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.

Management and outcome of inoperable Wilms tumor. A report of National Wilms Tumor Study-3.

METHODS: The authors reviewed 131 children enrolled in National Wilms Tumor Study-3 (NWTS-3) who received preoperative treatment for tumors unable to be resected at surgery or judged inoperable by imaging evaluation. Preoperative biopsies were performed on 103 patients. Patients were assigned a pretreatment stage: stage II (11 patients), stage III (39 patients), stage IV (66 patients), and unknown (15 patients). The chemotherapy regimen included dactinomycin and vincristine (81 patients), dactinomycin, vincristine, and doxorubicin (30 patients), dactinomycin, vincristine, doxorubicin, and cyclophosphamide (10 patients), and other (8 patients). Preoperative radiation therapy was started concurrently with chemotherapy (27 patients) or because of lack of response (14 patients). Two patients were given preoperative irradiation without chemotherapy. RESULTS: Response to therapy was assessed after the first trial of chemotherapy. Partial responses were noted in 110 patients (85%), 3 had complete responses, 13 had no response or progression of disease, and 5 patients were not able to be evaluated. There were no significant differences in preoperative response to the different chemotherapy regimens. Median time interval from diagnosis to nephrectomy was 58.5 days. When compared with NWTS-3 patients not receiving preoperative treatment, survival was reduced for patients treated preoperatively (88% vs. 74%, respectively, 4-year survival), which was only partially explained by differences in stage distribution. Median duration of follow-up was 5.9 years. Lack of response to the preoperative treatment was associated with a poor prognosis. Eight children died before removal of the primary tumor. All eight had either progressive disease or no response to the preoperative treatment. CONCLUSIONS: The use of preoperative treatment can facilitate subsequent surgical resection in selected patients with inoperable Wilms tumors. Although these very large tumors--judged unable to be resected--have a somewhat worse prognosis, nephrectomy was completed in 93% of patients after preoperative treatment. However, preoperative treatment will lead to less accurate surgical and pathologic staging, and undertreatment should be avoided in these high-risk patients.

Hydronephrosis in renal ectopia: incidence, etiology and significance.

The incidence, cause and significance of hydronephrosis in patients with renal ectopia are unknown. Therefore, we conducted a retrospective review of 77 patients with 82 ectopic kidneys. Of 82 kidneys 46 (56%) had hydronephrosis. Dilatation of the renal pelvis was the result of primary ureteropelvic or ureterovesical obstruction in 52%, grade 3, 4 or 5 vesicoureteral reflux in 26% and extrarenal collecting systems with malrotation that produced apparent ureteropelvic junction obstruction in 22%. Surgery was performed in 41 patients, including primary nephrectomy in 18, ureteral reimplantation in 14 and ureteropelvic junction repair in 8. Hydronephrosis was present in 15 of 58 contralateral nonectopic kidneys, and 11 required surgery mostly for vesicoureteral reflux. Solitary ectopic kidneys with no associated obstruction or reflux demonstrated normal renal function. Our data indicate that the prognosis in renal ectopia relates directly to the associated urological disease and timely surgical intervention, not to ectopia alone.

Small bowel obstruction after nephrectomy for Wilms' tumor. A report of the National Wilms' Tumor Study-3.

OBJECTIVE: This study was undertaken to define the incidence and etiology of small bowel obstruction (SBO) after nephrectomy for Wilms' tumor. SUMMARY BACKGROUND DATA: Intestinal obstruction is one of the most common postoperative complications after nephrectomy for nephroblastoma. However, few reports have evaluated risk factors for SBO. Radiation therapy has been associated with increased intestinal complications in some adult cancer patients, but this has not been reported in children undergoing cancer surgery. METHODS: Postoperative SBO occurred in 131 of 1,910 children (6.9%) enrolled in the Third National Wilms' Tumor Study (NWTS). The etiology of the SBO was bowel adhesions in 104 cases, intussusception in 17, internal hernia in 2, and uncertain in the remaining 8 children. RESULTS: The factors found to be of potential importance in explaining the incidence of SBO were higher local tumor stage, extrarenal intravascular involvement, and en bloc resection of other organs at the time of nephrectomy. The incidence of postoperative SBO was not increased in children who received postoperative radiation therapy. CONCLUSIONS: Although the overall incidence of SBO after nephrectomy for Wilms' tumor is comparable to that after other major abdominal operations in children, it can be responsible for significant morbidity. There were 4 children among the 1,910 patients with infectious complications of SBO, which contributed to their death.

Preoperative therapy for intracaval and atrial extension of Wilms tumor.

BACKGROUND: Primary surgical management of Wilms tumor with intravascular tumor extension is associated with significant morbidity. Retrospective analysis of a group of Wilms tumor patients with intravascular tumor extension treated with preoperative therapy was performed to evaluate the feasibility of this approach. METHODS: Thirty children with caval (15 patients) or atrial (15 patients) extension of Wilms tumor who received preoperative therapy were reviewed. Patients were classified according to the stage of the disease as follows: (1) Stage III, 7 patients; (2) Stage IV, 18 patients; and (3) Stage V, 5 patients. The histologic type was favorable in 20 patients, anaplastic Wilms tumor in 7, and unknown in 3. All of the children received preoperative chemotherapy, ranging from 1-16 weeks with an average of 7.2 weeks. RESULTS: One child died of progressive disease and another from toxicity before surgery. In 23 patients, a decrease in the size of the intravascular extension was noted preoperatively, without tumor embolization in any case. There was complete resolution of tumor thrombus in seven patients. Two-year survival for the entire group is 70%, with a median follow-up period of 21 months. CONCLUSIONS: The use of preoperative therapy is appropriate in selected patients with extensive intravascular tumor involvement. Surgical management was facilitated in the majority of cases due to shrinkage of the primary tumor and reduction in the size of the tumor thrombus.

Incidental appendectomy during nephrectomy for Wilms' tumor.

Incidental appendectomy is frequently performed during nephrectomy for Wilms' tumor. The rationale for this approach is that the onset of appendicitis during a period of neutropenia after chemotherapy may cause increased morbidity. Additionally, children receiving chemotherapy or radiation therapy, or both, may experience abdominal pain, producing a diagnostic dilemma if the appendix is still present. We reviewed the charts of 1,910 children enrolled in the Third National Wilms' Tumor Study who underwent primary nephrectomy. Four hundred and fifty-five patients (23.8 percent) had appendectomy at the time of nephrectomy. An inversion appendectomy was performed upon 188 patients, and the appendix was excised in 267. Infectious complications and postoperative intestinal obstructions occurred with equal frequency in children who did or did not undergo appendectomy. The median follow-up period for the entire group of patients was 5.1 years. Only three of the 1,455 children (0.2 percent) who did not have an incidental appendectomy had appendicitis at two, seven and ten months after nephrectomy. None of the three children experienced any perioperative morbidity after appendectomy. These data suggest that incidental removal of the appendix is not essential for children undergoing removal of a Wilms' tumor.

Surgical complications after nephrectomy for Wilms' tumor.

We reviewed the charts of 1,910 children enrolled in the Third National Wilms' Tumor Study who underwent primary nephrectomy. Four hundred and ninety-five surgical complications occurred in 379 children (19.8 percent). Patients with inoperable tumors, bilateral renal tumors, peroperative therapy and those who refused treatment were excluded from this review. The most common complication was intestinal obstruction, which occurred in 132 patients (6.9 percent). This was followed by extensive intraoperative hemorrhage (112 patients), defined as blood loss exceeding 50 milliliters per kilogram of body weight. Intraoperative injuries to other visceral organs (including intestine, liver and spleen) occurred in 21 children and extensive vascular injuries were reported in 27 patients. There were nine deaths attributed to surgical complications (0.5 percent), only one of which was intraoperative. Survival of patients with complications was similar to patients without complications when stratified by histologic study and stage. Factors associated with the development of surgical complications included advanced local tumor stage at diagnosis, intravascular tumor extension and resection of other visceral organs at the time of nephrectomy. Complete removal of the tumor is important, but not at the expense of radical removal of adjacent structures, because of gross appearances at operation. They are often not invaded by the tumor, but rather are compressed, distorted or adherent without tumor infiltration. Identification of these groups will aid the surgeon in choosing the appropriate management for these patients at high risk. When initial exploration and precise surgical staging indicate that only a formidable operation will achieve total excision, shrinkage of the tumor with selective use of chemotherapy or radiotherapy, or both, may facilitate removal and decrease surgical morbidity. Preoperative therapy may also be the preferred approach for children with extensive intravascular tumor.

Extrarenal Wilms' tumor: results of the National Wilms' Tumor Study.

Extrarenal Wilms' tumor is extremely rare and occurs predominantly in children. Eight cases of extrarenal Wilms' tumor were reported to the National Wilms' Tumor Study from 1980 to 1986. Patients were followed in the study and not randomized to a particular treatment protocol. Seven patients had a favorable histology. One tumor located in the sacrococcygeal region showed immature teratoma with nephroblastic tissue. The embryogenesis of extrarenal Wilms' tumor is controversial; however, tumor containing teratomatous elements most likely represents a different embryologic origin and, therefore, should be classified separately. All eight patients were treated with operative excision and chemotherapy. Seven of the eight patients were disease-free with a mean follow-up of 34.3 months. It can be inferred from this small group of patients that the prognosis is comparable to intrarenal Wilms' tumor in the National Wilms' Tumor Study.

Superior mesenteric artery injury during nephrectomy for Wilms' tumor.

Iatrogenic injury to the aorta or its major branches during nephrectomy for Wilms' tumor in children is rarely reported but may be more common than is currently acknowledged. We identified four patients with ligation of the superior mesenteric artery (SMA) that occurred during nephrectomy for nephroblastoma and another child in whom SMA thrombosis developed postoperatively. All of the tumors were on the left side. Interruption of the SMA was recognized intraoperatively in all four children, and primary repair was done. In three patients, appearance of the bowel remained normal before repair of the injury. Three of the arteries were repaired by primary reanastomosis, and one was joined with an interpositioned hypogastric artery graft. None of these patients had gastrointestinal complications postoperatively. In the fifth patient, SMA thrombosis developed after repair of an aortic tear during nephrectomy. This patient required subsequent small bowel resection for bowel infarction and died in the perioperative period. Every surgeon treating children with Wilms' tumor should be aware of the possibly distorted vascular anatomy and take precautions to avoid such a significant injury. Attempts at early ligation of the vessels may not be justified until the renal vasculature is clearly identified.

Strategies for ureteral catheterization after antireflux surgery by the Cohen technique of transverse advancement.

The Cohen technique for antireflux surgery is well established and provides excellent results. A major drawback with this technique is the difficulty in catheterizing the ureter postoperatively. We describe different strategies that can be used to catheterize the ureter successfully.

Prognostic factors in nonmetastatic, favorable histology Wilms' tumor. Results of the Third National Wilms' Tumor Study.

A comprehensive statistical analysis of relapses to lung and abdomen and of deaths due to tumor that occurred among 1466 patients with nonmetastatic, favorable histology (FH) Wilms' tumor entered on the Third National Wilms' Tumor Study (NWTS-3) was undertaken. In addition to lymph node involvement, age at diagnosis and tumor size as measured by the weight of the excised specimen were the most important determinants of outcome. The effects of tumor size were most apparent for patients with localized (Stage I) disease; age effects were found for patients with regional (Stage II or III) disease. The presence of microscopic tumor in the margin of surgical resection was an independent predictor of abdominal recurrence and death in the latter group. Although the report of the surgeon of diffuse soilage of the peritoneal cavity from tumor spilled or cut across in the course of nephrectomy was highly correlated with outcome, it was not possible to establish an independent prognostic role for such a finding after adjustment for the aforementioned factors. Patients with intralobar nephrogenic rests (ILNR) had a favorable survival outlook even after accounting for their generally younger ages and lower stages.

Extended followup of bilateral Wilms tumor: results of the National Wilms Tumor Study.

The long-term survival of patients with synchronous bilateral Wilms tumor is not well defined. Retrospective review of 185 patients registered with the National Wilms Tumor Study from January 1974 to July 1986 with stage V tumors suggests that the long-term outcome remains good. Over-all survival is 83%, 73% and 70% at 2, 5 and 10 years, respectively. Unfavorable histology, age at diagnosis and the most advanced stage of the individual tumors remain the most important prognostic variables. No significant difference in survival was noted between patients undergoing initial surgical resection of the tumor and those managed with initial tumor biopsy followed by chemotherapy with or without radiotherapy and subsequent surgical resection. Survival does not appear to be compromised by attempting to conserve native renal function with renal-sparing operations.

Malignant potential of the cryptorchid testis.

A follow-up study of 224 male patients from Rochester, Minnesota, diagnosed with cryptorchidism during the period from 1935 through 1974 was conducted to assess the frequency of subsequent testicular neoplasms. Age-specific rates for testicular neoplasm in this community were used to estimate an expected number for comparison with that observed. Two malignant testicular neoplasms have occurred in this cohort; thus, the standardized morbidity ratio was 11.4 (95% confidence interval, 1.4 to 41.1). Of the 158 patients born in the community, 11% were known to have birth weights of less than 2,500 g, approximately twice the expected occurrence. Increased risks were also noted for inguinal hernia, hypospadias, Down's syndrome, cleft lip or palate (or both), clubfoot, and congenital heart disease, for which the standardized morbidity ratios were 3.6, 4.7, 17.8, 11.3, 11.7, and 2.7, respectively. The increased risk for malignant neoplasms observed in this cohort of patients with cryptorchidism is consistent with that found in earlier studies.

Pediatric urological complications with intraoperative radiation therapy.

Intraoperative radiotherapy with variable energy electrons has been used as a supplemental boost to treat 6 children with locally advanced retroperitoneal malignancies. Of the patients 4 had treatment-related injuries to portions of the urinary tract within the intraoperative and external radiation fields. Three patients had significant renal impairment requiring surgical correction. The pathogenesis and management of treatment-induced injury to the urinary tract are discussed.

Renal vein involvement with nephroblastoma: a report of the National Wilms' Tumor Study-3.

The records of children enrolled in the National Wilms' Tumor Study-3 who had Wilms' tumor and thrombosis into the renal vein were reviewed. There were 164 patients with gross involvement of the extrarenal vein and 47 patients with microscopic involvement, an incidence of 11.3% (211 of 1,865 evaluable patients). Two-year survival rates were 90, 79 and 72% for stages II, III and IV, respectively. The most important predictors of survival were histologic pattern and stage. Complete en bloc excision of the tumor and thrombus continues to be the most effective initial management.

Ureterocalicostomy: indications and results in 21 patients.

Ureterocalicostomy was performed in 21 patients for ureteropelvic junction obstruction. Ten patients had failed pyeloplasty, 10 had anomalies of renal fusion, ascent or rotation in conjunction with ureteropelvic junction obstruction and 1 had failed prior ureterocalicostomy. Patient age at operation ranged from 6 months to 17 years and averaged 9 years. Of the 21 patients in this series 19 had excellent results after ureterocalicostomy with decrease or total elimination of hydronephrosis. There were 2 postoperative complications in 2 patients: prolonged anastomotic urinary leakage in 1 and a Candida perinephric abscess in 1. Ureterocalicostomy should be considered in selected patients with previous unsuccessful pyeloplasty, ureteropelvic junction obstruction associated with anomalies of renal fusion, rotation or ascent, an intrarenal pelvis or a short ureter. Although endopyelotomy or ureteropelvic junction dilation should be considered in patients who fail pyeloplasty, ureterocalicostomy continues to be a reliable salvage procedure in these patients; it bypasses extensive peripelvic scarring, provides for dependent drainage and compensates for lack of adequate ureteral length.

Intracaval and atrial involvement with nephroblastoma: review of National Wilms Tumor Study-3.

We reviewed the records of 77 children enrolled in the National Wilms Tumor Study-3 who had involvement of the inferior vena cava with tumor thrombus. None of these patients received preoperative chemotherapy or radiotherapy. Ultrasonography and inferior venacavography were more helpful than computerized tomography in the preoperative diagnosis. The median followup for the group was 2.7 years. The 3-year survival rates for patients with intracaval involvement were determined by stage (88, 89 and 62 per cent for stages II, III and IV, respectively). The most important prognostic factor was histological type. The level of vena caval involvement had no effect on survival; all 16 patients with atrial involvement survived 3 or more years. We continue to recommend appropriate surgical excision of the tumor and thrombus when it is technically feasible.

Prepubertal yolk sac testicular tumors--report of the testicular tumor registry.

In 1980 the Section on Urology of the American Academy of Pediatrics established a registry of prepubertal testicular tumors. A total of 181 yolk sac tumors has been reported to the registry. Complete followup is available for 154 of these 181 patients. Most of the patients presented with low stage disease. Radical orchiectomy without adjunctive retroperitoneal lymphadenectomy, chemotherapy or radiotherapy was sufficient therapy for most stage 1 cancer patients. alpha-Fetoprotein is a reliable marker for this tumor. Chest x-rays and abdominal computerized tomography are reliable for staging. When metastases appeared they did so within 14 months of presentation so that 2 years of followup after any evidence of disease seems to be adequate. Approximately two-thirds of the patients with metastases were salvaged by chemotherapy, radiotherapy and/or an operation.

Embryonal rhabdomyosarcoma of bladder and prostate: nuclear DNA patterns studied by flow cytometry.

Nuclear deoxyribonucleic acid ploidy studies with paraffin-embedded archival tumor specimens were performed by flow cytometry on extracted nuclei from 13 embryonal rhabdomyosarcomas of the bladder and prostate. Preparation of embedded tissue specimens into single dissociated nuclei was by the Hedley technique and they were stained with propidium iodide according to the Vindeløv method. Before the era of chemotherapy, 6 of 7 patients died of disease at a median of 5.5 months post-treatment. All 6 deaths occurred in patients with deoxyribonucleic acid aneuploid patterns that were stage II or greater. The 1 survivor had a deoxyribonucleic acid aneuploid pattern and stage I disease and is alive at 12 years of followup. Since 1971, 6 patients were treated with primary polychemotherapy and surgery. All 6 patients are alive without evidence of disease at a mean followup of 75 months (range 12 to 180 months). All 6 patients had deoxyribonucleic acid aneuploid tumors. One patient was stage I and 5 patients were stage III. Thus, all patients with pediatric embryonal rhabdomyosarcoma of the bladder and prostate had deoxyribonucleic acid aneuploid tumors. These patients responded well to treatment with the combination of chemotherapy and surgery.

Management of müllerian duct remnants in the male patient.

We evaluated 36 patients for müllerian duct remnants that were manifest in several forms. The most common type was an enlarged prostatic utricle communicating with the urethra in 22 younger patients, which was associated with hypospadias or intersex disorders in more than 90 per cent of the cases. A cystic müllerian duct remnant was the other configuration noted in 14 older patients who had normal external genitalia and often presented with a rectal mass. The diagnostic evaluation consists of voiding cystourethrography, retrograde urethrography and cystoscopy. Other useful imaging techniques are ultrasonography and computerized tomography. Careful delineation of the anatomy of the lower urinary and genital tracts will help to plan surgical therapy. Suprapubic excision was the most frequent operation and it was successful in all 18 patients in whom it was performed.