The rationale for nephron-sparing surgery in unilateral non-syndromic Wilms tumour.

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.

Robotic Surgery in Pediatric Oncology: Lessons Learned from the First 100 Tumors-A Nationwide Experience.

BACKGROUND: While robotics has become commonplace in adult oncology, it remains rare in pediatric oncology due to the rarity of childhood cancers. We present the results of a large nationwide experience with robotic oncology, with the aim of providing practical and feasible guidelines for child selection. METHODS: This was a prospective analysis performed over a period of 4 years. Treatment was delivered according to the Société Internationale d'Oncologie Pédiatrique/International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOP/SIOPEN) protocols. Indications were approved by a certified tumor board. RESULTS: Overall, 100 tumors were resected during 93 procedures (abdomen, 67%; thorax, 17%; pelvis, 10%; retroperitoneum, 6%) in 89 children (56 girls). The median age at surgery was 8.2 years (range 3.6-13); 19 children (21%) harbored germinal genetic alterations predisposing to cancer. No intraoperative tumor ruptures occurred. Seven conversions (8%) to an open approach were performed. Neuroblastic tumors (n = 31) comprised the main group (18 neuroblastomas, 4 ganglioneuroblastomas, 9 ganglioneuromas) and renal tumors comprised the second largest group (n = 24, including 20 Wilms' tumors). The remaining 45 tumors included neuroendocrine (n = 12), adrenal (n = 9), germ-cell (n = 7), pancreatic (n = 4), thymic (n = 4), inflammatory myofibroblastic (n = 4), and different rare tumors (n = 5). Overall, 51 tumors were malignant, 2 were borderline, and 47 were benign. The median hospital stay was 3 days (2-4), and five postoperative complications occurred within the first 30 days. During a median follow-up of 2.4 years, one child (Wilms' tumor) presented with pleural recurrence. One girl with Wilms' tumor died of central nervous system metastasis. CONCLUSIONS: Robotic surgery for pediatric tumors is a safe option in highly selected cases. Indications should be discussed by tumor boards to avoid widespread and uncontrolled application.

Arterial abnormalities identified in kidneys transplanted into children during the COVID-19 pandemic.

Graft artery stenosis can have a significant short- and long-term negative impact on renal graft function. From the beginning of the COVID-19 pandemic, we noticed an unusual number of graft arterial anomalies following kidney transplant (KTx) in children. Nine children received a KTx at our center between February and July 2020, eight boys and one girl, of median age of 10 years. Seven presented Doppler features suggesting arterial stenosis, with an unusual extensive pattern. For comparison, over the previous 5-year period, persistent spectral Doppler arterial anomalies (focal anastomotic stenoses) following KTx were seen in 5% of children at our center. We retrospectively evidenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in five of seven children with arterial stenosis. The remaining two patients had received a graft from a deceased adolescent donor with a positive serology at D0. These data led us to suspect immune postviral graft vasculitis, triggered by SARS-CoV-2. Because the diagnosis of COVID-19 is challenging in children, we recommend pretransplant monitoring of graft recipients and their parents by monthly RT-PCR and serology. We suggest balancing the risk of postviral graft vasculitis against the risk of prolonged dialysis when considering transplantation in a child during the pandemic.

Feasibility and safety of magnetic-end double-J ureteral stent insertion and removal in children.

PURPOSE: The need for surgical removal of a double-J ureteral stent (DJUS) is considered one of its disadvantages. Apart from increased cost, repeated exposure to general anesthesia is a concern in children. Alternative techniques have been described, all failing to become integrated into mainstream practice. Stents with a distal magnetic end, although introduced in the early 1980s, have only recently gained acceptance. We report the feasibility and safety of insertion and removal of a magnetic-end double-J ureteral stent (MEDJUS) in a pediatric population. MATERIALS AND METHODS: We retrospectively analyzed the use of the Magnetic Black-Star Urotech® MEDJUS between 11/2016 and 12/2019 in children. Stents were removed in the outpatient clinic using a transurethral catheter with a magnetic tip. RESULTS: MEDJUS insertion was attempted in 100 patients (65 boys). Mean age was 7.8 years (0.5-18). The stent was placed in an antegrade procedure (n = 47), by a retrograde route (n = 10), and during open surgery (n = 43). Stent insertion was successful in 84 cases (84%). All 16 failures occurred during the antegrade approach in laparoscopic pyeloplasty, with inability to push the stent and its magnet through the ureterovesical junction in 14. Magnetic removal was attempted in 83 patients, successful in 81 (98%). There was no added morbidity with the MEDJUS. CONCLUSIONS: The use of MEDJUS is a safe and effective strategy that obviates the need for additional general anesthesia in children. Its insertion is similar to that with regular DJUS, and its easy and less time-consuming removal benefits both the patient and the hospital and validates its clinical use.

Minimally invasive surgery for unilateral Wilms tumors: Multicenter retrospective analysis of 50 transperitoneal laparoscopic total nephrectomies.

PURPOSE: To evaluate feasibility and outcomes of minimally invasive surgery (MIS) in Wilms tumor (WT). METHODS: International multicenter review of MIS total nephrectomies for WT between 2006 and 2018. Medical records of confirmed WT were retrospectively assessed for demographic, imaging, treatment, pathology, and oncological outcome data. RESULTS: Fifty patients, with a median age of 38 months (6-181), were included in 10 centers. All patients received neoadjuvant chemotherapy, as per SIOP protocol. Median tumor volume post-chemotherapy was 673 mL (18-3331), 16 tumors crossed the lateral border of the spine, and three crossed the midline. Six patients with tumors that crossed the lateral border of the spine (tumor volumes 1560 mL [299-2480]) were converted to an open approach. There was no intraoperative tumor rupture. Overall, MIS was completed in 19% of the 195 nephrectomies for WT presenting during the study period. Tumor was stage I in 29, II in 16, and III in 5, and histology was reported as low in three, intermediate in 42, and high risk in five. Three patients had positive tumor margins. After a median follow-up of 34 months (2-138), there were two local recurrences (both stage I, intermediate risk, 7 and 9 months after surgery) and one metastatic relapse (stage III, high risk, four months after surgery). The three-year event-free survival was 94%. CONCLUSION: MIS is feasible in 20% of WT, with oncological outcomes comparable with open surgery, no intraoperative rupture, and a low rate of local relapse. Ongoing surveillance is, however, needed to evaluate this technique as it becomes widespread.

Robotic-assisted laparoscopic management of renal tumors in children: Preliminary results.

AIM: We present the preliminary results of robotic-assisted laparoscopic (RAL) total and partial nephrectomy for renal malignant tumors in children. METHODS: This is a prospective study of patients operated with RAL between December 2016 and September 2018. Patients with Wilms tumors were treated according to the SIOP-2001 protocol. Patient and tumor characteristics, type of surgery, surgical-related morbidity, and oncologic outcomes were recorded. Results were compared with a series of patients with similar age- and tumor-related characteristics operated during the same period by an open surgical approach. RESULTS: Ten children underwent RAL nephrectomy with a mean age of five years (3.2-14.1 years). Total nephrectomy was done in six cases for Wilms tumor and in one case for renal sarcoma; three cases were converted. Complete removal of tumor without rupture was achieved in all cases. Postoperative course was uneventful, and patients were discharged between days 2 and 7. Neither recurrence nor medium-term complications occurred. Nine patients are alive with a median follow-up of 16 months (6-27 months) and one female died from complications of central nervous system metastases one year after surgery. When compared with the open surgical approach group, median tumor volume was smaller (P = 0.005), hospital stay was shorter (P = 0.01), and operative time was similar (P = 0.20). CONCLUSIONS: RAL total and partial nephrectomy procedure for renal tumor in children may be an option in carefully selected cases. Indication should be discussed at tumor boards and surgery performed while adhering strictly to oncological surgical rules.

Wilms Tumor Associated With the 9q22.3 Microdeletion Syndrome: 2 New Case Reports and a Review of The Literature.

BACKGROUND: The 9q22.3 syndrome is an autosomal dominant microdeletion syndrome with similarities to Gorlin syndrome (GS). It encompasses the PTCH1 gene locus that harbors mutations for GS. Although the 9q22.3 syndrome is associated with Wilms tumor (WT), WT is not a GS-associated tumor, implying a different mechanism involving PTCH1, or a different locus in the 9q22.3 region. The goal of this study is to report the association between WT and 9q22.3 syndrome and review the outcome of treatment. OBSERVATIONS: We report 2 new cases of WT with 9q22.3 deletion and review the literature. Among the 44 described patients with 9q22.3 deletion, 7 developed WT (16%) at a mean age of 45 months (range, 4 to 84 mo). All patients had dysmorphic features, macrocephaly, and developmental delay, and there was an association with overgrowth (4/7). One patient had bilateral WT, another had a synchronous rhabdomyosarcoma. The outcome was excellent with all cases reported to be in complete remission. CONCLUSIONS: The 9q22.3 microdeletion syndrome should be considered at diagnosis of WT in children with dysmorphic features. Conversely, patients with a known 9q22.3 deletion syndrome should be considered for a WT predisposition surveillance program, especially those with overgrowth. The management should be individualized and given the excellent prognosis, and the unknown future risk of metachronous disease or other malignancy, the surgical approach should be carefully considered.

A short report on current fertility preservation strategies for boys.

BACKGROUND: Advances in cancer treatment have led to improved long-term survival after childhood cancer, but often at a price of impaired future fertility. Fertility preservation (FP) in male children and early adolescents poses unique challenges as efficacy is unproven. OBJECTIVES: To describe characteristics of testicular tissue cryopreservation (TTCP) specimens taken from paediatric and adolescent patients, stratified by age, and prior chemotherapy, if any, and to demonstrate evidence for germ cells. MATERIALS AND METHODS: Retrospective review of gonadal biopsies and clinical records of patients consented into the Royal Children's Hospital FP programme between 1987 and 2015. Tissue was sliced into blocks, with one section sent for histopathology prior to cryopreservation. In boys ≥12 years where spermatogenesis could be expected, a portion of tissue was disaggregated completely to look for mature sperm and if found, additional tissue was dissected and the resulting suspension frozen. RESULTS: Testicular tissue cryopreservation specimens in 44 males (0.3-16.8 years) provided an average of 7.8 slices per patient. All the specimens were taken at the same time as another necessary surgical procedure, under one general anaesthesic. There was only one complication of scrotal wound dehiscence. Seven of the forty-four (15.9%) patients had chemotherapy prior to testicular biopsy, while the rest were chemotherapy naïve. Five of these were prepubertal, and two were pubertal patients. Eleven subjects had tissue dissected with mature sperm found in eight. Of these eight patients where sperm were found, all were pubertal with testicular size of more than 10 mL and showing histological evidence of spermatogenesis. No histologic specimen demonstrated any malignant cells. CONCLUSIONS: Testicular tissue cryopreservation can be performed in young patients without delay, preferably prior to cancer treatment. As testicular tissue contains germ cells from which haploid spermatozoa are ultimately derived, future technologies may allow their utilization for fertility in humans. This may be the only hope for biological offspring in some patients undergoing fertility compromising treatment. Retrieval of mature sperm from some pubertal patients, however, offers realistic hope to these patients of future fertility.

Retrograde continence enema in children with spina bifida: Not as effective as first thought.

AIM: The aim of the study is to investigate the effectiveness of Peristeen retrograde continence enema (RCE) in the management of faecal incontinence in children with spina bifida. METHODS: We identified a homogenous group of spina bifida patients in whom RCE was initiated (Jan 2006-July 2013). Confidential assessments included (i) Fecal Incontinence Quality Of Life (FIQOL), (ii) St Marks Faecal Incontinence score, (iii) Cleveland Clinic Constipation score and (iv) Neurogenic Bowel Dysfunction score. RESULTS: Of 20 patients, 11 (mean age 14.5 ± 5.3 years) were male. Of 20 patients, nine were still using RCE (mean follow-up 4.1 years). Three patients ceased RCE within 10 days, six after 4-12 months and two after 36-48 months. Reasons for cessation included balloon difficulties (n = 4), procedure deemed too difficult (n = 4) and pain (n = 3). There were no differences between the groups in length of training time for technique, instillate fluid/volume used and time taken to perform RCE. There were no differences between the groups for quality of life, faecal incontinence or constipation scores. CONCLUSIONS: We demonstrated a high rate of cessation with RCE in patients with spina bifida. This could not be explained by associated conditions, or by enema-related parameters. One possible explanation is the lack of ongoing outpatient support for the children and their families.

Foreskin reconstruction vs circumcision in distal hypospadias.

PURPOSE: The purpose of the study was to determine if there were differences in the complication rates between foreskin reconstruction (FR) and circumcision (CIRC) in distal hypospadias repairs. The primary outcomes were urethrocutaneous fistula (UF) and dehiscence. METHODS: The data of distal hypospadias operated between 2005 and 2013 were retrospectively reviewed. The inclusion criteria were any distal hypospadias repair that required an urethroplasty. The exclusion criteria were follow-up <1 year, redo procedures, chordee greater than 20°, and incomplete data. Univariate and multivariate analysis was performed on the results. RESULTS: 213 patients were included (95 FR and 118 CIRC). The 2 groups were comparable for age at surgery 19.32 months in FR and 14.25 months in CIRC. Mathieu repair was more common in FR (47/95-49.47%) than in CIRC (45/118-38.14%). The total subsequent procedures required were 23 in FR and 57 in CIRC. The incidence of UF was 6.3% (6/95) in FR and 27.1% (32/118) in CIRC (p < 0.001, OR 5.52, 95% CI 2.2-13.9). Complete dehiscence rates were 3.16% (3/95) FR vs 11.02% (13/118) for CIRC (p = 0.037, OR 3.8, 95% CI 1.05-13.74). The incidence of patients requiring reoperation was 18.9% (18/95) in FR versus 45.8% (54/118) in CIRC (p < 0.001, OR 3.61, 95% CI 1.93-6.76). CONCLUSIONS: Foreskin Reconstruction conferred a significantly lower rate of complications, particularly the UF rate, dehiscence rate, and number of patients that required reoperation. Our rate of complications in the CIRC group is much higher than other published data.

Copy-number variation associated with congenital anomalies of the kidney and urinary tract.

BACKGROUND: The most common cause of end-stage renal disease in children can be attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Despite this high incidence of disease, the genetic mutations responsible for the majority of CAKUT cases remain unknown. METHODS: To identify novel genomic regions associated with CAKUT, we screened 178 children presenting with the entire spectrum of structural anomalies associated with CAKUT for submicroscopic chromosomal imbalances (deletions or duplications) using single-nucleotide polymorphism (SNP) microarrays. RESULTS: Copy-number variation (CNV) was detected in 10.1 % (18/178) of the patients; in 6.2 % of the total cohort, novel duplications or deletions of unknown significance were identified, and the remaining 3.9 % harboured CNV of known pathogenicity. CNVs were inherited in 90 % (9/10) of the families tested. In this cohort, patients diagnosed with multicystic dysplastic kidney (30 %) and posterior urethral valves (24 %) had a higher incidence of CNV. CONCLUSIONS: The genes contained in the altered genomic regions represent novel candidates for CAKUT. This study has demonstrated that a significant proportion of patients with CAKUT harbour submicroscopic chromosomal imbalances, warranting screening in clinics for CNV.

Adults with previous hypospadias surgery during childhood: Beware of bulbar strictures.

BACKGROUND: Urethral strictures represent the most frequent long-term complication in men after history of hypospadias surgery. OBJECTIVES: To better define the spectrum of men previously treated for hypospadias during childhood, presenting at an adult urology clinic with persistent urethral complications. STUDY DESIGN: Retrospective review of the records of 42 consecutive adult patients with a personal history of hypospadias repair during childhood referred at one adult tertiary urology center between 2004 and 2017. Those with persistent urethral strictures were included: 28 patients (median age 28yr [17-81]). Residual chordee, aesthetic concerns, isolated fistulas, and motives of consultation unrelated to hypospadias were excluded. Early initial success rate and location of urethral stricture were studied. Statistical Analysis was done by non-parametric tests. RESULTS: On the 42 consecutive adults eligible, a total of 28 patients had a persistent urethral stricture. During childhood, 13/28 boys had required multiple surgical revision procedures, including six of them for postoperative urethral strictures. During adulthood, initial urethral assessment revealed 29 urethral strictures in 28 patients (penile urethra 23/29, bulbar urethra 8/29). The early initial success rate of stricture treatment was 50% (median follow-up: 4 years [1-7]). Additional surgical procedures were needed and performed in 11 patients. Eight patients were eventually diagnosed with a bulbar stricture, either isolated (n = 5) or combined with a distal stricture (n = 3), without significant relationship with initial position of meatus. DISCUSSION: Predictive factors for bulbar strictures locations could not be identified. It was however observed that symptomatic bulbar strictures do exist in adults, in the long term after penile hypospadias repair during childhood, independently of the initial site of hypospadias, initial success of primary repair, and the type of surgical reconstructions performed during childhood. CONCLUSION: Bulbar strictures represent more than 25% of the overall strictures diagnosed in adult patients treated for hypospadias during childhood, independently of the original site of urethral reconstruction.

Familial acampomelic form of campomelic dysplasia caused by a 960 kb deletion upstream of SOX9.

Campomelic dysplasia (CD) is a rare autosomal dominant osteochondrodysplasia with or without XY disorders of sexual development (DSD). Campomelia is absent in about 10% of the cases, referred to as the acampomelic form of CD (ACD). Most CDs are caused by mutations within the SOX9 coding region. Several CD patients with balanced chromosome rearrangements involving the 17q24 region have been reported suggesting the presence of cis-regulatory elements upstream and/or downstream of the gene. Deletions upstream of SOX9 represent a third mechanism of mutation. To date, a 1.5 Mb de novo deletion in the SOX9 upstream region has been identified in a single 46,XY patient with ACD and DSD. We report here for the first time on a familial ACD caused by an inherited deletion mapping upstream of the SOX9 gene. Using high-density oligoarray comparative genomic hybridization (CGH), we showed that the size of the deletion was 960 kb in the XY-DSD child and her mother, both affected. The deletion lying from 517 kb to 1.477 Mb upstream of SOX9 remove several highly conserved elements and reduce the minimum critical size and therefore the number of highly conserved sequence elements responsible for ACD.

Follow-up and surgical management of Peutz-Jeghers syndrome in children.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is an autosomal dominant syndrome with an increased risk of polyposis complications and intestinal and extraintestinal tumours. METHODS: During the last 15 years, we reviewed a series of 11 children with PJS, with special attention to evolution and follow-up. Diagnosis was based on at least 1 hamartomatous polyp associated with 2 of the 3 following criteria: family record of PJS, polyposis localised on small bowel, and mucocutaneous pigmentation. Diagnosis of PJS also could be raised by a single genetic analysis of STK11 gene. RESULTS: Median age at beginning of symptoms was 6 years old. Seven of the 11 children had genetic tests, which were positive for STK11 gene mutation. Among the 10 children presenting with gastrointestinal complications, 8 were operated on, 6 had at least 1 small bowel resection, and 4 had repeat surgery for recurrent intussusceptions. In case of complications leading to a surgical procedure, we performed intraoperative enteroscopy to remove all large polyps. To prevent any polyposis complications, we suggest a complete check-up of polyposis topography with some of the new endoscopic tools, either double-balloon endoscopy or videocapsule endoscopy. CONCLUSIONS: Children with PJS have a high risk of numerous laparotomies due to polyps' complications. Therefore, a screening of intestinal polyposis by videocapsule endoscopy is recommended, as well as a screening of the most frequent sites of cancers for the patient's whole life. During any abdominal procedure, they should have an intraoperative endoscopy, this management allowing an increased time interval between 2 laparotomies.

Minimally invasive surgery for anorectal malformation in boys: a multicenter study.

INTRODUCTION: The laparoscopic pull-through for high imperforate anus in boys has recently been developed in France and Benelux. The purpose of this study was to evaluate technical difficulties and surgical complications of this approach. PATIENTS AND METHODS: This report was based on a retrospective study from January 2002 to December 2007,including 34 patients from 10 centers. The rectourinary fistula found in 33/34 cases was bulbar in 10, prostaticin 20, and cervical in 3. RESULTS: Patients were 3.7 months old (range, 1.6-10.4) at surgery. Fistula was cut without closure in 11 cases or divided and closed on the genitourinary side with a suture in 15, with clips in five and linear stapler in two.Median operative duration was 152 mm (range, 80-410). The main per-operative complication, occurring in five cases, was leakage of stools from the rectum after the fistula section, requiring in one case a second laparoscopic procedure for washing and for all five cases intravenous antibiotics. Median hospital stay was 6 days(range, 3-15). During the follow-up, patients experienced eight anal stenoses and three prolapses, requiring in three cases perineal redo surgery. CONCLUSION: The laparoscopic approach of high imperforate anus allowed an easy control of the fistula and helped to determine the accurate passage through the levator ani. Nevertheless, technical points have to be improved,such as coprostasis before fistula section to avoid stool leakage, rectum tacking to prevent prolapse,and calibration of muscle channel to avoid stenosis.

Laparoscopic resection of abdominal neuroblastoma.

BACKGROUND: Since indications for laparoscopic adrenalectomy have progressively expanded to pediatric surgery, preliminary reports have studied the laparoscopic approach for abdominal neuroblastoma (NB). We aimed to report on the indications and the results of laparoscopic resection in a large series of abdominal NBs. METHODS: A retrospective multicenter study included 45 children with abdominal NBs (28 localized, 11 stage 4, 6 stage 4s) and laparoscopic resection of their abdominal primary tumor. Primary site of the tumor was the adrenal gland in 41 cases and retroperitoneal space in 4. The median age at surgery was 12 months (1-122); median tumor size was 37 mm (12-70). Resection was performed through transperitoneal laparoscopy (n = 38) or retroperitoneoscopy (n = 7). RESULTS: Complete macroscopic resection was achieved in 43 of 45 children (96%). The median duration of pneumoperitoneum was 70 min (30-160), and the length of hospital stay was 3 days (2-9). Four procedures (9%) were converted to open surgery, and tumor rupture occurred in three cases. Of the 28 children with localized disease, there was a 96% overall survival (OS) rate after a median follow-up of 28 months (4-94). There was one local relapse in this subgroup, with subsequent complete remission. For the entire 45-children cohort, four children died and three presented a recurrence resulting in OS, disease-free survival, and event-free survival rates of 84% +/- 8.1, 84% +/- 8.2, and 77% +/- 9.1 respectively. CONCLUSION: Laparoscopic resection of abdominal primary allows effective local control of the disease in a wide range of clinical situations of neuroblastoma, with an acceptable morbidity.