Bilateral Wilms' tumor and secondary malignancies

A series of six patients with bilateral Wilms' tumor (nephroblastoma) is presented. Multimodal therapy yielded a survival rate of 83% at 2 yr of follow-up. However, at the end of a later follow-up period only two patients (33%) were alive. of the 4 patients who died. Only 1 died of Wilms' tumor. One died of complications of aggressive chemotherapy and two patients died after 12 and 16 yr following treatment of secondary malignant tumors arising in the irradiated region. Patients with bilateral tumor should be followed at regular intervals for the duration of life for the occurrence of secondary malignant tumors.     

Survival in bilateral Wilms' tumor--review of 30 National Wilms' Tumor Study cases.

Bilateral tumors were found in 33 patients or 5.4% of 606 children enrolled in the National Wilms' Tumor Study. Twenty six of 30 patients (87%) for whom detailed clinical information is available survived 2 yr after conservative surgery and radiation therapy. All patients were given one or more chemotherapeutic agents. A variety of surgical procedures were used including biopsy only, nephrectomy, and partial nephrectomies. Radiation therapy doses ranged widely, but between 1000 and 2000 rad apparently sufficed for local control in most cases. Recommendations regarding management by surgery, radiation therapy, and chemotherapy are given.     

Wilms' tumor in the neonate: a report from the National Wilms' Tumor Study

Renal neoplasms in the neonate are quite uncommon. Twenty-seven of the 3,340 patients (0.8%) registered on the National Wilms' Tumor Studies from 1969 through April 1984, were 30 days old or less. Of these 27 patients, 18 had mesoblastic nephroma, 1 had a malignant rhabdoid tumor of the kidney, and 4 others had nonneoplastic lesions. The remaining four infants were reviewed in detail. All had favorable histology Wilms' tumors; none had distant metastasis at diagnosis. Treatment ranged from surgery alone to excision plus three-drug therapy for 15 months. All fared well. The patient with Stage I rhabdoid tumor died at eight weeks of age in spite of aggressive four-drug therapy. This review supports the view that Wilms' tumor in the neonate is extremely rare.     

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.     

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.     

Ureteral extension in Wilms' tumor: a report from the National Wilms' Tumor Study Group (NWTSG)

Background

Extension of Wilms' tumor into the ureter is a rare event. We reviewed the National Wilms' Tumor Study Group (NWTSG) database to define the clinical presentation, associated pathologic features, and clinical outcome of these patients.

Methods

Records of children identified to have ureteral extension of Wilms' tumor enrolled in NWTS-3, 4, and 5 were reviewed. Presenting symptoms, diagnostic studies, histopathologic findings, operation performed, and outcome were recorded. The NWTS-5 surgical data were prospectively collected as part of the quality assurance program.

Results

Forty-five children were identified with ureteral extension. For NWTS-5, the incidence of ureteral extension was 2%. Clinical presentations were gross hematuria in 22 patients, 2 had passage of tissue per urethra, and 1 child had a urethral mass. The remainder had nonspecific presentations. Ureteral extension was seen on preoperative imaging in 14 patients, intraoperatively in 22, and on pathologic examination in 9 patients. Hydronephrosis was noted in 12 patients, and there was nonfunction of the kidney in another 8. Laterality of the tumor was right side in 26 and left in 19. Cystoscopy was performed in 12 children. Findings included tumor seen at the ureteral orifice in 6 patients and bleeding from the orifice in one child. All patients had radical nephrectomy including partial ureterectomy. The ureteral margin was positive in 3 patients, including 2 of the 7 with separate removal of the ureteral extension. The number of patients in each clinical stage was as follows: stage I, 10; stage II, 18; stage III, 14; and stage IV, 3. The tumor extended into the proximal ureter in 23 patients, distal ureter in 13, 7 had extension into the bladder, and 1 had urethral involvement. The level of ureteral extension was not clearly noted in the 45th child. The median follow-up was 96 months. Overall, 41 of 45 patients were alive at last contact. There were 3 deaths because of tumor in patients with unfavorable histologic tumors, and 1 because of treatment toxicity in a child with favorable histologic findings.

Conclusions

Ureteral extension occurs in approximately 2% of patients with Wilms' tumor. The diagnosis should be suspected in patients with gross hematuria, hydronephrosis, or nonfunctioning kidney. Cystoscopy with retrograde ureterogram may aid in preoperative diagnosis in these patients. Preoperative diagnosis is important because complete resection of the involved portion of ureter at the time of nephrectomy can avoid residual disease and the need for second surgery or radiation therapy.     

The surgical treatment of Wilms' tumor: results of the National Wilms' Tumor Study.

Surgical data derived from the 606 patients in the National Wilms' Tumor Study have been analyzed to determine the effect of surgical technique on results of treatment. In addition to surgical excision of the tumor, patients were treated with chemotherapy and radiation therapy according to the study protocol. Under these controlled conditions, certain aspects of surgical technique which have traditionally been thought to be important for success appear to be irrelevant. Physical characteristics of the tumor, preoperative rupture and vascular invasion by tumor were not associated with higher relapse rates. Large tumors, those with capsular infiltrations, and tumors with spread to lymph nodes higher recurrence rate. Operative spill increased the chance of abdominal recurrence. There was no evidence that early ligation of the renal vein was of value in prevention of recurrence, nor was incomplete removal of tumor associated with an increase in relapse rate. Although several critical factors of surgical technique were not studied, it is clear that others are not significant and need not be continued.     

Quality assessment for Wilms' tumor: a report from the National Wilms' Tumor Study-5

Background/Purpose

Surgical technique impacts both local tumor stage and risk of local recurrence in Wilms' tumor. A surgical quality assurance program was part of National Wilms' Tumor Study-5 to assess protocol compliance.

Methods

Surgical checklists, operative, and pathology reports were reviewed concurrently to arrive at the final local tumor stage. If a protocol violation occurred, a letter was sent to the responsible surgeon. Tumor laterality, extent, type of resection, contralateral exploration, node involvement, spills, and local recurrence were reviewed. Relative risk and logistic regression analyses were performed.

Results

There were 1305 nephrectomies. Lymph node sampling was not performed in 117 (9%) patients: stage I, 41 (11.5%), stage II, 57 (12%), and stage III, 19 (4%). Of importance, 41% (187/457) of stage III cases were designated stage III solely on the basis of positive lymph nodes. Tumor spill occurred in 19.3% (253/1305) of children. Fifty-four local spills were in stage II tumors and 97 in stage III. Diffuse spill occurred in 102 patients with stage III tumors. Seventeen preoperative and 13 intraoperative biopsies were performed. Intraoperative tumor rupture was the most common cause of tumor spill accounting for 139 (55%) spills. Nineteen (7.5%) children were upstaged, receiving more intensive therapy because of spill. Included in the group were 3 of 17 preoperative biopsies and 5 of 13 intraoperative biopsies. Spills (13/253) were determined to be avoidable. Eight were biopsies, 5 because tumor was transected in the renal vein (4) or ureter (1). In stage II patients where lymph nodes were not sampled, there is an increase in local relapse rate that did not achieve statistical significance because of the small number of events.

Conclusions

Although most surgeons complied with the surgical guidelines, numerous deviations were identified including failure to sample lymph nodes (117 cases) and unnecessary biopsies leading to tumor spill (30 cases). Protocol violations have an adverse impact on tumor staging, potentially increasing the risk for local tumor recurrence or intensity and toxicity of therapy.     

Bilateral Wilms' tumors: a single-center experience with 19 cases

Background/Purpose

Bilateral Wilms' tumors present a therapeutic challenge, particularly with delay in presentation, when there is poor response to chemotherapy and when associated with nephroblastomatosis. The primary aim of management is eradication of neoplasm, while at the same time preserving of renal function.

Methods

Nineteen bilateral Wilms' tumors were seen in our service between 1981 and 2003. This represented 10% of the 190 patients with Wilms' tumors seen during this period. There were 12 female and 7 male patients ranging in age from 7 months to 8 years. Fourteen had synchronous presentation, one of whom had liver metastasis at diagnosis. Of the 5 patients with metachronous tumors, 3 had their initial nephrectomies done elsewhere. Nephroblastomatosis was identified in 18 (95%) of the patients. Treatment was, in most cases, according to National Wilms Tumor Study Group protocols, with initial bilateral biopsy, neoadjuvant chemotherapy, and tumorectomy. Where indicated, nephrectomy (partial or complete) involved using ice dam topical cooling and vascular control, and in one case, bench surgery and extensive renal reconstruction with orthotopic autotransplantation. Revision tumorectomy was used on 3 occasions for recurrence in areas of nephroblastomatosis. There were 6 extrarenal relapses.

Results

Ten patients are alive and free of disease 1 to 15 years after treatment, all with well preserved renal function (lowest recorded glomerular filtration rate was 85 mL/min per 1.73 m²). Nine have died (2 of unrelated disease), including 6 of the 7 with spread outside the kidney. All 3 with unfavorable histology are alive. Of the 5 with metachronous presentations, 4 are alive, as are 7 of 10 who presented in the last decade.

Conclusions

Appropriate chemotherapy and conservative nephron-sparing and innovative surgery can achieve good results with preservation of adequate renal function in nearly all cases. Nephroblastomatosis was an almost universal finding and requires close monitoring because Wilms' tumors developed in residual suspect areas. Revision surgery was effective. Unfavorable histology did not have a reduced survival in our series. Metastatic spread outside the kidney had a poor prognosis.     

The value of surgery in directing therapy for patients with Wilms' tumor with pulmonary disease. A report from the National Wilms' Tumor Study Group (National Wilms' Tumor Study 5)

Background/Purpose

Computed tomography (CT) of the chest with its increased sensitivity frequently identifies lesions not visible on chest radiograph. Treatment of such lesions is controversial. A recent review suggests that patients with Wilms' tumor with pulmonary lesions detected only by CT, who were treated with dactinomycin and vincristine, have an inferior outcome compared with those who also received pulmonary radiation therapy (RT) and doxorubicin. It is important to determine if these small lesions seen only on CT represent metastatic disease and whether patients with these lesions require RT and/or doxorubicin for optimal outcome.

Methods

Patients with Wilms' tumor with lung metastasis, registered on National Wilms' Tumor Study 5, were reviewed, and those with CT-only lesions who had a radiology and surgical checklist submitted were identified. The treatment regimens of these patients and the histological findings of the pulmonary lesions are presented. We analyzed the pathological findings by whether the patients had single or multiple lesions.

Results

Of 2498 patients registered on National Wilms' Tumor Study 5, 252 had pulmonary metastases. Of these patients, 129 (5.2%) had CT-only lesions (<1 cm). Forty-two of these patients (20 boys and 22 girls) underwent lung biopsy at the discretion of the attending physicians. The local tumor stages in these patients were stage I (7%), II (34%), and III (59%). The treatment stages in these patients were stage I (n = 3, 2 drugs), II (n = 3, 2 drugs), III (n = 12, 3 drugs); and IV (n = 24, 3 drugs + RT). There were 16 patients with isolated lung lesions and 26 with multiple lesions, average size 5.8 ± 0.5 mm. Of 16 isolated lesions, 13 patients (82%) and 69% (18/26) with multiple lesions had tumor on biopsy. Of the 24 who received RT, 8 had a negative biopsy and, thus, may not have needed the RT. Five of 6 treated with just 2 drugs may have been undertreated. Nine of 12 treated with 3 drugs had tumor on biopsy.

Conclusions

Computed tomography-only pulmonary lesions are not invariably tumor, demonstrating the need for histopathological confirmation. Biopsy remains critical until radiographic techniques allow differentiation between benign and malignant lesions to optimally direct therapy.     

Bilateral Wilms' tumors with progressive or nonresponsive disease

Background

To provide guidelines for future cooperative group trials, we reviewed the outcomes of children with bilateral Wilms' tumors (BWTs) treated on National Wilms Tumor Study-4 (NWTS-4) who had progressive or nonresponsive disease (PNRD).

Methods

NWTS-4 enrolled 3335 patients from August 1986 to September 1994 including 188 patients with BWT (5.6%). Treatment and outcome data were collected on patients with BWT. Treatment guidelines were outlined in the protocol, but patients were not on study.

Results

Thirty-eight children with BWT had PNRD. Preoperative chemotherapy was given for a median of 7 months (range, 2-29 months) before definitive resection. After the initial chemotherapy regimen, 36 children went on to a second regimen, and of these, 21 children received a third regimen before resection. Eleven patients received irradiation to one or both kidneys. Pathology at resection revealed previously undiagnosed anaplasia in 3 patients (2 diffuse and 1 focal) treated for 14, 15, and 15 months before resection. A fourth patient developed a diffusely anaplastic tumor 13 months after therapy. Other pathological findings included rhabdomyomatous (4 patients) or differentiated stromal elements (10 patients) and complete necrosis (1 patient). Ten kidneys from 7 patients lacked biopsy at presentation or pathology review of those specimens.

Conclusions

BWT patients with PNRD received prolonged courses of chemotherapy. Early and sequential biopsies to establish the reason for failure to respond should be obtained. This will identify anaplastic tumors managed best by early nephrectomy and intensive chemotherapy and will also distinguish differentiated tumors that are best managed with early resection, but less intensive therapy after nephrectomy.     

The role of surgical excision in the management of relapsed Wilms' tumor patients with pulmonary metastases: a report from the National Wilms' Tumor Study.

To determine the effect of surgical excision of pulmonary metastases from Wilms' tumor on postrelapse survival, we retrospectively analyzed the clinical courses of 211 patients with stages I to III, favorable or unfavorable histology Wilms' tumor entered on National Wilms' Tumor Study-1, -2, or -3 whose first recurrence was limited to the lungs. There was no difference in the 4-year postrelapse survival percentage of favorable-histology patients with a solitary pulmonary metastasis who did or did not undergo surgical removal of the metastasis in addition to pulmonary irradiation and chemotherapy. Although histological confirmation of pulmonary relapse is frequently indicated, the present data suggest that therapeutic removal of pulmonary metastases from patients with relapsed Wilms' tumor does not increase the percentage of patients who survive for 4 years postrelapse, compared with treatment with whole-lung irradiation and chemotherapy.     

Rhabdoid tumor of kidney. A report of 111 cases from the National Wilms' Tumor Study Pathology Center

We review 111 cases of rhabdoid tumor of kidney (RTK), including 79 entered on the National Wilms' Tumor Study (NWTS). Median age at diagnosis was 11 months, with a range from 0 to 106 months. The male:female ratio was 1.5:1. Gross features included a characteristic involvement of perihilar renal parenchyma. A wide histological spectrum was encountered, including nine major morphological patterns (classical, epithelioid, sclerosing, lymphomatoid, histiocytoid, etc.). These appearances invite confusion with other renal neoplasms. Ultrastructural studies were performed in 20 cases; immunocytochemical studies were performed in 11. Vimentin was demonstrated in all tumors; epithelial membrane antigen was seen in 7. Nonspecific decoration of cytoplasmic inclusions by a variety of immunostains was found in several cases. Several findings suggested that RTK might arise from primitive cells involved in formation of the renal medulla. There was no evidence of a histogenetic relationship to Wilms' tumor, although RTK may overlap with mesoblastic nephroma and clear cell sarcoma. Of the 70 NWTS patients with adequate follow-up, 56 (80%) have died. Every patient presenting with distant metastases died, whereas 10 of 20 with negative nodes survived. Survival rates were higher for girls (56.3% versus 11.1%). None of the histological variables had independent prognostic significance.     

Bilateral intrarenal pelvis Wilms' tumor with fibroepithelial polyp

Intrarenal pelvis Wilms' tumor is rare in children. A case of a 28-month-old boy with bilateral intrarenal pelvis Wilms' tumor associated with a fibroepithelial polyp is reported in this article. The tumor was evaluated by ultrasonography, computed tomography, and intravenous pyelography. The boy underwent bilateral renal pelviotomies. Now he is being treated and followed up by pediatric oncologists.     

Renal neoplasms mimicking rhabdoid tumor of kidney. A report from the National Wilms' Tumor Study Pathology Center.

Fifty-six renal neoplasms reviewed by the National Wilms' Tumor Study Pathology Center presented with histologic features that resulted in confusion with rhabdoid tumor of kidney, a usually lethal childhood renal tumor; all were eventually diagnosed as other entities. Conspicuous filamentous cytoplasmic inclusions or large nucleoli, typical findings in rhabdoid renal tumors, were the usual source of diagnostic difficulty. Most, but not all, tumors occurred in pediatric patients. Sixteen were examples of Favorable Histology Wilms' tumor, which invited confusion with rhabdoid tumors either on the basis of filamentous cytoplasmic inclusions (15 cases) or macronucleoli (one case). In most cases, foci of typical Wilms' tumor blastemal aggregation or evidence of definitive nephrogenic differentiation facilitated the correct diagnosis. All 10 patients for whom information about outcome was available were alive at last follow-up. The other 40 renal lesions mimicking rhabdoid tumor of kidney consisted of a clinically and histogenetically diverse group of neoplasms, including anaplastic Wilms' tumor, congenital mesoblastic nephroma, renal cell carcinoma, transitional cell carcinoma, collecting-duct carcinoma, oncocytoma, rhabdomyosarcoma, malignant neuroepithelial tumors, and lymphoma. Most of these lesions could be separated from renal rhabdoid tumors and correctly classified on the basis of careful attention to light microscopic details, but in several cases electron microscopy or immunocytochemical studies were helpful or essential.     

肾母细胞瘤综合治疗模式分析

目的 探讨肾母细胞瘤的综合治疗模式,提高肾母细胞瘤的疗效. 方法 回顾性分析1981年7月至2010年6月55例肾母细胞瘤患者资料.术前超声引导下细针穿刺活检确诊18例,术后病理确诊53例.其中Ⅰ期7例,Ⅱ期19例,Ⅲ期21例,Ⅳ期6例,Ⅴ期2例;35例有组织学分型,其中预后良好型30例,预后不良型5例.55例患者中,行肾脏肿物切除术48例,局部扩大切除术2例,双肾肿瘤剜除术1例,肾肿物切除术加肺转移灶切除术2例,2例未行手术治疗;术前化疗18例,术后化疗40例,术后放疗12例.根据年龄、分期、组织分型、治疗方式、治疗时间段及是否放疗分组,应用Kaplan-Meier法比较各组3年和5年总生存率、2年无病生存率及1年无复发生存率,分析各分组因素与肾母细胞瘤预后的关系. 结果 55例患者治疗后3年和5年总生存率及2年无病生存率分别为77.6％、69.0％和52.4％,不同分期对总生存率(P=0.006)、单纯手术与综合治疗对无病生存率(P =0.004)、是否放疗对无病生存率(P=0.03)影响有统计学意义(P＜0.05). 结论 规范的多学科协作的综合治疗模式可以显著提高肾母细胞瘤疗效.     

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.     

单纯后路全椎弓根螺钉技术矫正Wilms瘤综合治疗后并发脊柱畸形

目的探讨单纯后路全椎弓根螺钉技术矫正Wilms瘤综合治疗后并发脊柱畸形的安全性及其疗效。方法回顾分析2010年8月~2012年3月单纯后路全椎弓根螺钉技术矫正Wilms瘤综合治疗后并发脊柱畸形患者3例。分析术后畸形矫正率、并发症、融合情况及患者腰痛视觉模拟量表(visual analog scale,VAS)评分。结果术后脊柱侧凸、胸腰段后凸均显著改善。腰痛VAS评分也显著提高。均随访>2年,3例患者均无畸形明显进展,无假关节形成、感染等并发症,无疼痛症状复发。结论对于Wilms瘤综合治疗后并发脊柱畸形的患者,单纯后路全椎弓根螺钉矫形技术可取得良好的手术效果。