Renal failure in the Denys-Drash and Wilms' tumor-aniridia syndromes.

Nearly 6000 patients enrolled in four clinical trials of the National Wilms' Tumor Study Group during 1969-1995 were followed until death or for a median of 11.0 years of survival for the onset of renal failure (RF). Thirteen of 22 patients with Denys-Drash syndrome and 10 of 46 patients with the Wilms' tumor aniridia syndrome developed RF. The cumulative risks of RF at 20 years from Wilms' tumor diagnosis were 62% and 38%, respectively. Only 21 cases of RF were observed among 5358 patients with unilateral disease who did not have characteristic congenital genitourinary anomalies, and their risk was <1%. Although other explanations cannot be completely excluded, the high rate of RF in patients with the aniridia syndrome challenges the view that nephropathy is associated uniquely with missense mutations in the WT1 gene. It suggests the possibility of a further gradation in the spectrum of phenotypes associated with different WT1 mutations. Patients with Wilms' tumor and aniridia or genitourinary abnormalities should be followed closely throughout life for signs of nephropathy or RF.

Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: The National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 1,687 previously untreated children less than 16 years of age with stages I to II/favorable histology (FH) or stage I/anaplastic histology WT (low-risk [LR] group) or stages III to IV/FH WT or stages I to IV/clear cell sarcoma of the kidney (high-risk [HR] group) were randomized to treatment that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either STD courses (3 days) or PI treatment with doxorubicin. RESULTS: The 2-year relapse-free survival (RFS) rates for LR patients were 91.3% for 544 randomized to treatment with PI and 91.4% for 556 randomized to treatment with STD chemotherapy (P = .988). The 2-year RFS rates for HR patients were 87.3% for 299 randomized to treatment with PI and 90.0% for 288 randomized to treatment with STD chemotherapy (P = .865). CONCLUSION: We conclude that patients treated with PI combination chemotherapy for LR or HR WT or clear cell sarcoma of the kidney have equivalent 2-year RFS to those treated with STD regimens. PI drug administration is recommended as the new standard based on demonstrated efficacy, greater administered dose-intensity, less severe hematologic toxicity, and the requirement for fewer physician and hospital encounters.

Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.

Anastomotic obstruction after stapled enteroanastomosis.

We have recently treated two cases of anastomotic obstruction after side-to-side stapled enteroanastomosis. Complete obstruction of a stapled small-bowel anastomosis has not been reported to our knowledge. The mechanism of the obstruction appears to be the healing together of the cut edges of viable bowel beyond the inverted stapled lines. An alternative method of constructing the functional end-to-end enteroanastomosis that is offered is intended to prevent the occurrence of postoperative anastomotic obstruction.

Ring block for neonatal circumcision.

OBJECTIVE: To determine whether a difference in the behavioral and physiologic response to circumcision can be demonstrated between neonates undergoing the procedure with ring block and those receiving no anesthesia. METHODS: Forty healthy male newborns were assigned randomly to receive either ring block or no anesthesia. Indices of perceived pain including crying time, behavioral state, oxygen saturation, and heart and respiratory rates were recorded at baseline and at intervals during the circumcision. Infants were reassessed 2 minutes and 2 hours postoperatively. RESULTS: Infants receiving ring block cried less than did controls (P < .001). Anesthetized infants had smaller increases in heart rate (P < .005) and demonstrated less arousal (P < .005) during each operative interval. For all operative intervals combined, anesthetized infants had a smaller decrease in oxygen saturation (P < .001) and a smaller increase in respiratory rate (P = .005) than did controls. Two minutes postoperatively, anesthetized infants had returned to their baseline behavioral state, whereas controls remained significantly more aroused (P < .005). Two hours postoperatively, there were no significant differences in any variables between the groups, nor between each group and its baseline. There were no complications related to anesthesia administration. CONCLUSION: Neonatal circumcision causes behavioral and physiologic changes consistent with the perception of pain. Ring block is an effective method of anesthesia for this procedure.

Comparison of different techniques of stapled bowel anastomoses in a canine model.

OBJECTIVE: To evaluate different methods of creating a stapled enteroanastomosis and to determine which method would create a larger anastomosis. DESIGN: Prospective comparison of three groups with a total of 17 mongrel dogs. SETTING: Clinical investigation facility. MAIN OUTCOME MEASURES: Stapled side-to-side enteroanastomoses were created with the stapled edges touching or separated. Anastomoses were created in both functional bowel and in a defunctionalized limb. The anastomotic circumference was measured in a blinded fashion after 28 days. The third group had anastomoses created and measured the same day. Groups were compared using the t test. RESULTS: There was significant narrowing after healing with both types of anastomoses. Anastomoses created by separating the stapled lines were larger than those fashioned with the cut edges touching, both immediately and after healing. CONCLUSIONS: While clinically significant narrowing of a stapled anastomosis is uncommon, separating the staple lines of a functional end-to-end anastomosis may be the preferable method.

Modified dartos pouch orchiopexy.

Experimental evidence suggests that transparenchymal suture fixation may risk testicular damage. Even very small sutures can result in inflammation and tubular damage. An alternative to transparenchymal suture fixation of the testis is presented.

Cost-effective endoscopic examination of the contralateral inguinal ring.

OBJECTIVES: Laparoscopic examination of the contralateral inguinal ring has recently been advocated to exclude contralateral hernia in young children. We report a modification using nondisposable cystoscopic equipment, which is quick and reliable. METHODS: Either an 8 or 10 F soft straight catheter or a cystoscope sheath is passed through the open hernia sac. Air is insufflated into the abdomen with a syringe. Once the pneumoperitoneum is completed, a 4-mm cystoscope lens (110 degrees) is used to inspect the contralateral ring. RESULTS: Twenty-four children between the ages of 6 weeks and 4 years (median, 6 months) underwent exploration for presumed unilateral inguinal hernia and laparoscopic examination of the contralateral inguinal ring. Thirteen patients (54%) had an open processus vaginalis and underwent contralateral inguinal herniorrhaphy. No false-positive or false-negative results were found, and there were no complications associated with the procedure. CONCLUSIONS: This method of laparoscopic examination of the contralateral inguinal ring using nondisposable cystoscopic equipment is rapid, safe, reliable, and cost effective in evaluating a contralateral patent processus vaginalis. Laparoscopic examination spares the need for formal surgical exploration in patients with a closed processus vaginalis.

Normal and abnormal pelviscopic anatomy at the internal inguinal ring in boys and the vasal triangle.

OBJECTIVES: We sought to explain and define normal and abnormal laparoscopic pelvic anatomy, which has only recently become the target of much attention. METHODS: The embryology, normal anatomic landmarks, and abnormal findings of the male pelvis, as discerned from more than 350 laparoscopic investigations in boys, were analyzed. RESULTS: The medial umbilical ligament, the wishbone at the internal inguinal ring, the transverse vesical fold, and the vasal triangle are principal laparoscopic landmarks of the male pelvis. Deficient spermatic vessels, abnormal gonadal locations, patent processus vaginalis, single medial umbilical ligament, and transverse testicular ectopia were the abnormal findings. CONCLUSIONS: Laparoscopic familiarity with the male pelvis permits safe and efficient diagnostic and therapeutic navigation in this new surgical arena.

Ureterocele associated with a single collecting system of the involved kidney.

OBJECTIVE: This is a study concerning ureteroceles associated with a single collecting system of the involved kidney. METHODS: Over an eight-year period 9 children (5 boys, 4 girls) had a ureterocele subtending a single collecting system, whereas 63 children had duplex ureteroceles. Malformations of other organ systems were present in only 1 patient. RESULTS: Three patients have undergone surgical interventions: a transurethral incision of bilateral obstructive ureteroceles in 1 and nephroureterectomy in 2. In 4 cases cystic/dysplastic kidneys involuted and were reabsorbed with collapse of the ureteroceles. The last 2 patients have received antibiotic treatment for single episodes of a urinary tract infection. CONCLUSIONS: Earlier reports of a high incidence of concomitant anomalies and male predominance in patients with single-system ectopic ureteroceles could not be verified by our experience. Our current policy for a patient is careful evaluation, individualized therapy, and long-term surveillance.

Outcome analysis of bilateral Cohen cross-trigonal ureteroneocystostomy.

OBJECTIVES: The perioperative and long-term outcomes of children with vesicoureteral reflux (VUR) treated by cross-trigonal ureteroneocystostomy were ascertained. METHODS: One hundred ten consecutive children with VUR who underwent bilateral cross-trigonal ureteroneocystostomy were studied retrospectively. Nineteen children with neurovesical dysfunction or megaureters requiring tapered reimplants were excluded. Outcome parameters of the remaining 91 children consisted of operative time, length of hospitalization, days of Foley catheter drainage perioperative complications, correction of reflux, subsequent morbidity, and parental satisfaction. RESULTS: Of 182 renal units, 11 (6%) had grade 0 VUR, 18 (10%) had grade I, 43 (24%) had grade II, 59 (32%) had grade III, 36 (20%) had grade IV, and 15 (8%) had grade V reflux. The mean operative and hospitalization times were 180 minutes and 5.6 days, respectively. No postoperative complications occurred. Three children were lost to follow-up, and the remaining 88 children had an extended mean follow-up in excess of 3 years. Voiding cystourethrogram documented a 98.3% (173 of 176 renal units) success rate. Sixteen children (18%) experienced nonfebrile clinically symptomatic cystitis episodes and 3 children (3%) experienced one febrile episode each. Telephone parental survey of overall surgical experience revealed a 94% very satisfied, 2% satisfied, and 3% dissatisified rate. CONCLUSIONS: Cross-trigonal ureteroneocystostomy is a safe and effective technique that is virtually complication free and has high parental satisfaction. The results of this study provide a baseline for comparison of non-operative treatment of reflux as well as laparoscopic and endoscopic techniques.

Urologic manifestations of Goldenhar syndrome.

OBJECTIVE: Goldenhar syndrome (oculoauriculovertebral dysplasia) is associated with anomalies in multiple organ systems. Renal abnormalities have also been reported with the complex, but the incidence of associated genitourinary malformations has not been defined. METHOD: We have reviewed our experience with 28 children with Goldenhar syndrome evaluated during the past twelve years. Twenty children underwent imaging evaluation of the urinary tract and 14 (70% of those imaged) children had urinary tract anomalies. RESULTS: The majority of anomalies presented as an incidental finding on a screening ultrasound (8 patients) or during cardiac catheterization (2 patients). Two children presented with urinary tract infection, 1 child presented with renal failure, and another was diagnosed antenatally. The genitourinary anomalies included the following: ectopic and/or fused kidneys (8 patients), renal agenesis (7), vesicoureteral reflux (5), ureteropelvic junction obstruction (2), ureteral duplication (2), and multicystic kidney (1 patient). Four children have undergone surgical intervention. CONCLUSION: Our experience in children with Goldenhar syndrome suggests that the incidence of genitourinary anomalies is higher than previously reported. A screening ultrasound in the neonatal period allows for early intervention in those children with significant urologic abnormalities.

Intravesical instillation of gentamicin sulfate: in vitro, rat, canine, and human studies.

OBJECTIVE: Intravesical instillation of gentamicin sulfate has been used empirically as prophylaxis and to treat bacilluria in spinal-cord-injured patients undergoing clean intermittent catheterization. To assess the risks of absorption and the effects of storage conditions on antimicrobial potency, a series of studies were conducted. METHODS: Four studies were carried out: (1) An infected fulgurated rat bladder model was created to determine the effects of inflammation and infection on absorption. (2) A canine model with bilateral vesicoureteral reflux and elevated bladder pressures (> 40 cmH2O) assessed the effects of reflux and storage pressure. (3) The effects in patients with associated conditions including renal transplantation, myelomeningocele, vesicoureteral reflux, and bladder augmentation, were analyzed. (4) To determine the effects of storage conditions, solutions of gentamicin sulfate (480 mg gentamicin sulfate in 1 L 0.9% NaCl) were made that controlled for pH, storage temperature, and duration. RESULTS: (1) Increased absorption was found in 43 percent of rat serum samples. (2) None of the dogs demonstrated measurable absorption. (3) None of the patients likewise had measurable absorption. (4) All solutions were equally potent when tested against a panel of common urinary pathogens. Storage up to two months at room temperature without alkalinization had no effect on potency. CONCLUSIONS: Instilled intravesical gentamicin sulfate has a low risk of absorption and is highly effective. Severe bladder inflammation can increase transvesical absorption. It has prolonged stability without special storage conditions and should be considered as a route of prophylaxis in patients who perform intermittent catheterization.

The management of synchronous bilateral Wilms tumor.

There has been a distinct evolution in the treatment philosophy for patients with BWT. Initial attempts at radical surgery have given way to the current use of preoperative chemotherapy to preserve as much kidney tissue as possible. With preoperative treatment, usually chemotherapy only, overall survival has become quite favorable in this group of patients, approaching 83% at 2 years. This has facilitated the use of parenchymal-sparing operations, with the potential advantage of decreasing the incidence of end-stage renal disease. The development of renal insufficiency in children with synchronous BWT nonetheless remains a concern. It is important that long-term survivors have systematic follow-up, with measurements of blood pressure, urine protein, serum creatinine, renal clearance, and renal size. Finally, despite the mentioned achievements, the management of children with synchronous BWT still needs standardization. The limited number of patients affected by BWT makes an international effort desirable to address this need.

Surgical complications after primary nephrectomy for Wilms' tumor: report from the National Wilms' Tumor Study Group.

BACKGROUND: Surgical complications are a recognized morbidity of the treatment of patients with Wilms tumor. This study examines the incidence of surgical complications in the most recently completed study from the National Wilms' Tumor Study Group (NWTSG). STUDY DESIGN: The fourth National Wilms' Tumor Study (NWTS-4) enrolled 3,335 patients from August 1986 to August 1994. A random sample of 534 patients was selected from 2,290 eligible patients randomized to treatment regimens or enrolled in the followed category and treated according to NWXTSG protocol. The patient records received at the NWTSG Data and Statistical Center were analyzed for surgical complications (intraoperative and postoperative). RESULTS: Sixty-eight patients (12.7%) experienced 76 complications. Intestinal obstruction was the most common complication (5.1% of patients), followed by extensive hemorrhage (1.9%), wound infection (1.9%), and vascular injury (1.5%). The incidence of surgical complications in NWTS-4 was significantly lower than NWTS-3 (12.7% versus 19.8%, p < 0.001). There has been a marked decrease in the risk of extensive intraoperative bleeding and major intraoperative complications. Factors previously shown to be associated with an increased risk for surgical complications, together with indicators of type of hospital and surgeon specialty, were analyzed by multiple logistic regression analysis. Intravascular extension into the inferior vena cava (IVC), the atrium, or both (p = 0.02; odds ratio [OR] 3.8, 95% confidence interval [CI] 1.2, 11.8), and nephrectomy performed through a flank or paramedian incision (p = 0.02; OR 5.3, 95% CI 1.3, 22) were both associated with increased risk of complications. Tumor diameter greater than or equal to 10cm was also associated with an increased risk of surgical complications (p = 0.05; OR 2.0, 95% CI 1.0, 3.9). The risk of complications was higher if the nephrectomy was performed by a general surgeon (OR 9.0, 95% CI 1.3, 65; p = 0.03) rather than a pediatric surgeon (reference group, OR 1.0) or pediatric urologist (OR 0.7, 95% CI 0.3, 1.8). CONCLUSIONS: The incidence of surgical complications in NWTSG patients undergoing primary nephrectomy has significantly decreased over the past decade. But surgical morbidity should not be overlooked. It is important that surgeons treating young children with solid tumors are aware of their role and the potential risks encountered in removal of the primary tumor. This study found that surgical specialists who primarily treat children can perform these operations with lower surgical morbidity.

Wilms' tumor. Overview of National Wilms' Tumor Study Group results.

Since its inception in 1969, the NWTSG has performed successful studies that are now the model for the management of pediatric malignancies. Future studies may use genetic markers to stratify high-risk patients beyond the traditional staging system. Therapy will continue to be evaluated to determine the minimal therapy necessary to achieve the best outcome for children with Wilms' tumor.

Wilms tumour: diagnosis and treatment.

Wilms tumour is the most common intra-abdominal solid tumour of childhood. Treatment includes surgical resection and chemotherapy for virtually all affected children and additional radiotherapy for those with advanced disease or adverse prognostic features. This approach leads to cure rates exceeding 80%. During the last decade there have been a number of advances which have increased our understanding of the biology of Wilms tumour. The development of Wilms tumour, for example, involves several genes, including WT1, the Wilms tumour suppressor gene at 11p13, and WT2, the putative Wilms tumour suppressor gene at 11p15. In addition, certain chromosomal regions, most notably 16q and 1p, might predict outcome and hence serve as a prognostic factor, useful for determining the intensity of therapy. This novel information is now being incorporated into current therapeutic protocols. We reviewed the medical literature and present a summary of the advances made, outlining the current treatment of Wilms tumour. Future protocols will continue incorporating biological markers. The goal is to identify patients at low risk for relapse, which will allow a reduction in treatment intensity and subsequent toxicity. Children at an increased risk for relapse can be selected for more intensive treatment.

Controversies in the management of Wilms' tumor.

Wilms' tumor is the most common malignant renal tumor of childhood; it represents 5% to 6% of childhood cancers in the United States. The survival rate of children with Wilms' tumor has improved dramatically, partly due to large multicenter studies conducted by the National Wilms' Tumor Study Group and the International Society of Pediatric Oncology. To ensure optimal patient outcome, the surgical management of these patients must be appropriate. Controversial issues in the management of Wilms' tumor include the value of preoperative chemotherapy; whether pre-resection biopsy is indicated and if so, how this is best performed; indications for partial nephrectomy; the treatment of low-risk patients with surgery only; and the reliability of preoperative imaging to assess the contralateral kidney.

Nephroblastoma.

Effective diagnosis, staging, and multimodality therapies dramatically decreased the morbidity and mortality of children with Wilms Tumor. Increasing awareness of the disease, biology, genetics, and epidemiology improved assessment of clinical syndromes and led to more risk-based treatment. The role of tumor imaging is being defined, and primary exploration with nephrectomy remains of value to confirm histological diagnosis and disease stage. Primary chemotherapy with delayed resection is evolving into the preferred approach for large inoperable tumors, bilateral disease, and those tumors with extensive intravascular involvement. Current therapeutic trials will be nonrandomized and emphasize biological tumor features for future patient stratification. A selected group of young patients with small localized favorable histology tumors will be treated with surgery alone.

Neonatal Wilms tumor.

Neonatal renal tumors are very rare. We have identified 15 cases of Wilm's tumors diagnosed in the first 30 days of life. The most common presentation was an abdominal mass on routine newborn examination, and three tumors were noted on an antenatal ultrasound. All of the infants underwent primary excision of the tumor. Five infants were not given postoperative chemotherapy after surgical excision. One of these children had a relapse and later died of progressive disease. The remaining children are alive at a median follow-up of 31 months. Eight of the tumors had evidence of nephrogenic rests. More frequent follow-up physical and imaging examinations are indicated in children not given adjuvant chemotherapy or whose tumors show nephrogenic rests.