Background: Genital malformations are frequently diagnosed in patients with VACTERL, but are currently not included in the acronym. This study aimed to analyze the frequency of genital anomalies in patients with esophageal atresia (EA) and/or anorectal malformation (ARM), with a subgroup analysis of children fulfilling the VACTERL criteria. Method: This was a cross-sectional retrospective analysis of two prospectively collected registries of patients operated on for ARM and EA between 2012 and 2022 at a specialized national center. Children were screened routinely for malformations according to the VACTERL acronym. Results: A total of 174 children were included in the study. VACTERL was diagnosed in 60 children (34%), while 114 children (66%) were defined as non-VACTERL. Genital malformations were diagnosed in 38% (23/60) of the children with VACTERL, and in 11% (13/114) of the children without VACTERL (p < 0.001). The presence of genital malformations correlated linearly with the number of diagnosed component features (CFs). In boys with VACTERL, the most common genital malformation was undescended testes present in 10/27 (21%) compared to 1/71 (1%) in non-VACTERL boys (p < 0.001). M & uuml;llerian duct anomalies were found in 26% of girls with VACTERL vs. 7% in non-VACTERL girls (p < 0.05). Conclusion: There was a higher frequency of genital malformations in patients with VACTERL emphasizing the importance of genital assessment for these patients. We propose VACTERL-G as an extension of the current acronym aiming to reduce the risk of long-term morbidity due to delayed diagnosis of reproductive anomalies. Level of Evidence: 4. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

AIM:To investigate underlying factors for previously reported shortcomings in child health centres' (CHC) referral process of boys with undescended testicles. METHODS:A total of 386 physicians working at Swedish CHCs were surveyed regarding their knowledge about undescended testicles and their clinical management. Multivariate regression analyses were performed to identify risk factors of non-adherence to guidelines and self-reported lack of clinical skills. RESULTS:The overall knowledge of the health benefits of undescended testicle surgery was high (89%), while two-thirds were unaware of surgery being recommended <1 year of age. One-fifth of respondents had never received guidance on examination techniques. Male gender (adjusted odds ratio [aOR] 0.51, 95% confidence interval [95% CI] 0.31-0.86), education in paediatrics (aOR 0.37, 95% CI 0.18-0.76) and more experience (aOR 0.02, 95% CI 0.01-0.09) significantly decreased the risk of unfamiliarity with examinations. More experience decreased the risk of stating the incorrect indications for undescended testicle surgery (aOR 0.17, 95% CI 0.03-0.95) and finding examinations difficult (aOR 0.22, 95% CI 0.07-0.72). Medical education outside Nordic countries was a risk factor for unawareness of guidelines (aOR 2.06, 95% CI 1.21-3.51). CONCLUSION:The knowledge and confidence level of the study population varied widely. The results indicate a need for further theoretical and practical education among Swedish CHC physicians.

Purpose This study aimed to investigate the rate of re-ascent requiring re-operation after primary orchidopexy and to investigate eventual differences between the inguinal and scrotal approach as well as other potential predictors for re-ascent.Methods A retrospective cohort study of children treated for undescended testis (UDT) with orchidopexy between 2018 and 2022 was conducted. The primary outcome was re-ascent requiring re-operation, and the secondary outcome was atrophy rate. Independent variables were age, underlying conditions, side, surgical approach, operation time, bilaterality, congenital/ascended UDT, presence of scrotal hypoplasia, presence of a patent processus vaginalis, division of external oblique, and suture of the testis. Univariate and logistic regression were used to evaluate differences between groups and risk for re-ascent.Results A total of 662 testes in 554 patients were included. Re-operation occurred in 6% (7% with inguinal approach, 3% with scrotal approach, p = 0.04). Re-operation was associated with younger age, congenital UDT, and inguinal approach, but neither of these variables remained significant in multivariate analyses. Atrophy occurred in one testis.Conclusion The rate of re-ascent was 6% and the atrophy rate was 0.15%. A larger study may find predictors for re-ascent but with very low absolute risk. The lower rate of re-ascent with the scrotal approach is probably due to selection bias.

BACKGROUND:Accurate referral of boys with suspected undescended testes (UDT) is of importance to preserve fertility and reduce risk of future testicular cancer. While late referral is well studied, there is less knowledge about incorrect referrals, hence, referral of boys with normal testes.OBJECTIVE:To evaluate the proportion of UDT referrals that did not lead to surgery or follow-up, and to assess risk factors for referral of boys with normal testes.STUDY DESIGN:All UDT referrals to a tertiary center of pediatric surgery during 2019-2020 were retrospectively assessed. Only children with suspected UDT in the referral (not suspected retractile testicles) were included. Primary outcome was normal testes at examination by a pediatric urologist. Independent variables were age, season, region of residence, referring care unit, referrer's educational level, referrer's findings, and ultrasound result. Risk factors for not needing surgery/follow-up were assessed with logistic regression and presented as adjusted odds ratios with a 95% confidence interval (aOR, [95% CI]).RESULTS:A total of 378 out of 740 included boys (51.1%) had normal testes. Patients >4 years (aOR 0,53, 95% CI [0,30-0,94]), referrals from pediatric clinics (aOR 0.27, 95% CI [0.14-0.51]) or surgery clinics (aOR 0.06, 95% CI [0.01-0.38]) had lower risk of normal testes. Boys referred during spring (aOR 1.80, 95% CI [1.06-3.05]), by a non-specialist physician (aOR 1.58, 95% CI [1.01-2.48]) or referrer's description of bilateral UDT (aOR 2.34, 95% CI [1.58-3.45]), or retractile testes (aOR 6.99, 95% CI [3.61-13.55]) had higher risk of not needing surgery/follow-up. None of the referred boys that had normal testes had been re-admitted at the end of this study (October 2022).DISCUSSION:Over 50% of boys referred for UDT had normal testes. This is higher or equal to previous reports. Efforts to reduce this rate should in our setting probably be directed towards well-child centers and training in examination of testicles. The main limitation of this study is the retrospective design and the rather short follow-up time, which however should have very modest effect on the main findings.CONCLUSION:Over 50% of boys referred for UDT have normal testes. A national survey regarding the management and examination of boys testicles has been launched and directed at well-child centers to further evaluate the findings of the current study.

Supplementary Table S3. Related to Figure 3. Gene ontology for genes with higher expression in patient tumors vs. PDOXs. Supplementary Table S4. Related to Figure 3. List of the gene clusters defined across PDOXs #1-5 obtained from serial orthotopic passaging. Supplementary Table S5. Related to Figure 3. List of enriched Gene Ontology terms by cluster defined in PDOXs #1-5.

Supplementary methods and legends to supplementary figures and tables

BACKGROUND:Children with suspected ureteropelvic junction obstruction (UPJO) may present with a paradoxical ipsilateral supranormal differential renal function (snDRF) on 99mTechnetium mercaptoacetyltriglycine scintigraphy (MAG3 scan). OBJECTIVE:The aim was to investigate the prevalence of snDRF, the risk of pyeloplasty among children with UPJO and snDRF, and to explore the experience of snDRF among international pediatric urologists. METHODS:A retrospective cohort study of children with suspected unilateral UPJO who underwent MAG3 scan at four hospitals in Sweden between 2005 and 2020. SnDRF was defined as DRF ≥55%. Normal DRF was defined as DRF 45-54%. Primary outcome was risk of pyeloplasty. Indications for pyeloplasty were loss of >10%-points of differential renal function (DRF), ipsilateral DRF <40%, or symptomatic UPJO. Logistic and cox regressions were performed in univariate and multivariable analyses, adjusting for age, gender, year, laterality, antenatal hydronephrosis, anterior-posterior diameter (APD), and kidney size. An international questionnaire regarding the management of snDRF was developed and distributed to pediatric urologists. RESULTS:The prevalence of snDRF was 19%. SnDRF was more common in boys, children with antenatal hydronephrosis, children undergoing their first MAG3 scan at a younger age, and in the left kidney. After further exclusion of 70 children with DRF <45%, a total of 264 were included for longitudinal follow-up of median 6.6 (IQR 2.5-11.5) years. SnDRF was not associated with increased risk of pyeloplasty (adjusted OR 0.98 (95% CI 0.41-2.33), p = 0.96, and adjusted HR 1.00 (95% CI 0.53-1.91), p = 0.99) or time to pyeloplasty (1.1 years vs. 1.6 years, p = 0.40). Among the 79 surveyed pediatric urologists, a majority would not change clinical UPJO-management based on the presence or absence of ipsilateral snDRF. DISCUSSION:There are only a few studies considering the need of pyeloplasty based on the presence of snDRF and this is the first survey among pediatric urologists on its management. With more included patients than previous studies, this study showed a snDRF prevalence of 19%, congruent with the findings of others. The underlying cause of snDRF is debated, but it cannot solely be explained as an artifact of hydronephrotic kidneys. Further studies on the clinical implications of snDRF are warranted, since DRF influences the decision to operate. CONCLUSION:A fifth of all children with suspected UPJO presented with ipsilateral snDRF on initial MAG3 scan, and snDRF was not associated with a greater risk of pyeloplasty. Supported by a large group of international pediatric urology colleagues, this study concludes that the same clinical follow-up and management apply, regardless of presence of snDRF.

Supplementary Table S6. Related to Figure 4. Top 1000 varying genes based on SD across all samples derived from Patient/PDOX #5. Supplementary Table S7. Related to Figure 4. List of enriched Gene Ontology terms by cluster derived from the gene clusters defined in Suppl. Table S6.

Supplementary Figure S3. Related to Figure 5. Proteomic analysis of multiple samples derived from Patient #5.

Supplementary Table S8. Related to Figure 5. List of top varying peptides based on SD across all samples derived from Patient/PDOX #5. Supplementary Table S9. Related to Figure 5. List of top varying phospho-peptides based on SD across all samples derived from Patient/PDOX #5. Supplementary Table S10. Related to Figure 5. List of enriched Gene Ontology terms by cluster derived from the protein clusters defined in Suppl. Table S8. Supplementary Table S11. Related to Figure 5. List of enriched Gene Ontology terms by cluster derived from the phospho-protein clusters defined in Suppl. Table S9. Supplementary Table S12. Related to Figure 5. List of differentially expressed proteins from group 1-3 of PDOX #5. Supplementary Table S13. Related to Figure 5. List of differentially expressed phosphorylated proteins from group 1-3 of PDOX #5. Supplementary Table S14. Related to Figure 5. List of peptides measured in the targeted PRM assay.

Supplementary Figure S2. Related to Figure 4. Intratumor heterogeneity is less prominent than intertumor heterogeneity.

Supplementary Figure S1. Related to Figure 3. Correlation of PDOX gene signatures to overall survival.

Supplementary Table S1. Related to Figure 1. List of all somatic mutations detected in patient tumors, and in PDOXs from low and high in vivo generations. Supplementary Table S2. Related to Figure 2. List of all chromosomal copy number changes in patient tumors, and in PDOXs from low and high in vivo generations.

Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. Methods and Materials: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. Results: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. Conclusions: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability. (C) 2022 Elsevier Inc. All rights reserved.

Aim Information about healthy children's urinary tract symptoms is scarce but would be helpful in children with congenital urinary tract conditions. The aim of this study was to develop and evaluate a Lower Urinary Tract Dysfunction (LUTD) questionnaire. Methods A 15-item questionnaire based on definitions by the International Children's Continence Society (ICCS) about urinary tract function, was given to children 4-15 years old with no gastrointestinal or urinary tract conditions. The study was approved ethically. Results The response rate was 82% (311/377), 50% (n = 155) were girls. Children were of the age groups 3.5-7 years (n = 136), 8-12 years (n = 127), and 13-15 years (n = 48). More girls than boys reported urinary tract infections (20% vs 3%, p < 0.001), while prevalences of incontinence and enuresis were equivalent in both sexes. In the youngest age group, enuresis was the most frequently reported symptom (11%), then daytime incontinence (10%). The older children more frequently reported previous urinary tract infections (12% and 17% in respective groups) and daytime incontinence (9% and 6%, respectively). Conclusion A LUTD questionnaire is developed and evaluated within this study. Daytime urinary incontinence is the overall most common lower urinary tract symptom and girls report infections more frequently than boys.

Background: The primary aim was to describe patient-reported morbidity from neurogenic bladder and bowel dysfunction in a cohort of children with spina bifida. The secondary aim was to describe the overall surgical burden in these children. Methods: Children with meningocele or myelomeningocele, born between 2000–2016, and followed by a tertiary spina bifida center were evaluated in a cross-sectional cohort study using data from charts and a prospective national follow-up program. Results: In the group of 62 patients, clean intermittent catheterization (CIC) was used by 47 (76%) of the patients, and anticholinergic treatment was used by 36 (58%). More than one third of the patients reported inadequate results with daily urinary leakage. Laxatives and enema were used regularly by 45 (73%) and 39 (63%) patients, respectively. Inadequate results were reported by seven (11%) patients. One or more urogenital or gastrointestinal operations had been performed in 26 (42%) patients, with a total of 109 procedures overall. Conclusions: Despite substantial bowel and bladder management, a significant portion of children suffered from inadequate results concerning bladder and bowel control. Many surgeries were performed in a defined group of the children. Prospective, long-term studies can evaluate if more aggressive medical and/or surgical management could increase bowel and bladder control.

Aim The aims of this study were to evaluate health-related quality of life (HRQoL) in children with sacrococcygeal teratoma and to explore the effect of the scar on physical, emotional and behavioral aspects. Methods A cohort of children operated on for sacrococcygeal teratoma between 2000 and 2013 at Lund University Hospital, Sweden, and their parents were interviewed. HRQoL was evaluated with PedsQL, and scar satisfaction was estimated through Patient Observer Scar Assessment Score (POSA). Results All eligible children (n = 17) were included (100% response rate). Median age was 7.3 years (range 3.5-16.0). Mean total PedsQL score was 92.3 (range 72.0 to 99.0). Patients with comorbidity scored lower (87.5) than those without (95.0) (p < 0.05). Pain during sitting down was reported by two (20%) patients, and itching was reported by another two patients (20%) aged > 8 years. No children reported that they avoided situations due to the scar, and most (80% of children and 90% of parents) reported absent or only mild negative emotions when considering the scar. Conclusion Children with sacrococcygeal teratoma had a good overall HRQoL, but comorbidity reduced the outcome. A few children reported scar-related impact on physical, behavioral and emotional aspects.

Phimosis in boys is a common condition. In the majority of cases it is physiological without symptoms. Symptomatic phimosis can often be treated successfully with local steroid cream - only a minority of patients need surgery. This study concludes that diagnosis, information to patients and guardians, initiation and follow-up of local steroid treatment can successfully, and safely, be delegated to trained assistant nurses.

Phimosis in boys is a common condition. In the majority of cases it is physiological without symptoms. Symptomatic phimosis can often be treated successfully with local steroid cream - only a minority of patients need surgery.  This study concludes that diagnosis, information to patients and guardians, initiation and follow-up of local steroid treatment can successfully, and safely, be delegated to trained assistant nurses.

BACKGROUND:There is still a lack of knowledge regarding the natural course of resolution of hydronephrosis after pyeloplasty, and no consensus exists on how resolution of hydronephrosis is defined or when resolution is expected to occur. OBJECTIVE:To determine when resolution of hydronephrosis occurs following pyeloplasty, by type of obstruction and by surgical approach. METHODS:This retrospective study included 125 children age <15 years treated with pyeloplasty and followed for two years with repeated ultrasound and MAG3 scan. Children with single kidneys, bilateral disease, and without hydronephrosis were excluded. Children with re-interventions were excluded in the evaluation of hydronephrosis but not in terms of success rate. Outcomes time to resolution of hydronephrosis (Anterior-Posterior diameter (APD) <10 mm or >50% reduction of APD) and 2-year success rate. Exposure was surgical approach and type of obstruction (intrinsic/extrinsic). Survival analysis was performed, adjusting for age, gender, year, laterality, preoperative renal function on MAG3, calyces dilatation and APD in the multivariable analysis. RESULTS:At 12 months and 24 months follow-up, 90% and 93% had reached resolution, respectively. All children with persistent dilatation had improved drainage and stable or improved function on MAG3. There was no difference in time to resolution of hydronephrosis between open versus robotic-assisted laparoscopic surgery (adjusted HR 0.90, [0.54-1.52], p = 0.70), nor between different types of obstruction (aHR 0.84 [0.53-1.34], p = 0.47). Eight children had re-intervention, all identified within 3 months after primary surgery, and four had a postoperative drop on MAG3, giving a total success rate of 91% (121/135). DISCUSSION:The vast majority of cases resolve and do so within 12 months from surgery. Since the improvement of hydronephrosis seems small between the first and second year after surgery, the value of follow-up beyond 12 months could be questioned. Based on the present study and previous literature we would recommend that children with persisting dilatation should continue their follow-up with ultrasound beyond 12 months. Children with complete resolution of their hydronephrosis at 12 months do not likely benefit from further follow-up. The same follow-up protocol should be applied, regardless of whether the obstruction is intrinsic or extrinsic in nature, or the surgery is performed with open or robotic-assisted approach. Overall, the definition of resolution of hydronephrosis varies in the literature and have impact on the results and may compromise comparisons. CONCLUSION:Surgical approach or type of obstruction does not seem to affect time to resolution of hydronephrosis after pyeloplasty in children. Follow-up with ultrasound beyond 12 months does not seem to benefit children with complete resolution.