Synchronous bilateral Wilms' tumor with liver metastasis.

BACKGROUND: Wilms' tumor (nephroblastoma) is mostly unilateral; however, bilateral Wilms' tumors are seen in about 5-8% of patients. This can be synchronous or metachronous. It is uncommon to get liver metastasis from bilateral Wilms' tumor. CASE PRESENTATION: An 8-year-old male Ugandan presented with a history of abdominal swelling and flank pains for 1 year. There was no history of hematuria. Both ultrasound and computed tomography of the abdomen demonstrated multiple solid lesions in both kidneys and a huge solid mass in segments V, VI, VII and VIII of the liver. Histological examination of renal biopsy specimen was favorable for chemotherapeutic regimens. However, following a multidisciplinary tumor board consensus, a nephron-sparing surgery was deemed unsuitable, and he was managed conservatively with chemotherapy (adriamycin and vincristine) with a palliative intent. CONCLUSIONS: Metastatic bilateral Wilms' tumor has a particularly poor prognosis. There are no clear evidence-based guidelines for the management of this rare presentation. This patient benefited from early palliative care and symptom management.

Heart-sparing volumetric modulated arc therapy for whole lung irradiation.

PURPOSE: Whole lung irradiation (WLI) is indicated for subgroups of patients with lung metastases from Wilms' tumor (nephroblastoma). WLI has traditionally been performed with an anterior/posterior field arrangement with poor potential for heart sparing; thus, new techniques are desirable to achieve a lower dose to the heart. MATERIALS AND METHODS: We utilized volumetric modulated arc therapy (VMAT) for WLI with 18 Gy in a patient with metastatic nephroblastoma. The planning results were compared against a three-dimensional (3D) conformal plan. RESULTS: VMAT resulted in adequate target volume coverage with the prescribed dose. Mean heart dose was 10.2 Gy. The dose to organs at risk (OAR) was generally more favorable with VMAT when compared with a 3D-conformal radiotherapy plan. DISCUSSION: WLI with VMAT provides superior sparing of OARs and especially a considerably lower dose to the heart.

Relapse of Wilms' tumour and detection methods: a retrospective analysis of the 2001 Renal Tumour Study Group-International Society of Paediatric Oncology Wilms' tumour protocol database.

BACKGROUND: Wilms' tumour is the most common renal cancer in childhood and about 15% of patients will relapse. There is scarce evidence about optimal surveillance schedules and methods for detection of tumour relapse after therapy. METHODS: The Renal Tumour Study Group-International Society of Paediatric Oncology (RTSG-SIOP) Wilms' tumour 2001 trial and study is an international, multicentre, prospective registration, biological study with an embedded randomised clinical trial for children with renal tumours aged between 6 months and 18 years. The study covers 243 different centres in 27 countries grouped into five consortia. The current protocol of SIOP surveillance for Wilms' tumour recommends that abdominal ultrasound and chest x-ray should be done every 3 months for the first 2 years after treatment and be repeated every 4-6 months in the third and fourth year and annually in the fifth year. In this retrospective cohort study of the protocol database, we analysed data from participating institutions on timing, anatomical site, and mode of detection of all first relapses of Wilms' tumour. The primary outcomes were how relapse of Wilms' tumour was detected (ie, at or between scheduled surveillance and with or without clinical symptoms, scan modality, and physical examination) and to estimate the number of scans needed to capture one subclinical relapse. The RTSG-SIOP study is registered with Eudra-CT, number 2007-004591-39. FINDINGS: Between June 26, 2001, and May 8, 2015, of 4271 eligible patients in the 2001 RTSG-SIOP Wilms' tumour database, 538 (13%) relapsed. Median follow-up from surgery was 62 months (IQR 32-93). The method used to detect relapse was registered for 410 (76%) of 538 relapses. Planned surveillance imaging captured 289 (70%) of these 410 relapses. The primary imaging modality used to detect relapse was reported for 251 patients, among which relapse was identified by abdominal ultrasound (80 [32%] patients), chest x-ray (78 [31%]), CT scan of the chest (64 [25%]) or abdomen (20 [8%]), and abdominal MRI (nine [4%]). 279 (68%) of 410 relapses were not detectable by physical examination and 261 (64%) patients did not have clinical symptoms at relapse. The estimated number of scans needed to detect one subclinical relapse during the first 2 years after nephrectomy was 112 (95% CI 106-119) and, for 2-5 years after nephrectomy, 500 (416-588). INTERPRETATION: Planned surveillance imaging captured more than two-thirds of predominantly asymptomatic relapses of Wilms' tumours, with most detected by abdominal ultrasound, chest x-ray, or chest CT scan. Beyond 2 years post-nephrectomy, a substantial number of surveillance scans are needed to capture one relapse, which places a burden on families and health-care systems. FUNDING: Great Ormond Street Hospital Children's Charity, the European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment, The Danish Childhood Cancer Foundation, Cancer Research UK, the UK National Cancer Research Network and Children's Cancer and Leukaemia Group, Société Française des Cancers de l'Enfant and Association Leon Berard Enfant Cancéreux and Enfant et Santé, Gesellschaft für Pädiatrische Onkologie und Hämatologie and Deutsche Krebshilfe, Grupo Cooperativo Brasileiro para o Tratamento do Tumor de Wilms and Sociedade Brasileira de Oncologia Pediátrica, the Spanish Society of Pediatric Haematology and Oncology and the Spanish Association Against Cancer, and SIOP-Netherlands.

Short term surgical outcomes of Wilms tumour from a single institute.

Wilms tumour is the commonest solid tumour of childhood in Pakistan. In developed world the long-term outcome of Wilms tumour have significantly improved reaching up to 98% long term survival. We have no National data of prevalence, treatment and survival of this condition in Pakistan. Surgical treatment also varies in various parts of the country. We have studied our patients presenting with a diagnosis of Wilms tumour to our institute from Jan 2014 to April 2016. A total of 42 patients were operated for Wilms tumour. The most common symptoms were abdominal mass (75%), pain (28%) and fever (19%). A total of 48 tumour resections were performed, 45 total nephrectomies and 3 had nephron sparing surgery (NSS). Mean operative time was 225±78.7 minutes. Mean blood loss was 165±223.5ml. Mean size of the tumour was 102±48.4mm and mean weight of the tumour was 433±400.7gm. Ninety percent patients had a favourable histology. Mean high dependency unit (HDU) stay was 1.16±1.2 day and mean hospital stay was 6.89±3.47 days. Complications were observed in 8 patients. Surgery remains a major part of treatment for Wilms tumour.

Outcome of patients with intracranial relapse enrolled on national Wilms Tumor Study Group clinical trials.

BACKGROUND: The occurrence of brain metastases (at diagnosis or at relapse) in patients with Wilms tumor is very rare. METHODS: We retrospectively reviewed the clinical characteristics of patients with Wilms tumor and relapse to the brain enrolled on the National Wilms Tumor Studies (NWTSs) 1-5. RESULTS: Intracranial relapse was documented in 47 patients (0.5%). Of the 45 patients with adequate data, 26 (58%) patients were male. Thirty-eight (84%) patients had favorable histology Wilms tumor. In 30 patients (67%), the appearance of intracranial disease was preceded by relapse at another site. Ten patients did not have any disease-directed therapy. Surgical resection was attempted in 15 patients; gross total resection was achieved in 11 patients. Twenty-nine patients received brain irradiation; the median dose was 3,000 cGy (range 1,080-4,000 cGy). Twenty-seven patients received chemotherapy. The 5-year overall survival from the time of intracranial relapse was 28.7% (95% confidence interval: 14.4-43.1%). Nine patients (all favorable histology Wilms tumor) were alive with a median follow-up from brain relapse of 140 months (range 35-381 months). All nine survivors received radiation therapy, eight received chemotherapy, and four underwent surgery (two gross total resection, two partial resection). The overall survival after brain metastases of the NWTS-5 patients was significantly higher than the overall survival of the NWTS 1-4 patients (P value = 0.029, log-rank test). CONCLUSIONS: Patients with Wilms tumor recurrence involving the brain may have durable survival, particularly those treated in recent years. Multimodality therapy including radiation and chemotherapy should be considered for these patients.

Outcome of Nephroblastoma Treatment According to the SIOP-2001 Strategy at a Single Institution in Argentina.

OBJECTIVE: Wilms tumor (WT) is a disease with a good prognosis. The aim of this study was to evaluate the outcome of patients with WT, treated according to the SIOP-2001 strategy. METHODS: A retrospective analysis of 141 consecutive patients with WT diagnosed at our institution between December 2001 and 2013 was performed. RESULTS: A total of 114 patients, median age 38.8 months (3 to 155 mo), were assessable for analysis. Fine-needle aspiration was initially performed in 88 patients (84.6%). Stage distribution was: I: 33%, II: 9.6%, III: 28%, IV: 14%, V: 14.9%. Six patients were stage III because of tumor spillage. The remaining patients received preoperative chemotherapy. Adjuvant chemotherapy was given without randomization, using vincristine-actinomycin for stage II and vincristine-doxorubicin-actinomycin plus radiotherapy for stage III. After a median follow-up of 52 months, 5-year overall survival and event-free survival were 91% and 85%, respectively. Overall survival according to stage was: I: 96%, II: 99%, III: 88%, IV: 78%, V: 90% (P=0.16). There was no significant difference in event-free survival (P=0.7). Seventy-eight (85.7%) were intermediate-risk and 11 (12%) were high-risk patients. Seventeen patients (14.9%) relapsed within 2 to 99 months (median 29.9 mo). Eight patients (7%) died of progressive disease. There were no treatment-related deaths. CONCLUSIONS: The SIOP-01 protocol proposes a treatment strategy that is feasible in our institution, achieving good results.

Considerations in the Diagnosis and Management of Pediatric Patients With Favorable Histology Wilms Tumor Who Present With Only Pulmonary Nodules.

More than 70% of children with stage IV, favorable histology (FH) Wilms tumor will be relapse-free survivors 16 years after diagnosis. Successful treatment generally includes whole lung radiation therapy and doxorubicin. Such therapy is associated with adverse, long-term effects, including impaired pulmonary function, congestive heart failure, and second malignant neoplasms, especially breast cancer. Cooperative groups have adopted a risk-based approach to the treatment of these patients. It is important to recall the good overall prognosis for this group before recommendations for intensification are made based on preliminary data and in the absence of histological confirmation of persistent malignant disease.

Visual Diagnosis: New Lung Nodules in a 3-year-old Girl with Wilms Tumor.

The most significant oncologic concern with finding new pulmonary nodules on imaging in a pediatric patient who has anaplastic Wilms tumor is progressive disease with new pulmonary metastases. This case emphasizes the importance of employing a creative clinical differential diagnosis, even for patients with known underlying oncologic disease.

Secondary Hemophagocytic Lymphohistiocytosis in a Patient With Favorable Histology Wilms Tumor.

Secondary hemophagocytic lymphohistiocytosis (HLH) is most commonly associated with malignancy, infection, or an underlying autoimmune disorder. Malignancy-associated hemophagocytic syndrome is responsible for most secondary HLH cases, but it has not been well described in children. We present a case of a 4-year-old female with favorable histology of Wilms tumor who developed secondary HLH after unsuccessful resection of the tumor and initiation of chemotherapy.

The expression of IL-6 and STAT3 might predict progression and unfavorable prognosis in Wilms' tumor.

PURPOSE: To investigate the expression profiles of IL-6 and STAT3 in Wilms' tumor (WT) and their relationship with disease progression. METHODS: Immunohistochemistry was used to examine IL-6 and STAT3 expression in 58 primary tumors and 18 invasive/metastatic ones. RESULTS: Positive expression rate of IL-6/STAT3 was 39.7% (23/58)/29.3% (17/58) in primary WT tissues, while 61.1% (11/18)/33.3% (6/18) in associated invasive/metastatic tissues. The expression rate of IL-6 and STAT3 was higher in primary WT tumors of invasive/metastatic group than that of non-invasive/metastatic group (P=0.033; P=0.012). There was a positive correlation between IL-6 and STAT3 expression in 76 WT tissues (P<0.001, r=0.444). The expression of IL-6 /STAT3 between primary WT and matched invasive/metastatic tissues was concordance (P=0.727; P=0.99). IL-6 expression status and histopathological type were associated with disease-free survival (DFS) and overall survival (OS) (P<0.05), while STAT3 was only correlated with DFS (P<0.05). CONCLUSIONS: IL-6 and STAT3 expression in WT might be correlated with progression and predict unfavorable prognosis, highlighting a new therapy target for invasive or metastatic WTs.

Surgery for metastatic disease.

PURPOSE OF REVIEW: Outcomes for children with cancer have steadily improved and the long-term survival for most early-stage childhood malignancies is now greater than 90%. On the contrary, the prognosis for children with metastatic cancer, though significantly improved from a generation ago, is generally still very disappointing. Surgery continues to play a role in the increasingly aggressive treatment of children with metastatic disease with the ultimate goal of prolonging survival and improving quality of life. RECENT FINDINGS: Most childhood tumors are relatively rare and are therefore studied using a multi-institutional cooperative group model that standardizes protocols and pools resources and data, accounting for the remarkable progress that has been made in the care of children with cancer. In some cases, this has also allowed us to recognize the utility of certain surgical therapies and the need to further study others. SUMMARY: Modern surgery and critical care allow us to consider offering children with metastatic disease more aggressive surgical options in circumstances where the data suggest the potential for long-term survival. In situations where data are lacking, children might be offered a surgical option as part of an ongoing trial.

Understanding the principles in management of Wilms' tumour: can imaging assist in patient selection?

The management of Wilms' tumour has evolved through thorough systematic research, predominantly lead by two groups: the Wilms' Tumour Study Committee of the International Society of Paediatric Oncology (SIOP) and National Wilms' Tumor Study Group (NWTSG) of North America. These two groups differ in their approach: SIOP advocates initial chemotherapy of 4-6 weeks followed by surgery, whereas the NWTSG advocates upfront surgery, with certain exceptions. This review briefly discusses the principles, and pros and cons of each approach. Both the treatment approaches have equivalent outcomes (in the form of event-free survival and overall survival), when compared stage-wise. With this knowledge, modern imaging can be used for individualizing treatment in anticipation of minimizing complications. The review identifies critical imaging features and discusses the reliability of imaging based on current reports in the literature.

Bilateral Wilms' tumour in a developing country: a descriptive study.

PURPOSE: To present our experience of 20 children with bilateral Wilms' tumour seen in a resource-challenged environment over a 10-year period. METHOD: All patients with a diagnosis of bilateral synchronous Wilms' tumour were identified and recruited. RESULTS: Study patients represented 11 % of a cohort of 177 new patients with Wilms' tumour seen over the same period. Three patients had a syndromic predisposition to Wilms' tumour. Metastatic disease was seen at presentation in four patients (20 %) and three children presented with unilateral tumour rupture. One patient presented with paraplegia and one with obstruction of the duodenum. All children received neoadjuvant chemotherapy. One HIV-infected child died of IRIS after neoadjuvant treatment, but before surgery. One child died of progressive disease after unilateral nephrectomy. Nephron-sparing surgery was performed in 22 kidneys and 15 kidneys were removed in toto. Following enucleation of tumours, three children had positive margins. Discordant histopathology was seen in 53 % of patients. Overall survival at 2 years is 85 %. CONCLUSION: Despite significant co-morbidity and advanced disease, bilateral Wilms' tumour is a treatable disease in a resource-constrained environment.

Chronic kidney disease in children with unilateral renal tumor.

PURPOSE: In patients who have undergone nephrectomy lower stage chronic kidney disease may develop, which is an independent risk factor for cardiovascular disease and overall mortality. We investigated whether the prevalence of lower stage chronic kidney disease is related to the amount of renal parenchyma excised in children with unilateral renal tumor. MATERIALS AND METHODS: A total of 15 patients treated with nephrectomy and 10 treated with nephron sparing surgery were enrolled at a single academic center. The Kidney Disease Outcomes Quality Initiative guidelines were used to classify patients by chronic kidney disease stage based on estimated glomerular filtration rate values. The Modification of Diet in Renal Disease study equation and Schwartz equation were used in patients older and younger than 17 years, respectively. RESULTS: At a mean followup of more than 12 years 8 patients who had undergone nephrectomy and 1 treated with bilateral nephron sparing surgery presented with stage II chronic kidney disease (estimated glomerular filtration rate 60 to 89 ml/min/1.73 m(2)). Sequential measurements from diagnosis to 12 to 17 years postoperatively showed that stage II chronic kidney disease in patients who had undergone nephrectomy manifested as a negligible postoperative increase in mean ± SD estimated glomerular filtration rate (75.7 ± 25.5 vs 79.4 ± 3.9 ml/min/1.73 m(2), p = 0.6). Five of the 8 patients presented with stage II chronic kidney disease even before nephrectomy. The other 7 patients who had undergone nephrectomy and those treated with nephron sparing surgery presented with a significant postoperative increase in mean ± SD estimated glomerular filtration rate (81.1 ± 24 vs 102.3 ± 3 ml/min/1.73 m(2), p = 0.02, and 88.7 ± 2 vs 107.4 ± 14 ml/min/1.73 m(2), p = 0.005, respectively). CONCLUSIONS: A subset of children with unilateral renal tumor presents before and/or after nephrectomy, and not after nephron sparing surgery, with stage II chronic kidney disease, probably due to a reduced renal reserve capacity. Whether patients with preoperative renal dysfunction may benefit from nephron sparing surgery should be studied in a cooperative clinical trial setting.

Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and -5: a report from the Children's Oncology Group.

BACKGROUND: Metastatic lung disease in Wilms tumor (WT) patients was traditionally identified by chest radiograph (CXR). It is unclear whether patients with small lesions, detectable only by computed tomography ("CT-only" lesions), require the more intensive therapy, including doxorubicin and lung irradiation, given to patients with metastases detectable by CXR. PROCEDURES: This study involved 417 patients with favorable histology WT and isolated lung metastases (detected by CXR or CT) who were registered on National Wilms tumor Study (NWTS)-4 or -5. Outcomes by method of detection (CXR vs. CT-only), use of lung radiation, and 2- or 3-drug chemotherapy (dactinomycin and vincristine ± doxorubicin) were determined and compared using the log-rank test. RESULTS: There were 231 patients with lung lesions detected by CXR and 186 by CT-only. Of the patients with CT-only nodules, 37 received only 2 drugs and 101 did not receive lung radiation. Five-year event-free survival (EFS) was greater for patients receiving three drugs (including doxorubicin) with or without lung radiation than for those receiving two drugs (80% vs. 56%; P = 0.004). There was no difference seen in 5-year overall survival (OS) between the 3- and 2-drug subsets (87% vs. 86%; P = 0.91). There were no significant differences in EFS (82% vs. 72%; P = 0.13) or OS (91% vs. 83%; P = 0.46) for patients with CT-only nodules whether they received lung radiation or not. CONCLUSIONS: Our results suggest that patients with CT-only lung lesions may have improved EFS but not OS from the addition of doxorubicin but do not appear to benefit from pulmonary radiation.

Favorable response of heavily treated Wilms' tumor to paclitaxel and carboplatin.

BACKGROUND: Heavily treated Wilms' tumor responding to the combination of paclitaxel and carboplatin has not yet been reported. CASE REPORT: A 17-year-old man presented with hematuria. He received a diagnosis of Wilms' tumor with multiple lung metastases and was treated with preoperative chemotherapy including vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he suffered from 4 relapses and has been treated with multiple anticancer agents including high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Finally, the disease progressed due to peritoneal and pleural metastases. With opioid administration for left shoulder pain due to pleural metastasis, he received combination chemotherapy with carboplatin (area under the curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a partial response with mild toxicity. He received 7 cycles of the chemotherapy and the time to progression was 200 days. CONCLUSION: In a refractory case after intensive treatments, we succeeded to control the disease for a while.

Tumor biology influences the prognosis of nephroblastoma patients with primary pulmonary metastases: results from SIOP 93-01/GPOH and SIOP 2001/GPOH.

OBJECTIVE: To analyze the outcome of Wilms' tumor patients with primary lung metastases. SUMMARY BACKGROUND DATA: Radiotherapy and/or surgery are used for local control of primary pulmonary Wilms' tumor metastases. A widely accepted treatment standardization is still lacking. METHODS: Data for 210 patients with Wilms' tumor and primary lung metastases from the collaborative multicenter trials SIOP 93-01/GPOH and SIOP 2001/GPOH of the German Society of Pediatric Oncology and Hematology were reviewed. Analyses included patient data, tumor characteristics, local treatment, outcome and possible prognostic factors. RESULTS: Five-year overall survival (OS) was 83.3% and 5-year event free survival (EFS) was 72.3% for all children. Survival was significantly poorer in children with high risk primary tumor histology (OS 44.4%) compared to low risk (OS 100.0%) and intermediate risk histology (OS 89.2%, P < 0.001). Within the high risk group, tumors of the blastemal subtype (OS 56.5%) were associated with a significantly better outcome than those presenting with diffuse anaplasia (OS 22.2%, P = 0.02). Further, prognostic markers were lacking response to chemotherapy (P = 0.011), persistence of metastases after local treatment (P = 0.007), and vitality of metastases (P = 0.01). CONCLUSIONS: The prognosis of children with primary Wilms' tumor lung metastases mainly depends on the biology of primary tumors and metastases and is excellent with adequate treatment. Pulmonary metastasectomy is indicated if complete remission can be achieved to avoid lung irradiation. In the future a standardized local approach to nonresponding lung metastases (metastasectomy, irradiation, or both) will have to be prospectively evaluated regarding outcome, acute toxicity, and late effects.

The first case of primary testicular germ cell tumor containing nephroblastoma as the only one non-germ cell component.

Adult extrarenal nephroblastomas (Wilms' tumor) are extremely rare tumors. They show a higher incidence of non-seminomatous elements and these so-called 'teratoid' Wilms' tumors are suggested to be of germ cell origin. To date, however, the number of reported cases with gonadal teratoma containing nephroblastoma is very low, and due to this reason, there are no standardized criteria for the categorization and treatment of these lesions. To our knowledge, the first case of nephroblastoma arising in a non-atrophic testis has been reported and it is associated with a teratoma as morphologically identifiable germ cell tumor and rhabdomyosarcoma as a second non-germ cell element. We report the second case of an adult nephroblastoma that arose within the primary testicular teratoma in a non-atrophic testis. Teratoma and nephroblastoma within the same testis may have an important point to clarify the developmental mechanism in nephroblastomatous differentiation of germ cell tumors.