Relapsed Wilms' tumor in pediatric patients: challenges in low- to middle-income countries-a single-center experience.

BACKGROUND: Wilms' tumor (WT) affects one in 10,000 children and accounts for 5% of all childhood cancers. Although the overall relapse rate for children with WT has decreased to less than 15 %, the overall survival for patients with recurrent disease remains poor at approximately 50 %. The aim of the study to evaluate the outcome of relapsed Wilms' tumor pediatric patients treated at the National Cancer Institute (NCI), Egypt, between January 2008 and December 2015. RESULTS: One hundred thirty (130) patients diagnosed with WT during the study period, thirty (23%) patients had relapsed. The median follow up period was 22.3 months (range 3.6-140 months). The Overall Survival (OS) was 30.9% while the event-free survival (EFS) was 29.8% at a 5-year follow up period. Median time from diagnosis to relapse was 14.4 months. A second complete remission was attained in 18/30 patients (60%). The outcome of the 30 patients; 11 are alive and 19 had died. Three factors in our univariate analysis were prognostically significant for survival after relapse. The first was radiotherapy given after relapse (p = 0.012). The 5-year EFS and OS for the group that received radiotherapy were 41.9% versus 16.7% and 11.1% respectively for those that did not. The second was the state of lymph nodes among patients with local stage III (p = 0.004). Lastly, when risk stratification has been applied retrospectively on our study group, it proved to be statistically significant (p = 0.029). CONCLUSION: Among relapsed pediatric WT, radiotherapy improved survival at the time of relapse and local stage III with positive lymph nodes had the worst survival among other stage III patients.

Volumetric assessment of unaffected parenchyma and Wilms' tumours: analysis of response to chemotherapy and surgery using a semi-automated segmentation algorithm in children with renal neoplasms.

OBJECTIVE: To present our proof of concept with semi-automatic image recognition/segmentation technology for calculation of tumour/parenchyma volume. METHODS: We reviewed Wilms' tumours (WTs) between 2000 and 2018, capturing computed tomography images at baseline, after neoadjuvant chemotherapy (NaC) and postoperatively. Images were uploaded into MATLAB-3-D volumetric image processing software. The program was trained by two clinicians who supervised the demarcation of tumour and parenchyma, followed by automatic recognition and delineation of tumour margins on serial imaging, and differentiation from uninvolved renal parenchyma. Volume was automatically calculated for both. RESULTS: During the study period, 98 patients were identified. Of these, based on image quality and availability, 32 (38 affected moieties) were selected. Most patients (65%) were girls, diagnosed at age 50 ± 37 months of age. NaC was employed in 64% of patients. Surgical management included 27 radical and 11 partial nephrectomies. Automated volume assessment demonstrated objective response to NaC for unilateral and bilateral tumours (68 ± 20% and 53 ± 39%, respectively), as well as preservation on uninvolved parenchyma with partial nephrectomy (70 ± 46 cm3 at presentation to 57 ± 41 cm3 post-surgery). CONCLUSION: Volumetric analysis is feasible and allows objective assessment of tumour and parenchyma volume in response to chemotherapy and surgery. Our data show changes after therapy that may be otherwise difficult to quantify. Use of such technology may improve surgical planning and quantification of response to treatment, as well as serving as a tool to predict renal reserve and long-term changes in renal function.

Beyond Point-of-Care Ultrasound: Bedside Ultrasound in the Diagnosis of Soft Tissue Mass.

Cancer is diagnosed in 1 in 7000 children annually. Here, we report 6 cases of a mass identified by the author, a novice sonographer in a pediatric emergency medicine fellowship, using point-of-care ultrasound, from January of 2017 to May of 2018. Identification of these cases early in presentation allowed for earlier involvement of the relevant specialist and shorter time to diagnosis and treatment, and might be expected to increase parent satisfaction as well.

Fifteen-minute consultation: Assessment, surveillance and management of hemihypertrophy.

This article aims to provide a structured and concise guide for the general paediatrician managing a child with hemihypertrophy. Hemihypertrophy is a relatively uncommon condition. The significance is that a proportion of those affected are at risk of developing malignancies in childhood. For these children regular surveillance is required. We have outlined how one might assess and investigate a child presenting with hemihypertrophy. We have also formulated a practicable surveillance strategy which is in line with the current Royal College of Paediatrics and Child Health (RCPCH) guideline 'Wilms' tumour surveillance in at-risk children'.

Assessment of promoter methylation and expression of SIX2 as a diagnostic and prognostic biomarker in Wilms' tumor.

This study was designed to evaluate the utility of expression and DNA methylation patterns of the sine oculis homeobox homolog 2 (SIX2) gene in early diagnosis and prognosis of Wilms' tumor (WT). Methylation-specific polymerase chain reaction (MSP), real-time quantitative polymerase chain reaction (qRT-PCR), receiver operating characteristic (ROC), and survival curve analyses were utilized to measure the expression and DNA methylation patterns of SIX2 in a cohort of WT tissues, with a view to assessing their diagnostic and prognostic value. Relative expression of SIX2 mRNA was higher, while the promoter methylation level was lower in the WT than control group (P < 0.05) and closely associated with poor survival prognosis of WT children (P < 0.05). Increased expression and decreased methylation of SIX2 were correlated with increasing tumor size, clinical stage, vascular invasion, and unfavorable histological differentiation (P < 0.05). ROC curve analysis showed areas under the curve (AUCs) of 0.579 for methylation and 0.917 for expression in WT venous blood, indicating higher diagnostic yield of preoperative SIX2 expression. The preoperative venous blood SIX2 expression level serves as an underlying biomarker for early diagnosis of WT. SIX2 overexpression and concomitantly decreased promoter methylation are significantly associated with poor survival of WT children.

Assessment of gonadal function in boys and adolescents at the diagnosis of neoplastic disease.

OBJECTIVE: We assessed the gonadal function in boys with a newly diagnosed neoplastic disease prior to chemotherapy. Eighty-four boys (48 prepubertal and 36 pubertal) were evaluated, including 50 with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL), 10 with Hodgkin lymphoma (HL), and 24 with solid tumors. The control group consisted of 24 healthy prepubertal and 24 pubertal boys. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and testosterone were determined, and testicular volumes were measured. RESULTS: Patients in prepuberty and early puberty (Tanner stages 1-3) diagnosed with ALL/NHL or solid tumor presented normal serum reproductive hormone levels, whereas in ALL/NHL patients in Tanner stages 4-5, the mean values of inhibin B were significantly lower (45.18 +/- 33.85 vs. 153.57 +/- 71.44 ng/L, p = 0.0027). In patients with HL in Tanner stages 4-5, a statistically significant lower mean inhibin B level (100.44 +/- 67.45 versus 153.57 +/-71.44 ng/L, p = 0.0027), higher mean FSH level (6.3 +/- 3.6 versus 4.6 +/- 2.2 mIU/mL, p = 0.05), and higher mean LH level (5.9 +/- 4.0 versus 3.6 +/- 1.8 mIU/mL, p = 0.05) were observed. No statistically significant differences were noted in assessed hormones in patients with solid tumors, independently of Tanner stage. CONCLUSION: Our analysis indicates that adolescents with ALL/NHL and HL prior to treatment, exhibit reduced levels of inhibin B, which indirectly suggests the possibility of spermatogenesis dysfunction.

Potential role of PET-CT in chemotherapy efficacy assessment and recurrence diagnosis in a patient with a Wilms' tumour.

BACKGROUND: Wilms' tumour is the most frequent renal malignancy in children. There is no worldwide consensus regarding treatment and PET-CT role in this neoplasm. The aim of this report is to demonstrate the potential role of PET-CT in chemotherapy efficacy assessment and recurrence diagnosis. CASE DESCRIPTION: a 7-year-old boy was diagnosed with blastemic type Wilms' tumour and underwent neoadjuvant chemotherapy, nephrectomy, and adjuvant chemotherapy in compliance with SIOP protocol. Three years later the patient underwent surgical resection of the metastasis and chemoradiotherapy. Nine months later tomography and PET-CT were performed (during the third month of the treatment due to a second recurrence). The results were equivocal but within four months the boy underwent surgical resection of a third recurrence. Fourteen months later a second PET-CT revealed an active disease with extensive involvement of the left lung and pleura. The patient was referred to oral palliative chemotherapy. DISCUSSION: Equivocal PET-CT results during chemotherapy should be interpreted with caution. The first, during third line chemotherapy, was equivocal; however, an early massive recurrence three months later indicates that treatment was ineffective. The second PET-CT examination fourteen months later, as the only modality, depicted massive progression of the disease. This suggests the value of this examination in recurrence diagnosis. CONCLUSIONS: PET-CT seems to be valuable technique in recurrence detection in patients with histologically unfavourable tumours. Equivocal results of PET-CT should raise suspicion of recurrence even in recently treated patients. The timing of CIM and PET-CT should be considered individually--no universal and reliable schedule exists.

Children treated with metronomic chemotherapy in a low-income country: METRO-MALI-01.

BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. As off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, MC seems to be well adapted to low-income countries. OBJECTIVE: The aim of this study was to assess the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types. METHODS: This prospective, pilot, single-center study evaluated the use of MC with a first cycle consisting of weekly vincristine (1.5 mg/m) on days 1, 8, 15, and 22, daily cyclophosphamide (25 mg/m) on days 1 to 21, and twice weekly methotrexate (15 mg/m) on days 21 to 42, followed by a 1-week break. For the following cycles, vincristine was administered only at weeks 1 and 5 of the cycle. This treatment was proposed to children with refractory cancer following treatments with the standard protocols available in our institution and to patients who were not eligible for the protocol. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From November 2008 to December 2009, 12 children (median age, 3.7 y; range, 2 to 7 y) were included. The most frequent diagnoses were Wilms tumors (6) and retinoblastoma (5). No objective response was observed, but 7 patients experienced disease stabilization (58%) and continued their treatment for 15 to 24 weeks. After a median follow-up of 39 weeks, 6 patients (50%) were alive. Most importantly, in 3 patients (25%), disease remained stable for at least 6 months after completion of treatment. One grade 4 anemia was observed in 1 patient and 1 grade 4 nonfebrile neutropenia in 1 patient. No other grade 3 or 4 toxicities were noted. CONCLUSION: The MC regimen that we report here was well tolerated and was associated with disease stabilization. Most importantly, stabilization could be maintained for over 6 additional months after completion of treatment in 3 patients. The potential of MC in children and young adults in low-income countries warrants further studies.

Recognizing health risks in childhood cancer survivors.

PURPOSE: To provide information about the special health needs of childhood cancer survivors through a discussion of Wilms' tumor, a common childhood renal tumor, and case studies of two survivors of Wilms' tumor, who encountered significant health problems as adults. This information may be generalized to many cancer survivors. DATA SOURCES: Actual case studies as well as extensive review of the current literature on childhood cancer survivorship. CONCLUSIONS: Adult healthcare practitioners may help to decrease morbidity of childhood cancer survivors in adulthood when they are knowledgeable about the risks of this population. Resources are readily available, both in the medical literature and on the Internet. IMPLICATIONS FOR PRACTICE: With well-established success in the treatment of childhood cancer, there are many young and middle-aged adult survivors of the disease. However, as many as two-thirds of survivors may have chronic long-term effects of treatment. Most survivors eventually discontinue follow-up with their pediatric oncologists and receive primary health care from adult providers, many of whom are unaware of survivors' health risks. Awareness of primary care providers regarding the special health needs of childhood cancer survivors is critical to decrease morbidity and improve quality of life. The ever-increasing number of childhood cancer survivors is creating a public health issue as they transition into adulthood.

Risk-based management: current concepts of treating malignant solid tumors of childhood.

BACKGROUND: Improved survival with pediatric malignancies has been positively influenced by multidisciplinary cooperative studies using surgery, chemotherapy, and radiation therapy, but one-third of all children with cancer succumb to their condition. The identification of biologic and genetic characteristics as risk factors for the various tumors has led to changes in treatment using risk-based management as the template for care. STUDY DESIGN: The purpose of this report is fourfold: (1) to review survival data concerning three solid malignant tumors of childhood (Wilms' tumor, rhabdomyosarcoma, and neuroblastoma), (2) to describe important prognostic genetic and biologic risk factors for each tumor, (3) to update changes in staging criteria, and (4) to familiarize the reader with the concept of risk-based management, which individualizes treatment in an attempt to maximize survival and minimize longterm morbidity. RESULTS: The overall survival rates for Wilms' tumor, rhabdomyosarcoma, and neuroblastoma are currently 90%, 70%, and 40%, respectively. Most patients with Wilms' tumor have favorable histology and survive after nephrectomy and chemotherapy, but 10% have poor prognostic variables, including unfavorable (anaplastic) histology, chromosomal loss on 1p and 16q, and diploidy. Instances of lung or liver metastases, major tumor spillage during resection, remote lymph node involvement, and bilateral tumors have worse outcomes. Rhabdomyosarcoma is associated with chromosomal translocation of t(2:13) in alveolar types, the p53 tumor suppressor gene, and 11p15. Survival is dependent on the tumor site and pretreatment clinical group. Orbit, paratesticular, vulvar, and vaginal tumors have a good prognosis, but other genitourinary tumors, extremity and trunk lesions, and parameningeal head and neck tumors have a worse prognosis. Survival rates by clinical group are stage I, 93%; II, 81%; III, 73%; and IV, 30%. Resectability, lymph node involvement, DNA ploidy, and pretreatment TNM staging affect outcomes. Neuroblastoma is an embryonal tumor with bizarre behavior and can regress, mature, or rapidly progress. Most patients have advanced disease at diagnosis. Neuroblastoma is associated with loss of heterozygosity on chromosome 1p36 and occasionally deletions on 14q and 17q. Survival is affected by age and stage (at less than 1 year, stages I [95% to 100%], II [85% to 90%], and IV-S [more than 80%] do better) and other risk factors. Patients with advanced disease (older than 1 year, stage III [70%], and stage IV [12%]) often have amplification of the N-myc oncogene, diploid tumors, 1p36 deletion, and unfavorable histology and fare worse. CONCLUSIONS: On the basis of these data, children with solid tumors are currently categorized into low-, intermediate-, and high-risk groups. Newer protocols individualize treatment using risk factors as predictors of outcomes. Risk-based management allows the clinician to weigh the risks and benefits of treatment for each patient to maximize survival, minimize longterm morbidity, and improve the quality of life.

Wilms tumor imaging: patient costs and protocol compliance.

PURPOSE: To evaluate the patient costs for imaging and compliance with imaging protocols in pediatric patients in the National Wilms Tumor Study (NWTS) IV. MATERIALS AND METHODS: The medical and imaging records of 60 patients (28 male, 32 female; aged 3 days to 12.6 years) in NWTS IV were reviewed. Initial imaging and follow-up imaging were evaluated separately. Three levels of follow-up compliance were evaluated. RESULTS: The total patient cost for imaging was $442,180: $94,212 for initial and $347,968 for follow-up studies. Many areas of potential cost savings were identified. Protocol compliance was variable. Seventy-five percent of patients underwent studies in full compliance with the initial protocol requirements. For follow-up, compliance was 0%-80% for different studies at different compliance levels. For no study was compliance 100%. CONCLUSION: Imaging costs in pediatric patients with Wilms tumor are substantial. Protocol compliance was not optimal.

Position paper: imaging methods for primary renal tumors of childhood: costs versus benefits.

The patterns of disease distribution at diagnosis and during follow-up were cataloged for the primary renal tumors of childhood. These data, derived from more than 1,500 patients, were used to define the most rewarding and cost-effective imaging methods required for patient management. The basic information needed prior to surgery includes whether there is a functioning kidney on the opposite side, and whether there are lung metastases or inferior vena cava thrombi. Simple X-ray examinations and ultrasonography (US) will provide the necessary data. Postoperatively, when the histology is known, examination of the brain (MRI or CT scan) is needed for patients with the rhabdoid tumor and clear cell sarcoma of the kidney (CCSK) who are prone to develop brain lesions; and the skeletal system (bone scan, X-ray skeletal survey) for CCSK and for renal cell carcinoma patients who tend to develop bone metastases. Continuing examination of the lung (chest films) is required for all histologies except perhaps for mesoblastic nephroma, which seldom metastasizes. The opposite kidney needs follow-up (US) for 5 or more years to exclude metachronous involvement if nephrogenic rests are present in either kidney. Sophisticated imaging studies, which cost five times or more than simple X-ray examinations or US, are not warranted routinely, and should be reserved for those cases where simpler, less expensive studies do not suffice for reaching patient management decisions.

[Renal injury on a pathological kidney. Incidence, management, and results of treatment]. / Traumatismo renal sobre riñón patológico. Incidencia, manejo y resultados de tratamiento.

The present study reports our experience in the management of 13 patients with trauma to previously asymptomatic pathological kidney (11.6% of 112 cases of renal trauma treated over the period 1980-1990). The diagnostic difficulties and treatments, which are unlike those of trauma to normal kidney, are discussed and the literature reviewed. Hydronephrosis from ureteropelvic junction stenosis was the preexisting pathology that was frequently diagnosed (41.6%), followed by trauma to kidney with tumor (30.7%). Twelve (92%) patients underwent surgery: 2 (15.3%) were emergency and the rest were elective surgery. One patient with hilar sinus cysts received medical treatment. Conservative surgery was performed in 5 renal units (1 with bilateral involvement) and nephrectomy was performed in 8 patients (65.1%). The kidney with a tumor is more compromised by the renal injury. Furthermore, post trauma contusion/laceration of the tumor may present problems relative to tumor stage.