option--experience with 25 cases.

OBJECTIVES: To assess the surgical and long-term results of renal transplantation in 25 patients with bladder dysfunction and augmentation cystoplasty. METHODS: We retrospectively reviewed the evolution and surgical outcome of 25 renal transplants in 24 recipients with augmentation cystoplasty. The mean patient age at transplantation was 27.6 years. The etiology of bladder dysfunction was neurogenic bladder with detrusor hyperreflexia (11 patients), tuberculosis (5 patients), vesicoureteral reflux (4 patients), posterior urethral valves (3 patients), and interstitial cystitis (1 patient). Seventeen transplants were from living donors. Augmentation cystoplasty was performed before transplantation in 21 patients. The bowel segments used in the augmentation cystoplasty included ileum in 16, ileocecal segments in 2, and sigmoid in 5 patients. The donor ureter was anastomosed to the native bladder in 16 patients, to the bowel segment in 6, and to the native ureter in 3. RESULTS: Twenty kidneys (80%) were functioning at a mean follow-up of 53.2 months (range 6 to 118). The mean serum creatinine was 1.56 mg/dL (range 0.7 to 2.6). Three patients died of unrelated causes and 1 of adenocarcinoma that originated at the vesicointestinal anastomosis. The actuarial graft survival at 1, 2, and 5 years was 96%, 92%, and 78%, respectively. Complications included symptomatic urinary infection, ureteral stenosis, and lymphocele. CONCLUSIONS: Augmentation cystoplasty is a safe and effective method to restore function in noncompliant bladders. Renal transplantation can be performed safely after augmentation cystoplasty.

Adolescent↗

A strategy to calculate cyclosporin A area under the time-concentration curve in pediatric renal transplantation.

The complete area under the time-concentration curve (AUC) is considered the gold standard for cyclosporin A (CsA) monitoring, particularly in pediatric kidney graft recipients who have great absorption and drug clearance variability. However, complete AUC is time-consuming and expensive. For this reason, we retrospectively reviewed 131 complete 4-h AUC (AUC0-4) performed in 34 children (mean age 10.6 +/- 2 yr) in order to construct an equation to calculate AUC0-4. The median time after transplantation was 540 (range: 247-1,358) days. Multiple regression analysis was performed either with a single variable or with a combination of two variables. CsA blood concentration at the second hour after the oral morning dose (C2) was the best predictor of AUC0-4, where AUC0-4 = 424 + (2.65 x C2), R2 = 0.81, p < 0.001. Only the combination of C1 and C2 offered mathematical improvement over the C2 equation. The same analysis was made for pharmacokinetic curves performed earlier than 6 months (79 +/- 55 days, range 8-169 days) and after 1 yr of transplantation. In both time-periods, C2 was the best parameter to use to calculate AUC0-4. The equations obtained during these two time-periods were very close to the one for the whole population. Our data shows that C2 can be safely used to estimate AUC0-4. However, for values above 4,000 ng/h/mL, the formula overestimates the trapezoidal AUC0-4. The C2 equation simplifies the CsA monitoring as a result of its high predictive value and clinical feasibility.

Algorithms↗