Evaluation of renal function after successful treatment for unilateral,non‐syndromic wilms tumor

Impaired renal function may occur in experimental animals following surgical removal of most functioning renal tissue (“hyperfiltration injury”). Although end‐stage renal disease is uncommon among long‐term survivors of unilateral, non‐syndromic Wilms tumor, concern has been expressed that there may be an increased risk of less serious, but progressive, renal function impairment among these individuals. The recent development of equations for estimating glomerular filtration rate (eGFR) has facilitated the study of renal function in Wilms tumor survivors. However, the estimating equations were developed to categorize individuals with chronic kidney disease and have significant limitations with regard to the accuracy of individual GFR estimates. These limitations must be considered when utilizing the estimating equations in cross‐sectional or longitudinal evaluations of renal function in cohorts of patients who have been treated successfully for Wilms tumor or other childhood cancers. Pediatr Blood Cancer 2013;60:1929–1935. © 2013 Wiley Periodicals, Inc.     

Perirenal hemorrhage as first presentation of Wilms tumor

Wilms tumor typically presents as an abdominal mass, though occasionally patients present with other manifestations. We report a case of a child presenting with a perirenal hemorrhage and an initially occult Wilms tumor, found only on subsequent renal arteriography. Symptoms in this patient were caused by the presence of perirenal and subcapsular hemorrhage rather than the tumor itself. Despite an unusual presentation, we need to consider underlying neoplasia in children with renal hemorrhage and the absence of a history of trauma. Follow-up studies might help clarify initial negative imaging results.     

Characterization of a WiT49 cell line derived orthotopic model of Wilms tumor

Wilms tumor is the most common malignant renal tumor in children. However, to date no Wilms tumor mouse model is available due to the lack of Wilms tumor cell lines. Herein for the first time we report an orthotopic xenograft mouse model utilizing the recently described Wilms tumor cell line WiT49. It has a high tumor occurrence rate (85%) without metastasis. Hematoxylin and eosin staining showed it is subcapsular in location and mainly biphasic with stromal and epithelial components while blastemal component is unappreciable. This model provides the prerequisite for the screening and development of new anti‐tumor agents for Wilms tumor. Pediatr Blood Cancer 2010;54:316–318. © 2009 Wiley‐Liss, Inc.     

Long‐term remission of bilateral Wilms tumors that developed from premature separation of chromatids/mosaic variegated aneuploidy syndrome due to bilateral nephrectomy and peritoneal dialysis

We report a 38‐month‐old Japanese male with premature chromatid separation/mosaic variegated aneuploidy syndrome bearing biallelic BUB1B germline mutations who suffered from bilateral Wilms tumor. After right nephrectomy, dactinomycin monotherapy was administered for the left Wilms tumor; however, severe adverse reaction prevented the patient from receiving further chemotherapy. Left nephrectomy was then performed without postoperative chemotherapy. The patient survived for 15 months after bilateral nephrectomy without peritoneal relapse, metastasis of Wilms tumor, or the occurrence of rhabdomyosarcoma and maintained a good quality of life while receiving peritoneal dialysis at home.     

Renal function after tandem high-dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor

Lee SH, Paik KH, Sung KW, Son MH, Yoo KH, Koo HH, Kim JY, Cho EJ. Renal function after tandem high‐dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor. Pediatr Transplantation 2011: 15: 855–860. © 2011 John Wiley & Sons A/S. Abstract: Despite increasing evidence that tandem HDCT and autoSCT might improve the survival of patients with high‐risk solid tumors, patients with Wilms tumor may be at high risk of acute and chronic renal impairment during and after tandem HDCT/autoSCT because they usually have a single kidney. We investigated the feasibility of tandem HDCT/autoSCT in patients with Wilms tumor, focusing on renal function. Six patients with relapsed/progressed Wilms tumor were assigned to undergo tandem HDCT/autoSCT. One patient developed transient ARF during the first HDCT/autoSCT. All other patients underwent the second HDCT/autoSCT as scheduled. Acute renal dysfunction during the second HDCT/autoSCT was transient and manageable. Indicators of glomerular function such as creatinine clearance, serum creatinine, and albumin excretion were in the normal range at three yr after tandem HDCT/autoSCT. Subclinical tubular dysfunctions, such as increased excretion of β‐N‐acetylglucosaminidase and β2‐microglobulin, were identified at one and three yr after tandem HDCT/autoSCT; however, no patient required treatment for these conditions. These results are helpful to consider tandem HDCT/autoSCT as a treatment option in patients with Wilms tumor. Longer duration of follow‐up and close monitoring of tubular function are required if tandem HDCT/autoSCT is indicated in patients with Wilms tumor.     

A case report of simultaneous occurrence of wilms tumor and acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most and Wilms tumor is the sixth most common malignancy in childhood. Genetic changes in WT1 or WT2 in Wilms tumor and a wide range of chromosomal mutations are reported in ALL that may predispose them to other congenital anomalies especially in Wilms tumor patients. Hospitalized patient was a 3-year-old girl with high-grade fever, petechia, and solid abdominal mass. The patient had anemia, thrombocytopenia, and leukocytosis in her initial homogram, and a large renal mass originated from left kidney in abdominal imagings. Bone marrow aspiration revealed ALL, and simultaneous kidney biopsy uncovered her Wilms tumor. Leukemia and Wilms tumor are 2 independent malignancies but occurred together in this patient. It is reasonable to investigate cellular and genetic relation of these 2 independent malignancies.     

Management of Wilms tumors in Drash and Frasier syndromes

Background

Children with WT1 gene‐related disorders such as Denys–Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end‐stage renal disease. We investigated whether Wilms tumors in these patients displayed a specific phenotype or behavior and whether nephron‐sparing surgery was beneficial.

Procedure

We retrospectively studied all patients with DDS, FS, or other WT1 mutations treated at our institutions between 1980 and 2007.

Results

We identified 20 patients, of whom 18 had benign or malignant tumors. Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5 (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had metastases. According to the International Society of Pediatric Oncology Working Classification, there were 19 intermediate‐risk tumors and one high‐risk tumor; no tumor was anaplastic. In patients with nephropathy who underwent unilateral nephrectomy for Wilms tumor or nephron‐sparing surgery for bilateral Wilms tumor, mean time to dialysis was 11 or 9 months, respectively. Other tumors included three gonadoblastomas (in two patients), one retroperitoneal soft‐tissue tumor, and one transitional cell papilloma of the bladder. Two patients, both with stage I Wilms tumor, died from end‐stage renal disease‐related complications. The median follow‐up time for the 18 survivors was 136 months (range, 17–224 months).

Conclusion

Most Wilms tumors in children with WT1‐related disorders were early‐stage and intermediate‐risk tumors, with a young age at diagnosis. In patients without end‐stage renal disease, nephron‐sparing surgery should be considered for delaying the onset of renal failure. Pediatr Blood Cancer 2009;52:55–59. © 2008 Wiley‐Liss, Inc.     

Wilms tumor in Africa: A systematic review of management challenges and outcome in two decades (2000‐2019)

We performed a systematic review to highlight trends in management and outcome of Wilms tumor (WT) in Africa in the past two decades (2000‐2019). Twenty‐seven studies involving 2250 patients were analyzed. Overall, barring regional variations, 57.7% of the cases presented with advanced disease, 57.3% completed planned treatment, and survival was 56.5%. The publications in the two decades did not show significant differences in proportions of cases with advanced disease, completion of treatment rate, and cases lost to follow up. However, significantly more cases received preoperative chemotherapy, and survival improved in the last decade (2010‐2019) compared to the earlier decade (2000‐2009). Survival of WT in Africa might have improved in the last decade, but challenges of delayed presentation and abandonment of treatment have persisted. Measures that will encourage early access to expert care as well as improve on treatment compliance may further improve survival of WT in Africa.     

Introduction to the genetics of primary renal tumors in children

Wilms tumor can be explained only partially by the “two hit” model that was originally developed for retinoblastoma. Heterogeneity of two kinds, operates. The first is that four other primary tumors are regularly observed in children, and the second is that Wilms tumor itself appears to represent more than one genetic entity. All five of these primary renal tumors arise from primary or secondary mesenchyme, renal blastema, or renal epithelium. Mesoblastic nephroma, and possibly clear cell sarcoma, may have some genetic affinity with Wilms tumor, but rhabdoid tumor of the kidney and renal carcinoma do not. At least three different genes seem to be important in the origin of Wilms tumor. One, WT1, whose mutations may be associated with aniridia, may follow the “two hit” model in that there are cases in which both copies of the gene are defective or lost, as expected for a tumor suppressor gene. A second gene, which is associated with Beckwith-Wiedemann Syndrome (BWS) and which has not been cloned, appears to be imprinted in females, and may have an oncogene function. It is evidently activated by gain of a paternal allele or by loss of the inactive, but possibly trans-sensing, maternal allele. Activation of the insulin-like growth factor II gene may be a final common pathway for mutation in both WT1 and BWS. A third gene is unlinked to either of the other two, but its location and function are unknown. It shares with WT1 specificity for Wilms tumor, which is not true of the BWS gene. © 1993 Wiley-Liss, Inc.     

Diagnosis of Beckwith–Wiedemann syndrome in children presenting with Wilms tumor

Beckwith–Wiedemann syndrome (BWS) is a genetic syndrome associated with overgrowth and cancer predisposition, including predisposition to Wilms tumor (WT). Patients with BWS and BWS spectrum are screened from birth to age 7 years for BWS‐associated cancers. However, in some cases a BWS‐associated cancer may be the first recognized manifestation of the syndrome. We describe 12 patients diagnosed with BWS after presenting with a WT. We discuss the features of BWS in these patients and hypothesize that earlier detection of BWS by attention to its subtler manifestations could lead to earlier detection of children at risk for associated malignancies.     

Late relapsing Wilms tumor with rhabdomyomatous differentiation

The authors report a patient with abdominally relapsed Wilms tumor with rhabdomyomatous differentiation leading to renal failure and death 9 years after the initial diagnosis. The patient was treated with intensive chemotherapy because of inoperable tumor but no response was obtained. The prognosis of children with Wilms tumor relapsed in abdomen and in previously irradiated fields is poor and intensive chemotherapy protocols for differentiated tumors after chemotherapy will increase the risk of complications without obvious benefit. Pediatr Blood Cancer 2009;52:675–677. © 2008 Wiley‐Liss, Inc.     

Survivin Caspase-3 mRNA在肾母细胞瘤中的表达及意义

目的：在大多数肿瘤组织中都发现了Survivin异常高表达现象,它直接抑制Caspase-3,这说明Survivin在肿瘤发生中具有重要作用。本文的目的在于探讨Survivin、Caspase-3表达与肾母细胞瘤发生发展的关系。方法：应用RT-PCR技术检测Survivin、Caspase-3 mRNA在48例肾母细胞瘤、24例癌旁组织标本中的表达。结果：48例肾母细胞瘤组织中Survivin阳性表达率为 72.9%(35/48),在24例肾母细胞瘤癌旁组织中未检测到Survivin的表达,肾母细胞瘤组织与癌旁组织之间Survivin表达阳性率差异有非常显著性(P<0.01);48例肾母细胞瘤组织中Caspase-3阳性表达率为 8.3%(4/48),在24例肾母细胞瘤癌旁组织中Caspase-3阳性表达率为 45.8%(11/24),肾母细胞瘤组织与癌旁组织之间Caspase-3表达阳性率差异有显著性(P<0.05)。结论：Survivin在肾母细胞瘤组织中高度表达和Caspase-3在肾母细胞瘤中低表达可能与肾母细胞瘤的发生发展有关,与预后的关系有待进一步的探讨。［中国当代儿科杂志,2004, 6(5): 381-384]     

Maintenance chemotherapy to reduce the risk of a metachronous Wilms tumor in children with bilateral nephroblastomatosis

From 2009 to 2018, 10 consecutive patients with Wilms tumors and bilateral nephroblastomatosis, who had completed standard therapy, were provided a maintenance chemotherapy regimen consisting of vincristine and dactinomycin every 3 months for 12 months in order to prevent an early metachronous Wilms tumor. One patient (10%) with Beckwith‐Wiedemann syndrome developed a new tumor, without anaplasia. There were no significant toxicities reported during maintenance. All patients are currently alive with no evidence of disease. Further investigations are recommended to determine the utility of this approach.     

Successful pulmonary artery embolectomy in a patient with a saddle Wilms tumor embolus

Denys-Drash syndrome is a genetic disorder characterized by ambiguous genitalia, cryptorchidism, nephrotic syndrome, and a high predilection for Wilms tumor with intravascular invasion. We report a 5-year-old male with Denys-Drash syndrome who rapidly developed Wilms tumor with vascular invasion, subsequent saddle tumor embolus, and required emergent embolectomy. This case illustrates the rapid emergence of Wilms tumor in a patient with Denys-Drash syndrome and the importance of considering embolectomy over thrombolytic therapy for PE in this population, given a high likelihood of tumor embolus.     

Wilms tumor in a child with trisomy 13

A 4-year-old black boy with trisomy 13, a history of frequent urinary tract infections, and a horseshoe kidney with painless gross hematuria was examined. An abdominal mass was detected and surgically resected. Examination of the surgical specimen revealed a Wilms tumor. Given the concurrence of trisomy 13 and Wilms tumor and the presence of another such case in the literature, there may be just cause to suspect a locus on chromosome 13 that affects the probability of developing Wilms tumor. Given the increasingly longer survival of patients with trisomy 13, clinicians may need to be aware of the possibility of renal malignant disease in this population of patients.     

Wilms’ Tumor: A 24-year Retrospective Study from a Single Center

Medical records of 71 children with Wilms’ tumor at Sisli Etfal Education and Research Hospital between 1990 and 2014 were reviewed. Mean age at diagnosis was 3.11 years (2 days–7 years). Male to female ratio was M/F = 6/10. The incidence of associated anomaly was 16.9%. Clinical manifestations included abdominal mass (89%), hematuria (30%), hypertansion (25%), abdominal pain (15%), fever (5%), restlessness (2%), weight loss (2%), varicocele (1%). Ultrasound (USG) was the most often initial study in a child presenting with abdominal mass. Doppler USG was also made to evaluate the inferior vena cava (IVC) for the presence of tumor extension in children with renal mass. The left kidney was affected in 33 patients (46.5%), the right was affected in 31 patients (43.7%). Two patients was extrarenal (2.8%). And 5 patients (7.04%) were bilateral on the presentation. Preoperative chemotheraphy was done in 14 cases. In 63 patients with unilateral Wilm tm, unilateral radical nefrectomy is performed. In one patient with solitary kidney, nephron sparing surgery (NSS) is performed. In 3 patients with bilateral tm NSS is performed and in 2 patients with bilateral Wilms’ tm NSS is performed in one side and nefrectomy on the other side. Out of 71 Wilms tumor (WT) patients, 17 of them has been out of our follow. And 4 of them are died. Ten of them has metastases. Forty children are under follow with no metastases. Patients with WT needs a multimodal, multidisiplinary treatment with the cooperation of pediatric oncologist and pediatric surgeon and needs close follow-up.     

Management of pediatric renal tumor: Past and future trials of the Japan Wilms Tumor Study Group

The Japan Wilms Tumor Study group (JWiTS) was founded in 1996 to improve outcomes for children with renal tumor in Japan, and a nationwide multicenter cooperative study was initiated thereafter. JWiTS‐1 (1996–2005) was analyzed, and JWiTS‐2 (2005–2014) is now under analysis; the following problems have been identified and used to decide future study protocol: (i) there has been a decline in survival rate for patients with rhabdoid tumor of the kidney (RTK) and new treatment strategies are required; (ii) the survival rate for bilateral Wilms tumors (BWT) has improved, but results for renal preservation are unsatisfactory; (iii) the prognosis of stage IV favorable nephroblastoma is very good, suggesting that the current protocols provide overtreatment, particularly for patients with lung metastasis; and (iv) no effective biological risk factors exist for predicting the outcome of Wilms tumor, and a study of the genetic changes of these tumors is necessary to determine biological markers for use in risk classification. To solve these issues, the development of a new risk classification of pediatric renal tumors is required. In addition, different study protocols should be developed according to the risk‐based classification of the patients. Further, a new study protocol for BWT began in 2015, and new study protocols are being prepared for RTK, and for Wilms tumor with lung metastasis. In addition, an analysis of biological markers with regard to risk classification is to be performed. Furthermore, to create new protocols for patients with rare renal tumors, international collaboration with Children's Oncology Group and International Society of Pediatric Oncology is necessary.     

Post‐transplant lymphoproliferative disorder resembling Wilms tumor. Diagnostic dilemma: Renal biopsy or nephrectomy?

Cheng E, Fustino N, Klesse L, Chinnakotla S, Sanghavi R. Post‐transplant lymphoproliferative disorder resembling Wilms tumor. Diagnostic dilemma: Renal biopsy or nephrectomy?
Pediatr Transplantation 2011: 15: E187–E191. © 2010 John Wiley & Sons A/S. Abstract: Post‐transplant lymphoproliferative disorder is a life‐threatening neoplasm that can occur after orthotopic liver transplant. We report a 14‐month‐old female status‐post OLT with an atypical presentation of PTLD as a solitary renal mass. At eight‐wk post‐transplant, she presented with elevated transaminases, CMV counts (73 000 copies/mL), and EBV counts (35 000 copies/mL). CT scan revealed a solid heterogeneously enhancing right renal mass measuring 2.6 × 2.4 × 3.3 cm. The radiological diagnosis was Wilms tumor, although PTLD could not be excluded. Complete resection of a Wilms tumor is potentially curative. A needle biopsy would upstage the malignancy and result in radiochemotherapy that is deleterious to a liver graft. The mass was not amenable to partial nephrectomy. A total nephrectomy, given life‐long nephrotoxic immunosuppressants, was an unfavorable option. Thus, needle biopsy was performed. Histology confirmed monoclonal, EBV‐associated PTLD and diffuse large B‐cell lymphoma. Her therapy included immunosuppression reduction, cyclophosphamide, steroids, and anti‐CD20 monoclonal antibody. Concomitantly, she received Cytogam and gancyclovir. Complete remission was achieved three months after chemotherapy. This case illustrates that young age, CMV infection, and EBV infection are strong risk factors for PTLD. With such risk factors present, any mass or lesion in a solid organ transplant patient should be considered PTLD until proven otherwise.     

Severe polyuria and polydipsia in hyponatremic‐hypertensive syndrome associated with Wilms tumor

The combination of hyponatremia and renovascular hypertension is known as hyponatremic‐hypertensive syndrome (HHS) and so rarely described in children but associated with various kinds of occlusions of the renal artery. We describe two children who presented HHS with severe hypokalemia, polyuria, and polydipsia associated with Wilms tumor, which required treatment with an angiotensin‐converting enzyme inhibitor before nephrectomy. All HHS signs and symptoms resolved only following surgical resection of the tumor, allowing chemotherapy to be given. Pediatr Blood Cancer. 2010;55:566–569. © 2010 Wiley‐Liss, Inc.     

Treatment of Wilms tumor according to SIOP 9 protocol in Casablanca, Morocco

BACKGROUND: Childhood Wilms tumor represents one of the challenge for pediatric oncologists in developing countries. We report the characteristics and treatment results of patients with Wilms tumor according to SIOP 9 protocol in Morocco. PROCEDURE: From January 1989 to December 2000, 86 children with Wilms tumor were admitted. The diagnosis was based on physical exam and abdominal ultrasound. The metastatic work-up was based on abdominal ultrasound and chest X-ray. RESULTS: The mean age was 36 months (3-120 months). The sex-ratio was 1. Abdominal mass was the main symptom at presentation (84 cases). There were 13 metastatic cases. Treatment applied was according to SIOP 9 Protocol without randomization. Local deases was present in 75 patients with stage I in 38 cases (50%), IIN0 in 4 cases (6%), IIN1 in 9 cases, and III in 24 cases (44%). The distribution of pathologic groups was: favorable in 4 cases, standard in 69 cases, and unfavorable anaplastic type in 2 cases. Sixty-nine patients were evaluable for therapeutic evaluation. Other patients were lost to follow-up. Three patients died of treatment related toxicity and 13 patients relapsed. With a median follow-up of 70 months, the 5-year EFS and 5 years overall survival for evaluable patients are 77.4% and 79%, respectively while the 5-year EFS for all patients was 56%. CONCLUSION: These results are encouraging for a developing country but special efforts should be done to reduce the rate of abandonment.