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.     

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.     

Wilms-Tumoren im Erwachsenenalter

Wilms’ tumors develop from persistent, primitive metanephrogenic stem cells. Their biology and etiology in adults is still unknown even though remnants of primitive metanephrogenic tissue, which tends to malignancy, is suspected, and there are very few scientific studies on the biology of Wilms’ tumors in adults. Such a tumor occurs at a rate of 0.2/million adults in Europe and the USA. In this article, we describe the course of the disease in two adults with histologically confirmed Wilms’ tumors. Both patients underwent a radical nephrectomy followed by chemotherapy as indicated by the SIOP nephroblastoma study.     

Metachronous bilateral Wilms tumor. Report of longest-known survivor and guidelines for conservative management

In a one-year-old black male patient a classic Wilms tumor of the left kidney was treated with left nephrectomy, chemotherapy, and irradiation to the entire abdomen. Two years later a mature Wilms tumor, consisting predominantly of rhabdomyomatous elements, was discovered in the right kidney. Although a second course of chemotherapy was given and 2,000 rad were delivered to the right flank, the mass continued to enlarge with progressive deterioration of renal function. A nephron-sparing procedure was performed, in which a 3,400-g tumor measuring 19 cm X 16 cm X 9 cm was enucleated from the right kidney without compromise to the remaining normal tissue. Pathologic examination of the surgical specimen revealed a mature Wilms tumor with a malignant anaplastic sarcoma arising in the central portion. Currently, he is disease-free with normal renal function more than twenty years after diagnosis of the metachronous bilateral Wilms tumor. We believe he is the longest known surviving metachronous Wilms tumor patient and emphasizes the importance of conservative, meticulous surgery in the management of both unilateral and bilateral Wilms tumors. The role of multimodal therapy (chemotherapy, irradiation, and surgery) as well as the current guidelines for the management of bilateral Wilms tumors as proposed by the National Wilms Tumor Study are reviewed.     

Bilateral Wilms tumors.

The current management of bilateral Wilms tumor is reviewed and the high incidence of concurrent anomalies with bilateral Wilms tumor is demonstrated in 4 of 5 children. Standardization of management has not been established. Of the 5 patients 3 survived 30 months to 11 years without recurrent tumor. Two had unilateral nephrectomy and partial nephrectomy, while 1 had bilateral nephrectomy and allotransplant. All survivors have had adjunctive chemotherapy and radiotherapy.     

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.     

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.     

Renal leiomyoma in a child: a rare renal tumor

Renal leiomyoma is a rare benign smooth muscle tumor of the kidney. Most cases are reported in adults, with very few cases described in children. We report a case of right renal leiomyoma in a 6-year-old boy which was suspected of being a Wilms tumor. Contrast-enhanced computed tomography could not differentiate leiomyoma in the kidney, and the mass was diagnosed as a Wilms tumor. Right radical nephrectomy was performed. Diagnosis of renal leiomyoma could only be achieved after histopathologic examination and immunohistochemistry. We recommend that total nephrectomy has to be done in most cases of pediatric renal tumors to avoid the risk of malignancy. There may be a role for nephron sparing surgery, provided the tumor is small, and one has a strong suspicion for the lesion being benign.     

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.     

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.     

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.     

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.     

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.     

Long-term outcome of nephron sparing surgery and simple nephrectomy for unilateral localized Wilms tumor

PURPOSE: We retrospectively assessed survival and local recurrence rates in children with unilateral localized Wilms tumor (WT) treated with nephron sparing surgery (NSS) or simple nephrectomy with removal only of the perirenal fat adherent to the tumor surface. MATERIALS AND METHODS: The records of 70 children with renal tumor, operated on by the same surgeon between January 1968 and December 2003, were reviewed. Of 64 children with WT 52 with localized nonanaplastic WT were enrolled. Treatment was administered according to International Society of Pediatric Oncology protocols 1 to 2001 in all patients but 7, who were operated on between 1968 and 1971. Patients were stratified as having stage I (27), stage II (23) or stage III (2) disease. Surgical treatment included 40 simple nephrectomies, 10 NSSs (only stage I cases ascertained by frozen section) and 2 radical nephrectomies. Mean patient age at operation was 39.5 months (range 1 to 126). Followup ranged from 27 to 431 months (mean 188.4). RESULTS: Event-free survival rate in all localized stages was 88.5% (stage I 92.6%, stage II 87%, stage III 50%). Two infants with stage I disease died after surgery for reasons not related to malignancy. Only 1 patient with stage II lymph node negative WT had local relapse. CONCLUSIONS: Our results are similar to those achieved by radical nephrectomy in previous studies. Leaving Gerota's fascia in situ does not seem to confer a higher risk of local recurrence in patients with low stage nonanaplastic WT. After NSS Gerota's fascia may be used to cover the defect and to maintain tissue plains, thus, facilitating reintervention if necessary.     

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.     

Wilms' tumor 1991. Clinical evaluation and treatment.

Wilms' tumor is the most common malignant tumor of the kidney in children. Although only 500 cases per year are diagnosed in the US, the tumor has been studied extensively in the National Wilms' Tumor Committee Cooperative Studies. These prospective studies have led to improved survival and at the same time reduced treatment and complications in the more favorable cases. Similar results have been shown by the European cooperative study group SIOP using different treatment protocols. These studies have identified a group of tumors with unfavorable histology that are more resistant to treatment and will require more intensive protocols. Diagnosis of Wilms' tumor by the finding of a large flank mass in an otherwise healthy-appearing child is usually easy. Imaging techniques of CT or IVU will give accurate confirmation of Wilms' tumor in 95% of children. Modern treatment in the US by radical nephrectomy followed by chemotherapy with or without radiotherapy depends on tumor stage and histology. Early-stage tumors with favorable histology can be controlled by shorter courses of two-drug treatment (dactinomycin and vincristine) without radiation. Advanced tumors respond to treatment but require more intensive chemotherapy combined with radiation. The final challenge is the child with a tumor of unfavorable histology, particularly if there is advanced-stage disease. Whereas Wilms' tumor showing favorable histology now has a survival rate exceeding 90%, survival of those with tumors of unfavorable histology remains poor. The European (SIOP) studies have shown similar survival figures using preoperative chemotherapy. This technique produces shrinkage of tumors, making them less hemorrhagic and producing a lower incidence of rupture at subsequent surgery. Preoperative chemotherapy does not change the histologic diagnosis of Wilms' tumor and is a useful alternative approach for the large hemorrhagic or infiltrating tumors.     

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.     

Should radical nephrectomy be performed in the face of surgically incurable disease?

The role of cytoreductive nephrectomy in the management of metastatic renal cancer remains controversial. Recent trials, like SWOG 8949 have suggested the usefulness of this approach at least in selected patients with good performance status and other favorable indicators. The timing of cytoreductive nephrectomy has also been controversial and remains so to this time.CommentaryAn estimated 30,000 new cases of renal cell carcinoma (RCC) are detected annually in the U.S. In approximately one-third of these cases, metastatic disease is diagnosed at presentation. Multi-modality treatment combines biologic response modifier (BRM) therapy with surgery in an attempt to improve survival with either form of treatment alone. The optimal timing of surgery relative to BRM therapy continues to be debated.Prior to the advent of multi-modality therapy, there were relatively few indications for nephrectomy in patients with metastatic RCC. The incidence of spontaneous regression of metastatic RCC following removal of the primary tumor is only 1–4% and, therefore, nephrectomy on this basis is not justified. There is a palliative role for nephrectomy in selected patients with metastatic RCC who are experiencing severe disability from associated local symptoms; however, some patients in this category can be managed with percutaneous renal angioinfarction. A small subset of patients with a solitary metastasis may benefit from nephrectomy and resection of the metastatic lesion based on reported 5-year survival rates of up to 30–35%.There has been controversy concerning the appropriate timing of adjuvant or cytoreductive nephrectomy in the multi-modality approach to treatment of metastatic RCC. Many protocols have involved preliminary removal of the primary tumor before the administration of BRM therapy. The rationale for this has been to enhance response rates to BRM therapy by reducing tumor volume and, in some cases, to provide immunoreactive cells for treatment. A drawback of this approach was that many patients underwent nephrectomy without subsequently receiving BRM therapy due to postoperative morbidity/mortality or rapid tumor progression. This prompted interest in an alternative approach of delayed adjuvant nephrectomy wherein BRM therapy was administered initially and nephrectomy was subsequently performed only in those patients who demonstrated a response to systemic therapy.The relative merits of initial versus delayed adjuvant nephrectomy in conjunction with BRM therapy for metastatic RCC have recently been clarified through two phase III prospective multicenter clinical trials conducted in Europe (EORTC) and the United States (SWOG). The results of both of these carefully done studies have indicated improved survival with initial nephrectomy followed by BRM therapy. The latter comprised interferon monotherapy in both studies, which opens the studies to criticism, however the essential observation of extended survival with preliminary nephrectomy appears to be valid. On this basis, there is now objective evidence to suggest that initial cytoreductive nephrectomy is the preferred approach in patients with metastatic RCC who are candidates for multi-modality therapy. The most appropriate candidates for such therapy remain patients with good performance status and low-volume (preferably pulmonary) metastatic disease. The ability to perform cytoreductive nephrectomy laparoscopically in some of these patients, with reduced morbidity, is a further development that has strengthened the argument in favor of initial nephrectomy.Andrew C. Novick, M.D.     

The role of computerized tomography in the diagnosis and management of patients with bilateral Wilms tumor

We report 2 cases of bilateral Wilms tumor. In both cases computerized tomography provided accurate data for the diagnosis of bilateral tumors and predicted surgical resectability, without nephrectomy, of the smaller tumor. In 1 patient computerized tomography demonstrated tumor growth while on chemotherapy and radiotherapy. The role of angiography in the management of these patients is discussed.     

An enhanced recovery after surgery protocol in children who undergo nephrectomy for Wilms tumor safely shortens hospital stay

BackgroundPediatric unilateral renal tumors in the US are treated with upfront nephrectomy and surgical staging. We applied enhanced recovery after surgery (ERAS) principles in care of children after Wilms nephrectomy.MethodsWe reviewed records of pediatric unilateral nephrectomies for Wilms tumors, and analyzed tumor stage, surgical approach, length of operation, use of anesthesia adjuncts and catheters, diet advancement, hospital length of stay (LOS), and complications. Our ERAS protocol includes: parental education regarding discharge criteria and anticipated LOS, avoiding thoraco abdominal incisions, avoiding routine nasogastric tubes, clear liquids starting day of surgery, minimizing opiates, routine IV ketorolac use, and avoiding routine ICU stay. We examined the effects of our protocol on postoperative hospital LOS and complication rates.ResultsSixty six children (31 boys, mean age 3.8y, range 0–11.9) underwent unilateral total nephrectomy for Wilms tumor. Mean nephrectomy duration was 2.7 h. Post operatively, seven (11%) had temporary gastric tubes and 24 (36%) had epidural catheters. Ten (15%) recovered in the ICU. Patients were given regular diets mean of 1.9 days post op. Mean LOS was 3.7 days, with 56% of patients being discharged within 2–3 days. Presence of tumor thrombus, longer epidural catheter duration, delayed diet advancement, and total IV narcotic usage were associated with longer LOS. Routine use of IV ketorolac was associated with shorter LOS.ConclusionsUse of an ERAS protocol in children undergoing nephrectomy for Wilms tumor is safe, resulting in rapid return to regular diet and compared to the published literature, shorter postoperative LOS without an increase in complications or return to ED/OR.Level of evidenceLevel III