Wilms-Tumor – Update 2007

Due to the close interdisciplinary work of surgeons, radiologists and oncologists, the prognosis for Wilms' tumor (the most common renal tumor in childhood) has been dramatically improved over the last few decades. The treatment of such tumors is currently carried out worldwide by two study groups, in North America the National Wilms' Tumor Study (NWTS) and in Europe the Society of Paediatric Oncology (SIOP). Here we present an overview of the current treatment results and discuss future diagnostic and therapeutic strategies.     

Wilms tumor in an adult patient: case report

Nephroblastoma or Wilms tumor is the most common renal neoplasia in children, representing 1/5 of the malignant tumors in this group. Nevertheless, the incidence of such tumor in adults is much rarer with less than 250 cases reported. Due to the low-frequency of this pathology in adults there is not a world widely accepted treatment modality. Currently, the therapeutic options derive from the National Wilms Tumor Study (NWTS). We report a new case with the radiological images, histologic findings, outcomes and follow-up.     

Relapse of unilateral favorable histology Wilms’ tumor: Significant clinicopathological factors

Purpose

To evaluate the clinicopathological features that indicate relapse and suggest a new risk based therapeutic strategy for unilateral Favorable Histology Wilms Tumor (FH-WT).

Materials & Methods

Thirty-three patients with unilateral WT were treated in two institutions between 1986 and 2010. Twenty-eight patients with FH-WT received primary nephrectomy according to the National Wilms’ Tumor Study (NWTS) or the Japanese Wilms’ Tumor Study (JWiTS) protocol. Retrospective analyses of the non-relapsed group (n = 23) and the relapsed group (n = 5) compared age, gender, tumor laterality, tumor weight, initial tumor stage, known histological subtype, chemotherapy (2 or 3 drugs), and any irradiation delivered. Stages and histological subtypes of the tumors were re-evaluated according to the Japanese staging system.

Results

Five of the twenty-eight tumors relapsed, and one patient died. The initial staging (P = 0.029) and the histological subtype (P = 0.003) were the only factors indicating relapse. Nine of the twenty-three tumors were histologically classified as blastemal predominant subtype (BPT-WT). Five relapsed.

Conclusion

According to the basic Japanese therapeutic strategy, all patients underwent a primary nephrectomy before chemotherapy. This study suggests that the histological subtype pre-treatment “BPT-WT” should be included as a strong indicator of poor prognosis. Such patients should be treated as a high-risk group.     

The prognostic significance of blastemal predominant histology in initially resected Wilms’ tumors: A report from the Study Group for Pediatric Solid Tumors in the Kyushu Area,Japan

Background and Purpose

The strategy used to treat pediatric renal tumors in Japan is based on the Japanese Wilms’ Tumor Study (JWiTS) protocol, which was based on the National Wilms’ Tumor Study (NWTS)-5 regimen. The regimen is characterized by an initial radical operation, followed by adjuvant chemotherapy and radiotherapy. Concerning the histological classification, a new classification based on the International Society of Pediatric Oncology (SIOP) classification was used beginning in 2008. The main points of revision are that the “blastemal predominant type” was classified as an independent category in the Wilms’ tumor subtypes. The purpose of this study was to analyze the biological characteristics from the standpoint of the newly established histological classification.

Materials and Methods

From 1971 to 2005, 174 cases of Wilms’ tumors treated with an initial operation followed by adjuvant therapy were re-evaluated by the new histological classification. Histologically, all these materials showed no secondary changes associated with adjuvant therapy.

Results

According to the new classification, Wilms’ tumors were classified into four subtypes, including the mixed type (n = 112), epithelial type (n = 17), mesenchymal type (n = 15), and blastemal predominant type (n = 26). The 5 year overall survival rates were as follows; mixed type (90.1%), epithelial type (100%), mesenchymal type (93.3%), and blastemal predominant type (65.4%).

Conclusion

The patients with blastemal predominant tumors demonstrated a significantly worse prognosis compared with those of other subtypes. The treatment strategy of blastemal predominant category should be distinguished from the other favorable subtypes.     

Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center

We reviewed 351 cases of clear cell sarcoma of the kidney (CCSK), including 182 cases entered on National Wilms Tumor Study Group (NWTSG) trials 1-4 for which clinical follow-up information was available. Tumors were restaged using NWTS 5 criteria. Mean age at diagnosis in the NWTS group was 36 months with a range of 2 months to 14 years. The male to female ratio was 2:1. Typical gross features included large size (mean diameter 11.3 cm), a mucoid texture, foci of necrosis, and prominent cyst formation. Nine major histologic patterns were identified (classic, myxoid, sclerosing, cellular, epithelioid, palisading, spindle, storiform, and anaplastic); virtually all tumors contained multiple patterns that blended with one another. Immunohistochemical stains were performed on 45 cases; only vimentin was consistently immunoreactive. Consistently negative results with other antibodies helped exclude other tumors in the differential diagnosis; all CCSKs were cytokeratin-negative, including epithelioid tumors that mimicked Wilms tumor, and MIC2-negative, including cellular tumors that mimicked primitive neuroectodermal tumor. The p53 gene product was rarely overexpressed in non-anaplastic CCSKs, but strikingly overexpressed in two of three anaplastic CCSKs. Overall survival was 69%. Multivariate analysis revealed four independent prognostic factors for survival: treatment with doxorubicin, stage, age at diagnosis, and tumor necrosis. Of note, stage 1 patients had a remarkable 98% survival rate. No other histologic or clinical variable independently correlated with survival.     

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 management

PURPOSE OF REVIEW: The management of Wilms' tumor continues to evolve with two different approaches being taken by the National Wilms Tumor Study in North America and the International Society of Pediatric Oncology in Europe in regards to preoperative chemotherapy. Limiting the duration, dosage, and number of chemotherapeutic agents and the dosage of radiotherapy are common goals in both trials. RECENT FINDINGS: Contralateral exploration of unilateral tumors will no longer be recommended in future National Wilms Tumor Studies. Percutaneous biopsy for tissue diagnosis is quite accurate, but there are concerning complications with its use. Partial nephrectomy is successful for low risk unilateral Wilms tumor, but its indications remain controversial. The surgical complication rate was similar between the National Wilms Tumor Study and the International Society of Pediatric Oncology, but intraoperative tumor spill was higher in the North American trials. Doxorubicin decreased the risk of recurrence in stage III tumors by 50%, and its current dose is not associated with late congestive heart failure. For selected patients, shorter courses of vincristine/dactinomycin or vincristine alone show equivalent results compared to current regimens. A longer course of chemotherapy (including doxorubicin) for clear cell sarcoma improves recurrence-free survival. Patients with Wilms' tumor, aniridia, major genitourinary malformations, and mental retardation, the WAGR syndrome, have a 50% chance of unexplained end-stage renal disease 20 years after treatment. SUMMARY: Less aggressive means of diagnosis and treatment for Wilms' tumor are continuing to achieve very good cure rates while lowering long term morbidity for low risk patients. High-risk patients with unfavorable histology or the WAGR syndrome benefit from more intensive treatment and long-term follow-up.     

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.     

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.     

Preoperative Wilms tumor rupture in children

Purpose

According to the guidelines of International Society of Pediatric Oncology (SIOP) and National Wilms Tumor Study (NWTS), Wilms tumor with preoperative rupture should be classified as at least stage III. Few clinical reports can be found about preoperative Wilms tumor rupture. The purpose of this study was to investigate our experience on the diagnosis, treatment and prognosis of preoperative Wilms tumor rupture.

Methods

Patients with Wilms tumor who underwent treatment according to the NWTS or SIOP protocol from January 2008 to September 2017 in Beijing Children’s Hospital were reviewed retrospectively. The clinical signs of preoperative tumor rupture were acute abdominal pain, and/or fall of hemoglobin. The radiologic signs of preoperative tumor rupture are as follows: (1) retroperitoneal and/or intraperitoneal effusion; (2) acute hemorrhage located in the sub-capsular and/or perirenal space; (3) tumor fracture communicating with peritoneal effusion; (4) bloody ascites. Patients with clinical and radiologic signs of preoperative tumor rupture were selected. Patients having radiologic signs without clinical symptoms were also selected. The clinical data, treatments and outcomes were analyzed. Meanwhile, patients without preoperative Wilms tumor rupture during the same period were collected and analyzed.

Results

565 Patients with Wilms tumor were registered in our hospital. Of these patients, 45 patients were diagnosed with preoperative ruptured Wilms tumor. All preoperative rupture were confirmed at surgery. Spontaneous tumor rupture occurred in 41 patients, the other 4 patients had traumatic history. Of the 45 patients, 41 were classified as stage III, 3 patients with pulmonary metastases were classified as stage IV, and one patient with bilateral tumors were classified as stage V. Of these patients with preoperative tumor rupture at stage III, 30 patients had clinical and radiologic signs of tumor rupture, the other 11 patients had radiologic signs without clinical symptoms. Among the 41 patients at stage III, 13 patients had immediate surgery without preoperative chemotherapy (immediate group), and 28 patients had delayed surgery after preoperative chemotherapy (delayed group). In immediate group, 12 patients had localized rupture, 1 patient underwent emergency surgery because of continuous bleeding. In delayed group, 4 had inferior vena cava tumor embolus (1 thrombus extended to inferior vena cava behind the liver, three thrombi got to the right atrium), 4 crossed the midline with large tumors, 20 had extensive rupture without localization. In immediate group, tumor recurrence and metastasis developed in 2 patients, and no death occurred. In the delayed group, tumor recurrence and metastasis developed in 8 patients, and 7 patients died. During the same period, 41 patients were classified as stage III without preoperative rupture. In the non-ruptured group, tumor recurrence and metastasis developed in 3 patients, and 4 patients died. The median survival time in the ruptured group (both immediate group and delayed group) and non-ruptured group were (85.1 ± 7.5) and (110.3 ± 5.6) months, and the 3-year cumulative survival rates were 75.1% and 89.6%, respectively. The overall survival rate between the ruptured and non-ruptured groups showed no statistic difference (P = 0.256). However, there was significant difference in recurrence or metastasis rate between the ruptured and non-ruptured groups (24.4% vs 7.3%; P = 0.031).

Conclusion

Contrast-enhanced computed tomography (CT) and ultrasonography (US) are of major value in the diagnosis of preoperative tumor rupture, and immediate surgery or delayed surgery are available therapeutic methods. The treatment plan was based on patients’ general conditions, tumor size, position and impairment degree of tumor rupture, extent of invasion and experience of a multidisciplinary team (including surgeon and anesthesiologists). In our experience, for ruptured preoperative tumor diagnosed with stage III, the criteria for immediate surgery are as follows: tumor not acrossing the midline, tumor without inferior vena cava thrombus, localized rupture, being capable of complete resection. Selection criteria for delayed surgery after preoperative chemotherapy are as follows: large tumors, long inferior vena cava tumor thrombus, tumors infiltrating to surrounding organs, unlocalized rupture, tumors can not being resected completely. Additionally, patients with preoperative Wilms tumor rupture had an increased risk of postoperative recurrence or metastasis.

     

Wilms tumor in horseshoe kidneys: a report from the National Wilms Tumor Study

An analysis of information on 2,961 patients with Wilms tumor entered in the National Wilms Tumor Study up to July 1983 revealed 13 tumors occurring in horseshoe kidneys. The correct preoperative diagnosis was made in 6 of the 13 patients. At presentation 5 patients had stage 1, 3 stage 2 and 5 stage 3 disease. Major preoperative or intraoperative tumor spillage occurred in 3 patients. The over-all survival rate was 85 per cent after a mean followup of 45 months. The surgical, pathological and therapeutic aspects of Wilms tumor in horseshoe kidneys were analyzed carefully. The frequency of horseshoe kidneys in patients with Wilms tumor registered with the National Wilms Tumor Study was determined and was used in conjunction with population data to estimate the relative risk of Wilms tumor occurrence in children with horseshoe kidneys.     

A case of adult Wilms' tumor --review of the Japanese literature

The patient was a 23-year-old-woman who was referred to our hospital with chief complaints of right flank pain and macroscopic hematuria. Right radical nephrectomy was performed with the diagnosis of right renal cancer. Histopathological examination revealed Wilms' tumor of favorable histology, stage I according to the National Wilms Tumor Study classification. She received adjuvant chemotherapy consisting of actinomycin D and vincristine at another hospital. One year and three months later, she developed lung metastasis. She underwent partial pulmonary resection, and then received chemotherapy. She is presently disease-free more than forty months after the initial operation. Wilms' tumor is rare in adults and has a poor prognosis compared with that in children. We analyzed 112 cases in the Japanese literature from 1981 to 2004. The mean age was 36.9 years, with males and females equally affected. No difference was found between the left and right sides in frequency of tumor. We also examined the relationship between histological features and prognosis based on 43 Japanese reports. Twenty-two of the 43 (51%) cases had unfavorable histology. The 2-year survival rate with unfavorable histology was 18%, while that with favorable histology was 87%. The 2-year survival rates for stages under II and over III were 67% and 27%, respectively. Based on these findings, we conclude that the prognosis of adult Wilms' tumor is very poor since many patients have unfavorable histology and no effective treatment guidelines have been established.     

Extrarenal Wilms tumor in children with unfavorable histology: a case report

Extrarenal Wilms tumor is extremely rare, and only 25 cases in children have been reported to date in Japan. A 2-year-old girl presented with a large left lower quadrant abdominal mass. Abdominal computed tomography revealed a retroperitoneal tumor located below the left kidney. At laparotomy, the tumor was encapsulated without evidence of metastasis to other abdominal organs. Pathologic diagnosis of the tumor was extrarenal Wilms tumor with diffuse anaplasia. After complete tumor resection, chemotherapy was administered according to the treatment protocol (Regimen I) of the Japan Wilms Tumor Study Group. Cyclophosphamide and etoposide were administered in combination with vincristine and doxorubicin. Two years after treatment, the patient has had no evidence of recurrence.     

The relationship of deoxyribonucleic acid content to conventional prognostic factors in Wilms tumor

Deoxyribonucleic acid ploidy as determined by flow cytometric analysis was compared to histological findings and tumor stage for accuracy of prediction of patient survival in a series of Wilms tumors. While anaplastic tumors were more likely aneuploid or tetraploid than diploid, no statistically significant relationship was found between deoxyribonucleic acid ploidy and patient survival in our series. Tumor histology and stage as defined by the National Wilms Tumor Study were more accurate predictors of patient survival than deoxyribonucleic acid ploidy.     

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.     

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.     

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.     

Adult Wilms tumor: a case of prolonged survival achieved by multimodal treatment

Wilms tumor is one of the most common malignant neoplasms in children. In the last 2 decades the survival rate of children with this disease has dramatically increased. However, in adults, the guideline for its management is less clear. We herein report the prolonged survival of a patient with advanced adult Wilms tumor after treatment with chemotherapy, irradiation and operations. Adult Wilms tumor should be treated aggressively with a well-timed combination of surgery, chemotherapy and radiotherapy (i.e., multimodal treatment), even if the stage of the disease was advanced. Thereby, we suspect that the prognosis of adult Wilms tumor would be markedly improved.     

小儿肾母细胞瘤患者细胞免疫状况与生物学特征的关系

应用单克隆抗体碱性磷酸酶抗碱性磷酸酶法（ＡＰＡＡＰ法）检测３５例小儿Ｗｉｌｍｓ瘤患者外周血总Ｔ细胞（ＣＤ３＋）、Ｔ辅助／诱导细胞（ＣＤ４＋）、Ｔ抑制／杀伤细胞（ＣＤ８＋）。按ＮＷＴＳ标准，对患者进行临床分期、组织学分型、组织分化程度等病理学分类。把患者的免疫状况与其形态学特征联系分析，结果显示：晚期肿瘤、胚细胞型、组织分化差的不顺利型细胞免疫抑制明显较重（Ｐ＜０．００１），预后也明显较差。提示小儿Ｗｉｌｍ瘤细胞免疫状况与其生物学特征有一定内在关系。     

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。