Lymph node involvement in Wilms tumor: Results from National Wilms Tumor Studies 4 and 5
Department of Surgery, St Jude Children's Research Hospital, Memphis, Tenn 38105, USA. Journal of Pediatric Surgery
(Impact Factor: 1.39).
04/2012; 47(4):700-6. DOI: 10.1016/j.jpedsurg.2011.08.017
The aim of the study was to determine the prognostic impact of lymph node (LN) involvement and sampling in patients with Wilms tumor (WT) and the minimum number of LNs needed for accurate staging.
We reviewed all patients with unilateral, nonmetastatic WT enrolled in the National Wilms Tumor Study 4 or 5. Data were abstracted on patient demographics, tumor histology, staging, number of LNs sampled, and disease-specific and overall patient outcomes.
A total of 3409 patients had complete information on LN sampling. Five-year event-free survival (EFS) was lower in patients with nodal disease (P < .001); the effect of LN positivity was greater for patients with anaplastic (P = .047) than with favorable histology (P = .02). The likelihood of obtaining a positive LN was higher when sampling at least 7 LNs. However, after controlling for tumor histology and stage, the number of LNs sampled did not predict EFS variations (P = .75). Among patients with stage II disease, patients with LN sampling (P = .055) had improved EFS, largely reflecting poorer EFS in patients with anaplastic tumors (P = .03).
Lymph node sampling is particularly important for patients with stage II anaplastic WT. Although the likelihood of finding a positive LN was greater when more than 7 LNs were sampled, EFS was not impacted by the number of LNs sampled.
Available from: Peter Liou
- "Some authors have suggested that this depends on the number of lymph nodes sampled. In a large retrospective study, Kieran et al. found that the likelihood of finding a positive lymph node, and thus upstaging to stage III, was greater when more than 7 were sampled, suggesting that insufficient sampling may limit the accuracy of stage determination . Understaging could therefore lead to inadequate treatment of Stage III tumors, with consequent poorer outcomes [7,8]. "
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Despite high long-term survival rates in patients with Wilms tumor, there is a need to develop better prognostic biomarkers in order to maximize cure while avoiding treatment-associated morbidities. Tumor-associated macrophages have been recently associated with poorer prognosis and increased disease progression in a number of adult cancers. We investigated the relationship between macrophages and clinicopathological fators in this pediatric solid tumor.
Tissue microarray sections of 124 Wilms tumor cases obtained from the Cooperative Human Tissue Network were stained with CD68, a macrophage marker using standard immunohistochemical techniques and quantified using digital image processing techniques. Macrophage densities were correlated by tumor stage, and survival analyses were conducted with available clinical data. Immunohistochemistry was performed on 25 additional Wilms tumor cases obtained from the tumor bank at Columbia University Medical Center and correlated with presence of tumor microvascular invasion.
Mean macrophage count densities in stage IV tumors were significantly greater than densities in stage I and III tumors (p=.021, .036). Although the overall and disease-free survival did not differ between high and low macrophage presence groups across all stages, increased macrophage presence was associated with decreased disease-free survival in patients with stage II tumors (p=0.035). Increased macrophage presence may have also correlated with decreased disease-free survival in stage IV patients, but the sample size was too small to allow detection of this difference with significance (p=0.575). Increased macrophage presence was associated with tumor microvascular invasion (p=0.0004).
Our results suggest that macrophage recruitment may be associated with disease progression in Wilms tumor. Quantitation of macrophage presence may therefore be a useful adjunct in refining staging algorithms for patients with stage II Wilms tumor. Such data might be useful in the effort to reduce the risk of adverse effects associated with under- or overtreatment of this neoplasm.
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ABSTRACT: The aim was to report a multicentric study with a longer follow-up to evaluate the laparoscopic radical nephrectomy in children with renal cancer.
This was a retrospective multicentric study, from October 2005 to January 2012, of children who underwent a laparoscopic radical nephrectomy for small renal malignant tumors.
Seventeen children were included in this study. Sixteen underwent chemotherapy before surgery according the SIOP (Société Internationale d'Oncologie Pédiatrique) protocol and one was treated by surgery only for a carcinoma. All except one could be treated by laparoscopy; the biggest tumoral size was 8 cm. The median hospital stay was 3 days (2-10). The pathologic examination showed 15 Wilms' tumors, one clear cell sarcoma and one TFE3 renal cell carcinoma. With a median follow-up of 42 months (range 12 and 77 months) after laparoscopic radical nephrectomy, 15 children had no oncological complications (port site or local recurrence, pulmonary metastasis) and one had a local recurrence without intraoperative tumoral rupture. The child with TFE3 renal cell carcinoma died 4 years after surgery from brain and lung metastases without local recurrence. No small bowel obstruction occurred.
Radical nephrectomy in children for Wilms' tumor or other renal cancer can be safely performed laparoscopically and our indications can be summarized, for trained laparoscopic surgeons, by small tumors under about 8 cm diameter, especially without crossing the lateral edge of the vertebra on the CT scan at the time of surgery.
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ABSTRACT: Nephron-Sparing Surgery (NSS) is the standard of care for many adults with renal tumors and has been described in some children with Wilms tumor (WT). Beyond case series, however, data concerning NSS utilization and outcomes in WT are scarce. We therefore examined NSS outcomes and factors associated with NSS use in WT.
We retrospectively reviewed the 1998-2010 Surveillance, Epidemiology, and End Results (SEER) database. We identified WT patients aged ≤ 18 years. Clinical, demographic and socioeconomic data were abstracted, and statistical analysis was performed using multivariate logistic regression (predicting use of NSS, limited to unilateral tumors <15cm) and Cox regression (predicting Overall Survival, OS) models.
We identified 876 boys and 956 girls with WT (mean age 3.3 ± 2.9 years). Of these, 114 (6.2%) underwent NSS (74 unilateral, 37 bilateral WT). Median follow up was 7.1 years. Regarding procedure choice, NSS was associated with unknown lymph node status (NX vs N0, p<0.001) and smaller tumor size (p<0.001). Regarding survival, only age (HR=1.09, p=0.002), race (HR=2.48, p=0.002), stage (HR=2.99, p<0.001), and LN status (HR=2.17, p=0.001) predicted reduced OS. Survival was not significantly different for children undergoing NSS vs. RN (HR=0.79, p=0.58).
Among children with WT included in the SEER database, NSS is infrequently performed. NSS use is associated with smaller, bilateral tumors and with omission of lymphadenectomy; however, there are no evident differences in NSS use by demographic or socioeconomic factors. Despite lymph node under-staging, overall survival after NSS remains similar to radical nephrectomy.
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