Multimodal treatment of advanced adult Wilms tumor

We report 2 cases of advanced adult Wilms tumor that were treated with surgery, radiation and chemotherapy. The first patient had relapse of a Wilms tumor in the liver 2 years after nephrectomy. Combination chemotherapy, consisting of actinomycin D and vincristine, radiation therapy and final resection of the liver metastasis were successful and the patient has been free of disease for 4 years. The second patient had undergone transcatheter embolization of the renal artery elsewhere with the tentative diagnosis of an inoperable renal cell carcinoma metastatic to both lungs. A left renal tumor, weighing 4,500 gm., and a tumor thrombus in the vena cava extending to the right atrium were removed, and histologically diagnosed as a Wilms tumor. Subsequent chemotherapy and radiotherapy resulted in complete disappearance of the lung metastases. We conclude that multimodal treatment, namely a well timed combination of surgery, chemotherapy and radiotherapy, could potentially eradicate the disease even at an advanced stage.     

Management of Wilms tumor: current standard of care

Wilms tumor is the most common renal malignancy in children. In the 1930s, overall survival for children with Wilms tumor was approximately 30%. Use of multidisciplinary therapy, guided by results from multi-institutional, randomized trials, has substantially improved overall survival to about 90%. Management of Wilms tumor differs substantially between Europe and the US. In Europe, the International Society of Pediatric Oncology protocols call for management of patients with presumptive Wilms tumor with neoadjuvant chemotherapy followed by nephrectomy and further chemotherapy. In the US, protocols developed by the National Wilms Tumor Study Group advise primary nephrectomy followed by a chemotherapy regimen tailored to the pathologic tumor stage. Despite these disparate strategies, overall survival is similar in patients managed according to European and US protocols. Patients with Wilms tumor now have excellent survival. Therefore, current goals aim to reduce the morbidity associated with therapy. Important complications of treatment for Wilms tumor include cardiomyopathy, renal failure, and increased risk of a secondary malignancy. Currently, the role of laparoscopic surgery in management of Wilms tumor remains extremely limited.     

Wilms' tumor in adults

A rare case of metastatic nephroblastoma on the right side in a 28-year-old female patient is presented. Complete remission was achieved by inductive chemotherapy with vincristine, Adriamycin, actinomycin D and cyclophosphamide and subsequent radical nephrectomy. There was no evidence of disease 24 months after the initial diagnosis had been made. The problems specific to the diagnosis and treatment of adult Wilms tumor are discussed. A chemotherapy regimen known to be successful in childhood Wilms tumor was shown to be equally effective in our adult patient.     

Adult Wilms tumor. Treatment with surgery, radiotherapy, and chemotherapy

A twenty-nine-year-old patient with a Wilms tumor on the right side was treated with surgery, radiotherapy, and chemotherapy. Since no study of treatment of adult Wilms tumor is yet available, the combined therapy was instituted in accordance with the one existing for children. The results of the 5 adult cases previously reported which were treated with triple therapy, and the relevant literature, are reviewed.     

The role of renal salvage procedures for bilateral Wilms tumor: a 15-year review

PURPOSE: We reviewed our experience with renal salvage procedures in patients with bilateral Wilms tumor to determine the clinical outcome. MATERIALS AND METHODS: From 1982 to 1997, 23 children with bilateral Wilms tumor were treated with partial nephrectomy at our institution, including 7 who were also treated with brachytherapy. Medical history, use and response to chemotherapy and brachytherapy, operative records, renal function, pathological results, survival, and techniques for partial and repeat nephrectomy and brachytherapy were reviewed. RESULTS: We treated 8 boys and 15 girls, of whom 21 who presented with synchronous bilateral Wilms tumor underwent primary chemotherapy followed by secondary partial nephrectomy. A total of 44 partial nephrectomies were performed and brachytherapy was done in 7 patients. Ten children have normal renal function and no disease, 10 are dead and 2 have metastatic disease. Anaplasia was the most significant factor associated with an unfavorable outcome (p = 0.003). Of the patients who were cured 60% had a positive response to initial chemotherapy compared with only 25% who had an unfavorable outcome (p = 0.09). No significant differences were noted with respect to gender, age at presentation, highest local tumor stage at presentation or initial nephrectomy. No patient treated with brachytherapy had local recurrence. CONCLUSIONS: Preoperative chemotherapy followed by nephron sparing surgery is indicated in patients with bilateral Wilms tumor, while in those with diffuse anaplasia nephron sparing surgery is contraindicated. Brachytherapy should be considered for treating local disease involving chemoresistant tumors.     

Triple therapy for adult Wilms tumor

Adult Wilms tumor is still considered a rarity. Approximately 170 adult Wilms tumors have been reported. The final diagnosis is usually established with surgery. There is no specific radiologic diagnosis of adult Wilms tumor. We report on a case of Wilms tumor in a twenty-two-year-old black man. The tumor was removed with radical nephrectomy and classified as Stage II. Radiation of the renal fossa (4,000 rad) and chemotherapy with actinomycin D and vincristine were administered after surgery. Six years after surgery the patient is disease free. A review of published cases of adult Wilms tumor is presented, and a plea is made for triple therapy.     

成人肾母细胞瘤的诊断与治疗（附12例报告）

目的探讨成人肾母细胞瘤的诊断和治疗方法。方法回顾性分析12例成人肾母细胞瘤患者的临床资料。结果本组患者年龄16-63岁,表现为肉眼血尿2例,腰腹痛6例,4例为体检发现;术前诊断为肾肿瘤9例,肾盂肿瘤3例。12例均行手术治疗,术后病理均诊断为肾母细胞瘤。按照美国国家肾母细胞瘤研究组（NWTS）分期标准,本组分别为Ⅰ期5例、Ⅱ期3例、Ⅲ期3例、Ⅳ期1例。术后辅以放疗和化疗,平均随访41个月,3年生存率为48%。结论成人肾母细胞瘤是一种比较少见的恶性肿瘤,术前确诊困难,手术治疗并辅以放疗、化疗是其主要的治疗方法。     

成人肾母细胞瘤的诊疗及预后分析（附10例报告）

目的：探讨成人肾母细胞瘤的诊疗方法和预后。方法：回顾性分析10例成人肾母细胞瘤患者的临床资料。男8例,女2例,年龄16～62岁,平均29岁。就诊症状为单纯肉眼血尿3例、腰腹部肿块或腰腹痛4例（伴血尿2例）、无症状查体发现3例。患者均行B超、IVU、尿脱落细胞学检查,8例行CT平扫＋强化检查。影像学检查提示肾占位6例、肾盂占位3例、输尿管占位1例。CT提示肾门或腹腔淋巴结肿大4例。10例均行手术治疗,根治性肾切除6例,患肾、输尿管全段切除＋膀胱输尿管口袖口状切除4例,2例根治性肾切除患者因肿物与周围粘连严重切除部分腹膜。行腹膜后淋巴结清扫5例。结果：所有病例均于术后病理确诊为肾母细胞瘤,预后良好组织型（FH）4例,预后不良组织型（UH）6例,病理证实淋巴结转移3例。按美国国家肾母细胞瘤研究组（NWTS）分期标准,分别为Ⅰ期4例、Ⅱ期3例、Ⅲ期3例。7例患者接受术后辅助放化疗。随访9例患者1～13年,5例无瘤生存,生存时间为1．5～13年,平均4．4年。1例术后1年死于肿瘤肺转移,1例术后1年死于肿瘤脑转移,2例术后2年内局部复发,再次接受手术。结论：成人肾母细胞瘤为罕见的恶性肿瘤,预后较差,确诊主要依靠病理诊断,目前尚无公认的最佳治疗手段。手术治疗并辅以合理、及时的放疗、化疗是改善其预后的有效措施。     

CONSERVATIVE SURGICAL MANAGEMENT OF BILATERAL WILMS TUMOR: RESULTS OF THE UNITED KINGDOM CHILDREN''S CANCER STUDY GROUP

Purpose

Bilateral Wilms tumor presents the clinician with a treatment dilemma. Since 1980 most centers of the United Kingdom Children's Cancer Study Group have used a conservative surgical approach with initial biopsy followed by chemotherapy and delayed surgical resection. We assess the outcome of this treatment approach in terms of survival, and preservation of renal mass and function.

Materials and Methods

We retrospectively analyzed the records of 71 children with bilateral Wilms tumor diagnosed between 1980 to 1995 at 17 United Kingdom Children's Cancer Study Group centers. In 57 patients conservative surgical treatment with initial biopsy was followed by chemotherapy and delayed tumor resection, while 13 underwent initial surgical resection followed by chemotherapy. One patient was excluded from study because the lesion in 1 kidney proved to be a benign cyst. Mean followup was 6 years (range 1 to 15). The percentage of renal tissue involved with tumor and preserved was estimated, and renal function at the last followup was recorded.

Results

Overall survival was 69% with similar survival in the conservatively treated and initial surgical resection groups. At the last followup renal function was normal in 80% of the patients in each group. Mean preserved renal mass was 45 and 35% in the conservatively treated and initial resection groups, respectively, with a trend toward better preservation in those treated conservatively. Bilateral Wilms tumor with an unfavorable histology was associated with a poor prognosis.

Conclusions

Conservative surgical treatment of favorable histology bilateral Wilms tumor may improve the preservation of renal mass and function without impairing patient survival.     

Repeat nephron-sparing surgery for children with bilateral Wilms tumor

Background

Renal insufficiency is a significant complication of Wilms tumor treatment in the 5% with bilateral disease. Nephron-sparing surgery (NSS) is recommended after neoadjuvant chemotherapy initially. However, the role of NSS in recurrent disease is unknown. We reviewed our experience to assess the feasibility and oncologic and functional outcomes of repeat NSS for children with recurrent disease.

Methods

A retrospective review was performed of all children treated at our institution for bilateral, favorable histology (FH) Wilms tumor. Patients undergoing repeat NSS for locally recurrent disease were identified. The outcomes evaluated included tumor recurrence, renal function, and patient survival.

Results

Since 2001, 36 children with bilateral FH Wilms tumor have been treated at our institution. Eight patients (22%) underwent repeat NSS for locally recurrent disease. Two patients had a second local recurrence and underwent a third NSS. Six patients are alive without disease (75%) with an average follow-up of 4.5 years. Two patients have died, each with blastemal-predominant histology at repeat NSS. The surviving patients have normal renal function, although two patients require medical management of hypertension.

Conclusions

Our experience suggests that repeat NSS for local recurrence of FH bilateral Wilms tumor is feasible and affords acceptable oncologic outcome with preservation of renal function. However, more aggressive therapy may be required for patients whose recurrence has blastemal-predominant histology, given the poor outcome for these patients in our series.     

Management of unresectable Wilms tumor

Wilms tumor has become a model of highly curable cancer. With the addition and refinement of chemotherapy protocols, survival rates have risen from 20 per cent three decades ago to 80 per cent or greater in the past decade. Surgery remains an integral part of the management of Wilms tumor both as a diagnostic tool and for removal of tumor bulk. Few primary tumors cannot be surgically removed during the initial phase of therapy. However, bilateral Wilms tumor and large unilateral tumors may occasionally be initially unresectable without prohibitive loss of renal or nonrenal organ function. The National Wilms Tumor Study group has no protocol for management of these tumors but does offer guidelines unsupported by large numbers of patients. Two cases are presented in which the tumors were initially deemed surgically unresectable. Initial management with chemotherapy (both cases) and radiotherapy (1 case) followed by surgical removal of tumor left both patients free of gross tumor, with relapse-free survivals of two and one-half years and six years thus far. Based on our experience and that found in the literature, we believe that preoperative chemotherapy is indicated for children suspected of having Wilms tumors judged surgically unresectable.     

The current management of bilateral Wilms tumor

The good prognosis of synchronous bilateral Wilms tumor seems inappropriate for the magnitude of the disease process. Our experience with 11 cases demonstrates the unusual tumor response to chemotherapy and limited preservative surgery. Although 2 patients died 2 with metastatic disease have responded to chemotherapy and are alive at 5 and 8 years after treatment. In addition, 1 patient has survived with biopsy only and no definitive surgery. Although all surgical options have been used, ranging from biopsy alone to bench surgery with autotransplantation to bilateral nephrectomy, our experience demonstrates the effectiveness of a conservative approach with initial biopsy, chemotherapy and subsequent partial nephrectomy if needed. Our survival data and the histological examination of the tumors after chemotherapy suggest a strong relationship of bilateral Wilms tumor to the nodular renal blastema-nephroblastomatosis complex, and a mechanism to explain the excellent tumor response to chemotherapy.     

Wilms tumor in adult patient

The pathology of Wilms tumor in adults is similar to that in infants. Aggressive multidisciplinary therapy already established for children may give similar survival figures for adults. We report on a case of Wilms tumor in an adult who underwent radical nephrectomy and inferior vena cava resection.     

巨大成人型肾母细胞瘤3例报告并文献复习

目的探讨巨大型成人肾母细胞瘤的诊断和治疗方法,提高该病的诊断率与治愈率。方法回顾性分析南京医科大学第一附属医院2007至2008年间收治的3例巨大成人肾母细胞瘤的临床表现、分期、治疗及预后。结果 3例患者按照美国国家肾母细胞瘤研究组分期：Ⅱ期2例,Ⅲ期1例。3例均行根治性肾切除术,术后辅以放疗和化疗。所有病例均获得随访,随访2～3年,3例均生存。结论成人肾母细胞瘤是一种比较少见的恶性肿瘤,早期诊断、手术治疗、辅以放疗和化疗等可明显提高治愈率并改善其预后。     

Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4

OBJECTIVE: To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA: Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS: Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS: The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS: This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence.     

Intravascular Extension of Wilms Tumor

OBJECTIVE: To define the incidence and manifestations of and optimal therapy for children with intravascular extension of Wilms tumor. METHODS: Children on a collaborative study of Wilms tumor who had intravascular extension into the inferior vena cava (IVC) or atrium were identified. Surgical checklists and surgical and pathology reports were reviewed. RESULTS: One hundred sixty-five of 2,731 patients had intravascular extension of Wilms tumor. The level of extension was IVC in 134 and atrium in 31. Sixty-nine had received preoperative therapy (55 with IVC extension and 14 with atrial extension) for a median of 8 weeks. Complications during preoperative chemotherapy were seen in five patients (tumor embolism and tumor progression in one each, and three with adult respiratory distress syndrome, one of which was fatal). The intravascular extension of the tumor regressed in 39 of 49 children with comparable pre- and posttherapy radiographic studies, including 7 of 12 in whom the tumor regressed from an atrial location, thus obviating the need for cardiopulmonary bypass. Surgical complications occurred in 36.7% of the children in the atrial group and 17.2% in the IVC group. The frequency of surgical complications was 26% in the primary resection group versus 13.2% in children with preoperative therapy. When all the complications of therapy were considered, including those that occurred during the interval of preoperative chemotherapy (one of the five also had a surgical complication), the incidence of complications among those receiving preoperative therapy was not statistically different from the incidence among those who underwent primary resection. The difference in 3-year relapse-free survival (76.9% for 165 patients with intravascular extension, 80.3% for 1,622 patients with no extension) was not statistically significant whether or not it was adjusted for stage and histology. CONCLUSIONS: Preoperative treatment of these children may facilitate resection by decreasing the extent of the tumor thrombus, but the overall frequency of complications is similar in both groups.     

Nephroblastoma in adults

Nephroblastoma, or Wilms tumor, is the most common renal neoplasm in children and accounts for approximately a fifth of all malignant growths in this age group. However, the incidence of Wilms tumor in adults is much less common, with less than 200 cases having been reported in the literature. In addition, since there are at least 53 synonyms for this tumor an adequate computer search for articles relating to this subject is difficult. Because of the scarcity of this disease in adults definite treatment modalities have not been accepted thoroughly until recently. The rationale for the present treatment modalities is based largely on the National Wilms Tumor Study groups 1 to 3. We present radiologic and histologic findings of this tumor in 2 additional cases. The current treatment modalities, consisting of chemotherapy with or without adjunctive radiotherapy, are discussed.     

Pediatric urologic oncology

Effective chemotherapy combined with surgery has produced excellent disease-free survival rates in most children with genitourinary malignancy. For patients with Wilms' tumor, the overall 2-year survival rate with no evidence of disease is greater than 90 per cent, and the interval of chemotherapy continues to be reduced for those children with low-stage lesions and favorable histologic patterns. In children with pelvic rhabdomyosarcoma, primary cytoreductive chemotherapy has proved to be an effective alternative to exenterative surgery. Patients with yolk-sac tumor who have localized disease need not be subjected to the potential morbidity of retroperitoneal lymph-adenectomy or the toxicity of adjuvant chemotherapy. Conversely, patients with advanced disease can be salvaged with recently developed combination chemotherapeutic regimens.     

p53 immunopositivity in histologically favorable Wilms tumor is not related to stage at presentation or to biological aggression

PURPOSE: Previous studies have suggested that increased p53 expression is associated with advanced stage and biologically aggressive (chemotherapy resistant) Wilms tumors. We decided to test the hypothesis that increased immunopositivity of p53 is associated with biological aggressiveness in patients with histologically favorable Wilms tumors. MATERIALS AND METHODS: We reviewed the charts of all patients with unilateral Wilms tumor treated at our institution between 1976 and 2001. Histological characteristics, tumor stage, clinical course and p53 expression as determined by immunohistochemical analysis were determined. All immunohistological evaluations were performed on tissue obtained before administration of chemotherapy. RESULTS: A total of 63 cases of unilateral histologically favorable Wilms tumor were assessed. Five cases (8%) were p53 positive. No significant relationship to p53 expression or stage at presentation was noted in 1 of 21 (5%) stage 1, 3 of 21 (14%) stage 2, 1 of 11 (9%) stage 3 and 0 of 10 stage 4 tumors positive for up-regulation of p53. Of the 5 patients with up-regulated p53 expression 1 (20%) had documented disease progression or relapse while on standard National Wilms Tumor Study chemotherapy. Of the 58 patients who were p53 negative 10 (17%) had disease progression or relapse while on standard National Wilms Tumor Study chemotherapy (p >0.3). CONCLUSION: In contrast to previously published studies, we found no correlation of p53 expression to either tumor stage at presentation (p >0.3) or prognosis (p >0.3) in individuals with histologically favorable Wilms tumor assessed for immunopositivity before administration of chemotherapy.