Unilateral Wilms Research Articles

Wilms tumour experience in a South African centre

In Africa, Wilms tumour frequently presents with advanced disease. This study reports our results over 25 years using the National Wilms Tumour Study Group (NWTSG) approach of primary surgery followed by chemotherapy. A retrospective analysis was performed on all patients diagnosed with unilateral Wilms tumour between January 1979 and December 2003. The records of 188 children with newly diagnosed Wilms tumour were examined. Of these 57 (30.3%) were stage I, 33 (17.6%) were stage II, 60 (31.9%) were stage III and 38 (20.2%) were stage IV. Twenty-four patients (12.8%) had unfavourable histology (UFH). The estimated 5-year overall survival (OS) for the whole group was 80.5% (84.8% for favourable histology (FH) and 51.6% for UFH). Among those with FH, estimated 5-year OS was 94.4% for stage I, 96.2% for stage II, 84.9% for stage III and 54.2% for stage IV. There was no difference in OS between those FH stage III tumours that were operable and those deemed inoperable. Intra-operative spillage was uncommon (8%), and did not increase local relapse rate. National Wilms Tumour Study Group protocols employed in an African setting with highly competent and experienced surgical care, produced results for non-metastatic FH Wilms tumour comparable to those of the NWTSG.

END STAGE RENAL DISEASE IN PATIENTS WITH WILMS TUMOR: RESULTS FROM THE NATIONAL WILMS TUMOR STUDY GROUP AND THE UNITED STATES RENAL DATA SYSTEM

We sought to assess accurately the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the United States Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in patients with the Wilms tumor-aniridia syndrome (WAGR). ESRD was ascertained in 5,910 patients enrolled in NWTSG studies during 1969 to 1994 by record linkage to USRDS and by direct followup. Cumulative ESRD incidence was estimated accounting for intercurrent mortality. Of 115 cases of ESRD 10 (9%) were ascertained by the NWTSG alone, 13 (11%) by USRDS alone and 92 (80%) by both. Cumulative incidence of ESRD at 20 years from diagnosis of unilateral Wilms tumor was 74% for 17 patients with the Denys-Drash syndrome, 36% for 37 patients with WAGR, 7% for 125 male patients with hypospadias or cryptorchidism (genitourinary [GU] anomalies) and 0.6% for 5,347 patients with none of these conditions. The incidence of ESRD after diagnosis of bilateral Wilms tumor was 50% for the Denys-Drash syndrome (6 patients), 90% for WAGR (10), 25% for GU anomaly (25) and 12% for other (409). ESRD in patients with WAGR or GU anomalies tended to occur relatively late, often during or after adolescence. The risk of ESRD is remarkably low for the majority of patients with Wilms tumor. However, those with WAGR or associated GU anomalies are at higher risk and should be screened indefinitely to facilitate prospective treatment of impaired renal function.

Prognóstico de pacientes com tumor de Wilms unilateral no Rio de Janeiro, 1990-2000

To analyze the survival and the main prognostic factors among patients with unilateral Wilms' tumor patients. The study cohort included 132 patients with unilateral Wilms' tumor aged under 15 years, who were enrolled in a pediatric oncology service. Survival curves were calculated using the Kaplan-Meier method and the prognostic factors were analyzed using the Cox proportional hazards model. The overall survival rate for five years was 84.6%. The survival probabilities for disease in stages I, II, III and IV stages were: 100%, 94.2%, 83.2% and 31.3%, respectively. The survival rate was 89.4% for patients with favorable histology, 66.7% for focal anaplasia and 40% for diffuse anaplasia. All patients with stage IV disease and diffuse anaplasia died (n=4). All patients with stage I disease, regardless of histology, remained alive at the end of the follow-up period. Among the variables selected for the final model, only the staging and the histology remained associated with high risk of death risk, while patients aged 24 - 47 months presented better prognosis than the other patients. These results showed the importance of establishing the diagnosis at an early stage, and that the histology is fundamental for guiding the appropriate therapy.

Wilms’ tumor management

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. 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. 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.

Variceal Hemorrhage 13 Years After Nephrectomy For Wilms Tumor

Variceal Hemorrhage 13 Years After Nephrectomy For Wilms Tumor

LAPAROSCOPIC NEPHRECTOMY FOR WILMS TUMOR AFTER CHEMOTHERAPY: INITIAL EXPERIENCE

We describe 2 cases of laparoscopic nephrectomy for unilateral Wilms tumor in children who underwent preoperative chemotherapy. Two children with unilateral nonmetastatic Wilms tumor included in the International Society of Pediatric Oncology 2001 protocol were preoperatively treated with vincristine/actinomycin D and subsequently underwent laparoscopic nephrectomy and lymph node sampling. A 5 and 10 mm trocar transperitoneal approach was used in each case. The tumor was extracted without morcellation through a 4 cm Pffannensteil incision. The 2 tumors were completely removed as well as lymph node samples. Intraoperative bleeding was minimal (50 ml). The postoperative period was free of complications and patients were discharged home after 3 days. Laparoscopic nephrectomy for Wilms tumor is feasible in children after chemotherapy. It is a safe procedure and it allows the complete surgical approach required to treat this tumor. Longer followup is necessary to evaluate long-term results and more cases are necessary to compare the results of laparoscopic techniques with those of open surgical procedures.

CONSERVATIVE MANAGEMENT OF HYPERPLASTIC AND MULTICENTRIC NEPHROBLASTOMATOSIS

The treatment of hyperplastic nephroblastomatosis remains controversial. We report the advantages of conservative management of hyperplastic and multicentric nephroblastomatosis associated with unilateral Wilms tumor (WT). During the last 10 years 48 children with unilateral WT were consecutively treated at our 2 institutions. Children with multiple solid renal masses on imaging were treated with 2-drug chemotherapy until disappearance of the lesions. Stabilization or progression of the lesions despite chemotherapy, as well as heterogeneity of the lesions on imaging, prompted nephron sparing surgery (NSS). Three female infants (12, 13 and 20 months old, respectively) presented with multiple solid renal tumors at imaging. Despite chemotherapy, small and unilateral WT developed in 2 cases of hyperplastic nephroblastomatosis, which was excised. One of these infants subsequently presented with a small contralateral metachronous WT, which was excised. Both infants are disease-free with 2 normal kidneys at followup of 6 and 2 years, respectively. The third infant, who presented with unilateral multicentric WT and unilateral hyperplastic nephroblastomatosis nodules, was successfully treated with preoperative chemotherapy and enucleation of 5 tumors. Subsequently, nephrectomy was performed at another institution because the abnormal kidney outline due to NSS was misinterpreted as a recurrence of WT. She was lost to followup. Hyperplastic and multicentric nephroblastomatosis is not a rare lesion and is most often associated, either initially or subsequently, with WT. In some infants with multiple solid renal masses on imaging chemotherapy and for developing WT NSS may safely allow maximum sparing of the parenchyma of both kidneys.

RE: PARTIAL NEPHRECTOMY FOR UNILATERAL WILMS TUMOR: RESULTS OF STUDY SIOP 93–01/GPOH: Reply by Authors

RE: PARTIAL NEPHRECTOMY FOR UNILATERAL WILMS TUMOR: RESULTS OF STUDY SIOP 93–01/GPOH: Reply by Authors

A single-institution Wilms' tumor and localized neuroblastoma series.

Since January 1980, 120 children affected by Wilms' tumor have been treated at Bambino Gesù, mostly with multimodality treatment according to Société Internationale d'Oncologie Pediatrique (SIOP) protocols, including chemotherapy, surgery and radiotherapy in selected cases. This treatment approach emphasizes the role of preoperative (neoadjuvant) chemotherapy as opposed to the approach favored by the National Wilms' Tumor Study, which is focused on optimizing postoperative chemotherapy after primary surgery. Thus, using SIOP guidelines, staging occurs at the time of surgery, after chemotherapy administration. These differences will constitute the baseline for a comparison between the two experiences. Bilaterality, nephroblastomatosis, partial nephrectomy in unilateral Wilms' tumor and thrombosis of the vena cava are the main topics discussed. For the present study, the analysis was restricted to 98 consecutive cases diagnosed until December 1999, for whom at least 24 mo of follow-up is available. The more recent experience of treating resectable neuroblastoma in cooperative studies dates back to 1979, when the first Italian Cooperative Group Neuroblastoma protocol was introduced. This experience was continued within the frame of the first Localized Neuroblastoma European Study Group protocol (LNESG 94), and will be compared to North American Cooperative Group approaches and outcomes. Preoperative evaluation of surgical risk factors, intraoperative complications and their management, and long-term outcome will be discussed.

Partial Nephrectomy for Unilateral Wilms Tumor: Results of Study SIOP 93–01/GPOH

We evaluate results and long-term outcome after partial nephrectomy (PN) for unilateral Wilms tumor (ulWT) in relation to different histological features, performed as initial surgery or after induction chemotherapy (ChT). Data from patients with ulWT who had undergone PN in the German Study SIOP 93-01/GPOH were analyzed for time of surgery in the treatment schedule, postoperative stage, histological features, surgical radicality and outcome. The results were correlated with overall survival and relapse-free survival, and compared with those of patients who had undergone total tumor nephrectomy (TN). A total of 770 patients underwent TN and 37 underwent PN, of which 766 (99.5%) and 36 (97.3%), respectively, were radical procedures. A total of 139 TNs and 15 PNs were performed at primary surgery, 630 TNs and 22 PNs after ChT, and 1 TN after irradiation. Two of 15 patients following primary PN and 1 of 22 following delayed PN had local recurrence. Two patients died of metastatic disease. Tumor stage, overall survival of 93% and relapse-free survival of 88% were equal after PN and TN in analysis of the whole group. This was also true for patients with surgery after ChT. One of 2 patients with histologically unfavorable disease had relapse after PN compared to only 3 of 35 patients with histologically low or intermediate risk disease. PN should be performed only for small, histologically low or intermediate risk tumors after good response to ChT to secure a complete resection.

Nephron-sparing procedures in 11 patients with Wilms' tumor.

In unilateral Wilms' tumor (WT), tumor nephrectomy is the standard surgical approach, whereas partial nephrectomy (PN) is controversially discussed. The aim of our retrospective study was to show that in selected cases of unilateral WT kidney-sparing operations could be a reasonable alternative to nephrectomy and to discuss the results of patients with bilateral WT treated by tumor enucleation. From 1981 to 1998, seven patients with unilateral nephroblastoma (four stage I, one stage III and two stage IV) had tumor resection by PN (five right side, two left side), which was planned when the tumor volume was reduced after 4 to 6 weeks of chemotherapy by at least 50%, when the tumor occupied one pole or was easily resectable, when 50% or more of the kidney tissue remained and when paraaortic lymph nodes were free by intraoperative histological examination. In four patients with bilateral WT (stage V) bilateral tumor enucleation was carried out-except in one patient in whom the contralateral kidney had to been removed because of extension of the tumor via the inferior vena cava to the right atrium. All patients ( n = 11) received pre- and postoperative chemotherapy followed by radiotherapy in four patients. All patients with unilateral WT ( n = 7) are still alive and disease free (follow-up time: mean 6.6 years, range: 28 months to 11 years) with normal renal function, although two patients with secondary nephrectomy revealed creatinine clearance levels at the lower range. In six patients primary PN was performed successfully. In a stage III tumor patient (intraperitoneal metastasis, free lymph nodes), secondary nephrectomy was necessary due to renal arterial thrombosis 2 days after PN. In one stage IV tumor patient (lung metastasis, free lymph nodes), the primary resection was not far enough away from the tumor margin so that an additional slice of tissue with then tumor-free margins had to be resected. This patient evolved a local relapse 19 months after PN and had to be nephrectomised thereafter. In the group of bilateral WT patients ( n = 4), one child died 2 months after surgery during chemotherapy because of central venous line sepsis. One patient who additionally suffered from inferior vena cava tumor thrombosis extending to the right atrium making nephrectomy of the right kidney necessary developed chronic renal failure 4.7 years postoperatively. The other two stage V tumor patients have creatinine clearance levels within the normal range. Kidney-sparing procedures remain the operative approach of choice in patients with bilateral WT, but bear the risk of chronic renal failure when one kidney has to be removed. PN in children with unilateral WT, carried out by an experienced surgeon, is a reasonable alternative to nephrectomy if strict guidelines such as excellent tumor response to preoperative chemotherapy and easy resectability far away from the tumor margins through healthy kidney tissue are followed. Paraaortic lymph nodes must be free of tumor invasion in order to avoid local radiotherapy. PN prevents the patient from having to have dialysis in cases of contralateral nephrectomy resulting from metachronous WT or subsequent renal trauma.

P53 Immunopositivity in Histologically Favorable Wilms Tumor Is Not Related To Stage At Presentation Or To Biological Aggression

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. 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. 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). 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.

Partial nephrectomy in unilateral wilms — yes or no?

Partial nephrectomy in unilateral wilms — yes or no?

16q heterozygosity loss in Wilms» tumour in children and its clinical importance

Introduction: The loss of heterozygosity (LOH) of 16q is a structural change detected in about 20–30% of Wilms» tumour cases. Aberrations which result in deletion of 16q are also found in breast cancer, prostate cancer and liver cancer, where they are connected with a worse prognosis. The hypothesis of a bad prognosis in nephroblastomas with LOH 16q was first formulated by scientists from NWTS (National Wilms Tumor Study) on the basis of 232 cases of Wilms» tumour. However, SIOP studies (International Society of Paediatric Oncology) which included 28 cases of Wilms» tumour, did not show any clinico-pathological correlations with LOH 16q. Therefore, we aimed to evaluate the importance of LOH 16q in relation to clinico-pathological factors in a group of children, treated according to the SIOP criteria. Aims: The aim of this work was to evaluate the frequency of LOH 16q in sporadic unilateral Wilms» tumour and to study the relationship between LOH 16q and selected patho-clinical parameters. The study comprised 66 children (31 girls and 35 boys) aged from 2 days to 13 years. Methods: LOH 16q was studied by the examination of polymorphism of marker sequences in the region 16q24. DNA was isolated from paraffin sections of tissue for routine microscopic examination by the microdissection method. The method of study involved the amplification of polymorphic sequences from the 16q24 region by polymerase chain reaction (PCR) and separation of the products of amplification by polyacrylamide gel electrophoresis. The results were the subject of statistical analysis in relation to gender, age of child at first diagnosis, stage of clinical advancement and histological type of tumour. The connection between LOH 16q and recurrences, metastases and death, and failure free survival and absolute survival of children followed-up for over 24 months after nephrectomy were studied. Results: The study revealed a lack of correlation between LOH 16q and gender, however LOH 16q was more frequent in children with Wilms» tumour aged >24 months, P<0.05. Also, LOH 16q was more frequent in tumours classified as clinical stage (CS) II or III than in CS I, P<0.05, but there were no differences in the occurrence of LOH 16q in tumours classified as CS II and CS III. We have found no correlation between LOH 16q and the histological type of tumour. However, LOH 16q has been found three times as frequently in tumours from children who died than in tumours of children who survived, P<0.0024.

Genetic Analysis of Two Female Patients with Incomplete Denys-Drash Syndrome.

Denys-Drash syndrome (DDS) is characterized by genital anomaly, early onset nephropathy and high risk for developing Wilms' tumor (WT). Recently, mutations in exon 8 or 9 of the Wilms' tumor suppressor gene (WT1) have been found in the majority of DDS patients studied. We analyzed these two exons of the WT1 gene in genomic DNA from two female patients with DDS by using polymerase-chain reaction (PCR) and direct sequencing. The patients were accompanied with normal external genitalia, early onset renal failure between 6 and 12 months of age, and unilateral Wilms' tumor. Genomic DNA was isolated from peripheral blood leucocytes of the patients. Amplification of exons 8 and 9 of the WT1 gene by PCR was performed, and direct sequencing of the PCR product was performed using an automatic DNA sequencer. Two heterozygous missense mutations were found in these patients, including a missense mutation in exon 9 at codon 388 replacing the wild-type Cys with Phe, and a previously described mutation in exon 9 at codon 398 replacing the wild-type Leu with Pro. Cys388Phe is a novel mutation in the WT1 gene in the DDS. These cases are considered to be "incomplete DDS" with nephropathy and Wilms' tumor and without genital anomaly, the validity of which has been confirmed by mutation analysis.

THE ROLE OF RENAL SALVAGE PROCEDURES FOR BILATERAL WILMS TUMOR: A 15-YEAR REVIEW

We reviewed our experience with renal salvage procedures in patients with bilateral Wilms tumor to determine the clinical outcome. 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. 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. 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.

Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group.

Approximately 1% of children with unilateral Wilms tumor develop contralateral disease. The authors assessed the demographic and histologic features associated with metachronous bilateral Wilms tumor (BWT). Characteristics of all children registered on the first four National Wilms Tumor Studies (NWTS) were recorded. The primary endpoint for evaluation was the first appearance of Wilms tumor in the remaining kidney. The cumulative risk of contralateral disease as a function of time since initial presentation was calculated as 1 minus the Kaplan-Meier estimate of remaining free of contralateral disease. A matched case control study was conducted to determine whether the presence and type of nephrogenic rests (NRs) were associated with metachronous BWT. Fifty-eight of 4669 registered children developed metachronous BWT; 38 of 2445 females (expected, 30.2) versus 20 of 2224 males (expected, 27.8) (P = 0.04) developed BWT. The cumulative incidence of contralateral disease 6 years after initial diagnosis decreased from greater than 3% in the first NWTS to approximately 1.5% in the three subsequent studies (P = 0.08). Patients with NRs had a significantly increased risk of metachronous BWT. This was particularly true for young children (20 of 206 age < 12 months compared with 0 of 304 age > 12 months). Data from the matched case control study confirmed the increased relative risk associated with young age and the presence of NRs. Children younger than 12 months diagnosed with Wilms tumor who also have NRs, in particular perilobar NRs, have a markedly increased risk of developing contralateral disease and require frequent and regular surveillance for several years. Surveillance is also recommended for those with NRs who are diagnosed after the age of 12 months.

Is Partial Nephrectomy Appropriate Treatment for Unilateral Wilms’ Tumor?

Is Partial Nephrectomy Appropriate Treatment for Unilateral Wilms’ Tumor?

Is Partial Nephrectomy Appropriate Treatment for Unilateral Wilms' Tumor?

Is Partial Nephrectomy Appropriate Treatment for Unilateral Wilms' Tumor?

Bilateral wilms’ tumor: a clinicopathologic review

Bilateral Wilms' tumor occurs at a younger age than unilateral disease. While it generally has a good prognosis, it presents a therapeutic dilemma to balance curative surgical resection with preservation of renal tissue. A 15 year review of bilateral Wilms' tumors diagnosed at Princess Margaret Hospital was undertaken. Of 46 Wilms' tumor cases, eight were designated bilateral by diagnostic imaging (median age 1.1 years compared with 3.5 years for unilateral tumors). The surgical management entailed primary nephrectomy with contralateral biopsy in two patients, and bilateral biopsy and delayed resection in all remaining surviving patients (one patient died of perioperative complications). Seven patients had localized disease (stage I/II) and the six surviving patients received chemotherapy with vincristine and actinomycin; no patient received radiotherapy. All are alive and well (median follow-up 5.1 years). The remaining patient presented with pulmonary metastases and died of disease progression. Pathologic review revealed that four patients had truly bilateral disease demonstrable by histology, three had unilateral Wilms' tumor with contralateral nephrogenic rests, and in one patient the biopsies of the contralateral kidney showed neither tumor nor nephrogenic rests. In most cases pathological material was subject to external review. Follow-up demonstrates excellent renal function with compensatory hypertrophy in the remaining renal tissue. Conservative surgery and simple out-patient based, low toxicity chemotherapy is curative in most patients.