Background and Aims

Children’s Oncology Group protocols mandate lymph node sampling (LNS) during extirpative surgery for pediatric renal tumors. While data suggests a minimum of 6-10 LNs should be sampled, LNS is often underperformed. Concerns over morbidity associated with extended LNS have led to hesitancy in adopting a formal LN dissection template. We hypothesized that complications in children undergoing LNS for renal tumors would be rare, and not associated with the number of LNs sampled.

Methods

A single-institution, retrospective review of patients aged 0 – 18yrs undergoing extirpative renal surgery with LNS for a suspected malignancy between 2005-2019 was performed. Patients with an unknown number of LNs sampled were excluded. Perioperative complications were categorized based on the Clavien-Dindo (CD) scale. A “clinically significant” (CS) complication was defined as any CD complication ≥ III, small bowel obstruction (SBO), ileus, chylous ascites, organ injury, or wound infection/abscess. Patients were separated into 2 cohorts for analysis using a cut-point of ≤ v >6 LNs sampled. Univariable and multivariable analysis (MVA) was performed.

Results

150 patients met inclusion criteria. Median patient age was 37.8 months (IQR 20.3-62.4). 24 patients (16%) had a CS complication, the most common of which was ileus/SBO (n=18). No CD grade IV or V complications were noted. There was no difference in complications, OR time, or length of stay between the two cohorts. On MVA, sampling >6 LNs was not predictive of CS complications (p=0.958). Left-sided tumors were protective against complications (p=0.019).

Conclusions

More extensive LNS during surgery for pediatric renal tumors does not appear to lead to an increase in complications. A standardized LNS template for pediatric renal tumors may lead to increased protocol adherence and more accurate staging without placing the patient at increased risk of morbidity.

Background and Aims

Interaction between developing tumor and the immunologic microenvironment is active. A tiny subset of CD4+ T cells that co-express IL2 are called T-regs most actively interact with the tumor.

Aims: To evaluate T-regs in patients with WT before and after tumour resection and evaluate the cytokine profile(IL-2, IL-10 and TGF-β).

Methods

Blood mononuclear cells were analysed for total T-helper(Th) and T-regs(CD4+CD25+Foxp3+) at presentation and three months following resection. Serum IL-2, IL-10 and TGF-ß levels were estimated. Immunohistochemistry for Foxp3+ CD4+T-cells, IL-2 and IL-10 in a subset of patients.

Results

Thirteen children with mean age 34.8 months were enrolled. Median baseline T-reg was 1.61(0.4-8.32, mean 2.71±0.67) as opposed to 3.05(1.65–4.86, mean 3.15±1.16) in controls. Significant negative correlation ( p=0.01) between total T helper cells (Th) before and after resection was observed. Before resection baseline mean 15.64±5.39 (9.95-24.29), post-resection mean 11.66±5.40 (4.50-20.83) was noted. T-regs showed a negative trend with tumour resection (p=0.064): Pre-resection mean 2.71±2.44, (range 0.40-8.32), and post-resection mean 1.71±1.11(range 0.39-3.86). IL-2 levels were significantly lower (p=0.029) in patients than controls (34.56±8.43 pg/ml vs. 63.43±2.08 pg/ml). Patients demonstrated higher than normal levels of TGF-ß (p=0.052), mean 7963.31±5.73 pg/ml (range: 2312.27-24,663.52 pg/ml) vs. control 3351.27±2.63 (range: 1219.89-8408.20 pg/ml). IL2, IL10 and Foxp3 positive monocytes were significantly greater in the tumour microenvironment compared with normal renal tissue. IL-2, IL-10 and TGF-ß showed a negative correlation with the T-regs (Correlation coefficients -0.267,-0.528 and -0.069 respectively; p=0.069).

Conclusions

Decrease in Th and T-regs suggests that resection removes the immune stimulus. Immunosuppressive role of TGF-ß is suggested by the negative correlation with number of Th. Larger percentage of IL-10 positive monocytes with lower than normal levels of T-reg support theories of T-regulatory type 1 (Tr1) genesis from the Foxp3+ T-cell population in the tumour microenvironment.

Background and Aims

To evaluate the incidence of loss of heterozygosity (LOH) at 11p13 and 11p15 in Wilms tumor (WT) in the Indian population and study its correlation with histopathology and outcome.

Methods

Prospective evaluation of 75 nephrectomy samples was done. LOH of 11p13 and11p15 were correlated with 2 year overall survival (OS) and event free survival (EFS) by Kaplan Meir analysis.

Results

LOH at 11p13 was observed in 28/75 (37.3%) and LOH11p15 in 17/75 (22.5%) samples. LOH11p13 was not observed in any of the epithelial predominant favorable histology (FH) tumors while it was observed in all the anaplatic tumors (UHF). LOH 11p15 was not observed in any of the anaplastic tumors. Among these 75 cases there were 11 deaths and 9 recurrences. There were 4 deaths among 28 with LOH11p13 and 7 among the 47 without LOH11p13 giving a 2-year OS of 84% (95CI 63-93) and 83% (95CI 67-91) respectively (p=0.98, hazard ratio 0.98). Two year EFS was 73 %(95CI 57-84) and 68 %(95CI46-82) for those with and without LOH11p13 respectively (p=0.66;HR 1.22). There were 2 deaths among 17 with LOH11p15 and 9 among 49 without LOH11p15 giving a 2-year O.S. of 87 %(95CI 58-96) 82% (95CI 68-90) respectively (p=0.68;HR0.72). Two year EFS was 75%(95CI 46-89) and70 % (95CI 55-81) respectively (p=0.70;HR 0.81).

Conclusions

The incidence of LOH at 11p13 and 11p15 in WT is in the Indian population is similar to western data. LOH at 11p13 and 11p15 is not correlated with OS or EFS in our patients.

Background and Aims

Most relapses in patients with unilateral WT occur by two years off therapy. However, for BWT there is concern that late events (ie after 3 years) are more common. This is particularly concerning for patients with anaplastic histology who outcomes are the poorest. The purpose of this study is to examine the long term outcomes in patients with anaplastic BWT from ARENO534

Methods

ARENO534 study patients with anaplastic BWT. (focal anaplasia – FA and diffuse anaplasia DA) were included in the study. All alive/dead anaplastic BWT are now 5 years or more from end of therapy. Location, timing and outcomes of events are reported from the end of therapy.

Results

There were 25 patients with anaplastic BWT. Median age of enrollment was 43.1 months (24.1- 113.7). Median follow up for those patients who are alive is 6.5 years. There were 8 patients with FA and 17 with DA. Of the 8 patients with FA only one had FA in both kidneys. 7/8 are alive with one patient dying from local relapse due to FHWT at 5 years off therapy . A second patient with stage II FA had progressive of disease while on therapy. This patient did not have their nodes sampled. Pathology at relapse was DA. For DA patients, only 4/17 had DA in both kidneys. 12/17 are currently alive. Three died from progression, two from relapse (one local and one both local and lung) within a year after end of therapy. Both patients had positive margins. Of the 12 who are alive, 2 relapsed within a year and both had positive margins. Of the 10 who are alive without an event 5 had positive margins.

Conclusions

Patient with BWT and anaplasia often have discordant pathology. Late events are rare. Margin status at the time of definitive surgery although worrisome does not seem to impact outcomes

Background and Aims

Videolaparoscopic nephrectomy in Wilms' Tumor was introduced with promising results. Studies are needed to assess surgical and oncological results. This study aims to compare the surgical and oncological results of nephroureterectomy laparoscopic versus open for the treatment of children with Wilms' tumor.

Methods

Retrospective analysis of pediatric oncology patients diagnosed with Wilms' Tumor, submitted to surgical treatment by open or laparoscopic approach treated with SIOP protocol. Pre-chemotherapy and pre-surgery tomographic images were reviewed and the tumor measurements were collected, the relationship between tumor and adjacent structures were evaluated (central vessels, spine). Information related to surgery, pos-operatory period and pacient evolution were collected.

Results

RESULTS: Fifty patients were included in the study, of which 38 underwent open nephroureterectomy and 12 by videolaparoscopic approach. All patients in the videolaparoscopy group received neoadjuvant chemotherapy, and 4 patients in the open group underwent primary surgery. The mean tumor volume was higher in the open surgery group both at diagnosis as in pre-surgery moment (p <0.001). The distance between hilar vessel and central vessel was obtained at two time-points: at diagnosis and after neoadjuvant chemotherapy. Pre-operatively the average distance in the open group was 5.42 mm and in the laparoscopy group, 10.83 mm (p = 0.005). The average number of lymph nodes sampled was 8.2 in the open group and 2.1 in the laparoscopy group (p <0.001). In patients undergoing laparoscopy, there was no local recurrence. The overall survival rate for the open surgery and laparoscopy groups were 86.8% and 100%, respectively. The event-free survival for the open group was 84.2% and for the laparoscopy group it was 91.7%.

Conclusions

CONCLUSIONS: Videolaparoscopic nephrectomy is a viable alternative to open surgery in selected cases, reducing long-term morbidity and without increasing rupture rates. Despite the smaller lymph node sampling in the laparoscopy group, the oncological results were not affected.