Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

Does bilateral Wilms' tumor involving the collecting system in children have a worse prognosis?

BACKGROUND: The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms' tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. METHODS: Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. RESULTS: Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). CONCLUSIONS: To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.

The pathophysiology of bilateral and multifocal Wilms tumors: What we can learn from the study of predisposition syndromes.

Approximately 5% of patients with Wilms tumor present with synchronous bilateral disease. The development of synchronous bilateral Wilms tumor (BWT) is highly suggestive of a genetic or epigenetic predisposition. Patients with known germline predisposition to Wilms tumor (WT1 variants, Beckwith Wiedemann spectrum, TRIM28 variants) have a higher incidence of BWT. This Children's Oncology Group (COG)-International Society for Pediatric Oncology (SIOP-) HARMONICA initiative review for pediatric renal tumors details germline genetic and epigenetic predisposition to BWT development, with an emphasis on alterations in 11p15.5 (ICR1 gain of methylation, paternal uniparental disomy, and postzygotic somatic mosaicism), WT1, TRIM28, and REST. Molecular mechanisms that result in BWT are often also present in multifocal Wilms tumor (multiple separate tumors in one or both kidneys). We identify priority areas for international collaborative research to better understand how predisposing genetic or epigenetic factors associate with response to neoadjuvant chemotherapy, oncologic outcomes, and long-term renal function outcomes.

Treatment of bilateral Wilms' tumor in children: how to improve the application of nephron-sparing surgery.

PURPOSE: To summarize the experience of nephron-sparing surgery (NSS) for bilateral Wilms tumors (BWT) in children. METHODS: This study included children with BWT admitted to our hospital between January 2008 and June 2022. The details of the treatments and outcomes were analyzed. RESULTS: In all, 70 patients (39 males and 31 females) were enrolled, including 66 patients with synchronous tumors and 4 patients with metachronous tumors. The median age at diagnosis was 13 (3-75) months. Overall, 59 patients received preoperative chemotherapy and 45.8% (54/118) of the 118 sides of WT achieved a partial response (PR). Of the 70 patients, 48 (68.6%) underwent bilateral NSS and 22 (31.4%) underwent unilateral NSS and contralateral total nephrectomy. The proportion of bilateral NSS in the preoperative chemotherapy group was significantly higher than in the non-chemotherapy group (P = 0.031). Additionally, there were 26, 25, 14, and 5 cases of stage I, stage II, stage III, and stage IV, respectively. Among the 70 children, 16 had a recurrence, and 8 died. The 4 years EFS and OS were 67.9% and 89.3%, respectively. CONCLUSIONS: The long-term survival rates of patients with BWT improved. Hence, preoperative chemotherapy should be administered to enhance the use of NSS in BWT.

RENAL nephrometry scoring system in bilateral Wilms tumor: predictive application.

AIM: This study aims to explore the application of RENAL nephrometry scoring system in bilateral Wilms tumor (BWT). METHODS: A retrospective review of patients with BWT from January 2010 to June 2022 was performed. Each kidney unit of the BWT was evaluated independently and scored according to RENAL nephrometry scoring system by 2 blinded reviewers, and reviewers were blinded to what surgery the patients ultimately had. Discrepancies were evaluated by a third reviewer to reach a consensus. Tumor anatomical characteristics were summarized and compared. RESULTS: 29 patients with 53 kidney units were included in the study. 53 kidney units included 12 (22.6%) low-complexity, 9 (17.0%) intermediate-complexity, and 32 (60.4%) high-complexity. 2 kidney units (3.8%) had tumor thrombus, and 14 (26.4%) had multiple lesions. A total of 42 kidney units (79.2%) underwent initial nephron-sparing surgery (NSS) and 11 (20.8%) underwent radical nephrectomy. Less complexity tumors were observed in the NSS group. Of the 42 kidney units undergoing initial NSS, 26 were performed in vivo and 16 ex vivo via autotransplantation. The latter group featured a higher complexity. During follow-up, 22 patients survived and 7 died, no statistically significant tumor complexity was observed between the two groups. CONCLUSIONS: The anatomical characteristics of BWT are complex. Despite this study did not indicate that the complexity correlates with prognosis, low-complexity tumors were candidates for NSS, and kidney autotransplantation provided a feasible procedure for high-complexity tumors. A refined system is required due to multiple lesions and tumor thrombus.

Synchronous bilateral Wilms' tumor with liver metastasis.

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

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

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

Synchronous Bilateral Wilms Tumor: Five-Year Single-Center Experience with Assessment of Quality of Life.

CONTEXT: Synchronous Bilateral Wilms tumor (sBWT). AIMS: This study aimed to assess the outcome of patients with sBWT treated on SIOP protocol. SETTINGS AND DESIGN: Retrospective and prospective randomized study. SUBJECTS AND METHODS: SIOP 93-01 protocol was used to study nine patients of sBWT in a single center and followed up over a period from 2 to 5 years. STATISTICAL ANALYSIS USED: Unpaired t-test and Mann-Whitney U-test were used for analysis. RESULTS: Of nine patients, six were included in the study as three patients lost to follow-up. Among the six patients, there were four girls and two boys with a median age of 2 years. Mean regression in the size of tumor was 87% in four out of six patients. Tumor with unfavorable histology showed 32% response (ratio of favorable: unfavorable histology 2:1). Event-free survival rate was 81.3% and overall survival was 90% over 2-5 years. Recurrence was seen in two patients of whom one had Denys-Drash syndrome. Mean DTPA glomerular filtration rate was 91.4/ml/min/1.73 m2 preoperatively and that of 3 months after completion of treatment was 84/ml/min/1.73 m2. Health-related quality of life (HRQOL) using Pediatric Quality of Life Inventory and Lansky Play Performance Scale revealed significant improvement results of all functioning domains such as physical, social, emotional, and school subscales with P < 0.05 and performance scale (P < 0.04). CONCLUSIONS: We suggest SIOP protocol for sBWT and bilateral nephron-sparing surgery in two stages. However, long-term follow-up is required to assess the ultimate renal function outcome. HRQOL is an essential guide in improving the conditions of pediatric cancer survivors.

Technical Considerations for Nephron-Sparing Surgery in Children: What Is Needed to Preserve Renal Units?

BACKGROUND: Chemotherapy is used preoperatively for children with bilateral Wilms tumor (BWT) or unilateral high-risk Wilms tumor (UHRWT) to promote tumor regression to facilitate renal preservation with nephron-sparing surgery (NSS). In adults, various surgical techniques have been described to preserve renal tissue. Few studies have examined the use of surgical adjuncts in NSS in children with renal tumors. METHODS: We performed a multi-institutional retrospective review of patients with BWT or UHRWT. Patient demographics, tumor size at diagnosis, following neoadjuvant chemotherapy, utilization of surgical adjuncts including intraoperative ultrasound (IOUS), margin status, complications, renal function, and follow-up were recorded. RESULTS: The cohort comprised 23 patients: 18 BWT, 3 UHRWT, and 2 patients with solitary kidney. Twenty-two of the 23 patients had successful NSS. IOUS was used 19 times, and seven had positive margins after surgery. Cooling/vascular isolation was used six times. At a median follow-up of 18 mo, median estimated glomerular filtration rate Schwartz was 126 mL/min/1.73 m2 and median serum creatinine 0.39 mg/dL in the 22 patients who had successful NSS. There have been no tumor recurrences. CONCLUSIONS: In patients with BWT and UHRWT, surgical adjuncts such as cooling/vascular isolation are uncommonly performed. IOUS may be helpful but does not guarantee negative microscopic margins. LEVEL OF EVIDENCE: Level 4, Case series with no comparison group.

Management and outcomes in massive bilateral Wilms' tumors.

PURPOSE: To evaluate the outcome of children with bilateral Wilms' tumor (BWT) treated on All India Institute of Medical Sciences-Wilms Tumor-99 (AIIMS-WT-99) protocol. MATERIALS AND METHODS: All children with BWT, registered in our solid tumor clinic from August 1999 through December 2010 were included. RESULTS: Of the 178 fresh cases of Wilms Tumor (WT) treated during this period, 11 (6.2%) had bilateral involvement. All patients except one (12 and 3 cm), had massive bilateral tumors of more than 10 cm on each side. There were eight boys and three girls in the age range 6-30 months. One patient had Denys-Drash syndrome. Twenty renal units were operated upon (12 tumorectomy, five partial nephrectomy, and three nephrectomies), while one patient with inferior vena cava (IVC) thrombus died of renal failure. Tumor spill occurred in three units, lymphnode was positive in two patients. Local recurrence occurred in four patients (six of 18 renal units (33%)-two bilateral and two unilateral). There was one recurrence in the liver that was treated with radio-frequency ablation. The 5-year overall survival (OS) was 90% (95% confidence interval (CI) = 50.8-98.6) and the relapse free survival (RFS) was 38% (95% CI = 6.1-71.6). CONCLUSION: Massive BWT respond poorly to preoperative chemotherapy, are often not amenable to partial nephrectomy/tumorectomy and have a higher local recurrence rate, giving a poor RFS.

Bilateral Wilms tumor: 10-year experience from a single center in China.

Background: Nephron sparing surgery (NSS) had become the main surgical treatment for bilateral nephroblastoma. But it remained a challenge for surgeons to balance the dilemma between complete tumor resection to reduce tumor recurrence and renal parenchyma preservation to reduce end-stage renal disease (ESRD). In this study, we summarized our clinical experience for bilateral Wilms tumors managed in our center and evaluated the influence of different surgical approaches on prognosis. Methods: The clinical data of patients with bilateral Wilms tumor in our hospital from January 2010 to December 2020 were retrospectively analyzed, and the clinical symptoms, surgical approaches and prognosis of the disease were summarized. Results: We reviewed medical records of 16 patients, including 13 (81.3%) girls and 3 (18.7%) boys. The mean age of the patients was 17.88±11.65 months (range, 6-42 months). Five patients presented with hypertension and two presented with hemihypertrophy. Fifteen cases had synchronous tumors, while only one patient had metachronous bilateral lesions. Thirteen patients received neoadjuvant chemotherapy and only 8 kidneys (30.8%) responded to chemotherapy. Two patients gave up surgery, and the other fourteen patients underwent radical resection, of which 2 patients only underwent unilateral radical nephrectomy (RN); 7 and 5 patients underwent single-stage and two-stage operation for bilateral lesions, respectively. In all surgical patients, RN was performed on 5 kidneys, and NSS was performed on 21 kidneys. The positive margins after NSS were found in 6 kidneys (35.3%). After a median follow-up period of 26.3 months, local tumor recurrence and renal insufficiency occurred in two and one patients. The 5-year overall and event-free survival rates were 78.1% and 58.6%, respectively. In univariable analysis, the survival rate in the initial chemotherapy group (92.3%) was significantly higher than that in the initial surgery group (33.3%) (P=0.048), whereas positive margin and staged operation (P>0.05) appeared not significantly associated with overall survival. Conclusions: The proportion of tumor reduction after preoperative chemotherapy is relatively low for bilateral Wilms tumor, but preoperative chemotherapy could improve overall survival. NSS is recommended for bilateral Wilms tumor, and the customized procedure can be selected according to the location and anatomical features of tumor.

Outcomes according to treatment using an established protocol in patients with bilateral Wilms' tumor: A national Canadian population-based study.

BACKGROUND: Bilateral Wilms tumor (BWT) is a rare entity. The goal of this study is to report outcomes (overall and event-free survival, OS/EFS) of BWT in a large cohort representative of the Canadian population since 2000. We focused on the occurrence of late events (relapse or death beyond 18 months), as well as outcomes of patients treated following the only protocol specifically designed for BWT to date, AREN0534, compared to patients treated following other therapeutic schemes. METHODS: Data was obtained for patients diagnosed with BWT between 2001 and 2018 from the Cancer in Young People in Canada (CYP-C) database. Demographics, treatment protocols, and dates for events were collected. Specifically, we examined outcomes of patients treated according to the Children's Oncology Group (COG) protocol AREN0534 since 2009. Survival analysis was performed. RESULTS: 57/816 (7%) of patients with Wilms tumor had BWT during the study period. Median age at diagnosis was 2.74 years (IQR 1.37-4.48) and 35 (64%) were female; 8/57 (15%) had metastatic disease. After a median follow-up of 4.8 years (IQR 2.8-5.7 years, range 0.2-18 years), OS and EFS were 86% (CI 73-93%) and 80% (CI 66-89%), respectively. Less than 5 events were recorded after 18 months from diagnosis. Since 2009, patients treated according to the AREN0534 protocol had a statistically significant higher OS compared to patients treated with other protocols. CONCLUSIONS: In this large Canadian cohort of patients with BWT, OS and EFS compared favorably to the published literature. Late events were rare. Patients treated according to a disease-specific protocol (AREN0534) had improved overall survival. TYPE OF STUDY: Original article. LEVEL OF EVIDENCE: Level IV.

Bilateral Wilms tumor in a patient with a horseshoe and duplex kidney: A case report.

The occurrence of horseshoe kidney with duplex urinary collecting systems is rare. Herein, we report a case of bilateral Wilms tumor (BWT) in a patient with a concurrent horseshoe kidney and left duplex kidney, which had not been previously reported. The patient was treated with neoadjuvant chemotherapy, followed by surgical resection and adjuvant chemotherapy. The tumor recurred 6 months postoperatively. A second resection was performed, followed by the administration of chemotherapy and radiotherapy. The patient passed away 15 months after the initial diagnosis of BWT.

A radiomics nomogram for preoperative prediction of nephron-sparing surgery in patients with bilateral Wilms tumor.

Background: Bilateral Wilms tumor (BWT) is a relatively rare malignant renal tumor in children. Nephron-sparing surgery (NSS) is the preferred surgical approach for treating BWT, but lacks uniform surgical indications worldwide. This study aimed to summarize the clinical and imaging features of BWT children, establish a radiomics nomogram, and predict the feasibility of NSS for improving outcomes. Methods: A 12-year retrospective single-center review was conducted on clinical data and preoperative imaging features of BWT patients. The tumor kidneys were divided into NSS and non-NSS groups. Logistic regression analysis was performed to identify independent predictors and develop a prediction model of the feasibility of NSS in BWT patients. A radiomics nomogram was constructed and internally validated by the parametric bootstrapping method. Results: A total of 58 BWT patients (115 renal units) were included in this study. After evaluations based on preoperative imaging and clinical data, 94 renal units underwent NSS with negative resection margins and were included in the NSS group, whereas 16 renal units with positive resection margins, macroscopic residual, or total nephrectomies were included in the non-NSS group. Tumor size [odds ratio (OR): 0.540, 95% confidence interval (CI): 0.308-0.945], relationship with the collecting system (OR: 0.013, 95% CI: 0.0004-0.370), and remaining renal parenchyma (RRP) proportion (OR: 71.23, 95% CI: 1.632-3108.8) were identified as independent predictors for NSS. A nomogram was constructed based on these factors, which demonstrated great consistency between the predicted and observed feasibility of NSS. The model presented with good discriminative ability [area under the curve (AUC), 0.982]. The decision curve analysis (DCA) revealed the clinical usefulness of the model. Conclusions: This study analyzed the clinical and preoperative imaging data of BWT patients and identified three independent predictors for the feasibility of NSS, including tumor size, relationship with the collecting system, and residual renal parenchyma proportion. The radiomics nomogram established in this study can provide individualized predictions to assist clinicians in making better decisions and improving patient outcomes.

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.

The Genetic and Epigenetic Features of Bilateral Wilms Tumor Predisposition: A Report from the Children's Oncology Group AREN18B5-Q Study.

This study comprehensively evaluated the landscape of genetic and epigenetic events that predispose to synchronous bilateral Wilms tumor (BWT). We performed whole exome or whole genome sequencing, total-strand RNA-seq, and DNA methylation analysis using germline and/or tumor samples from 68 patients with BWT from St. Jude Children's Research Hospital and the Children's Oncology Group. We found that 25/61 (41%) of patients evaluated harbored pathogenic or likely pathogenic germline variants, with WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%) and the BRCA-related genes (5%) BRCA1, BRCA2, and PALB2 being most common. Germline WT1 variants were strongly associated with somatic paternal uniparental disomy encompassing the 11p15.5 and 11p13/WT1 loci and subsequent acquired pathogenic CTNNB1 variants. Somatic coding variants or genome-wide copy number alterations were almost never shared between paired synchronous BWT, suggesting that the acquisition of independent somatic variants leads to tumor formation in the context of germline or early embryonic, post-zygotic initiating events. In contrast, 11p15.5 status (loss of heterozygosity, loss or retention of imprinting) was shared among paired synchronous BWT in all but one case. The predominant molecular events for BWT predisposition include pathogenic germline variants or post-zygotic epigenetic hypermethylation at the 11p15.5 H19/ICR1 locus (loss of imprinting). This study demonstrates that post-zygotic somatic mosaicism for 11p15.5 hypermethylation/loss of imprinting is the single most common initiating molecular event predisposing to BWT. Evidence of somatic mosaicism for 11p15.5 loss of imprinting was detected in leukocytes of a cohort of BWT patients and long-term survivors, but not in unilateral Wilms tumor patients and long-term survivors or controls, further supporting the hypothesis that post-zygotic 11p15.5 alterations occurred in the mesoderm of patients who go on to develop BWT. Due to the preponderance of BWT patients with demonstrable germline or early embryonic tumor predisposition, BWT exhibits a unique biology when compared to unilateral Wilms tumor and therefore warrants continued refinement of its own treatment-relevant biomarkers which in turn may inform directed treatment strategies in the future.

Ex vivo tumor dissection followed by kidney autotransplantation in bilateral wilms tumor.

Introduction: Successful management of bilateral Wilm's tumor (BWT) involves a radical resection while preserving enough normal kidney tissue. Nephron-sparing surgery often results in an R1/R2 resection with a high recurrence rate in children with huge or multiple tumors, or tumors proximity to the renal hilum. In contrast, kidney autotransplantation can completely resect the tumor while maintaining homeostasis and preserving the patient's healthy kidney tissues. Methods: We summarized the clinical data of 8 synchronous BWT patients who underwent kidney autotransplantation at the First Affiliated Hospital of Sun Yat-sen University from 2018 to 2020. Ex vivo tumor resection and kidney autotransplantions were performed on 11 kidneys. The baseline characteristics, perioperative management, and survival status were reported. Results: Nephron-sparing surgeries were performed on 5 kidneys in vivo. Among all the 8 patients, six of them (75%) received staged operation and the other 2 patients (25%) received single-stage operation. No residual tumors were found on the postoperative imaging in all the 8 patients. In total, 6 (75%) patients occurred complications after the autotransplantation, among which, 2 (33.3%) patients had complication of Clavien-Dindo grade IIIa, and 4 (66.7%) patients had complication of grade < 3. During the 38 months of follow-up, 87.5% (7/8) of patients were tumor-free survival with normal renal function. One patient died from renal failure without tumor recurrence. Discussion: Therefore, our study indicated that autologous kidney transplantation can be an option for patients with complex BWT if the hospital's surgical technique and perioperative management conditions are feasible.

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.

Bench surgery with autotransplantation for bilateral Wilms tumor-A feasible technique for renal sinus invasion.

Purpose: Bilateral Wilms tumor (BWT) with renal sinus invasion requires extremely difficult surgical care. This study presents an alternative strategy for tumor removal while at the same time preserving the renal parenchyma. Materials and methods: In total, 9 cases of synchronous BWT were admitted to our hospital between May 2016 to Aug 2020. We retrospectively reviewed the clinical data, surgical technique, and functional and oncological outcomes of these cases. Results: The 9 cases included 3 males and 6 females, with a median age of 12 months at surgery (range 7-40). A total of 14 kidney units had renal sinus invasion (77.8%), whereas multifocal neoplasms were observed in 7 units (38.9%). The local stage distribution revealed 1 kidney with stage I, 10 kidneys with stage II, and 7 kidneys with stage III. Nephron-sparing surgery was performed on 15 kidney units (83.3%), among which 13 (72.2%) underwent bench surgery with autotransplantation (BS-AT), whereas 2 (11.1%) were subjected to tumor enucleation in vivo. Urinary leakage was the most prevalent postoperative complication. We observed negative margins. During the mean follow-up of 28.4 months, 2 patients (22.2%) succumbed from sepsis and renal failure, respectively, whereas the other 7 (77.8%) survived without recurrence. Survivors experienced an estimated glomerular filtration rate of 81 ± 15.4 ml/(min × 1.73 m2). The endpoint renal volume of 9 renal units receiving BS-AT significantly increased (P = 0.02). Conclusions: In summary, the surgical management of bilateral Wilms tumor requires meticulous operative approach and technique. Besides, BS-AT provides a viable alternative to nephron-sparing surgery for BWT patients with renal sinus invasion.

Management of intravascular thrombus in cases of bilateral Wilms tumor or horseshoe kidney.

PURPOSE: To describe the oncologic and surgical management of bilateral Wilms tumor or Wilms tumor arising in a horseshoe kidney with intravenous tumor thrombus to help pediatric surgeons negotiate this rare and difficult anatomic circumstance. METHODS: A single-institution, retrospective medical record review identified 4 cases of bilateral WT and one case of WT arising in a horseshoe kidney with intravenous tumor thrombus between 2009 and 2021. The presentation, imaging, chemotherapy regimen, intraoperative approach, and surgical and oncologic outcomes were reviewed for each of these patients. RESULTS: All patients received a total of 12 weeks of neoadjuvant chemotherapy. In two patients, a staged approach to the bilateral tumors was undertaken with the first side being operated on after six weeks of therapy and the other side undergoing surgery after an additional six weeks of therapy. Of five patients, four underwent nephron-sparing surgery of all tumors and one underwent unilateral radical nephroureterectomy with contralateral nephron-sparing surgery. Tumor thrombectomy was performed in four of five cases; one patient demonstrated a complete response of the intravenous tumor thrombus to neoadjuvant chemotherapy and did not require thrombectomy. Three patients received adjuvant flank radiotherapy. Three patients developed medically managed stage II or III chronic kidney disease and no patient required renal replacement therapy or kidney transplant to date. CONCLUSION: Nephron-sparing surgery is feasible and safe to perform in selected cases of bilateral Wilms tumor with intravascular thrombus by utilizing three-drug neoadjuvant chemotherapy, staged approaches to each kidney when appropriate, and detailed preoperative and/or intraoperative mapping of renal venous anatomy. Successful nephron-sparing surgery with tumor thrombectomy is dependent on a branched renal venous system or the presence of accessory renal veins. LEVEL OF EVIDENCE: Level 4.