Abstract

Nephroblastoma [Wilms tumor (WT)] is a rare, but the most common, primary renal tumor in children. WT is usually diagnosed between the ages of 1 and 5, with the most common diagnosis at the age of 3. While imaging (ultrasound, computed tomography, and magnetic resonance) can accurately predict up to 95% of WTs, they cannot predict the histologic subtypes and require tissue examination. Surgery is one of the cornerstones of WT treatment. Other aspects of management include chemotherapy and radiation therapy. The Societe Internationale D’oncologie Pediatrique (SIOP) advocates primary chemotherapy in patients less than 6 months of age, whereas the Children’s Oncology Group (COG) recommends primary surgery in all cases except those considered not resectable by the surgeon. In this chapter, the surgical therapy of WT is reviewed.

Introduction

Wilms tumor (WT), also called nephroblastoma, was first described by Thomas F. Rance in 1814 (1, 2). In 1899, Carl Max Wilhelm Wilms, a German surgeon and pathologist, gave a detailed histological description and since then the tumor bears his name (1, 3). The incidence of WT is 1:10000 in children under 15 (4). WT is the most common renal malignancy in children, and it represents 6% of all childhood cancers. It is also the second most common intra-abdominal cancer, and it is an embryonal malignancy of the kidney (5). About 75% of children are diagnosed before the age of 5, and the median age is 3.5 years (6).

WT is primarily a sporadic disease, but family history exists in 1–2% of cases (7). There are a number of syndromes associated with WT, including WAGR (WT, aniridia, genitourinary anomalies, and mental retardation), Denys-Drash syndrome (progressive renal disease, male pseudohermaphroditism, and WT), and Beckwith-Wiedemann syndrome (8). While WAGR syndrome is associated with large deletion on the WT1 chromosome located on 11p13, Denys-Drash syndrome has point mutations on WT1 (9, 10). Beckwith-Wiedemann syndrome is a syndrome characterized by macrosomia, macroglossia, omphalocele, and growth retardation, and hemihypertrophy is caused by a mutation located on 11p15, also known as the WT2 gene locus (11). Normal kidneys complete differentiation at the end of the 36th week of gestation; however, in about 1–2% of newborns, nephrogenic blastemal cells, also called nephrogenic rests, persist. WT is thought to arise from these nephrogenic rests (12). These nephrogenic rests have been detected in almost 35% of unilateral and 100% of bilateral WT patients (13). The prognosis of WT is closely related to its histology. An unfavorable prognosis occurs when the tumor consists of anaplastic cells; the prognosis is favorable otherwise. This anaplastic type represents 11.5% of all WTs and is responsible for 52% of the mortality rate (14). However, for pretreated patients, there exist three subgroups: low-, intermediate-, or high-risk tumor, according to the Stockholm working classification of renal tumors used by the Societe Internationale D’oncologie Pediatrique (SIOP) (15). WT is associated with mutations in various tumor suppressor genes (16). In the anaplastic type of WTs, p53 mutation is frequent (17).

Clinical presentation

WT is usually unilateral, and the mean age of presentation is 3.3 years. In 4 to 7% of cases, they are synchronous bilateral and appear at a younger age (mean age of 2.6 years) (18). The most common clinical presentation of WT is an abdominal mass. Over 90% of children are referred with an abdominal mass. Other common symptoms are abdominal pain, macroscopic hematuria, fever, and hypertension (19). Abdominal pain can be a symptom of a rupture or intratumoral hemorrhage. Macroscopic hematuria may occur when the tumor has extended to the collecting system (20). Nonspecific symptoms, such as microscopic hematuria, urinary disturbances, malaise, weight loss, and anemia, may be present at initial presentation. If spermatic veins are occluded, varicocele can occur (3) and a thorough examination of the abdomen is necessary. Varicocele is always an alarming symptom, but even more if it occurs on the right side [symptom of inferior vena cava (IVC) thrombosis] or occlusion of the right spermatic vein by the lower part of the tumor (right spermatic vein goes directly to IVC). During the physical examination, a firm, nontender mass in the abdomen is usually identified. Due to elevated renin levels, a follow-up of the blood pressure is very important in WT patients. The most common intravascular tumor extension sites are the renal vein, IVC, and atrium (21). Although the lung is the most common metastatic site, respiratory symptoms are not common. In summary, during examination, the associated anomalies should be considered, and the patient should be examined for aniridia, hemihypertrophy, and genitourinary anomalies.

Diagnosis

Ultrasonography (US) is the primary diagnostic tool for children suspected of having WT. US allows for measuring the tumor size, identifying its origin, establishing the relationship between vena cava and aorta, as well as possible IVC or renal vein. The second important diagnostic tool is computerized tomography (CT). CT is recommended for WT along with US (Figure 1). During interpretation of the CT, and also the US, the contralateral kidney and the liver should always be carefully examined. Magnetic resonance imaging (MRI) is also helpful in detecting the vascular involvement. MRI, although requires longer general anesthesia in the preschool age, offers the most accurate imaging of the kidney. It serves best when nephron-sparing resection is considered or in case of the need to distinguish between WT and nephroblastomatosis. A plain chest X-ray is a routine procedure for the evaluation of pulmonary metastases. A routine pulmonary CT is still controversial (22); however, many physicians prefer the thoracic CT because of its high sensitivity. The definite diagnoses of WT and its subtypes are made by histological evaluation. The preoperative laboratory tests that should be performed are the total blood count, renal and liver function tests, calcium level examination, and urinary examination. In rhabdoid types, the serum calcium increases (23). In 8% of children with WTs, von Willebrand disease is a comorbidity (24). The routinely evaluated tumor markers include neuron-specific enolase, lactate dehydrogenase, alpha-fetoprotein, β-human chorionic gonadotropin, and ferritin. High-risk patients for the growth of WTs, such as patients with Beckwith-Wiedemann syndrome, should be routinely examined with an US (25). In addition, a 24-hour urine catecholamine test is essential to avoid misdiagnosing with neuroblastoma.

Figure 1.

A CT scan of a left Wilms tumor.

Staging

There are currently two major staging systems, the National Wilms Tumor Study (NWTS) and the SIOP, as summarized in Tables 1 and 2, respectively (26).

Table 1.

The NWTS staging system

Table 2.

The SIOP staging system

Surgical management

Surgery is the cornerstone for the treatment of WT. The Children’s Oncology Group (COG) from North America, a group that conducted the NWTS trials, recommends surgery before chemotherapy, whereas SIOP in Europe suggests preoperative chemotherapy (26). As the SIOP group, the National Wilms Tumor Study Group (NWTSG) has concerns about performing a biopsy first because of the risk of tumor upstaging (27). The SIOP recommends preoperative chemotherapy to decrease the risk of intraoperative rupture, downstage the tumor, and to reduce the need for irradiation. The advantage of preoperative chemotherapy is the identification of chemoresistant high-risk blastemal predominant subtype that benefits from treatment intensification.

The management of WT requires a multidisciplinary approach with a pediatric radiologist, an oncologist, a surgeon, and a radiotherapist. First, the patient must be carefully evaluated using appropriate imaging techniques in the preoperative period to identify the origin of the tumor, its position in relation to the adjacent tissue, and vascular involvement. The bilaterality of the tumor, and presence of nephrogenic rests, must be evaluated. If the imaging is not suggestive of any bilateral lesion, there is no need to explore the contralateral kidney at surgery (28, 29). Among the results of WTSG-4, WT is detected in 7% of the patients whose preoperative abdominal CT of contralateral kidney is normal (30). An abdominal Doppler US is advised to check for possible thrombus in the renal vein and the IVC. In tumors with a renal vein and caval extension, it is advised to delay surgery and to start with chemotherapy (31). If the thrombus extends to the thoracic vena cava, an echocardiography should be performed. In case of the thrombus extending to the heart, the risk of pulmonary thrombosis produced by fragmented floating atrial/ventricular thrombus versus benefits of chemotherapy-induced regression must be carefully balanced. Some of these patients are cardiosurgical emergencies and therefore an oncology-oriented pediatric surgeon and a cardiac surgeon are necessary, and the equipment must include the cardiopulmonary bypass device.

For unilateral WTs, a transperitoneal radical nephrectomy is the standard operation. Nephron-sparing surgery (NSS) is advocated only in selected cases of patients with solitary kidney or bilateral WTs (20).

Before the incision, rolled sterile pads should be placed under the patient in supine position. A nasogastric tube, a transient catheter, an arterial line, and a Foley catheter are placed in our center (Figure 2). A large transverse supraumbilical incision should be made, permitting the exploration of the entire abdomen and the contralateral kidney, if necessary (Figure 3). In patients with an intracardiac extension, where an upfront excision is not encouraged, a chevron incision or a combined transverse abdominal and sternal incision can be performed. Because the rupture of the tumor capsule and the spillage of the tumor increase with the tumor stage, and decrease survival, it is important to perform a suitably long incision to remove the tumor from the abdomen safely. At the beginning of the operation, the abdomen should be explored for any intra-abdominal implants. If deemed necessary based on preoperative imaging, the opening of Gerota fascia and careful exploration of the whole contra lateral kidney is recommended. Any suspicious areas should be biopsied. The peritoneum covering the tumor is opened as laterally as possible for easy closure of the peritoneum after the tumor resection (Figures 4 and 5). Most frequently, the best access to the right-sided WT is Kocher’ maneuver, which offers a good exposition of the right renal vessels. For left-sided WTs, laterocolonal access is usually sufficient (Figure 6). The renal vein and the IVC should be palpated first to exclude thrombus. The nephrectomy should begin by ligating the renal artery to avoid thrombus embolism. Afterward, the renal vein should be ligated immediately (Figure 7). The ureter should be ligated as low as possible. Titanium clips are mostly used for the marking of the tumor area for possible further radiotherapy. An en bloc resection of the tumor without any tumor spillage is the most important aspect. Lymph node sampling is another important goal in WT surgery. Lymph node samples should be collected from the renal hilum, iliac, paracaval, or para-aortic areas for accurate staging. Spillage of the tumor or inadequate lymph node dissection results in incomplete chemotherapy and thus decreased survival rates. NWTS suggests seven regional nodes to get reliable information on lymph node involvement (32).

Figure 2.

The position of the patient.

Figure 3.

A large transverse supraumbilical incision, permitting the exploration of the entire abdomen and the contralateral kidney.

Figure 4.

The peritoneal reflection covering a right Wilms tumor. P: peritoneum.

Figure 5.

The lateral peritoneal reflection opened from an avascular area on the lateral side. WT: Wilms tumor, P: peritoneum, C: colon.

Figure 6.

Image showing access to the right-sided WT in which the colon is reflected medially. C: Colon, I: ileum, GB: gall bladder, RK: right kidney, LK: left kidney, RRV: right renal vein, LRV: left renal vein, VCI: vena cava inferior, A: aorta.

Figure 7.

The ligation of the renal vein.

There is an emerging consensus on performing routine adrenalectomy during unilateral nephrectomy for WTs. One recent study proved that an adrenalectomy does not affect the 5-year survival rate, but it does increase the intraoperative spillage rates (33). Most surgeons leave the adrenal gland intact if it is not infiltrated by the tumor (34). In the study of van Waas et al. (35), it is stated that the removal of one adrenal gland does not result in clinical adrenal insufficiency.

Performing NSS by partial nephrectomy or enucleation in unilateral cases is also a matter of debate (36). We recommend this approach only in synchronous or metachronous bilateral cases or in solitary kidneys. Only less than 5% of all unilateral WTs are eligible for NSS because most of the tumors are locally advanced at the time of diagnosis (37). The surgical criteria for a partial resection are as follows: tumor is located in one pole and infiltrates approximately less than 1/3 of the kidney; no invasion of the renal vein; and the surgeon’s experience in pediatric oncology (38). The SIOP WT 2001 trial reported 91 children (3%) with excellent survival rates in which NSS was performed (39). Minimally invasive nephrectomy can offer the same outcome as the classical laparotomic approach (40, 41).

For bilateral cases, the current approach is preoperative chemotherapy followed by bilateral NSS (42). Timing of surgery is important. Both COG/NWTSG and SIOP/RTSG recommend surgery after 9–12 weeks of chemotherapy. Where possible, both sides can be operated in the same session. In difficult cases, the easier side can be operated first. The more difficult side can be operated after one or two courses of chemotherapy and stabilization of the renal function. The major goal of bilateral WT surgery is to achieve a cure by removing all tumoral renal tissue while preserving the maximum functioning kidney. Some authors suggest in situ topical cooling or perfusion with preservation solutions for meticulous dissection without the loss of renal function from ischemia. The ultrasonic scalpel is a useful tool in such resections (43). Millar et al. (44) reported 19 children with bilateral WT cases in which they achieved good results with appropriate chemotherapy and conservative NSS. They suggested a revision surgery if needed. Perioperative US is also a useful tool in NSS of bilateral cases for detecting the margins of normal renal tissue and the tumoral tissue.

Intracardiac extension of WT has been an important surgical challenge. First, an accurate preoperative radiological evaluation of the tumor and thrombus is necessary, and second, a multidisciplinary treatment plan by the cardiovascular surgeon and the pediatric surgeon is important. In general, upfront treatment with chemotherapy is advised. Then, surgical treatment can be considered as reported by SIOP group, which shows favorable results in patients who underwent surgery, including a cardiopulmonary bypass and hypothermia (45). Some surgeons have used this reported technique in pediatric WT cases (46–48).

Common surgical complications in primary nephrectomy patients with WT are ruptures, intestinal obstruction, bleeding, and surgical site infections. NWTSG conducted an analysis on 3335 children who received primary nephrectomy for WT. They observed surgical complications in 12.7% of the patients. These complications were intestinal obstruction (5.1%), excessive bleeding (1.9%), surgical site infection (1.9%), and major vascular injuries (1.5%). Also, the risk of complications increased when the tumor size had exceeded 10 cm (49). The risk of tumor rupture was 15% in NWTSG for primary surgery and 3% for chemotherapy-pretreated cases in SIOP. This was replicated by a randomized study in UK (50). Godzinski (51) reported that not only the intraoperative tumor rupture but also other surgery-related complications became rare after the pretreatment. The rate of these complications did not exceed 8% in the pretreated patients. In selected cases, preoperative biopsy was considered. Tru-cut biopsy instead of a needle biopsy may be used to avoid upstaging of the tumor. Preoperative chemotherapy is advised in most bilateral cases, inoperable tumors, and tumors with an intracaval/cardiac extension (43).

Recurrent disease

About 10–15% of WT results in recurrence (52). Spillage occurs in almost every 10 unilateral nephrectomies and is correlated with right-side and larger tumors (53). The recent analysis of COG demonstrated that a relapse in the flank or abdominal site occurred in only 7.4% and 9.5%, respectively, of stage II WT patients with spill, whereas it occurred in 2.5% and 3%, respectively, for those without spill (54). According to SIOP trials, even though the rupture frequency was much less in prechemotherapy group, event-free follow-up or overall survival rate was reported similarly (55). Drugs such as platinum compounds, ifosfamide, cyclophosphamide, etoposide (ICE), and their combinations are used in relapsed WT. Postrelapse survival rates of 50–60% have been reported with ICE chemotherapy (56). Survival rates also depend on the initial stage, initial treatment, metastatic burden, and the relapse-free interval (57). A complete resection of the recurrent lesion(s) has also been shown to be a favorable prognostic factor.

Conclusion

Whether chemotherapy is given preoperatively or not, surgery comprises the main part of the WT surgery. WT patients need a multimodal, multidisciplinary treatment with a close follow-up.

Conflict of Interest

The author declares no potential conflicts of interest with respect to research, authorship and/or publication of this article.

Acknowledgment

I convey my sincere gratitude to Prof. Dr. J. Godzinski for the revision of the chapter.

References

1.

Varan A. Wilms’ tumor in children: an overview. Nephron Clin Pract. 2008;108:c83–90. [PubMed: 18187945]

2.

Rance TF. Case of fungus haematodes of the kidneys. Med Phys J. 1814;32:19–25. [PMC free article: PMC5713550] [PubMed: 30493414]

3.

Wilms M. Die Mischgeschwülste der Niere. Leipzig: A Georgi; 1899. pp. 1–90.

4.

Ehrlich PF, Shamberger RC. Wilms’ tumor. In: Coran A, Adzic NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA., editors. Pediatric Surgery. 7th ed. Vol. 1. Philadelphia, PA: Elsevier Saunders; 2012. pp. 423–40.

5.

Adam MP, Fechner PY, Ramsdell LA, Badaru A, Grady RE, Pagon RA, et al. Ambiguous genitalia: what prenatal genetic testing is practical? Am J Med Genet A. 2012;158:1337–43. [PubMed: 22581420] [CrossRef]

6.

Breslow NE, Beckwith JB, Perlman EJ, Reeve AE. Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor. Pediatr Blood Cancer. 2006;47(3):260–7. [PMC free article: PMC1543666] [PubMed: 16700047] [CrossRef]

7.

Perlman EJ, Grundy PE, Anderson JR, Jennings LJ, Green DM, Dome JS, et al. WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms’ tumors treated with surgery alone: a children’s oncology group study. J Clin Oncol. 2011;29(6):698–703. [PMC free article: PMC3056654] [PubMed: 21189373] [CrossRef]

8.

Scott RH, Stiller CA, Walker L, Rahman N. Syndromes and constitutional chromosomal abnormalities associated with Wilm’s tumour. J Med Genet. 2006 Sep;43(9):705–15. [PMC free article: PMC2564568] [PubMed: 16690728] [CrossRef]

9.

Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, et al. Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991;67(2):437–47. [PubMed: 1655284]

10.

Pelletier J, Bruening W, Li FP, Haber DA, Glaser T, Housman DE. WT1 mutations contribute to abnormal genital system development and hereditary Wilms’ tumour. Nature. 1991 Oct 3;353(6343):431–4. [PubMed: 1654525] [CrossRef]

11.

Koufos A, Grundy P, Morgan K, Aleck KA, Hadro T, Lampkin BC, et al. Familial Wiedemann-Beckwith syndrome and a second Wilms’ tumor locus both map to 11p15.5. Am J Hum Genet. 1989 May;44(5):711–9. [PMC free article: PMC1715635] [PubMed: 2539717]

12.

Hammer E, Ernst FD, Thiele A, Karanam NK, Kujath C, Evert M, et al. Kidney protein profiling of Wilms’ tumor patients by analysis of formalin-fixed paraffin-embedded tissue samples. Clin Chim Acta. 2014 10 Jun;433:235–41. [PubMed: 24680863] [CrossRef]

13.

Beckwith JB. Precursor lesions of Wilms’ tumor: clinical and biological implications. Med Pediatr Oncol. 1993;21(3):158–68. [PubMed: 8383276]

14.

Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms’ tumors: results from the First National Wilms’ Tumor Study. Cancer. 1978 May;41(5):1937–48. [PubMed: 206343]

15.

Vujanić GM, Sandstedt B. The pathology of Wilms’ tumour (nephroblastoma): the International Society of Paediatric Oncology approach. J Clin Pathol. 2010;63:102–9. [PubMed: 19687012] [CrossRef]

16.

Coppes MJ, Haber DA, Grundy PE. Genetic events in the development of Wilms’ tumor. N Engl J Med. 1994 Sep 1;331(9):586–90. [PubMed: 8047084] [CrossRef]

17.

Bardeesy N, Falkoff D, Petruzzi MJ, Nowak N, Zabel B, Adam M, et al. Anaplastic Wilms’ tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nat Genet. 1994 May;7(1):91–7. [PubMed: 8075648] [CrossRef]

18.

Neville HL, Ritchey ML. Wilms’ tumor. Overview of National Wilms’ Tumor Study Group results. Urol Clin North Am. 2000 Aug;27(3):435–42. [PubMed: 10985143]

19.

Ganguly A, Gribble J, Tune B, Kempson RL, Luetscher JA. Renin-secreting Wilms’ tumor with severe hypertension. Report of a case and brief review of renin-secreting tumors. Ann Intern Med. 1973 Dec;79(6):835–7. [PubMed: 4357546]

20.

Ko EY, Ritchey ML. Current management of Wilms’ tumor in children. J Pediatr Urol. 2009 Feb;5(1):56–65. [PubMed: 18845484] [CrossRef]

21.

Aspiazu D, Fernandez-Pineda I, Cabello R, Ramirez G, Alvarez-Madrid A, De Agustin JC. Surgical management of Wilms’ tumor with intravascular extension: a single-institution experience. Pediatr Hematol Oncol. 2012 Feb;29(1):50–4. [PubMed: 22304010] [CrossRef]

22.

Owens CM, Veys PA, Pritchard J, Levitt G, Imeson J, Dicks-Mireaux C. Role of chest computed tomography at diagnosis in the management of Wilms’ tumor: a study by the United Kingdom Children’s Cancer Study Group. J Clin Oncol. 2002 Jun 15;20(12):2768–73. [PubMed: 12065552]

23.

Green DM, D’Angio GJ, Beckwith JB, Breslow NE, Grundy PE, Ritchey ML, et al. Wilms tumor. CA Cancer J Clin. 1996 Jan-Feb;46(1):46–63. Review. [PubMed: 8548525]

24.

Coppes MJ, Zandvoort SW, Sparling CR, Poon AO, Weitzman S, Blanchette VS. Acquired von Willebrand disease in Wilms’ tumor patients. J Clin Oncol. 1992 Mar;10(3):422–7. [PubMed: 1311024]

25.

Choyke PL, Siegel MJ, Craft AW, Green DM, DeBaun MR. Screening for Wilms’ tumor in children with Beckwith-Wiedemann syndrome or idiopathic hemihypertrophy. Med Pediatr Oncol. 1999 Mar;32(3):196–200. [PubMed: 10064187]

26.

Metzger ML, Dome JS. Current therapy for Wilms’ tumor. Oncologist. 2005 Nov-Dec;1010:815–26. [PubMed: 16314292] [CrossRef]

27.

Vujanić GM, Sandstedt B, Harms D, Kelsey A, Leuschner I, de Kraker J. SIOP Nephroblastoma Scientific Committee. Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol. 2002 Feb;38(2):79–82. [PubMed: 11813170]

28.

Green DM. The evolution of treatment for Wilms’ tumor. J Pediatr Surg. 2013 Jan;48(1):14–9. [PubMed: 23331787] [CrossRef]

29.

Powis M, Messahel B, Hobson R, Gornall P, Walker J, Pritchard-Jones K. Surgical complications after immediate nephrectomy versus preoperative chemotherapy in non-metastatic Wilms’ tumour: findings from the 1991–2001 United Kingdom Children’s Cancer Study Group UKW3 Trial. J Pediatr Surg. 2013 Nov;48(11):2181–6. [PubMed: 24210183] [CrossRef]

30.

Ritchey ML, Green DM, Breslow NB, Moksness J, Norkool P. Accuracy of current imaging modalities in the diagnosis of synchronous bilateral Wilms’ tumor. A report from the National Wilms’ Tumor Study Group. Cancer. 1995 Jan 15;75(2):600–4. [PubMed: 7812929]

31.

Nakayama DK, Norkool P, deLorimier AA, O’Neill JA Jr, D’Angio GJ. Intracardiac extension of Wilms’ tumor. A report of the National Wilms’ Tumor Study. Ann Surg. 1986;204(6):693–7. [PMC free article: PMC1251427] [PubMed: 3024596]

32.

Kieran K, Anderson JR, Dome JS, Ehrlich PF, Ritchey ML, Shamberger RC, et al. Lymph node involvement in Wilms tumor: results from National Wilms Tumor Studies 4 and 5. J Pediatr Surg. 2012;47:700–6. [PMC free article: PMC3976547] [PubMed: 22498384] [CrossRef]

33.

Kieran K, Anderson JR, Dome JS, Ehrlich PF, Ritchey ML, Shamberger RC, et al. Is adrenalectomy necessary during unilateral nephrectomy for Wilms’ tumor? A report from the Children’s Oncology Group. J Pediatr Surg. 2013 Jul;48(7):1598–603. [PMC free article: PMC5652039] [PubMed: 23895979] [CrossRef]

34.

Yao W, Li K, Xiao X, Gao J, Dong K, Xiao X, et al. Outcomes of Wilms’ tumor in eastern China: 10 years of experience at a single center. J Invest Surg. 2012 Jun;25(3):181–5. [PubMed: 22583015] [CrossRef]

35.

van Waas M, Neggers SJ, van Eck JP, van Noesel MM, van der Lely AJ, de Jong FH, et al. Adrenal function in adult long-term survivors of nephroblastoma and neuroblastoma. Eur J Cancer. 2012;48(8):1159–66. [PubMed: 22513228] [CrossRef]

36.

Ritchey ML. Nephron sparing surgery for Wilms tumor: where is the future? J Urol. 2011 Oct;186(4):1179–80. [PubMed: 21849180] [CrossRef]

37.

Wilimas JA, Magill L, Parham DM, Kumar M, Douglass EC. The potential for renal salvage in nonmetastatic unilateral Wilms’ tumor. Am J Pediatr Hematol Oncol. 1991;13(3):342–4. [PubMed: 1665316]

38.

van Dalen EC, de Lijster MS, Leijssen LG, Michiels EM, Kremer LC, Caron HN, et al. Minimally invasive surgery versus open surgery for the treatment of solid abdominal and thoracic neoplasms in children. Cochrane Database Syst Rev. 2015 Jan 5;1:CD008403. [PMC free article: PMC7180085] [PubMed: 25560834] [CrossRef]

39.

Wilde JC, Aronson DC, Sznajder B, Van Tinteren H, Powis M, Okoye B, et al. Nephron sparing surgery (NSS) for unilateral Wilms tumor (UWT): the SIOP 2001 experience. Pediatr Blood Cancer. 2014;61:2175–9. [PubMed: 25156758] [CrossRef]

40.

Godzinski J, Graf N, Audry G. Current concepts in surgery for Wilms tumor--the risk and function-adapted strategy. Eur J Pediatr Surg. 2014 Dec;24(6):457–60. [PubMed: 25478666] [CrossRef]

41.

Warmann SW, Godzinski J, van Tinteren H, Heij H, Powis M, Sandstedt B, et al. Minimally invasive nephrectomy for Wilms’ tumors in children: data from SIOP 2001. Surgical Panel of the SIOP Renal Tumor Strategy Group. J Pediatr Surg. 2014;49(11):1544–8. [PubMed: 25475791] [CrossRef]

42.

User IR, Ekinci S, Kale G, Akyüz C, Büyükpamukçu M, Karnak I, et al. Management of bilateral Wilms’ tumor over three decades: the perspective of a single center. J Pediatr Urol. 2015;11(3):118.e1–6. [PubMed: 25842994] [CrossRef]

43.

Ritchey ML. The role of preoperative chemotherapy for Wilms’ tumor: the NWTSG perspective. National Wilms’ Tumor Study Group. Semin Urol Oncol. 1999 Feb;17(1):21–7. [PubMed: 10073402]

44.

Millar AJ, Davidson A, Rode H, Numanoglu A, Hartley PS, Daubenton JD, et al. Bilateral Wilms’ tumors: a single-center experience with 19 cases. J Pediatr Surg. 2005;40(8):1289–94. [PubMed: 16080934] [CrossRef]

45.

Szavay P, Luithle T, Semler O, Graf N, Fuchs J. Surgery of cavoatrial tumor thrombus in nephroblastoma: a report of the SIOP/GPOH study. Pediatr Blood Cancer. 2004;43:40–5. [PubMed: 15170888] [CrossRef]

46.

Pannek J, Goepel M, Kremens B, Otto T, Sadony V. Surgical management of Wilms’ tumor with intracardiac neoplastic extension. Thorac Cardiovasc Surg. 1994;42(2):108–11. [PubMed: 8016824] [CrossRef]

47.

Hunt TM, Firmin RK, Johnstone MJ. Management of a patient with Wilms’ tumour extending into the right heart chambers: a case report and a review of other published reports. Br Heart J. 1988;60(2):165–8. [PMC free article: PMC1216541] [PubMed: 2843215]

48.

Rioja Zuazu J, Rodríguez-Rubio Cortadillas F, Zudaire Bergera JJ, Saiz Sansi A, Rosell Costa D, Robles García JE, et al. Extracorporeal circulation and hypothermy surgery in tumors with vena cava extension: 20 years experience at the University Clinic of Navarra. Actas Urol Esp. 2008;32(4):396–405. [PubMed: 18540260]

49.

Ritchey ML, Shamberger RC, Haase G, Horwitz J, Bergemann T, Breslow NE. Surgical complications after primary nephrectomy for Wilms’ tumor: report from the National Wilms’ Tumor Study Group. J Am Coll Surg. 2001 Jan;192(1):63–8. [PubMed: 11192924]

50.

Mitchell C, Pritchard-Jones K, Shannon R, Hutton C, Stevens S, Machin D, et al. Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms’ tumour: results of a randomised trial (UKW3) by the UK Children’s Cancer Study Group. United Kingdom Cancer Study Group. Eur J Cancer. 2006 Oct;42(15):2554–62. [PubMed: 16904312] [CrossRef]

51.

Godzinski J. The current status of treatment of Wilms’ tumor as per the SIOP trials. J Indian Assoc Pediatr Surg. 2015 Jan;20(1):16–20. [PMC free article: PMC4268749] [PubMed: 25552825] [CrossRef]

52.

Shamberger RC, Guthrie KA, Ritchey ML, Haase GM, Takashima J, Beckwith JB, et al. Surgery-related factors and local recurrence of Wilms’ tumor in National Wilms Tumor Study 4. Ann Surg. 1999 Feb;229(2):292–7. [PMC free article: PMC1191644] [PubMed: 10024113]

53.

Gow KW, Barnhart DC, Hamilton TE, Kandel JJ, Chen MK, Ferrer FA, et al. Primary nephrectomy and intraoperative tumor spill: report from the Children’s Oncology Group (COG) renal tumors committee. J Pediatr Surg. 2013 Jan;48(1):34–8. [PMC free article: PMC4556229] [PubMed: 23331790] [CrossRef]

54.

Green DM, Breslow NE, D’Angio GJ, Malogolowkin MH, Ritchey ML, Evans AE, et al. Outcome of patients with Stage II/favorable histology Wilms’ tumor with and without local tumor spill: a report from the National Wilms’ Tumor Study Group. Pediatr Blood Cancer. 2014 Jan;61(1):134–9. Epub 2013 Aug 23. [PMC free article: PMC3933291] [PubMed: 24038736] [CrossRef]

55.

Lemerle J, Voute PA, Tournade MF, Delemarre JF, Jereb B, Ahstrom L, et al. Preoperative versus postoperative radiotherapy, single versus multiple courses of actinomycin D, in the treatment of Wilms’ tumor. Preliminary results of a controlled clinical trial conducted by the International Society of Paediatric Oncology (S.I.O.P). Cancer. 1976;38:647–654. [PubMed: 184913]

56.

Dome JS, Liu T, Krasin M, Lott L, Shearer P, Daw NC, et al. Improved survival for patients with recurrent Wilms’ tumor: the experience at St. Jude Children’s Research Hospital. J Pediatr Hematol Oncol. 2002;24:192–8. [PubMed: 11990305]

57.

Grundy P, Breslow N, Green DM, Sharples K, Evans A, D’Angio GJ. Prognostic factors for children with recurrent Wilms’ tumor: results from the Second and Third National Wilms’ Tumor Study. J Clin Oncol. 1989;7:638–47. [PubMed: 2540289]