Nephroblastoma in Older Adult: Case Report and Review of Literature.

Introduction: Nephroblastoma, or Wilms' tumor, is a malignant renal neoplasm commonly found in children, is extremely rare in adults representing only 0.5% of all renal neoplasms. Adult Wilms tumor is rare, to our knowledge fewer than 300 cases have been reported in the English literature to date. However, in older adults after 60 years of age, only less than 45 cases have been reported. For this reason, treatment guidelines in adults still are lacking. Prognosis in nephroblastoma for adult patients is found to be worse than in children. Case Presentation: We report the case of a 65-year-old female with lumbar fossa mass, flank pain and hematuria, and pathologic diagnosis of Wilms tumor. We performed nephrectomy. No adjuvant treatment was given. Our patient remains asymptomatic and without evidence of recurrence 12 months after the surgery. Conclusion: Nephroblastoma in the elderly presents different clinical behavior and prognosis compared to nephroblastoma in children.

Real-world implementation of North American and SIOP strategies for the treatment of Wilms tumor in Uruguay.

Wilms tumor has been selected as an index tumor by the WHO Global Initiative for Childhood Cancer with the aim to improve cure rates worldwide. Nevertheless, there is a scarcity of published data on outcomes beyond those of the major cooperative groups. Therefore, we conducted a retrospective analysis including all patients with Wilms tumor treated at our referral center in Uruguay between 1995 and 2020. Treatment consisted of North American (NA) strategies in 23 cases (1995-2004), followed by the SIOP strategy in 35 cases thereafter. Staging included: I-II = 28, III = 7, IV = 14, and V = 9. There were no major surgical or medical complications; however, a delay in the administration of local radiotherapy was observed (median of 21 days after surgery). There were no cases of toxicity- or surgery-related deaths or treatment abandonment. Five-year probability of overall survival was 0.72 and 0.92 for the NA and SIOP groups, respectively. We conclude that outcomes were better for the SIOP strategy with no unexpected toxicities and high treatment compliance in both strategies. Timely implementation of radiotherapy was challenging.

Surgery in Bilateral Wilms Tumor-A Single-Center Experience.

The treatment of bilateral Wilms tumors (BWT) involves curing the cancer, preserving long-term renal function, and maintaining a good quality of life. Established methods for achieving these goals include preoperative chemotherapy and nephron-sparing surgery (NSS). This study aimed to evaluate the experience of a single institution in treating patients with BWT. We analyzed cases of BWT treated at the Pediatric Oncology Institute-GRAACC-Federal University of São Paulo over a period of 35 years. Bleeding control was performed with manual compression of the renal parenchyma. Thirty-three patients were included in the study. Thirty cases were synchronous tumors. The mean age at diagnosis was 30.4 months (±22 m) and 66.7% were girls. The median follow-up period was 83 months. Neoadjuvant chemotherapy was the primary approach in most patients (87.9%), with a simultaneous upfront surgical approach performed in 84.8%. Most patients underwent bilateral NSS (70.4%). There were no early complications in this series, but 39.4% had clinical complications. The five-year survival rate was 76%. Therefore, it is clear that the surgical approach to BWT plays a crucial role in achieving good outcomes. However, it is difficult to standardize surgical techniques and technology may have the potential to enhance safety.

11p15 Epimutations in Pediatric Embryonic Tumors: Insights from a Methylome Analysis.

Embryonic tumors share few recurrent mutations, suggesting that other mechanisms, such as aberrant DNA methylation, play a prominent role in their development. The loss of imprinting (LOI) at the chromosome region 11p15 is the germline alteration behind Beckwith-Wiedemann syndrome that results in an increased risk of developing several embryonic tumors. This study analyzed the methylome, using EPIC Beadchip arrays from 99 sporadic embryonic tumors. Among these tumors, 46.5% and 14.6% presented alterations at imprinted control regions (ICRs) 1 and 2, respectively. Based on the methylation levels of ICR1 and ICR2, four clusters formed with distinct methylation patterns, mostly for medulloblastomas (ICR1 loss of methylation (LOM)), Wilms tumors, and hepatoblastomas (ICR1 gain of methylation (GOM), with or without ICR2 LOM). To validate the results, the methylation status of 29 cases was assessed with MS-MLPA, and a high level of agreement was found between both methodologies: 93% for ICR1 and 79% for ICR2. The MS-MLPA results indicate that 15 (51.7%) had ICR1 GOM and 11 (37.9%) had ICR2 LOM. To further validate our findings, the ICR1 methylation status was characterized via digital PCR (dPCR) in cell-free DNA (cfDNA) extracted from peripheral blood. At diagnosis, we detected alterations in the methylation levels of ICR1 in 62% of the cases, with an agreement of 76% between the tumor tissue (MS-MLPA) and cfDNA methods. Among the disagreements, the dPCR was able to detect ICR1 methylation level changes presented at heterogeneous levels in the tumor tissue, which were detected only in the methylome analysis. This study highlights the prevalence of 11p15 methylation status in sporadic embryonic tumors, with differences relating to methylation levels (gain or loss), location (ICR1 or ICR2), and tumor types (medulloblastomas, Wilms tumors, and hepatoblastomas).

Wilms tumor in children: A multivariate analysis of prognostic factors, with emphasis on inferior vena cava/right atrium extension. Results from a single-center study.

BACKGROUND: To identify prognostic factors for overall survival through the analysis of 132 patients with Wilms tumor followed at a single center, with emphasis on the inferior vena cava/right atrium extension. METHODS: Retrospective analysis of overall survival using logistic regression models and including age, sex, clinical features, associated syndromes, comorbidities, tumor size before chemotherapy, stage, presence of metastatic disease and its site, invasion of adjacent structures, inferior vena cava/right atrium extension, laterality, tumor histology, chemotherapy protocol, and radiotherapy as potential risk factors. RESULTS: From January 2000 through November 2021, 132 patients met the inclusion criteria, 64 females and 68 males; 15 (11.4%) patients presented with tumoral extension to inferior vena cava/right atrium and 44 had metastatic disease (33.3%). Based on logistic regression, the factors correlating to a fatal outcome were male sex (p = 0.046), high risk histology (p = 0.036), and the presence of metastatic disease (p = 0.003). None of the patients presenting inferior vena cava/right atrium extension died (p = 0.992). In a specific analysis of metastatic sites, hepatic metastasis alone showed correlation with a fatal outcome (p = 0.001). CONCLUSION: These results underline the importance of identifying and treating metastatic disease and high-risk tumors. The female gender as a potential driver for a less aggressive disease is a new finding that deserves further investigation. The accurate identification of inferior vena cava/right atrium extension, subsequent preoperative chemotherapy, and resection with a skilled team promoted survival rates of all patients. LEVEL OF EVIDENCE: II.

Mechanism of action of DSP-7888 (adegramotide/nelatimotide) Emulsion, a peptide-based therapeutic cancer vaccine with the potential to turn up the heat on non-immunoreactive tumors.

BACKGROUND: Wilms' tumor 1 (WT1) is highly expressed in various solid tumors and hematologic malignancies. DSP-7888 (adegramotide/nelatimotide) Emulsion is an investigational therapeutic cancer vaccine comprising three synthetic epitopes derived from WT1. We evaluated the mechanism of action of DSP-7888 Emulsion, which is hypothesized to induce WT1-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs). METHODS: The ability of nelatimotide and adegramotide to induce WT1-specific CD8+ T cells and CD4+ T cells was assessed in human peripheral blood mononuclear cells (PBMCs). The ability of DSP-7888 Emulsion to induce WT1-specific CTLs in vivo was assessed using human leukocyte antigen-I (HLA-I) transgenic mice. To assess how adegramotide, the helper peptide in DSP-7888 Emulsion, enhances WT1-specific CTLs, HLA-I transgenic mice were administered DSP-7888 or nelatimotide-only Emulsion. Interferon-gamma secretion under antigen stimulation by splenocytes co-cultured with or without tumor cells was then quantified. The effects of combination treatment with DSP-7888 Emulsion and an anti-programmed cell death protein 1 (PD-1) antibody on tumor volume and the frequency of tumor-infiltrating WT1-specific T cells were assessed in HLA-I transgenic mice implanted with WT1 antigen-positive tumors. RESULTS: The peptides in DSP-7888 Emulsion were shown to induce WT1-specific CTLs and HTLs in both human PBMCs and HLA-I transgenic mice. Unlike splenocytes from nelatimotide-only Emulsion-treated mice, splenocytes from DSP-7888 Emulsion-treated mice exhibited high levels of interferon-gamma secretion, including when co-cultured with tumor cells; interferon-gamma secretion was further enhanced by concomitant treatment with anti-PD-1. HLA-I transgenic mice administered DSP-7888 Emulsion plus anti-PD-1 experienced significantly greater reductions in tumor size than mice treated with either agent alone. This reduction in tumor volume was accompanied by increased numbers of tumor-infiltrating WT1-specific CTLs. CONCLUSIONS: DSP-7888 Emulsion can promote both cytotoxic and helper T-cell-mediated immune responses against WT1-positive tumors. Adegramotide enhances CTL numbers, and the CTLs induced by treatment with both nelatimotide and adegramotide are capable of functioning within the immunosuppressive tumor microenvironment. The ability of anti-PD-1 to enhance the antitumor activity of DSP-7888 Emulsion in mice implanted with WT1-positive tumors suggests the potential for synergy.

Sobrecrecimiento lateral aislado - caracterización auxológica y clínico-radiológica de una cohorte de 76 casos de un único centro / Isolated lateralized overgrowth: clinical, radiological, and auxological characteristics of a single-site cohort of 76 cases

Introducción. El sobrecrecimiento lateral aislado (SLA), antes denominado hemihiperplasia/ hemihipertrofia, se refiere al sobrecrecimiento corporal lateral en ausencia de un patrón reconocible de malformaciones o síndromes genéticos. El objetivo fue analizar el crecimiento y las características clínico-radiológicas de pacientes con SLA en seguimiento en un hospital de tercer nivel en Argentina entre 1993 y 2020. Población y métodos. Estudio retrospectivo, observacional, de una cohorte de pacientes con SLA. Resultados. Se incluyeron 76 casos, 41 varones. Mediana de años de seguimiento: 5,85 (rango intercuartílico [RIC] 2,60-10,96), máximo 15,76 años. Cuarenta y ocho de 76 pacientes presentaron sobrecrecimiento en más de un segmento corporal (SLA complejo). El puntaje Z promedio de peso al nacer de niñas de término con SLA complejo fue +0,51 (desviación estándar [DE] 0,91) (p 0,022). El crecimiento en estatura de la mayoría de los niños se ubicó entre los centilos 50 y 97 de la población de referencia. La mediana de asimetría de longitud de miembros inferiores fue 1,5 cm (RIC 1,01-2,2) en pacientes con tratamiento médico y 3,70 cm (RIC 2,953,98 cm) en aquellos que requiriero epifisiodesis. El 75 % mostró una progresión de la asimetría menor o igual a 2 cm. Ocho casos presentaron asimetría renal mayor o igual a 1 cm; 2 casos presentaron nefroblastoma: edad promedio al diagnóstico 0,75 años. Conclusiones. El crecimiento prenatal de niños con SLA es normal, excepto en niñas con SLA complejo en quienes tiende a estar aumentado. La estatura promedio se ubica en centilos altos con crecimiento normal. Se recomienda realizar cribado de tumores embrionarios en este grupo de niños.

Introduction. Isolated lateralized overgrowth (ILO), formerly referred to as hemihyperplasia/hemihypertrophy, is the overgrowth of one-half of the body to its contralateral in the absence of a recognizable pattern of malformations or genetic syndromes. Our objective was to analyze the growth clinical and radiological characteristics of patients with ILO under follow-up in a tertiary care hospital in Argentina between 1993 and 2020. Population and methods. Retrospective, observational, single cohort study of patients with ILO. Results. A total of 76 cases were included; 41 were males. Median years of follow-up: 5.85 (interquartile range [IQR]: 2.60­10.96), maximum: 15.76 years. Forty-eight of 76 patients had overgrowth compromising more than 1 body segment (complex ILO). The mean birth weight Z-score of term girls with complex ILO was +0.51 (standard deviation [SD]: 0.91) (p 0.022). Most children grew between the 50th and 97th centile of the Argentinian population height reference. The median leg length discrepancy was 1.5 cm (IQR: 1.01­2.2) in patients receiving medical treatment and 3.70 cm (IQR: 2.95­3.98 cm) in those who required epiphysiodesis. Progression of discrepancy ≤ 2 cm was observed in 75% of cases. Renal asymmetry ≥ 1 cm was observed in 8 cases; Wilms tumor was noted in 2 cases: mean age at diagnosis: 0.75 years. Conclusions. Prenatal growth of children with ILO is normal, except in girls with complex ILO, in whom it tends to be increased. The average height of boys and girls tends to be located in high centiles with normal growth over time. Embryonal tumor screening is recommended in this group of children.

Isolated lateralized overgrowth: clinical, radiological, and auxological characteristics of a single-site cohort of 76 cases. / Sobrecrecimiento lateral aislado - caracterización auxológica y clínico-radiológica de una cohorte de 76 casos de un único centro.

INTRODUCTION: Isolated lateralized overgrowth (ILO), formerly referred to as hemihyperplasia/hemihypertrophy, is the overgrowth of one-half of the body to its contralateral in the absence of a recognizable pattern of malformations or genetic syndromes. Our objective was to analyze the growth clinical and radiological characteristics of patients with ILO under follow-up in a tertiary care hospital in Argentina between 1993 and 2020. POPULATION AND METHODS: Retrospective, observational, single cohort study of patients with ILO. RESULTS: A total of 76 cases were included; 41 were males. Median years of follow-up: 5.85 (interquartile range [IQR]: 2.60-10.96), maximum: 15.76 years. Forty-eight of 76 patients had overgrowth compromising more than 1 body segment (complex ILO). The mean birth weight Z-score of term girls with complex ILO was +0.51 (standard deviation [SD]: 0.91) (p 0.022). Most children grew between the 50th and 97th centile of the Argentinian population height reference. The median leg length discrepancy was 1.5 cm (IQR: 1.01-2.2) in patients receiving medical treatment and 3.70 cm (IQR: 2.95-3.98 cm) in those who required epiphysiodesis. Progression of discrepancy ≤ 2 cm was observed in 75% of cases. Renal asymmetry ≥ 1 cm was observed in 8 cases; Wilms tumor was noted in 2 cases: mean age at diagnosis: 0.75 years. CONCLUSIONS: Prenatal growth of children with ILO is normal, except in girls with complex ILO, in whom it tends to be increased. The average height of boys and girls tends to be located in high centiles with normal growth over time. Embryonal tumor screening is recommended in this group of children.

Introducción. El sobrecrecimiento lateral aislado (SLA), antes denominado hemihiperplasia/hemihipertrofia, se refiere al sobrecrecimiento corporal lateral en ausencia de un patrón reconocible de malformaciones o síndromes genéticos. El objetivo fue analizar el crecimiento y las características clínico-radiológicas de pacientes con SLA en seguimiento en un hospital de tercer nivel en Argentina entre 1993 y 2020. Población y métodos. Estudio retrospectivo, observacional, de una cohorte de pacientes con SLA. Resultados. Se incluyeron 76 casos, 41 varones. Mediana de años de seguimiento: 5,85 (rango intercuartílico [RIC] 2,60-10,96), máximo 15,76 años. Cuarenta y ocho de 76 pacientes presentaron sobrecrecimiento en más de un segmento corporal (SLA complejo). El puntaje Z promedio de peso al nacer de niñas de término con SLA complejo fue +0,51 (desviación estándar [DE] 0,91) (p 0,022). El crecimiento en estatura de la mayoría de los niños se ubicó entre los centilos 50 y 97 de la población de referencia. La mediana de asimetría de longitud de miembros inferiores fue 1,5 cm (RIC 1,01-2,2) en pacientes con tratamiento médico y 3,70 cm (RIC 2,95- 3,98 cm) en aquellos que requirieron epifisiodesis. El 75 % mostró una progresión de la asimetría menor o igual a 2 cm. Ocho casos presentaron asimetría renal mayor o igual a 1 cm; 2 casos presentaron nefroblastoma: edad promedio al diagnóstico 0,75 años. Conclusiones. El crecimiento prenatal de niños con SLA es normal, excepto en niñas con SLA complejo en quienes tiende a estar aumentado. La estatura promedio se ubica en centilos altos con crecimiento normal. Se recomienda realizar cribado de tumores embrionarios en este grupo de niños.

Primary Wilms tumor of the urinary bladder.

Wilms tumor (WT) can occur at various extrarenal sites; however, the urinary bladder as the primary site is occasional. A 4-year-old-female child presented with difficulty in micturition for the past month. The contrast-enhanced magnetic resonance imaging with magnetic resonance (MR) urography revealed a polypoidal, heterogeneous mass in the urinary bladder with no abnormality in the kidneys. Cystoscopy-guided biopsy was reported as an extrarenal Wilms tumor (ERWT) with triphasic components. Post-chemotherapy, a computed tomography scan revealed a residual tumor for which she underwent partial cystectomy. The diagnosis of ERWT was confirmed. She received adjuvant chemotherapy and remained well at the 9th month post completion of chemotherapy. The primary bladder WT must be considered in the differential of a small blue round cell tumor at an extrarenal site in the pediatric age group. The diagnosis is especially challenging in small biopsy material, although it has immense significance in management and prognosis.

Tumor de Wilms en displasia renal multiquística

RESUMEN Introducción: La displasia renal multiquística es una anomalía congénita caracterizada por un riñón afuncional con quistes de diferentes tamaños. Es considerada como una anomalía del desarrollo, aunque se han descrito casos hereditarios. Se ha puntualizado la degeneración maligna de esta displasia, pero su asociación es muy rara. Objetivo: Describir una paciente con tumor de Wilms asociado a una displasia renal multiquística. Presentación del caso: Paciente de sexo femenino y 10 años de edad que los ultrasonidos prenatales no detectaron anomalías del tracto urinario y a los 7 años un estudio ecográfico detectó quistes en el riñón izquierdo. No cumplió el seguimiento clínico y ultrasonográfico indicado y abandonó la consulta; los 10 años asistió al médico por síntomas respiratorios agudos y al palpar el abdomen se comprobó masa en flanco izquierdo de consistencia leñosa, no dolorosa y con contacto lumbar. Se realizó biopsia renal y se diagnosticó tumor de Wilms, se impuso tratamiento citostático y se realizó nefrectomía que confirmó el diagnóstico. Entre los antecedentes familiares se informa un hermano fallecido antes de las 72 horas de nacido por displasia renal multiquística bilateral y madre con nefropatía por reflujo vesicoureteral. Conclusiones: La paciente que se describe reúne tres características raras: un tumor maligno asociado a una displasia renal multiquística, la posibilidad hereditaria por el antecedente del hermano con la displasia bilateral y un tumor de Wilms a los 10 años de edad, lo que demuestra la importancia del seguimiento en estos pacientes.

ABSTRACT Introduction: Multicystic renal dysplasia is a congenital anomaly characterized by an afunctional kidney with cysts of different sizes. It is considered a developmental abnormality, although hereditary cases have been described. The malignant degeneration of this dysplasia has been pointed out, but its association is very rare. Objective: Describe a patient with Wilms tumor associated with multicystic renal dysplasia. Case Presentation: 10-year-old female patient to whom prenatal ultrasounds did not detect urinary tract abnormalities and at age 7 an ultrasound study detected cysts in the left kidney. She did not comply with the indicated clinical and ultrasonographic follow-up and left the consultation; at 10 years old, she attended the doctor for acute respiratory symptoms and when palpating the abdomen there was a mass on the left flank of woody consistency, not painful and with lumbar contact. A renal biopsy was conducted and Wilms tumor was diagnosed; cytostatic treatment was indicated, and a nephrectomy was performed that confirmed the diagnosis. Among the family history is reported a brother who died before 72 hours of birth due to bilateral multicystic renal dysplasia and a mother with nephropathy by vesicoureteral reflux. Conclusions: The described patient has three rare characteristics: a malignant tumor associated with multicystic renal dysplasia, the hereditary possibility due to the sibling's history of bilateral dysplasia, and a Wilms tumor at 10 years of age, which demonstrates the importance of follow-up in these patients.

Bilateral Wilms' tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region.

OBJECTIVES: Wilm's Tumor (WT) is the most common pediatric kidney cancer. Whereas most WTs are isolated, approximately 5% are associated with syndromes such as Denys-Drash (DDS), characterized by early onset nephropathy, disorders of sex development and predisposition to WT. CASE PRESENTATION: A 46,XY patient presenting with bilateral WT and genital ambiguity without nephropathy was heterozygous for the novel c.851_854dup variant in WT1 gene sequence. This variant affects the protein generating the frameshift p.(Ser285Argfs*14) that disrupts a nuclear localization signal (NLS) region. CONCLUSIONS: This molecular finding is compatible with the severe scenario regarding the Wilm's tumor presented by the patient even though nephropathy was absent.

Wilms or non-Wílms tumors? Imaging features of renal tumors in pediatrics / ¿Tumores de Wilms o no Wilms? Características por imagen de los tumores renales en pediatría

Abstract Introduction: Identifying the imaging features of renal tumors in pediatric population allows reaching more accurate diagnoses and implementing more appropriate treatments. Objective: To describe the imaging findings of renal tumors in children and to assess the association between imaging findings and histological diagnosis of Wilms tumors versus Non-Wilms tumors, and between imaging features and intraoperative rupture of Wilms tumors, as well as the level of agreement between radiological and histological diagnosis (Wilms vs. Non-Wilms tumor). Materials and methods: Cross-sectional study conducted in 47 children with a pathological diagnosis of kidney tumor and treated between 2012 and 2018 in a pediatric hospital in Bogotá D.C., Colombia. The patients' medical records, as well as their ultrasound, tomography and magnetic resonance studies were reviewed. Two univariate logistic regression analyses were performed to assess the association between imaging findings and histopathological diagnosis and between imaging features and intraoperative rupture of Wilms tumors, calculating the respective Odds Ratio (OR) with a 95% confidence interval. In addition, the level of agreement between radiological and histological diagnosis was determined using the Cohen's kappa coefficient. Results: A significant association was found between histological diagnosis of Wilms tumor and the presence of necrosis, tumor enhancement, pseudocapsule, rupture signs, tumor volume and tumor size (OR: 21.6, 15.17, 14.57, 8.21, 7.93, and 4.37, respectively; p<0.05). An association between having Wilms tumors and a lower frequency of metastases was also found (OR: 0.19; p<0.05). The kappa coefficient between radiological diagnosis of Wilms/non- Wilms tumors and histological diagnosis was 0.78 (CI95%: 0.59-0.96; p<0.05). Additionally, Wilms tumors volumen was significantly associated with the occurrence of rupture (OR: 3.08; p<0.05). Conclusions: There are imaging findings such as necrosis, tumor enhancement and tumor volume that can help predict the histological diagnosis of Wilms tumors, as well as perioperative rupture. In addition, a moderate to very good concordance between radiological diagnosis of Wilms/non-Wilms tumors and histological findings was found.

Resumen Introducción. Identificar las características por imagen de los tumores renales en la población pediátrica permite realizar diagnósticos más precisos e implementar tratamientos más apropiados. Objetivo. Describir los hallazgos de imagen de tumores renales en niños y evaluar la asociación entre hallazgos imagenológicos y el diagnóstico histopatológico de tumores de Wilms versus tumores no Wilms, y entre las características de imagen y ruptura quirúrgica de tumores Wilms, así como el grado de concordancia entre el diagnóstico radiológico e histológico. Materiales y métodos. Estudio transversal realizado en 47 niños con diagnóstico patológico de tumor renal atendidos entre 2012 y 2018 en un hospital pediátrico de Bogotá D.C., Colombia. Se revisaron las historias clínicas de los pacientes, así como sus estudios de ultrasonografía, tomografía y resonancia magnética. Se realizaron dos análisis de regresión logística univariados para evaluar la asociación entre hallazgos imagenológicos y diagnóstico histopatológico y entre las características imagenológicas de los tumores de Wilms y ruptura quirúrgica, calculando los respectivos odds ratio (OR) con un intervalo de confianza del 95%. Además, se determinó el grado concordancia entre el diagnóstico radiológico e histopatológico mediante el coeficiente de kappa de Cohen. Resultados. Se encontró una asociación significativa entre el diagnóstico histológico de tumor de Wilms y la presencia de necrosis, realce tumoral, pseudocápsula, signos de ruptura, volumen y tamaño del tumor (OR: 21.6, 15.17, 14.57, 8.21, 7.93 y 4.37, respectivamente; p<0.05). También se observó una asociación entre tener tumores de Wilms y menor frecuencia de metástasis (OR:0.19; p<0.05). El coeficiente de Kappa entre el diagnóstico radiológico de los tumores (Wilms/no-Wilms) y el diagnóstico histológico fue 0.78 (IC95%: 0.59-0.96; p<0.05). Además, el volumen de los tumores de Wilms se asoció significativamente con la ocurrencia de ruptura (OR: 3.08; p<0.05). Conclusiones. Hay hallazgos imagenológicos como la necrosis, el realce tumoral y el volumen tumoral que ayudan a predecir el diagnóstico histológico de tumores de Wilms, así como la ruptura perioperatoria. Además, se observó una muy buena concordancia entre el diagnóstico radiológico de tumores Wilms/no Wilms y los hallazgos histológicos.

Genitourinary Tract Tumors in Children: An Update.

BACKGROUND: Genitourinary tract tumors in children are less common than in adults. Most of these tumors have different genetic backgrounds, clinical presentation, and oncologic behavior than their adult counterpart. As a result of low prevalence in children, some of the treatment approaches and recommendations are based on treatment experience in adult patients. However, thanks to scientific and technological development, survival rates have risen considerably. OBJECTIVE: This paper presents a review of the principal features of the tumors involving the genitourinary tract in children and an update in genetic background, diagnosis, and treatment. METHODS: A narrative review was performed on published literature about genitourinary tract tumors in pediatric patients. Papers presented in English and Spanish literature were reviewed. PubMed, Science Direct, and SciELO databases were used to collect information and present this article. RESULTS: Kidney tumors are the most common type of genitourinary tumors in children. Among those, Wilms tumor represents the majority of cases and shows the successful work of clinical trial groups studying this tumor type. Other tumors involving the genitourinary tract in children include Rhabdomyosarcoma, Transitional cell carcinoma, Testicular, and Adrenal tumors. CONCLUSION: Genitourinary tract tumors in children represent significant morbidity and economic burden, so awareness in early diagnosis represents improvement in treatment, clinical, and oncological outcomes.

A Metabonomic View on Wilms Tumor by High-Resolution Magic-Angle Spinning Nuclear Magnetic Resonance Spectroscopy.

Pediatric cancer NMR-metabonomics might be a powerful tool to discover modified biochemical pathways in tumor development, improve cancer diagnosis, and, consequently, treatment. Wilms tumor (WT) is the most common kidney tumor in young children whose genetic and epigenetic abnormalities lead to cell metabolism alterations, but, so far, investigation of metabolic pathways in WT is scarce. We aimed to explore the high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) metabonomics of WT and normal kidney (NK) samples. For this study, 14 WT and 7 NK tissue samples were obtained from the same patients and analyzed. One-dimensional and two-dimensional HR-MAS NMR spectra were processed, and the one-dimensional NMR data were analyzed using chemometrics. Chemometrics enabled us to elucidate the most significant differences between the tumor and normal tissues and to discover intrinsic metabolite alterations in WT. The metabolic differences in WT tissues were revealed by a validated PLS-DA applied on HR-MAS T2-edited 1H-NMR and were assigned to 16 metabolites, such as lipids, glucose, and branched-chain amino acids (BCAAs), among others. The WT compared to NK samples showed 13 metabolites with increased concentrations and 3 metabolites with decreased concentrations. The relative BCAA concentrations were decreased in the WT while lipids, lactate, and glutamine/glutamate showed increased levels. Sixteen tissue metabolites distinguish the analyzed WT samples and point to altered glycolysis, glutaminolysis, TCA cycle, and lipid and BCAA metabolism in WT. Significant variation in the concentrations of metabolites, such as glutamine/glutamate, lipids, lactate, and BCAAs, was observed in WT and opened up a perspective for their further study and clinical validation.

WT1 Pathogenic Variants are Associated with a Broad Spectrum of Differences in Sex Development Phenotypes and Heterogeneous Progression of Renal Disease.

Wilms' tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of WT1 have been classically associated with Denys-Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between WT1 disorders has been frequently observed. New WT1 variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic WT1 variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of WT1 between exons 9 and 10. Two pathogenic missense WT1 variants were identified in two 46,XY individuals with Wilms' tumors; both patients were <1 year of age at the time of diagnosis. A novel WT1 variant, c.1453_1456 (p.Arg485Glyfs*14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with WT1 variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.

Abordaje mínimamente invasivo del tumor de Wilms unilateral: un reporte de caso y revisión de la literatura / Minimally invasive approach to unilateral Wilms tumor: a case report and literature review

Introducción. El tumor de Wilms es la neoplasia abdominal más común en pacientes pediátricos. En la mayoría de los casos se presenta como una masa unilateral indolora en el abdomen. El objetivo de este artículo fue presentar el caso de una paciente de 4 años con tumor de Wilms unilateral derecho manejado con cirugía mínimamente invasiva en el Hospital Universitario del Valle. Métodos. Revisión de la historia clínica e imágenes de la paciente, descripción de la técnica quirúrgica y revisión de la literatura del manejo de tumor de Wilms unilateral. Caso clínico. Paciente femenina de 4 años quien consultó en abril de 2019 por un cuadro clínico de dolor abdominal y sensación de masa en flanco derecho. Se realizó ecografía abdominal donde se encontró imagen nodular heterogénea de contornos definidos en riñón derecho, con riñón izquierdo normal. Se hizo diagnóstico de tumor de Wilms unilateral y se llevó a cirugía mediante abordaje mínimamente invasivo, con buena evolución postoperatoria. Conclusión. La cirugía es el pilar del manejo, y la nefrectomía mediante abordaje laparoscópico para casos seleccionados, en manos entrenadas, tiene la suficiente eficacia, seguridad y cumplimiento de los principios quirúrgicos y oncológicos que provee la cirugía abierta.

Introduction. Wilms tumor is the most common abdominal neoplasm in pediatric patients. In most cases it presents as a painless unilateral mass in the abdomen. The objective of this article was to present the case of a 4-year-old patient with right unilateral Wilms tumor managed with minimally invasive surgery at the Hospital Universitario del Valle. Methods. Review of the patient's clinical history and images, description of the surgical technique and review of the literature on the management of unilateral Wilms tumor.Clinical case. A 4-year-old female patient who consulted on April 4, 2019 with a clinical presentation of abdominal pain and sensation of mass in the right flank. Abdominal ultrasound was performed where a heterogeneous nodular image of defined contours was found in the right kidney, with a normal left kidney. A diagnosis of unilateral Wilms tumor was made and surgery was carried out using a minimally invasive approach, with good postoperative evolution. Conclusion. Wilms tumor is the most common abdominal neoplasm in pediatric patients. The most common presentation is a painless palpable mass. Surgery is the mainstay of management, and nephrectomy using a laparoscopic approach for selected cases, in trained hands, has sufficient efficacy, safety, and compliance with surgical and oncological principles that open surgery provides.

Primary Wilms tumor of the urinary bladder

ABSTRACT Wilms tumor (WT) can occur at various extrarenal sites; however, the urinary bladder as the primary site is occasional. A 4-year-old-female child presented with difficulty in micturition for the past month. The contrast-enhanced magnetic resonance imaging with magnetic resonance (MR) urography revealed a polypoidal, heterogeneous mass in the urinary bladder with no abnormality in the kidneys. Cystoscopy-guided biopsy was reported as an extrarenal Wilms tumor (ERWT) with triphasic components. Post-chemotherapy, a computed tomography scan revealed a residual tumor for which she underwent partial cystectomy. The diagnosis of ERWT was confirmed. She received adjuvant chemotherapy and remained well at the 9th month post completion of chemotherapy. The primary bladder WT must be considered in the differential of a small blue round cell tumor at an extrarenal site in the pediatric age group. The diagnosis is especially challenging in small biopsy material, although it has immense significance in management and prognosis.

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: -0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation.

Non-coding RNAs in Wilms' tumor: biological function, mechanism, and clinical implications.

Non-coding RNAs are involved with maintenance and regulation of physiological mechanisms and are involved in pathological processes, such as cancer. Among the small ncRNAs, miRNAs are the most explored in tumorigenesis, metastasis development, and resistance to chemotherapy. These small molecules of ~ 22 nucleotides are modulated during early renal development, involved in the regulation of gene expression and Wilms' tumor progression. Wilms' tumors are embryonic tumors with few mutations and complex epigenetic dysregulation. In recent years, the small ncRNAs have been explored as potentially related both in physiological development and in the tumorigenesis of several types of cancer. Besides, genes regulated by miRNAs are related to biological pathways as PI3K, Wnt, TGF-ß, and Hippo signaling pathways, among others, which may be involved with the underlying mechanisms of resistance to chemotherapy, and in this way, it has emerged as potential targets for cancer therapies, including for Wilms' tumors.

Management of Pediatric Tumors With Vascular Extension.

Background: Pediatric tumors can present with vascular extension to the inferior vena cava and right atrium, which impacts the surgical strategy and can be challenging during surgical treatment. Wilms tumor (WT) is the most common retroperitoneal tumor that can present with vascular extension, but also adrenal tumors, clear cell tumors from the kidney, and hepatoblastomas can present with this situation. Surgical aims include obtaining complete tumor resection without risk for patients, to avoid severe bleeding, cardiac arrest, and embolization, and to avoid cardiac bypass if possible. Objective: To describe and discuss the surgical strategies to deal with pediatric tumors with vascular extension and propose a protocol. Method: Retrospectivly review the experience of treating patients with vascular extension in a single institution, describing different scenarios and a decision making fluxogram based on the preoperative evaluation regarding the surgical techniques and the need for cardiac bypass that are adequate for each situation. Image studies are important to guide the surgical strategy. Depending on the quality of image available, computerized tomography (CT) or magnetic resonance imaging (MRI) can be enough to give the information needed for surgical decisions. Ultrasonography (US) with Doppler is helpful to confirm diagnosis and describes factors to guide the adequate surgical strategy, like the upper level extension and presence or absence of blood flow around the thrombus. Neoadjuvant chemotherapy is indicated in most cases, in order to reduce the upper level of extension (and avoid the need for cardiac bypass) and to lower the risk of embolization. The approach is based on the upper level of the thrombus and can include cavotomy or cavectomy, sometimes with cardiac bypass and cardiac arrest with hypothermia, when the thrombus reaches the diaphragmatic level or above. Pathology analysis of the thrombus can guide staging and the need for radiotherapy postoperatively. Results: A decision making fluxogram protocol is presented focusing on the surgical treatment of such condition. Conclusion: Surgery strategy is highly impacted by the presence of vascular extension in pediatric tumors. Surgeons should be aware of potential complications and how to prevent them. Such cases should be treated in reference centers.