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Journal of Indian Association of Pediatric Surgeons
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ORIGINAL ARTICLE
Year : 2014  |  Volume : 19  |  Issue : 4  |  Page : 208-212
 

Management and outcomes in massive bilateral Wilms' tumors


1 Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medical Oncology, BRAIRCH, AIIMS, New Delhi, India
3 Department of Radiotherapy, BRAIRCH, AIIMS, New Delhi, India
4 Department of Radiodiagnosis, BRAIRCH, AIIMS, New Delhi, India

Date of Web Publication30-Sep-2014

Correspondence Address:
Sandeep Agarwala
Professor, Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi-110029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9261.142005

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   Abstract 

Purpose: To evaluate the outcome of children with bilateral Wilms' tumor (BWT) treated on All India Institute of Medical Sciences-Wilms Tumor-99 (AIIMS-WT-99) protocol. Materials and Methods : All children with BWT, registered in our solid tumor clinic from August 1999 through December 2010 were included. Results: Of the 178 fresh cases of Wilms Tumor (WT) treated during this period, 11 (6.2%) had bilateral involvement. All patients except one (12 and 3 cm), had massive bilateral tumors of more than 10 cm on each side. There were eight boys and three girls in the age range 6-30 months. One patient had Denys-Drash syndrome. Twenty renal units were operated upon (12 tumorectomy, five partial nephrectomy, and three nephrectomies), while one patient with inferior vena cava (IVC) thrombus died of renal failure. Tumor spill occurred in three units, lymphnode was positive in two patients. Local recurrence occurred in four patients (six of 18 renal units (33%)-two bilateral and two unilateral). There was one recurrence in the liver that was treated with radio-frequency ablation. The 5-year overall survival (OS) was 90% (95% confidence interval (CI) = 50.8-98.6) and the relapse free survival (RFS) was 38% (95% CI = 6.1-71.6). Conclusion: Massive BWT respond poorly to preoperative chemotherapy, are often not amenable to partial nephrectomy/tumorectomy and have a higher local recurrence rate, giving a poor RFS.


Keywords: Bilateral Wilms′ tumor, chemotherapy, nephron-sparing surgery, partial nephrectomy, tumorectomy


How to cite this article:
Agarwala S, Mittal D, Bhatnagar V, Srinivas M, Bakhshi S, Bajpai M, Gupta DK, Iyer V K, Mohanti BK, Thulkar S. Management and outcomes in massive bilateral Wilms' tumors . J Indian Assoc Pediatr Surg 2014;19:208-12

How to cite this URL:
Agarwala S, Mittal D, Bhatnagar V, Srinivas M, Bakhshi S, Bajpai M, Gupta DK, Iyer V K, Mohanti BK, Thulkar S. Management and outcomes in massive bilateral Wilms' tumors . J Indian Assoc Pediatr Surg [serial online] 2014 [cited 2019 Nov 23];19:208-12. Available from: http://www.jiaps.com/text.asp?2014/19/4/208/142005



   Introduction Top


Approximately, 5-8% of Wilms' tumor (WT) patients present with bilateral disease. [1],[2] Current management protocol for bilateral WT (BWT) is neoadjuvant chemotherapy followed by nephron-sparing surgery (NSS), postoperative chemotherapy, and radiotherapy (RT). Main aim of management is to preserve normal renal parenchyma as much as possible. NSS can be partial nephrectomy or tumorectomy. Tumorectomy is a good option in large masses in which only rim of parenchyma is remaining or in cases where there are multiple tumor nodules. Tumorectomy may have a higher incidence of recurrence of disease. Aim of this study was to evaluate the outcome of children with massive BWT treated on AIIMS-WT-99 protocol.


   Materials and Methods Top


It was a prospective study. All children with BWT registered in our solid tumor clinic from August 1999 through December 2010 were included. Total of 11 patients of BWT were treated during this period. All patients were treated on AIIMS-WT-99 protocol. All patients received three drugs chemotherapy (actinomycin D, vincristine, and doxorubicin) for 24 weeks including neoadjuvant chemotherapy for 4-10 weeks. Radiological reevaluation was done after 4 and 10 weeks of chemotherapy for resectability. NSS was done in all patients, either partial nephrectomy or tumorectomy. Surgery was done as a single stage procedure for both sides or in a staged manner. The main renal artery and the vein, with the branch supplying/draining the remaining rim of parenchyma or the pole to be retained is preserved after being dissected from over the surface of the tumor (it is always found to be stretched over it, but outside the tumor capsule) and looped in vascular slings. The portion of the renal calyx draining the remaining rim of renal tissue is preserved and anastomosed to the ureter with a double-J (DJ) stent placed. A perinephric drain is also placed (removed on day 4-5 when it stops draining). The DJ stent is removed after 4 weeks by cystoscopy done under a short general anesthesia (GA). Postoperative adjuvant chemotherapy was given to all patients up to a total of 24 weeks. RT was given depending on the local stage (Stage 3 due to lymphnode positive, margins positive, or tumor spill). Renal dynamic scan (diethylenetriaminepentacetic acid (DTPA) or LLEC) and glomerular filtration rate (GFR) estimation by DTPA renography was done in all patients before and after surgery. The renal dynamic scan was performed both to evaluate the function of the renal moieties and also for the drainage pattern in view of the ureterocalycostomy performed during the resection. Kaplan-Meier survival estimates were calculated for 5 years overall survival (OS), 5 years relapse free survival (RFS), and 5 years event free survival (EFS). Events were defined as death or recurrence of disease.


   Results Top


Patient characteristics

Of the 178 fresh cases of WT treated during this period, 11 (6.2%) had bilateral synchronous involvement. There was no case of metachronous WT. All patients except one (12 and 3 cm) had massive bilateral tumors of more than 10cm on each side. There were eight boys and three girls in the age range 6-30 months (five < 12 months, six were 13-30 months). Presentation was with mass abdomen (nine, 80%), hematuria (two, 18%), fever (two, 18%), respiratory distress (one, 9%), ambiguous genitalia (one, 9%), and incisional hernia due to previous nephrectomy (one, 9%). Two (18%) patients had bilateral impalpable undescended testes. The patient with ambiguous genitalia and abnormal facies, deranged renal functions, proteinuria, and hypospadias with Mullerian remnant and was diagnosed as case of mixed gonadal dysgenesis and Denys-Drash syndrome. The review of the initial computed tomography (CT) scan of the patient with incisional hernia following nephrectomy for WT showed that there was contralateral tumor at presentation. All patients were confirmed as WT on contrast-enhanced CT (CECT) scan and fine needle aspiration cytology. Two patients (18%) had metastasis to lungs and one (9%) had an inferior vena cava (IVC) thrombus extending up to the hepatic vein ostia. None of the patients had family history of WT or any other syndromic associations.

Neoadjuvant chemotherapy

All patients received neoadjuvant chemotherapy. Two (18%) patients received for 12 weeks, four (36.4%) for 8 weeks, two (18%) for 5 weeks, and four (36.4%) for 4 weeks. As per protocol, all of them received three-drug regimen. Only four patients (36.4%) had response to neoadjuvant chemotherapy as confirmed on CECT scan. Two patients had lung nodules which showed complete response with neoadjuvant chemotherapy. In one patient (with IVC thrombus), who showed no response after 4 weeks of standard chemotherapy, ICE (ifosfamide + carboplatin + etoposide) chemotherapy regimen was instituted. This patient died after 2 weeks because of renal failure and respiratory distress due to progressively increasing tumor.

Surgery, adjuvant chemotherapy, and RT

As mentioned earlier, one patient with IVC thrombus died prior to resection and so 20 renal units were operated upon. Twelve units (60%) underwent tumorectomy, five (25%) partial nephrectomy, and three (15%) nephrectomies (including one nephrectomy done elsewhere) [Figure 1]. Four patients (40%) had undergone bilateral tumorectomy, two (20%) bilateral partial nephrectomy, partial nephrectomy and tumorectomy on each side in one (10%), and nephrectomy and tumorectomy on each side in three (30%) patients. Every attempt was made to save even thin rim of renal parenchyma as the tumors were massive bilaterally. Out of 12 tumorectomies, 10 were massive tumors with only thin rim of renal parenchyma and two were tumors at renal hilum and these were deemed unfit for partial nephrectomy [Figure 2]. Simultaneous bilateral surgery was done in three (30%). In remaining seven patients, there was gap of 5 days-4 weeks between two procedures. Tumor spill occurred in three (30%), lymph nodes were histologically positive in two (20%), and two (20%) had margins positive for disease. All patients received adjuvant chemotherapy totaling up to 24 weeks as per protocol. RT was given in six patients. Three of them received whole abdominal RT (for tumor spill), and three received right flank RT (due to lymph node and margin positivity).
Figure 1: Showing surgical treatment for bilateral tumors and recurrences

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Figure 2: Contrast enhanced computed tomography (CECT) of a patient showing massive bilateral Wilms' tumor (BWT) in axial (a) and coronal (b) views

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Histopathology

Histopathologically all were favorable histology WTs. Among the seven patients who had not responded to neoadjuvant chemotherapy; one (5%) was stroma predominant WT with teratoid features, two (10%) were WTs with extensive rhabdomyoblastic differentiation, one (5%) had a completely necrosed mass, one (5%) was having majority of cystic component, and remaining two (10%) were triphasic WTs.

Recurrences

There were five patients who developed recurrences among the 10 operated (50%) [Table 1]. Local recurrences occurred in four patients (six of 20 renal units (30%)-two bilateral and two unilateral). All the six local recurrences were in those undergoing tumorectomy (two with margins +ve and four with margins −ve), while there was no recurrence in any of the units that underwent partial nephrectomy. Both the patients with bilateral (B/L) recurrences were counseled for alternate chemotherapy, B/L nephrectomy, and need for renal transplantation; but they refused further treatment and were lost to follow-up. The two unilateral recurrences were treated with nephrectomy in one and retumorectomy in the other. Both of these patients are in remission. There was one (9%) recurrence in the liver that was treated with radio-frequency ablation and this patient is in complete remission.
Table 1: Data of patients with recurrence (n = 5)

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Morbidity

All patients had low but acceptable GFR postoperatively. No patient required dialysis postoperatively. One patient developed postoperative perinephric collection for which percutaneous drainage was done, but this unit ultimately required nephrectomy for nonfunctioning kidney. Two patients developed adhesive obstruction in follow-up. Out of these, one settled on conservative management while laparotomy, and resection and end-to-end anastomosis was done in the other for a segment of small bowel gangrene. Overall, of the 11 patients with massive BWT, one died preresection, two were lost to follow-up (with B/L recurrences) and eight (72.7%) are alive and on follow-up. None of our patient had secondary malignancies till their last follow-ups. The 5-year OS was 90% (95% confidence interval (CI) = 50.8-98.6), but the RFS and EFS was only 38% (95% CI = 6.1-71.6) and 31% [95% CI = 5.5-62.6), respectively [Figure 3].
Figure 3: Kaplan-Meier survival estimates for 5 years overall survival (OS), relapse free survival (RFS), and event free survival (EFS)

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   Discussion Top


The purpose of treatment in patients with BWT is to preserve as much renal parenchyma as possible to reduce the incidence of postoperative renal failure at the same time to achieve disease-free survival. [3] Initial few weeks of neoadjuvant chemotherapy, followed by NSS and adjuvant chemotherapy, with or without radiation therapy is the standard treatment. Duration of neoadjuvant chemotherapy depends on the tumor response and feasibility of NSS. The temptation to do nephrectomy of the more involved side and try NSS on the less involved side should be resisted. This is even more pertinent when both the sides are equally involved with extensive tumors not amenable to partial nephrectomy. With NSS, incidence of end-stage renal disease has decreased. [4],[5] In the current report, the incidence of BWT is similar to most reported series; [1],[2] however, all (except one) of these patients had massive bilateral tumors, making the task of renal conservation daunting. Further, most of these patients (7/11) had a poor response to neoadjuvant chemotherapy due to preponderance of stroma, rhabdomyoblastic differentiation, cystic areas, or necrosis in the tumors. These histological types have been reported to have poor response to neoadjuvant chemotherapy [6],[7] and prolonging chemotherapy or shifting to alternate chemotherapy protocols have no benefit. [3]

NSS can be either partial nephrectomy or tumorectomy, which can be performed simultaneously on both sides or in stages. [8],[9] It is reported that tumorectomy has higher chances of recurrence than partial nephrectomy [10] and therefore the preferred surgical option is partial nephrectomy. However, there are situations where partial nephrectomy is not feasible. These are massive tumors where there is only a rim of renal tissue which can be preserved; multiple tumors; tumor at renal hilum/central tumors. [8],[9] In the present series, out of 20 renal units operated upon; as partial nephrectomy was not feasible and so tumorectomy was performed in 12 (60%) due to either of these reasons. Six of these 12 renal units developed local recurrence, while there were no recurrences in the unit where partial nephrectomy or total nephrectomy had been performed. The overall incidence of local recurrence was six of the 20 renal units (30%). Further, two of the patients with bilateral recurrences refused further therapy when explained the possibility of need for renal replacement therapy in terms of temporary dialysis and later transplantation.

The OS in the present series is comparable to those reported, but the EFS was poor. [2],[11],[12] It was also observed that in a number of cases, where the preresection functional studies had demonstrated either no function or negligible function, and still tumorectomy had been performed, there was remarkable postoperative recovery of function. This emphasizes the relevance of doing tumorectomy in difficult situations where otherwise a nephrectomy would be done. This is all the more important in massive bilateral tumors where normally the patient would undergo bilateral nephrectomy and later renal transplantation. Renal salvage procedures in such situations usually results in conservation of significant renal function. Only 15% of the renal units, in the current report, underwent complete nephrectomy, while 75% could be salvaged with NSS. As bilateral nephrectomy and transplantation is not easily accepted by our population, doing bilateral tumorectomies seems to be the only reasonable option. This is however wrought with a higher risk of local recurrence which would then require some of these units to undergo complete nephrectomy.

 
   References Top

1.Breslow NE, Collins AJ, Ritchey ML, Grigoriev YA, Peterson SM, Green DM. End-stage renal disease in patients with Wilms tumor: Results from the National Wilms Tumor Study Group and the United States Renal Data System. J Urol 2005;174:1972-5.  Back to cited text no. 1
    
2.Aronson DC, Slaar A, Heinen RC, de Kraker J, Heij HA. Long-term outcome of bilateral Wilms tumors (BWT). Pediatr Blood Cancer 2001;56:1110-3.  Back to cited text no. 2
    
3.Hamilton TE, Ritchey ML, Haase GM, Argani P, Peterson SM, Anderson JR, et al. The management of synchronous bilateral Wilms tumor: A report from the National Wilms Tumor Study Group. Ann Surg 2011;253:1004-10.  Back to cited text no. 3
    
4.Bhatnagar S. Management of Wilms tumor: NWTS vs. SIOP. J Indian Assoc Pediatr Surg 2009;14:6-14.  Back to cited text no. 4
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5.Nakamura L, Ritchey M. Current management of Wilms tumor. Curr Urol Rep 2010;11:58-65.  Back to cited text no. 5
    
6.Gupta R, Sharma A, Arora R, Dinda AK. Stroma-predominant Wilms tumor with teratoid features: Report of a rare case and review of the literature. Pediatr Surg Int 2009;25:293-5.  Back to cited text no. 6
    
7.Weirich A, Leuschner I, Harms D, Vujanic GM, Tröger J, Abel U, et al. Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH. Ann Oncol 2001;12:311-9.  Back to cited text no. 7
    
8.Sulkowski J, Kolon T, Mattei P. Nephron-sparing partial nephrectomy for bilateral Wilms' tumor. J Pediatr Surg 2012;47:1234-8.  Back to cited text no. 8
    
9.Davidoff AM, Giel DW, Jones DP, Jenkins JJ, Krasin MJ, Hoffer FA, et al. The feasibility and outcome of nephron -sparing surgery for children with bilateral Wilms tumor. The St Jude Children's Research Hospital experience: 1999−2006. Cancer 2008;112:2060-70.  Back to cited text no. 9
    
10.Horwitz JR, Ritchey ML, Moksness J, Breslow NE, Smith GR, Thomas PR, et al. Renal salvage procedures in patients with synchronous bilateral Wilms' Tumors: A report from the National Wilms' Tumor Study Group. J Pediatr Surg 1996;31:1020-5.  Back to cited text no. 10
    
11.Shamberger RC, Haase GM, Argani P, Perlman EJ, Cotton CA, Takashima J, et al. Bilateral Wilms' tumors with progressive or nonresponsive disease. J Pediatr Surg 2006;41:652-7.  Back to cited text no. 11
    
12.Sudour H, Audry G, Schleimacher G, Patte C, Dussart S, Bergeron C. Bilateral Wilms tumors (WT) treated with the SIOP 93 protocol in France: Epidemiological survey and patient outcome. Pediatr Blood Cancer 2012;59:57-61.  Back to cited text no. 12
    


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