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Published radiotherapy results for spinal nephroblastomas in dogs are limited. In this retrospective longitudinal study (1/2007-1/2022), five dogs with a median age of 2.8 years received post-operative 3D conformal, conventional fractionated radiotherapy (CFRT) with 2-4 fields (parallel-opposed with or without two hinge-angle fields), for an incompletely resected nephroblastoma. Clinical findings prior to surgery included one or more of the following: pelvic limb paresis (5), faecal incontinence (2), flaccid tail (1), non-ambulatory (2) and deep pain loss (1). All masses were located between T11 and L3 and surgically removed via hemilaminectomy. Dogs received 45-50 Gray (Gy) in 18-20 fractions, and no dogs received chemotherapy post-radiation. At analysis, all dogs were deceased, with none lost to follow-up. The median overall survival (OS) from first treatment to death of any cause was 3.4 years (1234 days; 95% CI 68 days-upper limit not reached; range: 68-3607 days). The median planning target volume was 51.3 cc, with a median PTV dose of 51.4 Gy and median D98 = 48.3 Gy. Late complications or recurrence was difficult to fully determine in this small dataset; however, some degree of ataxia persisted throughout life in all dogs. This study provides preliminary evidence that post-operative radiotherapy may result in prolonged survival times dogs with spinal nephroblastomas.

Non‐invasive differentiation of paediatric kidney tumours is particularly important in the SIOP‐RTSG protocols, which recommend pre‐operative chemotherapy without histological confirmation. The identification of clinical and tumour‐related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analysed in 3306 patients enrolled in SIOP/GPOH 9, 93‐01, and 2001 including Wilms tumour (WT), congenital mesoblastic nephroma (CMN), clear cell sarcoma (CCSK), malignant rhabdoid tumour of the kidney (MRTK), and renal cell carcinoma (RCC). WT was diagnosed in 2927 (88.5%) patients followed by CMN 138 (4.2%), CCSK 126 (3.8%), MRTK 58 (1.8%) and RCC 57 (1.7%). CMN, the most common localized tumour (71.6%) in patients younger than 3 months of age, was diagnosed earliest and RCC the latest (median age [months]: 0 and 154, respectively) both associated with significantly smaller TV (median TV [mL]: 67.2 and 45.0, respectively). RCC occurred in >14% of patients older than 120 months or older than 84 months with TV <100 mL. Receiver operating characteristic analyses discriminated WT from CMN, RCC and MRTK regarding age (AUC = 0.976, 0.929 and 0.791) and TV (AUC = 0.768, 0.813 and 0.622). MRTK had the highest risk of metastasis (37.9%) despite young age, whereas the risk of metastasis increased significantly with age in WT. Age and TV at diagnosis can differentiate WT from CMN and RCC. MRTK must be considered for metastatic tumours at young age. Identification of CCSK without histology remains challenging. Combined with MRI‐characteristics, including diffusion‐weighted imaging, and radiomics and liquid biopsies in the future, our approach allows optimization of biopsy recommendations and prevention of misdiagnosis‐based neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Introduction: Kidney diseases have shown a rising upward trend in the last few decades due to the increase in incidence of associated chronic diseases like diabetes, hypertension. However the frequency and spectrum of renal pathology in autopsy specimens is not well documented or overlooked by physicians as well as pathologists. Aim: To analyse the spectrum of various types of renal pathologies, based on the histopathological analysis of renal tissue where autopsies were performed routinely with no history of renal diseases. Materials and Methods: This cross-sectional study was carried out over a period of two years from June 2021 to June 2023 in the Department of Pathology of SCB Medical College and Hospital, Cuttack, Odisha, India, and consisted of 84 cases of well-preserved renal autopsies. The autopsy samples were routinely processed and stained by Haematoxylin and Eosin (H&E) and then reported. Special stain of Periodic Acid Schiff (PAS) was done. Gross and microscopic findings were studied. The study was compared with other relevant studies. The data was analysed using Microsoft Excel 2019. Results: A total of 84 cases were included in the study. The male:female ratio was 1.27:1. The age group with the highest number of cases (35 cases) was 21-40 years. Among the 84 cases the commonest pathology was seen in tubules (40 cases, 47.62%) and glomeruli (7 cases, 8.33%), followed by vascular pathologies (5 cases, 5.95%) and interstitial lesions (4 cases, 4.76%). Renal cell carcinoma was incidentally detected in two cases and Wilms tumour in one case. Five cases had normal histology. Conclusion: The study illuminates the various renal lesions on autopsy and showed tubular lesions were more common than glomerular lesions in renal autopsy. Renal lesions are more common in males. The focus should be to develop more effective diagnostic methods for renal lesions so that intervention can be fast and sharp resulting in less mortality.

Wilms tumour (WT) is the fourth leading cause of cancer death in children. Elucidating modifiable risk factors is crucial in identifying venues for primary prevention of the disease. This study aimed to review literature and synthesize environmental risk factors for WT. We conducted a systematic review and meta-analysis of epidemiological studies using PubMed, Web of Science, and Embase databases. Studies were included if they were case-control or cohort studies of children under the age of 20 years at diagnosis and reported Relative Risks (RRs) with 95 % confidence intervals (CIs). Pooled effect sizes (ES) and 95 % CIs for risk factors associated with WT were estimated using random-effects models. We included 58 eligible studies from Asia, Europe, Latin and North America, and Oceania totalling approximately10000 cases of WT diagnosed between 1953 and 2019. We confirmed an association between high birthweight ((>4000 g) ES 1.54, CI 1.20–1.97) and WT. Similarly, consistent associations were suggested for Caesarean section (ES 1.23, CI 1.07–1.42), gestational age

The central question of nephron-sparing surgery in unilateral non-syndromic Wilms tumour sits at a crossroads between surgery, oncology, and nephrology. There has been a significant paradigm shift in paediatric oncology towards reducing toxicity and addressing long-term treatment-related sequalae amongst childhood cancer survivors. After paediatric nephrectomy and 30–50 years of follow-up, 40% of patients will have chronic kidney disease, including 22% with hypertension and 23% with albuminuria. It is difficult to predict which patients will progress to develop hypertension, reduced glomerular filtration rate, albuminuria, and a higher cardiovascular risk. For these reasons, nephron-sparing surgery when it is technically feasible must be considered. To decrease the incidence of positive surgical margins (viable tumour present at a resection margin), incomplete lymph node sampling, and complications, these procedures should be performed at specialist and experienced reference centres. Based on the impacts of individual treatment pathways, survivors of childhood WT need to be followed through adulthood for early detection of chronic kidney disease, hypertension, and prevention of cardiovascular events. [ABSTRACT FROM AUTHOR]

Aims: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma‐associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. Methods and Results: The five cases comprised three teratoma‐associated (two mature and one immature) and two pure WTs. Two of the teratoma‐associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel‐based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma‐associated WTs. Furthermore, copy number variation and clustering‐based whole‐genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma‐associated WTs. Conclusion: Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs. [ABSTRACT FROM AUTHOR]

Introduction: Kidney diseases have shown a rising upward trend in the last few decades due to the increase in incidence of associated chronic diseases like diabetes, hypertension. However the frequency and spectrum of renal pathology in autopsy specimens is not well documented or overlooked by physicians as well as pathologists. Aim: To analyse the spectrum of various types of renal pathologies, based on the histopathological analysis of renal tissue where autopsies were performed routinely with no history of renal diseases. Materials and Methods: This cross-sectional study was carried out over a period of two years from June 2021 to June 2023 in the Department of Pathology of SCB Medical College and Hospital, Cuttack, Odisha, India, and consisted of 84 cases of well-preserved renal autopsies. The autopsy samples were routinely processed and stained by Haematoxylin and Eosin (H&E) and then reported. Special stain of Periodic Acid Schiff (PAS) was done. Gross and microscopic findings were studied. The study was compared with other relevant studies. The data was analysed using Microsoft Excel 2019. Results: A total of 84 cases were included in the study. The male:female ratio was 1.27:1. The age group with the highest number of cases (35 cases) was 21-40 years. Among the 84 cases the commonest pathology was seen in tubules (40 cases, 47.62%) and glomeruli (7 cases, 8.33%), followed by vascular pathologies (5 cases, 5.95%) and interstitial lesions (4 cases, 4.76%). Renal cell carcinoma was incidentally detected in two cases and Wilms tumour in one case. Five cases had normal histology. Conclusion: The study illuminates the various renal lesions on autopsy and showed tubular lesions were more common than glomerular lesions in renal autopsy. Renal lesions are more common in males. The focus should be to develop more effective diagnostic methods for renal lesions so that intervention can be fast and sharp resulting in less mortality. [ABSTRACT FROM AUTHOR]

Abstract Background Metastatic tumors account for 80% of all lung tumors in children. Wilms tumour and osteosarcoma are the most tumors of childhood that produce lung metastases. The aim of the current study is to assess the prognostic factors of pulmonary metastatectomy in pediatric solid tumours as age, number, size, site,laterality, resectability of pulmonary nodules, and number of Thoracotomies. Calculate overall survival among patients who underwent pulmonary metastatectomy. Methods It is a retrospective study including all pediatric patients with metastatic solid tumors to lungs treated at pediatric oncology department, National Cancer Institute, Cairo University from 2008 to 2014. Fifty-five patients were included, 43 (78.2℅) patients of them had Osteosarcoma. Results Thirty (54.5℅)patients were male. The mean age was 15 years ranging from (4.5- 23) years. The site of primary disease was at lower limbs in 43 (78.2%) patients. All patients underwent complete surgical resection of the primary disease with negative margin, 22(51.1%) of the osteosarcoma patients did amputation with tumor necrosis less than 90%. All patients received chemotherapy and only 9 received radiation therapy. The patients were classified into four groups according to time of diagnosis of pulmonary metastasis: at time of diagnosis in 13 (21.8%) patients, within treatment in 16 (30.9%) patients, within first year follow up in 18 (32.7%) patients and detected late in 8 (14.5%) patients. Bilateral lung metastasis diagnosed by CT chest were detected in 42 (76.4%) patients. Size of metastatic nodules was ranging from (0.5 to 10 cm) with mean 3.4 cm. Number of metastatic nodules was ranging from (1 to 28) median 4.Metastatic complications were detected in 19 patients. 5-year OS was 74.8% in the study group, and 68% in osteosarcoma patients. Effect of prognostic factors as sex, time of respectability, laterality, tumor necrosis of the 1ry disease, Timing of lung metastasis, size and site of the primary, Surgical approach of metastatectomy, postoperative complications on overall survival of the studied patients was done with significant P-value of tumor necrosis of the 1ry disease and Timing of lung metastasis 0.017, 0.001 respectively. Conclusion Resection of pulmonary metastases of pediatric solid tumours is a safe and effective treatment that offers better survival.

Background: Metastatic tumors account for 80% of all lung tumors in children. Wilms tumour and osteosarcoma are the most tumors of childhood that produce lung metastases. The aim of the current study is to assess the prognostic factors of pulmonary metastatectomy in pediatric solid tumours as age, number, size, site,laterality, resectability of pulmonary nodules, and number of Thoracotomies. Calculate overall survival among patients who underwent pulmonary metastatectomy. Methods: It is a retrospective study including all pediatric patients with metastatic solid tumors to lungs treated at pediatric oncology department, National Cancer Institute, Cairo University from 2008 to 2014. Fifty-five patients were included, 43 (78.2℅) patients of them had Osteosarcoma. Results: Thirty (54.5℅)patients were male. The mean age was 15 years ranging from (4.5- 23) years. The site of primary disease was at lower limbs in 43 (78.2%) patients. All patients underwent complete surgical resection of the primary disease with negative margin, 22(51.1%) of the osteosarcoma patients did amputation with tumor necrosis less than 90%. All patients received chemotherapy and only 9 received radiation therapy. The patients were classified into four groups according to time of diagnosis of pulmonary metastasis: at time of diagnosis in 13 (21.8%) patients, within treatment in 16 (30.9%) patients, within first year follow up in 18 (32.7%) patients and detected late in 8 (14.5%) patients. Bilateral lung metastasis diagnosed by CT chest were detected in 42 (76.4%) patients. Size of metastatic nodules was ranging from (0.5 to 10 cm) with mean 3.4 cm. Number of metastatic nodules was ranging from (1 to 28) median 4.Metastatic complications were detected in 19 patients. 5-year OS was 74.8% in the study group, and 68% in osteosarcoma patients. Effect of prognostic factors as sex, time of respectability, laterality, tumor necrosis of the 1ry disease, Timing of lung metastasis, size and site of the primary, Surgical approach of metastatectomy, postoperative complications on overall survival of the studied patients was done with significant P-value of tumor necrosis of the 1ry disease and Timing of lung metastasis 0.017, 0.001 respectively. Conclusion: Resection of pulmonary metastases of pediatric solid tumours is a safe and effective treatment that offers better survival. [ABSTRACT FROM AUTHOR]

Despite being one of the most frequent solid tumours in children, renal tumours are uncommon. Their accurate diagnosis and staging are essential for the appropriate treatment because they comprise a variety of entities with a broad spectrum of clinical, histological, molecular biology, and prognostic features. Wilms tumour (WT) accounts for 80–85% of renal tumours of childhood, whereas other tumours including mesoblastic nephroma, clear cell sarcoma, rhabdoid tumour, renal cell carcinoma, and others are extremely uncommon (up to 2%–4% each), which explains why they pose a significant diagnostic challenge for pathologists. There are two major study groups with different treatment approaches but very comparable outcomes. The International Society of Paediatric Oncology approach (followed in most of the world) is based on preoperative chemotherapy, followed by surgery and further therapy, whereas the Children's Oncology Group approach (followed mainly in the United States and Canada) is based on primary surgery, followed by postoperative treatment. In both study groups for WT the most important prognostic factors are histological type and stage. The criteria for subtyping and staging are similar but still differ between the study groups, making a direct comparison impossible, but nevertheless, the outcomes are remarkably similar. The chapter provides an update on pathology, recent molecular discoveries and prognosis in paediatric renal tumours. [ABSTRACT FROM AUTHOR]

Background: Wilms tumour (WT) is caused by aberrant embryonic kidney development and associated with dysregulated expression of short, non-protein-coding RNAs termed microRNAs (miRNAs). At present, there is no reliable circulating biomarker of WT, and this remains an urgent unmet clinical need. Such biomarkers may assist diagnosis, subtyping/prognostication, and disease-monitoring. Here, we established the list of dysregulated circulating miRNAs in WT from the existing published literature. Methods: Regardless of publication date, PubMed, Scopus, Web-of-Science, and Wiley online library databases were searched for English/French studies on WT circulating miRNAs. The PRISMA-compliant search was registered in PROSPERO. The QUADAS tool measured retained article quality. The meta-analysis assessed the sensitivity and specificity of miRNAs for WT diagnosis. Results: Qualitative analysis included 280 samples (172 WT patients; 108 healthy controls) from five of 450 published articles. The study uncovered 301 dysregulated miRNAs (144 up-regulated, 143 down-regulated, 14 conflicting). The pooled sensitivity, specificity, and AUC of the 49 significantly dysregulated microRNAs from two studies was 0.67 [0.62; 0.73], 0.95 [0.92; 0.96] and 0.77 [0.73; 0.81] respectively, indicating a stronger diagnostic potential for WT. Conclusions: Circulating miRNAs show promise for WT diagnosis and prognosis. More research is needed to confirm these findings and determine associations with tumour stage/subtype. Prospero registration number: CRD42022301597.

Abstract Background The COVID‐19 pandemic had global catastrophic effects on the management of non‐communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic’s impact on the number of new diagnoses, disease characteristics and management delay for paediatric renal tumour patients included in the SIOP‐RTSG‐UMBRELLA study, as compared with data from a historical SIOP‐RTSG trial (2005–2009). Methods The number of intensive care admissions, population mobility rates and national lockdown periods/restrictions were used as proxies of the pandemic’s severity and impact on societies. Clinical and tumour data were extracted from the SIOP‐RTSG‐UMBRELLA study and from historical SIOP‐RTSG trials. Results During the first lockdown in Europe, the number of newly diagnosed patients decreased following restrictions and population immobilisation. Additionally, there was a higher proportion of advanced disease (37% vs. 17% before and after COVID‐9, p

Introduction: Renal artery embolization has been used in a palliative fashion for symptomatic relief of hematuria or flank pain in unresectable renal cell carcinoma in adults. There is limited data on using embolization for actively bleeding and unresectable tumours in the oncological pediatric population. Case description: A previously healthy, five-year-old boy with no significant past medical or surgical history presented to the clinic with gradually worsening abdominal distension associated with occasional abdominal pain, gross hematuria, and lethargy for four months. Diagnostic investigations showed an 18 cm left-sided metastatic (pulmonary) renal tumour (Wilms), which was deemed unresectable on imaging. Treatment was planned on SIOP-RTSG protocol. However, he became hemodynamically and vitally unstable with acute sudden distension of the abdomen on the left side after the first cycle of chemotherapy. Imaging showed active bleeding from an inferior branch of the left renal artery. Selective angioembolization was done, and chemotherapy was reinitiated with a patent left main renal artery. Following the fourth cycle of chemotherapy, he developed hemodynamic instability and abdominal pain; imaging revealed the resolution of pulmonary nodules and bleeding from the left renal artery (main); this was again embolized, and the patient was stabilized. The patient was operated on after optimization and complete resection of the mass was done with negative margins. On six months follow up, he is well. Practical implications: To the best of our knowledge, this is the first case where angioembolization has been done in conjunction with neoadjuvant chemotherapy to downsize a Wilms Tumor to achieve favourable outcomes. Continued research efforts are necessary to optimize strategies and improve the prognosis for pediatric patients, and this case is one of the prime examples.

Testicular germ cell tumours are the most common malignancies in young men. Germ cell tumours can be classified as seminomas or non-seminomas, each with different clinical features and treatment approaches. Germ cell tumours are occasionally associated with somatic-type malignancy, particularly in metastatic lymph nodes after adjuvant chemotherapy. Adenocarcinomas and rhabdomyosarcoma are the most common malignancies in this setting. In this report, we present a unique case of a 37-year-old patient who presented with a testicular teratoma containing a nephroblastoma component. The tumour exhibited characteristic morphology that resembled foetal kidney and expressed nuclear WT-1 and PAX-8 on immunohistochemistry. Following surgery, the patient opted for active surveillance and remains disease-free. To date, only 7 cases of nephroblastoma in primary testicular teratoma have been reported. This case highlights the importance of considering this rare entity in the differential diagnosis of testicular teratomas and the need for careful pathological examination.

Background: The COVID‐19 pandemic had global catastrophic effects on the management of non‐communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic's impact on the number of new diagnoses, disease characteristics and management delay for paediatric renal tumour patients included in the SIOP‐RTSG‐UMBRELLA study, as compared with data from a historical SIOP‐RTSG trial (2005–2009). Methods: The number of intensive care admissions, population mobility rates and national lockdown periods/restrictions were used as proxies of the pandemic's severity and impact on societies. Clinical and tumour data were extracted from the SIOP‐RTSG‐UMBRELLA study and from historical SIOP‐RTSG trials. Results: During the first lockdown in Europe, the number of newly diagnosed patients decreased following restrictions and population immobilisation. Additionally, there was a higher proportion of advanced disease (37% vs. 17% before and after COVID‐9, p < 0.001) and larger median tumour volume (559 cm3 vs. 328 and 434 cm3 before and after, p < 0.0001). Also in Brazil, the proportion of advanced disease was higher during the national decrease in mobilisation and start of restrictions (50% and 24% vs. 11% and 18% before and after, p < 0.01). Tumour volume in Brazil was also higher during the first months of COVID‐19 (599 cm3 vs. 459 and 514 cm3), although not significant (p = 0.17). We did not observe any delays in referral time nor in time to start treatment, even though COVID‐19 restrictions may have caused children to reach care later. Conclusion: The COVID‐19 pandemic briefly changed the tumour characteristics of children presenting with renal tumours. The longer‐term impact on clinical outcomes will be kept under review. [ABSTRACT FROM AUTHOR]

Introduction: Late Wilms tumour (WT) recurrences are rare events with poorly understood pathogenesis. They could be induced by previous chemo- and radiotherapy regimens, which can also prompt a rhabdomyomatous differentiation. Prostatic embryonal rhabdomyosarcoma (PER) is an extremely rare disease in adults, with an aggressive behaviour and abysmal prognosis. Radio-induced PER have been described. Case description: We report the case of a 29 years old man, with a history of WT, diagnosed with a symptomatic prostatic mass. Blastemic elements were shown at the transrectal biopsy, suggesting the possibility of a late WT recurrence. After laparoscopic resection, an unexpected pathologic diagnosis was reached: PER. Conclusion: We retrace and analyse the diagnostic and therapeutic path of the case that represents a mixture of two different conditions which might be unrelated or intertwined in a causal relationship. Among the differential diagnosis of a prostatic mass, the possibility of a prostatic sarcoma should not be overlooked, in presence of blastemic elements, even in a patient with a WT history. [ABSTRACT FROM AUTHOR]

Abstract Background Most children with Wilms tumour are successfully treated with multidrug chemotherapy and surgery. These treatments cause severe side effects for the patients, an issue that needs to be addressed by exploring other treatment options with less or no side effects. One option is to complement current therapies with agents that could potentially induce tumour cell differentiation, for example retinoic acid (RA). Aims To facilitate quick assessment of an agent's effect on Wilms tumour differentiation by a rapid in vitro model system. Methods and Results Here WiT49 and CCG99‐11 Wilms tumour cells were treated with 10 μM RA for 72 h or 9 days. Cultured cells were scraped off from Petri dishes, pelleted and embedded in paraffin in the same way as clinical tumour specimens are preserved. Cell morphology and differentiation were evaluated by analyses of haematoxylin eosin (H&E) and immunohistochemical stainings. Based on H&E, WT1 and CKAE1/3 stainings, RA treatment induced further epithelial differentiation of WiT49 cells, whereas there was no sign of induced maturation in CCG99‐11 cells. Ki67 staining showed that RA inhibited cell proliferation in both cell lines. Conclusions Our study shows that in vitro culturing of WiT49 and CCG99‐11 cells, followed by pelleting and paraffin embedding of cell pellets, could aid in a quick evaluation of potential differentiating agents against Wilms tumour. In addition, our results strengthen previous results that retinoic acid could be a potential complement to regular Wilms tumour treatment.

Testicular germ cell tumours are the most common malignancies in young men. Germ cell tumours can be classified as seminomas or non-seminomas, each with different clinical features and treatment approaches. Germ cell tumours are occasionally associated with somatic-type malignancy, particularly in metastatic lymph nodes after adjuvant chemotherapy. Adenocarcinomas and rhabdomyosarcoma are the most common malignancies in this setting. In this report, we present a unique case of a 37-year-old patient who presented with a testicular teratoma containing a nephroblastoma component. The tumour exhibited characteristic morphology that resembled foetal kidney and expressed nuclear WT-1 and PAX-8 on immunohistochemistry. Following surgery, the patient opted for active surveillance and remains disease-free. To date, only 7 cases of nephroblastoma in primary testicular teratoma have been reported. This case highlights the importance of considering this rare entity in the differential diagnosis of testicular teratomas and the need for careful pathological examination. [ABSTRACT FROM AUTHOR]

Background Unilateral nephrectomy is a relatively common procedure in children which results in a solitary functioning kidney (SFK). Living with an SFK predisposes to kidney injury, but it remains unknown which children are most at risk. We aimed to investigate kidney injury rates in patients who underwent unilateral nephrectomy in childhood and to investigate differences among nephrectomies performed for a congenital anomaly, malignancy or other condition. Methods MEDLINE and EMBASE were searched for studies reporting kidney injury rates [i.e. proteinuria, hypertension and/or a decreased glomerular filtration rate (GFR)] of patients who underwent unilateral nephrectomy during childhood. Studies including five or more patients with at least 12 months of follow-up were eligible. Analyses were performed using random effects models and stratified by indication for nephrectomy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were used for reporting. Results Over 5000 unique articles were screened, of which 53 studies reporting on >4000 patients were included in the analyses. Proteinuria, hypertension and a decreased GFR were present in 15.3, 14.5 and 11.9% of patients, respectively. Heterogeneity among the studies was large in several subgroups, impairing quantitative meta-analyses. However, none of our analyses indicated differences in injury rates between a congenital anomaly or malignancy as an indication for nephrectomy. Conclusions Unilateral nephrectomy during childhood results in signs of kidney injury in >10% of patients, with no clear difference between the indications for nephrectomy. Therefore, structured follow-up is necessary in all children who underwent nephrectomy, regardless of the indication. [ABSTRACT FROM AUTHOR]

Wilms tumour (WT), an embryonal kidney cancer, has been extensively characterised for genetic and epigenetic alterations, but a proportion of WTs still lack identifiable abnormalities. To uncover DNA methylation changes critical for WT pathogenesis, we compared the epigenome of foetal kidney with two WT cell lines, filtering our results to remove common cancer‐associated epigenetic changes and to enrich for genes involved in early kidney development. This identified four hypermethylated genes, of which ESRP2 (epithelial splicing regulatory protein 2) was the most promising for further study. ESRP2 was commonly repressed by DNA methylation in WT, and this occurred early in WT development (in nephrogenic rests). ESRP2 expression was reactivated by DNA methyltransferase inhibition in WT cell lines. When ESRP2 was overexpressed in WT cell lines, it inhibited cellular proliferation in vitro, and in vivo it suppressed tumour growth of orthotopic xenografts in nude mice. RNA‐seq of the ESRP2‐expressing WT cell lines identified several novel splicing targets. We propose a model in which epigenetic inactivation of ESRP2 disrupts the mesenchymal to epithelial transition in early kidney development to generate WT.

Preoperative Wilms tumour rupture has been reported sporadically. But when identified, SIOP (Societe Internationale d’Oncologie Pediatrique) recommends that these patients should be upstaged to the 3rd stage. The purpose of this publication was to present the clinical and radiological features of preoperative tumour rupture in our patient. A 4-year-old girl was treated in the oncology department for a large Wilms tumour. The child presented inconclusive clinical and radiographical features of preoperative tumour rupture. Therefore, standard 4-week preoperative chemotherapy was used. Unfortunately, a tight connection between the cystic part of the tumour and the peritoneum became the cause of tumour rupture during surgery. Not every child who meets the radiological criteria for preoperative tumour rupture should be upgraded. The radiological features of preoperative tumour rupture shouldvery much increase the caution of the surgeon.

This population-based study is the first to provide a detailed analysis of trends in incidence and survival of children and adolescents diagnosed with renal malignancies in the Netherlands. Data on all renal malignancies diagnosed in paediatric patients (0–18 years) between 1990 and 2014 [N = 648, 92% Wilms tumour (WT)] were extracted from the Netherlands Cancer Registry. Five-year overall survival (OS) was estimated using the actuarial method. Time trends in incidence were assessed by calculating average annual percentage change. A parametric survival model was used to compare the multivariable-adjusted risk of dying from WT between two diagnostic periods. The incidence was 8 per million person-years and was constant over time (average annual percentage change -0.8%, p = 0.29). Patients with WT had a favourable outcome in both time periods; 5-year OS was 88% in 1990–2001 and 91% in 2002–2014. Multivariable analysis showed that the risk of dying from WT was not significantly decreased in the latest period (hazard ratio, 95% CI: 0.7, 0.4–1.3). Five-year OS decreased with increasing disease stage, ranging from 95 to 100% for stage I-II and about 80% for stage III–IV to 74% for bilateral disease. Five-year OS were 81% for renal cell carcinoma, 77% for clear cell sarcoma of the kidney and 20% for malignant rhabdoid tumour of the kidney. Incidence of paediatric renal malignancies in the Netherlands has been stable since the 1990s. Five-year OS of WT reached 91% and was similar to findings for other developed countries. Contrary to the excellent outcome for WT, the outcome of malignant rhabdoid tumour of the kidney remained inferior. • The incidence of paediatric renal tumours in the Netherlands was stable between 1990 and 2014. • 5-year OS of Wilms tumour reached 91% and was similar to rates in other developed countries. • 5-year OS were 81% for renal cell carcinoma, 77% for clear cell sarcoma of the kidney and 20% for malignant rhabdoid tumour of the kidney. • Particular attention should be paid to adverse prognostic subgroups, especially malignant rhabdoid tumour of the kidney. [ABSTRACT FROM AUTHOR]

Wilms tumour (WT) is the most common kidney malignancy in children. Chemoresistance is the leading cause of tumour recurrence and poses a substantial therapeutic challenge. Increasing evidence has underscored the role of the tumour immune microenvironment (TIM) in cancers and the potential for immunotherapy to improve prognosis. There remain no reliable molecular markers for reflecting the immune landscape and predicting patient survival in WT. Here, we examine differences in gene expression by highthroughput RNA sequencing, focused on differentially expressed immunerelated genes (IRGs) based on the ImmPort database. Via univariate Cox regression analysis and Lasso-penalized Cox regression analysis, IRGs were screened out to establish an immune signature. Kaplan-Meier curves, timerelated ROC analysis, univariate and multivariate Cox regression studies, and nomograms were used to evaluate the accuracy and prognostic significance of this signature. Furthermore, we found that the immune signature could reflect the immune status and the immune cell infiltration character played in the tumour microenvironment (TME) and showed significant association with immune checkpoint molecules, suggesting that the poor outcome may be partially explained by its immunosuppressive TME. Remarkably, TIDE, a computational method to model tumour immune evasion mechanisms, showed that this signature holds great potential for predicting immunotherapy responses in the TARGET-wt cohort. To decipher the underlying mechanism, GSEA was applied to explore enriched pathways and biological processes associated with immunophenotyping and Connectivity map (CMap) along with DeSigN analysis for drug exploration. Finally, four candidate immune genes were selected, and their expression levels in WT cell lines were monitored via qRT-PCR. Meanwhile, we validated the function of a critical gene, NRP2. Taken together, we established a novel immune signature that may serve as an effective prognostic signature and predictive biomarker for immunotherapy response in WT patients. This study may give light on therapeutic strategies for WT patients from an immunological viewpoint. [ABSTRACT FROM AUTHOR]

Introduction: Markers of inflammation such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been found to be associated with survival in cancer patients. The aim of the current study was to establish the prognostic significance of simple laboratory markers of systemic inflammation in paediatric patients diagnosed with Wilms tumour (WT). Additionally, we aimed to compare the complete blood count (CBC) parameters of WT patients and the non-oncological control group.Material and methods: The study group included 88 children diagnosed with WT. Clinicopathological data, as well as CBC, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at diagnosis, were obtained. Additionally, the laboratory results of 62 healthy control paediatric patients were collected. Uni- and multivariate proportional Cox's hazard analyses were computed to create a model predicting relapse-free survival (RFS) and overall survival (OS) in the study group.Results: High CRP, LDH, and NLR were associated with a higher stage of WT and shorter RFS, whereas all parameters correlated with OS. In multivariate analysis, only LDH levels had adverse significance in predicting RFS. C-reactive protein and LMR retained their prognostic value in the multivariate model predicting OS. Comparing the WT group with controls, high LDH, high CRP, high NLR, and high PLR were associated with WT presence.Conclusions: Preoperative LDH, CRP, NLR, PLR, and LMR have significant prognostic value in patients with WT independently of age and stage. Combined low CRP and high LMR identified the group of patients with excellent OS. Patients with high LDH were characterized by the highest risk of relapse. [ABSTRACT FROM AUTHOR]

Background: Wilms tumour (WT), the second most reported childhood cancer in Morocco, is a malignant kidney tumour that affects children under 15 years old. Prognosis has improved with the adoption of multimodal treatment. However, data on WT in Morocco remain limited., Aims: This study aims to comprehensively describe and analyse the epidemiological, clinicopathological features and treatment outcomes of WT in Moroccan patients, including treatment response and recurrence rates., Methods and Results: A retrospective study involved 84 children under 15 years with WT, treated according to the SIOP protocol and followed at the Paediatric Haematology and Oncology Centre at Children's hospital of Rabat, between January 2014 and February 2018. The median age of participants was 36 months, with a male/female sex ratio of 0.79. Abdominal mass was the primary concern in 55 cases (66%). Five patients (6%) had bilateral WT. Metastatic WT occurred in 21 cases (25%). Stage III was predominant in 33 cases (43%). Twenty cases (26%) had high-risk WT, and IVC tumour thrombus was observed in 12 cases (14%). WT histotype correlated significantly with both sex and tumour localisation (p values of 0.040 and 0.013, respectively). Age correlated significantly with WT extension, overall stage and SIOP histology risk grades (p values of 0.003, 0.003 and 0.045, respectively). Overall stage was statistically related to the occurrence of IVC tumour thrombus (p = 0.002). Over a 5-year span post-nephrectomy, complete remission was achieved in 63 patients (75%), partial remission in one patient (1%), while 19 patients (23%) died and one patient (1%) relapsed., Conclusion: These findings are encouraging for a developing country. However, the elevated rates of Stages III and IVC thrombus in this series are still high, primarily attributed to delays in diagnosis and treatment and the limited number of paediatric haematology and oncology units at the time of the study. Nevertheless, further multicentric research is warranted to enrich Moroccan data and establish a national register for WT cases., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background and Aims: Tumour rupture (TR) signifies stage III disease and requires treatment intensification, which includes radiotherapy. We studied the associations between radiological, surgical and pathology TR in children with Wilms tumour (WT) in a United Kingdom multicentre clinical study., Patients and Methods: The IMPORT (Improving Population Outcomes for Renal Tumours of Childhood) study registered 712 patients between 2012 and 2021. Children with TR on central radiology review (CRR) at diagnosis and/or indication of preoperative TR on surgical forms were included. Correlation between radiology/surgery/pathology findings was made., Results: Total 141 patients had TR identified (69 on CRR, 43 on surgical form and 29 on both), and 124/141 had images available for CRR, and 98/124 had features suggestive of TR on diagnostic CRR (63 magnetic resonance imaging/35 computed tomography). TR was limited to the renal fossa in 47/98 (48%) and intraperitoneal in 51/98 (52%). Three of 98(3%) had upfront surgery, and 87/95 (92%) had TR confirmed on post-chemotherapy preoperative scans. Among 80/98 (82%) cases with TR on CRR and available surgical forms, TR was not confirmed on surgery or pathology in 38/80, giving a false-positive rate of 48%. Preoperative TR was indicated on 72 surgical forms, with images available for CRR in 55. Twenty-six of 55 (47%) were false-negative for TR on CRR and of those 10/26 (38%) had TR confirmed on pathology., Conclusions: Radiology alone should not be used to define TR, as it does not accurately correlate with surgical or pathology findings, and therefore cannot be relied upon for definitive staging and treatment. A multidisciplinary team should take the decision regarding the final abdominal stage and treatment using a multimodality approach considering clinical, radiological, surgical and pathological findings., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Wilms tumour, a common paediatric cancer, is difficult to treat in low- and middle-income countries due to limited access to imaging. Artificial intelligence (AI) has been introduced for staging, detecting, and classifying tumours, aiding physicians in decision-making. However, challenges include algorithm accuracy, translation into conventional diagnosis, reproducibility, and reliability. As AI technology advances, radiomics, an AI tool, emerges to extract tumour morphology and stage information., Objectives: This review explores the application of radiomics in Wilms tumour management, including its potential in diagnosis, prognosis, and treatment. Additionally, it discusses the future prospects of AI in this field and potential directions for automation-aided Wilms tumour treatment., Methods: The review analyses various research studies and articles on the use of radiomics in Wilms tumour management. This includes studies on automated deep learning-based classification, interobserver variability in histopathological analysis, and the application of AI in staging, detecting, and classifying Wilms tumours., Results: The review finds that radiomics offers several promising applications in Wilms tumour management, including improved diagnosis: it helps in classifying Wilms tumours from other paediatric kidney tumours, prognosis prediction: radiomic features can be used to predict both staging and response to preoperative chemotherapy, Treatment response assessment: Radiomics can be used to monitor the response of Wilms and to predict the feasibility of nephron-sparing surgery., Conclusions: This review concludes that radiomics has the potential to significantly improve the diagnosis, prognosis, and treatment of Wilms tumours. Despite some challenges, such as the need for further research and validation, AI integration in Wilms tumour management offers promising opportunities for improved patient care., Advances in Knowledge: This review provides a comprehensive overview of the potential applications of radiomics in Wilms tumour management and highlights the significant role AI can play in improving patient outcomes. It contributes to the growing body of knowledge on AI-assisted diagnosis and treatment of paediatric cancers., Competing Interests: There are no competing interests among authors related to the submitted manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Wilms tumour (WT) is the most common renal tumour in children, and studies of immune checkpoint inhibitors (ICIs) treatment and markers are limited in number. In this study we investigated the ICIs' related immune landscape by examining the expression of PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) proteins by immunohistochemistry (IHC), tumour mutation burden (TMB), and correlations with histology and clinical outcome. Positive PD-L1 (SP263) expression was defined as modified combined positive score (CPS) ≥1. A total of 59 WTs (from 2000 to 2017), including eight (14.0%) with anaplasia, from 46 patients were analysed (45 primary and 14 metastatic). Thirteen WTs (13/59, 22%) were positive for PD-L1 (8 primary, 5 metastatic; CPS 1.11-3.42). Positive PD-L1 expression was associated with diffuse anaplasia (p<0.05) and significantly shorter progression-free survival (p<0.05) among WTs with favourable histology (n=39). CD8+ lymphocytes were present in all analysed WTs. A subset of CD8+ cells co-expressed PD-1, which was associated with favourable histology and treatment. MMR IHC stains identified two (2/18, 11%) WTs with isolated PMS2 loss. All six WTs analysed for TMB showed low mutation burden. We found CD8+ lymphocytes in all analysed WTs and identified a fraction of WT (17.8% of primary and 35.8% of metastatic) with positive PD-L1 CPS, suggesting potential response to ICIs in some patients., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Spinal cord involvement of Wilms' tumour is rare. A 14-year-old girl presented with an abdominal mass, paraplegia and loss of bladder and bowel control. Radiological investigations confirmed the presence of a large intraabdominal mass with infiltration into the spinal canal with impingement of nerve roots and the spinal cord. Histopathological evaluation demonstrated a nephroblastoma. It was decided to commence prompt neoadjuvant chemotherapy to render the tumour amenable to surgical resection. The patient unfortunately demised before receiving her first dose. Early diagnosis and timeous initiation of treatment is critical in limiting morbidity and mortality associated with malignant spinal cord compression.

Introduction Markers of inflammation such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been found to be associated with survival in cancer patients. The aim of the current study was to establish the prognostic significance of simple laboratory markers of systemic inflammation in paediatric patients diagnosed with Wilms tumour (WT). Additionally, we aimed to compare the complete blood count (CBC) parameters of WT patients and the non-oncological control group. Material and methods The study group included 88 children diagnosed with WT. Clinicopathological data, as well as CBC, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at diagnosis, were obtained. Additionally, the laboratory results of 62 healthy control paediatric patients were collected. Uni- and multivariate proportional Cox’s hazard analyses were computed to create a model predicting relapse-free survival (RFS) and overall survival (OS) in the study group. Results High CRP, LDH, and NLR were associated with a higher stage of WT and shorter RFS, whereas all parameters correlated with OS. In multivariate analysis, only LDH levels had adverse significance in predicting RFS. C-reactive protein and LMR retained their prognostic value in the multivariate model predicting OS. Comparing the WT group with controls, high LDH, high CRP, high NLR, and high PLR were associated with WT presence. Conclusions Preoperative LDH, CRP, NLR, PLR, and LMR have significant prognostic value in patients with WT independently of age and stage. Combined low CRP and high LMR identified the group of patients with excellent OS. Patients with high LDH were characterized by the highest risk of relapse.

Anaplasia is an unfavourable prognostic histological feature in Wilms tumour (WT). Patients with stage I anaplastic WT (AWT) typically achieve good outcomes, albeit with more treatment than for stage I non-AWT. Since the SIOP-WT-2001 study, patients with focal AWT (FAWT) have been classified as intermediate risk and received less intense treatment than patients with diffuse AWT (DAWT). The aim of the study was to analyse outcomes in these patients. This was a retrospective analysis of clinicopathological features and outcomes of 59 patients with stage I AWT (19 FAWT, 40 DAWT) from the SIOP-WT-2001 GPOH and UK-CCLG groups. The patients with FAWT were treated as intermediate-risk WT, with 8 weeks of vincristine and actinomycin D (4 weeks pre-operatively, and 4 weeks post-operatively). For comparison, we also assessed outcomes in 818 patients with stage I intermediate-risk non-AWT (IR-non-AWT). The patients with DAWT were treated with vincristine, actinomycin D and doxorubicin for 31 weeks. No group received radiotherapy. Median follow-up was 67.6 months; 4-year event-free survival and overall survival were 87% (95% confidence interval [CI] = 72–100) and 100%, respectively, in the FAWT group, 85% (95% CI = 74–98) and 93% (95% CI 85–100), respectively, in the DAWT group and 91% (95% CI = 89–93) and 98% (95% CI = 97–99), respectively, in the IR-non-AWT group. Outcomes for patients with stage I FAWT were comparable with those of other, identically treated, patients with stage I IR-non-AWT. Patients with stage I DAWT also showed good outcomes, albeit with more intensive chemotherapy than IR-non-AWT, but without radiotherapy. [Display omitted] • Anaplasia is a powerful prognostic factor in patients with Wilms tumour (WT). • Previously, stage I focal anaplastic WT (FAWT) and diffuse anaplastic WT (DAWT) were treated the same. • In the present study, FAWT was treated as intermediate-risk WT (IR-WT). • FAWT and IR-non-AWT had comparable outcomes. • DAWT showed good outcomes with more intensive chemotherapy but without radiotherapy. [ABSTRACT FROM AUTHOR]

While all childhood cancers are rare, the abdomen and pelvis are common sites of origin. After haematological malignancies and intracranial tumours, neuroblastoma is the most common childhood cancer, most often arising in the adrenal gland. The next most common extracranial tumours are Wilms tumour, arising in the kidney (nephroblastoma) and rhabdomyosarcoma that may arise in a variety of sites, typically in the pelvis. Hepatoblastoma, non-Hodgkin lymphoma and germ cell tumours are other abdominal and pelvic tumours seen in childhood. Many childhood tumours appear to arise from residual embryonic cells which make them sensitive to chemotherapy and radiotherapy. Surgery plays a crucial role both in establishing the diagnosis and, in the majority of cases, by resection of the tumour. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of chemokines in Wilms tumours, especially their chemotaxis to immune cells and the role of DNA methylation in regulating the expression level of chemokines. Methods: RNAseqV2 gene expression and clinical data were downloaded from the TARGET database. DNA methylation data were downloaded from the GEO and cBioPortal database. The difference analysis and Kaplan-Meier(KM) analysis of chemokines were performed by edgeR package. Then predictive model based on chemokines was constructed by lasso regression and multivariate COX regression. ROC curve, DCA curve, Calibration curve, and Nomogram were used to evaluate the prognostic model. MCPcounter and Cibersort algorithm was used to calculate the infiltration of immune cells in Wilms tumour and para-tumour samples. Then the difference analysis of the immune cells was performed. The relationship between chemokines and immune cells were calculated by Pearson correlation. In addition, DNA methylation differences between Wilms tumour and para-tumour samples was performed. The correlation between DNA methylation and mRNA expression was calculated by Pearson correlation. Western blot(WB)and immunofluorescence were used to confirm the differential expression of CX3CL1 and T cells, and the correlation between them. Results: A total of 16 chemokines were differentially expressed in tumour and para-tumour samples. A total of seven chemokines were associated with survival. CCL2 and CX3CL1 were positively correlated with prognosis, while high expression of CCL3, CCL8, CCL15, CCL18 and CXCL9 predicted poor prognosis. By lasso regression and multivariate COX regression, CCL3, CCL15, CXCL9 and CX3CL1 were finally included to construct a prediction model. The model shows good prediction ability. MCPcounter and Cibersort algorithm both showed that T cells were higher in para-tumour tissues than cancer tissues. Correlation analysis showed that CX3CL1 had a strong correlation with T cells. These were verified by Weston blot and immunofluorescence. DNA methylation analysis showed that various chemokines were different in para-tumours and tumours. CX3CL1 was hypermethylated in tumours, and the degree of methylation was negatively correlated with mRNA expression. Conclusion: 1. There is low T cell infiltration in nephroblastoma. 2. Chemokines such as CX3CL1 indicate a favourable prognosis and positively correlate with the number of T cells. 3. chemokines such as CX3CL1 are negatively regulated by DNA hypermethylation. [ABSTRACT FROM AUTHOR]

Background: Wilms tumour (WT) survivors, especially patients with associated syndromes or genitourinary anomalies due to constitutional WT1 pathogenic variant, have increased risk of kidney failure. We describe the long-term kidney function in children with WT and WT1 pathogenic variant to inform the surgical strategy and oncological management of such complex children. Methods: Retrospective analysis of patients with WT and constitutional WT1 pathogenic variant treated at a single centre between 1993 and 2016, reviewing genotype, phenotype, tumour histology, laterality, treatment, patient survival, and kidney outcome. Results: We identified 25 patients (60% male, median age at diagnosis 14 months, range 4–74 months) with WT1 deletion (4), missense (2), nonsense (8), frameshift (7), or splice site (4) pathogenic variant. Thirteen (52%) had bilateral disease, 3 (12%) had WT-aniridia, 1 had incomplete Denys-Drash syndrome, 11 (44%) had genitourinary malformation, and 10 (40%) had no phenotypic anomalies. Patient survival was 100% and 3 patients were in remission after relapse at median follow-up of 9 years. Seven patients (28%) commenced chronic dialysis of which 3 were after bilateral nephrectomies. The overall kidney survival for this cohort as mean time to start of dialysis was 13.38 years (95% CI: 10.3–16.4), where 7 patients experienced kidney failure at a median of 5.6 years. All of these 7 patients were subsequently transplanted. In addition, 2 patients have stage III and stage IV chronic kidney disease and 12 patients have albuminuria and/or treatment with ACE inhibitors. Four patients (3 frameshift; 1 WT1 deletion) had normal blood pressure and kidney function without proteinuria at follow-up from 1.5 to 12 years. Conclusions: Despite the known high risk of kidney disease in patients with WT and constitutional WT1 pathogenic variant, nearly two-thirds of patients had sustained native kidney function, suggesting that nephron-sparing surgery (NSS) should be attempted when possible without compromising oncological risk. Larger international studies are needed for accurate assessment of WT1genotype-kidney function phenotype correlation. [ABSTRACT FROM AUTHOR]

Society of International Pediatric Oncology – Renal Tumor Study Group (SIOP-RTSG) treatment recommendations for relapsed Wilms tumour (WT) are stratified by the intensity of first-line treatment. To explore the evidence for the treatment of patients relapsing after vincristine and actinomycin-D (VA) treatment for primary WT, we retrospectively evaluated rescue treatment and survival of this patient group. We included 109 patients with relapse after VA therapy (no radiotherapy) for stage I-II primary low- or intermediate-risk WT from the SIOP 93–01 and SIOP 2001 studies. Univariate Cox regression analysis was performed to study the effect of relapse treatment intensity on event-free survival (EFS) and overall survival (OS). Relapse treatment intensity was classified into vincristine, actinomycin-D, and either doxorubicin or epirubicin (VAD), and more intensive therapies (ifosfamide/carboplatin/etoposide [ICE]/≥ 4 drugs/high-dose chemotherapy with haematopoietic stem cell transplantation [HD HSCT]). Relapse treatment regimens included either VAD, or cyclophosphamide/carboplatin/etoposide/doxorubicin (CyCED), or ICE backbones. Radiotherapy was administered in 62 patients and HD HSCT in 15 patients. Overall, 5-year EFS and OS after relapse were 72.3% (95% confidence interval [CI]: 64.0–81.6%) and 79.3% (95% CI: 71.5–88.0%), respectively. Patients treated with VAD did not fare worse when compared with patients treated with more intensive therapies (hazard ratio EFS: 0.611 [95% CI: 0.228–1.638] [ p -value = 0.327] and hazard ratio OS: 0.438 [95% CI: 0.126–1.700] [ p -value = 0.193]). Patients with relapsed WT after initial VA-only treatment showed no inferior EFS and OS when treated with VAD regimens compared with more intensive rescue regimens. A subset of patients relapsing after VA may benefit from less intensive rescue treatment than ICE/CyCED-based regimens and deserve to be pinpointed by identifying additional (molecular) prognostic factors in future studies. • On behalf of the Society of International Pediatric Oncology- Renal Tumor Study Group. • Risk stratification of relapsed Wilms tumour is based on primary treatment intensity. • Patients treated with vincristine and actinomycin-D are advised a four-drug therapy at relapse. • A three-drug therapy is adequate relapse treatment in a subset of patients. • Identification of this subset requires large-scale epidemiological and molecular studies. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the role of chemokines in Wilms tumours, especially their chemotaxis to immune cells and the role of DNA methylation in regulating the expression level of chemokines.MethodsRNAseqV2 gene expression and clinical data were downloaded from the TARGET database. DNA methylation data were downloaded from the GEO and cBioPortal database. The difference analysis and Kaplan-Meier(KM) analysis of chemokines were performed by edgeR package. Then predictive model based on chemokines was constructed by lasso regression and multivariate COX regression. ROC curve, DCA curve, Calibration curve, and Nomogram were used to evaluate the prognostic model. MCPcounter and Cibersort algorithm was used to calculate the infiltration of immune cells in Wilms tumour and para-tumour samples. Then the difference analysis of the immune cells was performed. The relationship between chemokines and immune cells were calculated by Pearson correlation. In addition, DNA methylation differences between Wilms tumour and para-tumour samples was performed. The correlation between DNA methylation and mRNA expression was calculated by Pearson correlation. Western blot(WB)and immunofluorescence were used to confirm the differential expression of CX3CL1 and T cells, and the correlation between them.ResultsA total of 16 chemokines were differentially expressed in tumour and para-tumour samples. A total of seven chemokines were associated with survival. CCL2 and CX3CL1 were positively correlated with prognosis, while high expression of CCL3, CCL8, CCL15, CCL18 and CXCL9 predicted poor prognosis. By lasso regression and multivariate COX regression, CCL3, CCL15, CXCL9 and CX3CL1 were finally included to construct a prediction model. The model shows good prediction ability. MCPcounter and Cibersort algorithm both showed that T cells were higher in para-tumour tissues than cancer tissues. Correlation analysis showed that CX3CL1 had a strong correlation with T cells. These were verified by Weston blot and immunofluorescence. DNA methylation analysis showed that various chemokines were different in para-tumours and tumours. CX3CL1 was hypermethylated in tumours, and the degree of methylation was negatively correlated with mRNA expression.Conclusion1. There is low T cell infiltration in nephroblastoma. 2. Chemokines such as CX3CL1 indicate a favourable prognosis and positively correlate with the number of T cells. 3. chemokines such as CX3CL1 are negatively regulated by DNA hypermethylation.

Wilms tumour (WT), an embryonal kidney cancer, has been extensively characterised for genetic and epigenetic alterations, but a proportion of WTs still lack identifiable abnormalities. To uncover DNA methylation changes critical for WT pathogenesis, we compared the epigenome of foetal kidney with two WT cell lines, filtering our results to remove common cancer‐associated epigenetic changes and to enrich for genes involved in early kidney development. This identified four hypermethylated genes, of which ESRP2 (epithelial splicing regulatory protein 2) was the most promising for further study. ESRP2 was commonly repressed by DNA methylation in WT, and this occurred early in WT development (in nephrogenic rests). ESRP2 expression was reactivated by DNA methyltransferase inhibition in WT cell lines. When ESRP2 was overexpressed in WT cell lines, it inhibited cellular proliferation in vitro, and in vivo it suppressed tumour growth of orthotopic xenografts in nude mice. RNA‐seq of the ESRP2‐expressing WT cell lines identified several novel splicing targets. We propose a model in which epigenetic inactivation of ESRP2 disrupts the mesenchymal to epithelial transition in early kidney development to generate WT. [ABSTRACT FROM AUTHOR]

Abstract Background Competitive endogenous RNAs (ceRNAs) have revealed a new mechanism of interaction between RNAs. However, an understanding of the ceRNA regulatory network in Wilms tumour (WT) remains limited. Methods The expression profiles of mRNAs, miRNAs and lncRNAs in Wilms tumour samples and normal samples were obtained from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database. The EdgeR package was employed to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analyses via the ClusterProfile R package were performed, and the lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape. Subsequently, the correlation between the ceRNA network and overall survival was analysed. Results A total of 2037 lncRNAs, 154 miRNAs and 3609 mRNAs were identified as differentially expressed RNAs in Wilms tumour. Of those, 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in the ceRNA regulatory network. The results of Gene Ontology (GO) analysis revealed that the differentially expressed genes (DEGs) were mainly enriched in terms related to response to mechanical stimuli, transcription factor complexes, and transcription factor activity (related to RNA polymerase II proximal promoter sequence-specific DNA binding). The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the DEGs were mainly enriched in pathways related to the cell cycle. The survival analysis results showed that 16 out of the 205 lncRNAs, 1 out of 26 miRNAs and 5 out of 143 mRNAs were associated with overall survival in Wilms tumour patients (P

Preoperative Wilms tumour rupture has been reported sporadically. But when identified, SIOP (Societe Internationale d'Oncologie Pediatrique) recommends that these patients should be upstaged to the 3rd stage. The purpose of this publication was to present the clinical and radiological features of preoperative tumour rupture in our patient. A 4-year-old girl was treated in the oncology department for a large Wilms tumour. The child presented inconclusive clinical and radiographical features of preoperative tumour rupture. Therefore, standard 4-week preoperative chemotherapy was used. Unfortunately, a tight connection between the cystic part of the tumour and the peritoneum became the cause of tumour rupture during surgery. Not every child who meets the radiological criteria for preoperative tumour rupture should be upgraded. The radiological features of preoperative tumour rupture shouldvery much increase the caution of the surgeon. [ABSTRACT FROM AUTHOR]

The congenital imprinting disorder, Beckwith‐Wiedemann syndrome (BWS) is associated with variable clinical features including hemihypertrophy/lateralised overgrowth (LO) and embryonal tumour predisposition. BWS‐associated (epi)genetic alterations occur in a subset of patients with isolated LO (ILO), leading to the concept of BWS spectrum disorder (BWSp). We investigated the relationship between clinical features and molecular diagnostic results in a cohort with LO using the BWSp international consensus group (BWSICG) clinical scoring system. Clinical/molecular findings in 94 previously‐unreported patients with LO referred for BWSp molecular studies were reviewed retrospectively. The BWSICG score was assigned and diagnostic rate calculated. BWSp‐associated (epi)genetic alteration was identified in 15/94 (16%). The molecular diagnostic rate by MS‐MLPA (blood DNA) for BWS‐related molecular findings in patients with LO was positively correlated with the BWSICG score. 3/48 with ILO had a molecular alteration. No individuals with ILO had developed an embryonal tumour at last follow up. Among a cohort of individuals with LO referred for BWSp molecular testing, the BWSICG score correlated with diagnostic yield. The embryonal tumour risk in children with ILO and negative molecular testing appeared very low, however longer‐ and more complete follow up is required to better define tumour risks in this group. [ABSTRACT FROM AUTHOR]

Since previous consensus-based Wilms tumour (WT) surveillance guidelines were published, novel genes and syndromes associated with WT risk have been identified, and diagnostic molecular tests for previously known syndromes have improved. In view of this, the International Society of Pediatric Oncology (SIOP)-Europe Host Genome Working Group and SIOP Renal Tumour Study Group hereby present updated WT surveillance guidelines after an extensive literature review and international consensus meetings. These guidelines are for use by clinical geneticists, pediatricians, pediatric oncologists and radiologists involved in the care of children at risk of WT. Additionally, we emphasise the need to register all patients with a cancer predisposition syndrome in national or international databases, to enable the development of better tumour risk estimates and tumour surveillance programs in the future. • Wilms tumour surveillance enables the detection of smaller and lower-stage tumours. • Guidelines are presented for all genes/syndromes associated with Wilms tumour risk. • Surveillance primarily recommended if >5% estimated childhood Wilms tumour risk. • Three-monthly renal ultrasonography until a child's 7th birthday. [ABSTRACT FROM AUTHOR]

Wilms tumour is the commonest renal tumour in children with peak age group of 2–5 years [1,2]. It commonly presents as an incidentally detected abdominal mass; however fever, hematuria and hypertension may also be seen [1]. Extra-renal Wilms tumour is extremely rare, with an incidence of 0.5%–1% [3,4]. Wilms tumour, most commonly metastasizes to the lungs, followed by lymph nodes and liver, however, metastasis to the bones and spinal cord at diagnosis is extremely rare [1,2,5–10]. We hereby, report an extremely rare presentation of suprarenal Wilms tumour with intraspinal metastases. Our case highlights the high degree of vigilance as well as timely intervention with multimodality therapy required to improve the outcomes in the setting of advanced metastatic disease; notwithstanding the potentially irreversible neurological weakness in the absence of optimal intervention.

The annotation of the tumour from medical scans is a crucial step in nephroblastoma treatment. Therefore, an accurate and reliable segmentation method is needed to facilitate the evaluation and the treatments of the tumour. The proposed method serves this purpose by performing the segmentation of nephroblastoma in MRI scans. The segmentation is performed by adapting and a 2D free hand drawing tool to select a region of interest in the scan slices. Results from 24 patients show a mean root-mean-square error of 0.0481 ± 0.0309, an average Dice coefficient of 0.9060 ± 0.0549 and an average accuracy of 99.59% ± 0.0039. Thus the proposed method demonstrated an effective agreement with manual annotations.

Wilms tumour (WT) accounts for about 6% of all childhood cancers and overall survival of WT is about 90% in international protocols. However, for WT subgroups with much poorer prognoses, i.e. typically high-risk (unfavorable) histology and/or relapse, there is an unmet need to better understand the biology of WT and to translate biological findings into clinics through early phase clinical trials that evaluate innovative therapies. The main challenges are the small numbers of children suitable for early phase trials, the genetic heterogeneity of WT and the low number of somatic mutations that are currently considered 'druggable'. Accordingly, a joint meeting between clinical and biology experts from the international cooperative groups of the Renal Tumour Study Group of the International Society of Paediatric Oncology, the Renal Tumour Committee of the Children's Oncology Group and the European Innovative Therapies for Children with Cancer consortium and parents representatives was organised during the first SIOPE meeting in Prague, 2019. We reviewed WT molecular features, ongoing/planned early phase trials and explored available knowledge on organoid technology. The key messages were: (1) relapsed WT should undergo whenever possible thorough molecular characterization and be enrolled in protocols or trials with systematic data collecting and reporting; (2) WT displays few known 'actionable' targets and currently no novel agent has appeared promising; (3) we need to improve the enrolment rate of WT candidates in early phase trials especially for the relatively small subgroup of relapses with an adverse prognostic signature; (4) despite some agnostic early phase trials existing, development of WT-focused trials are warranted; (5) growing organoids with parallel testing of drug panels seems feasible and may direct individual treatment and encourage clinical researchers to incorporate the most promising agents into early phase trials. • A meeting at the first SIOPE identified the unmet needs for relapsed Wilms tumour (WT). • WT displays few known actionable targets and no novel agent seems promising. • Improvement of the enrolment rate for WT candidates in early phase trials needed. • Models like organoids with parallel testing help to improve theory suggestions. [ABSTRACT FROM AUTHOR]

Characterisation of histological, immunohistochemical and molecular prognostic and predictive biomarkers has contributed significantly to precision medicine and better outcomes in the management of paediatric solid tumours. Prognostic biomarkers allow predictions to be made regarding a tumour's aggressiveness and clinical course, whereas predictive biomarkers help determine responses to a specific treatment. This review summarises prognostic biomarkers currently used in the more common paediatric solid tumours, with a brief commentary on the most relevant less common predictive biomarkers. MYCN amplification is the most important genetic alteration in neuroblastoma prognosis, and the histological classification devised by Shimada in 1999 is still used in routine diagnosis. Moreover, a new subgrouping of unfavourable histology neuroblastoma enables immunohistochemical characterisation of tumours with markedly different genetic features and prognosis. The predominant histology and commonly observed cytogenetic abnormalities are recognised outcome predictors in Wilms tumour. Evaluation for anaplasia, which is tightly associated with TP53 gene mutations and poor outcomes, is central in both the International Society of Paediatric Oncology and the Children's Oncology Group approaches to disease classification. Characterisation of distinct genotype-phenotype subclasses and critical mutations has expanded overall understanding of hepatoblastoma outcomes. The C1 subclass hepatoblastoma and CTNNB1 mutations are associated with good prognosis. In contrast, the C2 subclass, NFE2L2 mutations, TERT promoter mutations and high expression of oncofetal proteins and stem cell markers are associated with poor outcomes. Risk stratification in sarcomas is highly variable depending on the entity. The prognosis of rhabdomyosarcoma, for example, primarily depends on histological and molecular characteristics. Advances in our understanding of clinically significant biomarkers will translate into more precise diagnoses, improved risk stratification and more effective and less toxic treatment in this challenging group of patients., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Malignant renal tumours represent 5% of childhood cancers and include types with likely different aetiology: Wilms tumour (WT), rhabdoid renal tumour, kidney sarcomas and renal carcinomas. WT is the most common renal tumour in children, previously shown to vary internationally and with ethnicity. Using the comprehensive database of the International Incidence of Childhood Cancer study (IICC), we analysed global variations and time trends in incidence of renal tumour types in children (age 0‐14 years) and adolescents (age 15‐19 years). The results were presented by 14 world regions, and five ethnic groups in the US. We included 15 320 renal tumours in children and 800 in adolescents reported to the 163 contributing registries during 2001‐2010. In children, age‐standardised incidence rate (ASR) of renal tumours was 8.3 per million (95% confidence interval, CI = 8.1, 8.4); it was the highest in North America and Europe (9‐10 per million) and the lowest in most Asian regions (4‐5 per million). In the US, Blacks had the highest ASR (10.9 per million, 95% CI = 10.2, 11.6) and Asian and Pacific Islanders the lowest (4.4 per million, 95% CI = 3.6, 5.1). In adolescents, age‐specific incidence rate of renal tumours was 1.4 per million (95% CI = 1.3, 1.5). WT accounted for over 90% of all renal tumours in each age from 1 to 7 years and the proportion of renal carcinomas increased gradually with age. From 1996 to 2010, incidence remained mostly stable for WT (average annual percent change, AAPC = 0.1) and increased for renal carcinomas in children (AAPC = 3.7) and adolescents (AAPC = 3.2). Our findings warrant further monitoring. What's new? Based on more than 16,000 incident cases in the period 2001‐2010, this study offers the most complete overview to date of the worldwide patterns of renal tumours in children and adolescents. Using the comprehensive International Incidence of Childhood Cancer database, the authors also describe the distribution of rare entities such as rhabdoid renal tumour or kidney sarcomas. The results indicate the stable incidence of Wilms tumour, the most common renal tumour in children, consistently with a likely genetic origin. The rising incidence of renal carcinomas with age and over time is likely caused by environmental risk factors, warranting further monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy. Case Report: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up. Discussion: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases. [ABSTRACT FROM AUTHOR]