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Background: The International Neuroblastoma Risk Group (INRG) classifier utilizes a staging system based on pretreatment imaging criteria in which image-defined risk factors (IDRFs) are used to evaluate the extent of locoregional disease. Children's Oncology Group (COG) study ANBL0531 prospectively examined institutional determination of IDRF status and compared that to a standardized central review., Methods: Between 9/2009-6/2011, patients with intermediate-risk neuroblastoma were enrolled on ANBL0531 and had IDRF assessment at treating institutions. Paired COG pediatric surgeons and radiologists performed blinded central review of diagnostic imaging for the presence or absence of IDRFs. Second blinded review was performed in cases of discordance. Comparison of local and central review was performed using the Kappa coefficient to determine concordance in IDRF assessment., Results: 211 patients enrolled in ANBL0531 underwent IDRF assessment; 3 patients were excluded due to poor image quality. Central reviewer pairs agreed on the presence or absence of any IDRF in 170/208 (81.7%; κ = 0.48) cases. Thirteen (6.3%) cases could not be adjudicated after second blinded review. Radiologists were more likely to identify IRDFs as present than surgeons (p < 0.001). Local and central reviewers agreed on the presence or absence of any IDRF in only108/208 (51.9%; κ = 0.06) cases., Conclusions: Among experienced pediatric surgeons and radiologists participating in central review, concordance was moderate, with agreement in 81.7% of cases. On comparison of local and central assessment of IDRFs, concordance was poor. These data indicate that greater standardization, education, technology, and training are needed to improve the assessment of IDRFs in children with neuroblastoma., Level of Evidence: Treatment Study, Level III., Competing Interests: Conflict of interset Author AN serves on a data safety monitoring board for Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We previously reported excellent three-year overall survival (OS) for patients with newly diagnosed intermediate-risk neuroblastoma treated with a biology- and response-based algorithm on the Children's Oncology Group study ANBL0531. We now present the long-term follow-up results., Methods: All patients who met the age, stage, and tumor biology criteria for intermediate-risk neuroblastoma were eligible. Treatment was based on prognostic biomarkers and overall response. Event-free survival (EFS) and OS were estimated by the Kaplan-Meier method., Results: The 10-year EFS and OS for the entire study cohort (n = 404) were 82.0% (95% confidence interval (CI), 77.2%-86.9%) and 94.7% (95% CI, 91.8%-97.5%), respectively. International Neuroblastoma Staging System stage 4 patients (n = 133) had inferior OS compared with non-stage 4 patients (n = 271; 10-year OS: 90.8% [95% CI, 84.5%-97.0%] vs 96.6% [95% CI, 93.9%-99.4%], p = .02). Infants with stage 4 tumors with ≥1 unfavorable biological feature (n = 47) had inferior EFS compared with those with favorable biology (n = 61; 10-year EFS: 66.8% [95% CI, 50.4%-83.3%] vs 86.9% [95% CI, 76.0%-97.8%], p = .02); OS did not differ (10-year OS: 84.4% [95% CI, 71.8%-97.0%] vs 95.0% [95% CI, 87.7%-100.0%], p = .08). Inferior EFS but not OS was observed among patients with tumors with (n = 26) versus without (n = 314) 11q loss of heterozygosity (10-year EFS: 68.4% [95% CI, 44.5%-92.2%] vs 83.9% [95% CI, 78.7%-89.2%], p = .03; 10-year OS: 88.0% [95% CI, 72.0%-100.0%] vs 95.7% [95% CI, 92.8%-98.6%], p = .09)., Conclusions: The ANBL0531 trial treatment algorithm resulted in excellent long-term survival. More effective treatments are needed for subsets of patients with unfavorable biology tumors., (© 2024 Wiley Periodicals LLC.)

Purpose: The primary objective of the Children's Oncology Group study ANBL0531 (ClinicalTrials.gov identifier: NCT00499616) was to reduce therapy for subsets of patients with intermediate-risk neuroblastoma using a biology- and response-based algorithm to assign treatment duration while maintaining a 3-year overall survival (OS) of 95% or more for the entire cohort., Patients and Methods: Children younger than age 12 years with intermediate-risk stage 2A/2B or stage 3 tumors with favorable histology; infants younger than age 365 days with stage 3, 4 or 4S disease; and toddlers from 365 to younger than 547 days with favorable histology, hyperdiploid stage 4, or unfavorable histology stage 3 tumors were eligible. Patients with MYCN -amplified tumors were excluded. Patients were assigned to initially receive two (group 2), four (group 3), or eight (group 4) cycles of chemotherapy with or without surgery on the basis of prognostic markers, including allelic status of chromosomes 1p and 11q; ultimate duration of therapy was determined by overall response., Results: Between 2007 and 2011, 404 evaluable patients were enrolled. Compared with legacy Children's Oncology Group studies, subsets of patients had a reduction in treatment. The 3-year event-free survival and OS rates were 83.2% (95% CI, 79.4% to 87.0%) and 94.9% (95% CI, 92.7% to 97.2%), respectively. Infants with stage 4 tumors with favorable biology (n = 61) had superior 3-year event-free survival compared with patients with one or more unfavorable biologic features (n = 47; 86.9% [95% CI, 78.3% to 95.4%] v 66.8% [95% CI, 53.1% to 80.6%]; P = .02), with a trend toward OS advantage (95.0% [95% CI, 89.5% to 100%] v 86.7% [95% CI, 76.6% to 96.7%], respectively; P = .08). OS for patients with localized disease was 100%., Conclusion: Excellent survival was achieved with this treatment algorithm, with reduction of therapy for subsets of patients. More-effective treatment strategies still are needed for infants with unfavorable biology stage 4 disease.

Purpose: Infants with stage 4S neuroblastoma usually have favorable outcomes with observation or minimal chemotherapy. However, young infants with symptoms secondary to massive hepatomegaly or with unfavorable tumor biology are at high risk of death. Our aim was to improve outcomes for patients with symptomatic and/or unfavorable biology 4S neuroblastoma with a uniform treatment approach using a biology- and response-based algorithm., Patients and Methods: The subset of patients with 4S disease with MYCN-not amplified tumors with impaired or impending organ dysfunction, or with unfavorable histology and/or diploid DNA index, were eligible. Patients were assigned to receive two, four, or eight cycles of chemotherapy on the basis of histology, diploid DNA index, chromosome arm 1p or 11q loss of heterozygosity (LOH) status, and symptoms., Results: Forty-nine eligible patients were enrolled: 41 were symptomatic and 28 had unfavorable biology. Seventeen patients (symptomatic, favorable biology) were assigned two cycles, 21 patients (any unfavorable biologic feature without 1p or 11q LOH) were assigned four cycles, and 11 patients (unfavorable biology including 1p and/or 11q LOH [n = 7] or symptomatic with unknown biology [n = 4]), were assigned eight cycles. The 3-year overall survival was 81.4% ± 5.8%. Eight of nine deaths were in patients younger than 2 months of age at diagnosis (median, 9 days [range, 1 to 68 days]): five acute deaths were a result of hepatomegaly and associated toxicities; two were a result of late relapse in patients with unfavorable biology; and two were a result of treatment complications. No deaths occurred after protocol-mandated pre-emptive treatment of infants younger than 2 months with hepatomegaly, regardless of symptoms. A new scoring algorithm for emergent chemotherapy in patients with 4S disease was developed on the basis of this experience., Conclusion: The outcome for 4S neuroblastoma can be improved with pre-emptive chemotherapy for evolving hepatomegaly or other baseline comorbidities in infants younger than 2 months of age.

We recently revised a redundant colon conduit in a boy who was born with isolated esophageal atresia. In view of the paucity of reports dealing with correction of this common complication of esophageal replacement, it seemed appropriate to report our experience. Because of effective medical therapy of acid peptic disease, patients who formerly required conduit replacement may now be candidates for revision; however, the medical literature does not specify when conduit revision, as opposed to conduit replacement, is indicated; also, no guidance is provided regarding what constitutes effective operative revision. Innovative techniques that stretch and elongate the atretic esophagus will likely lessen the use of conduits in esophageal atresia; nevertheless, colon conduits are useful in many other clinical situations and will remain an essential part of the armamentarium of pediatric, general, and thoracic surgeons. This report highlights the DeMeester and Tannuri technique, whereby a colon conduit is prepared like a Roux limb. The mesentery is divided only once; the conduit's blood supply is not severed from the distal mesocolon. This innovation improves a conduit's blood supply and lessens its attendant complications. Lastly, we describe a muscle splitting, posterolateral thoracotomy technique that is simpler than the alternatives and is useful in a variety of clinical situations.

CBPFM is a rare finding associated with GERD in infancy. To our knowledge this case represents the twenty-fifth reported case in a child and the one-hundred and thirty first reported case in the literature overall. This case serves to remind the practitioner that children with symptoms of GER may not be just one of the endless number of happy spitters.

Background/purpose: Previous reports indicate that complete resection of high-risk neuroblastoma improves outcome but may entail high surgical complication rates. The authors evaluated the effect of complete primary site resection on event-free survival (EFS), overall survival (OS), and complication rates in patients entered on a high-risk neuroblastoma treatment protocol., Methods: A total of 539 eligible patients with high-risk neuroblastoma were entered on protocol CCG-3891. Patients were assigned randomly to continuation chemotherapy or autologous bone marrow transplantation. Surgical resection was performed at diagnosis or after induction chemotherapy. Surgeons assessed resection as complete (CR), minimal residual (<5%, MR), or partial (PR). Incomplete resections received secondary resection or 10 Gy of external beam radiation. Patients were evaluated for EFS, OS, and complications of surgery based on completeness of overall best resection., Results: The proportion of patients resectable at diagnosis was 27% for CR and 14% for MR. This improved after chemotherapy to 45% and 25%. Complication rates based on completeness of resection were 29%, 38%, and 36% for CR, MR, and PR, respectively. Estimated 5-year EFS rate was 30% +/- 3% for patients who achieved CR (n = 210) compared with 25% +/- 3% (P =.1010) for those with less than CR (n = 258)., Conclusions: Resectability improved after neoadjuvant chemotherapy. Complete resection did not increase complications. There was a small survival benefit for complete resection. This study suggests that complete resection may still be important in the current era of intense chemotherapy and transplant.

Objective: To develop a cost- and time-effective algorithm for differentiating hypertrophic pyloric stenosis (HPS) from other medical causes of emesis in infants referred from community-based pediatricians and family practitioners to the imaging department of a tertiary children's care facility., Methods: Eighty-nine vomiting infants (22 females, 67 males) between the ages of 11 and 120 days (mean, 43.5 days) had received nothing by mouth for at least 1 hour before the study. Each child was assessed for duration of vomiting, status of body weight, time and volume of last ingestion, and time of last emesis. A #8 French (Sherwood Medical, St Louis, MO) nasogastric feeding tube was placed in the child's stomach. The contents were aspirated and measured to determine likelihood of HPS. An aspirated volume >/=5 mL implicated gastric outlet obstruction, and ultrasonography (US) was performed. If this study was positive for HPS, the patient was referred for surgery. If US was negative, an upper gastrointestinal series (UGI) was performed. An aspirated stomach contents volume <5 mL suggested a medical cause for the emesis, and UGI was performed. Pediatric surgeons with no knowledge of the volume results palpated the abdomens of 73 of 89 infants (82%)., Results: Twenty-three of 89 patients (25%) had HPS. The aspirate criteria for HPS had a sensitivity of 91%, a specificity of 88%, and an accuracy of 89%. Of the false-positive studies (total = 8), six were related to recent significant ingestion (within 2 hours of the study), and two were attributable to antral dysmotility. The surgeons palpated the mass in 10 of 19 patients (53%). Sensitivity and specificity were 53% and 93%, respectively. Only 6 of 89 infants (7%) required both US and UGI to determine the etiology of the nonbilious vomiting. By performing the UGI in 66 patients, it was also found that 14% had slow gastric emptying and 79% had gastroesophageal reflux. Eighty-one percent of the gastroesophageal reflux was significant., Conclusion: The volumetric method of determining the proper imaging study is cost- and time-effective in the evaluation of the nonbilious vomiting infant for pyloric stenosis. If US was performed initially in all patients referred for imaging, two studies would have been performed in 68 of 89 patients (76%) to define the etiology of the emesis. Because we used the volumetric method, 62 fewer imaging studies were performed, representing a savings of $4464 and 30 hours of physician time. If children are given nothing by mouth for 3 to 4 hours before gastric aspiration, the specificity of the volumetric method improves to 94%, and the accuracy improves to 96%.

Background: Bronchography is occasionally needed for the evaluation and management of some congenital pulmonary anomalies as well as some acquired diseases, usually of the tracheo- bronchial tree. There is currently no effective, approved contrast agent for this imaging techniq ue., Objective: We evaluated five agents (barium sulfate, iohexol, propyliodone oily, propyliodone aqueous, and perflubron) in terms of image quality, histologic changes, and effects on hemodynamics, blood gases, and standard laboratory tests in New Zealand White rabbits., Materials and Methods: Animals were anesthetized and intubated. Each contrast agent (0.25 ml/kg) was administered intratracheally. Three animals in each group had intravenous lines placed for blood sampling and blood pressure monitoring and were sacrificed at 1 h. An additional three animals for each agent were sacrificed at 24 h and 1 week after imaging. Blood samples were taken immediately before contrast instillation and at 1 h postbronchography. Fluoroscopic images were recorded on standard VHS video tape and evaluated in blind fashion. Segments of lung tissue and bronchi were obtained for histologic examination., Results: Necrosis and/or inflammatory infiltrates were noted in 78 % of the bronchograms performed with propyliodone aqueous, 67 % with propyliodone oily, 55 % with perflubron, and 33 % with iohexol 120, 240 and 350. No histologic damage was observed with barium. The propyliodones gave the best-quality imaging results and the most histologic changes. Iohexol, in any concentration, gave the least acceptable images and a moderate number of histologic changes. Barium sulfate demonstrated acceptable images with virtually no histologic changes., Conclusion: From the histologic and imaging results, barium is the best available contrast material for bronchography.

Continuous ambulatory peritoneal dialysis (CAPD) is frequently used in the pediatric age group for reversible and end-stage renal failure. Most pediatric patients tolerate this therapy with few complications. Approximately 2% of children, however, develop massive unilateral hydrothorax. This major complication usually results in the discontinuation of peritoneal dialysis in all forms and the institution of hemodialysis. Occult diaphragmatic defects account for most adult and pediatric patients who develop this complication. Three pediatric patients receiving CAPD complicated by massive hydrothorax are described. All patients were successfully treated by thoracotomy and repair of the diaphragmatic eventration with an immediate return to CAPD. This is the first report of successful therapy of this kind in children. A review of the cause, diagnosis, and treatment of massive hydrothorax developing during CAPD therapy is presented.

In 17 fasted rabbits, a 20% solution of Intralipid was administered into the peritoneal cavity. Oral and intravenous feedings were not provided. Eight of the rabbits underwent resection of 50% of the intestine. Serial samples of serum and peritoneal fluid showed that half of the triglyceride was absorbed within 1 hour in rabbits with intact viscera, but not until 2 hours in rabbits with intestinal resection. The caval-arterial gradient for triglycerides was consistently positive in rabbits with intact intestine, whereas it was smaller and erratic after intestinal resection. The portal-arterial gradient was never significantly different from zero. These data indicate that the major triglyceride absorption occurred across the visceral peritoneum through lymphatic vessels, with little portal venous absorption. Transperitoneal absorption of triglycerides occurred to a sufficient degree to provide substantial nutritional supplementation in rabbits with intact intestine; absorption was less in rabbits with intestinal resection.

For evaluation of the effects of orchiopexy and orchiectomy on the contralateral descended testis, unilateral cryptorchidism was produced in 60 21-day-old mice by suturing of the left testis to the inner abdominal wall. A sham operation was performed on the left testis of 20 control mice (S). After creation of unilateral cryptorchidism, orchiopexy (P) or orchiectomy (O) was performed on the left testis at 2 (group I) and 10 (group II) weeks (ten mice each). All testes were removed for examination 2 weeks after orchiopexy or orchiectomy. In both groups the mean values of testicular weight, seminiferous tubular diameter, and tubular biopsy score of contralateral O testes were always statistically similar to the values of contralateral S testes (p greater than 0.01). The difference between TBS values of contralateral P and S testes was not significant in group I (p greater than 0.01), but it was significant in group II (p less than 0.01). The data from this murine experiment suggest that orchiectomy for unilateral cryptorchid testis is almost always helpful in improving contralateral morphology; however, orchiopexy can be helpful if it is not performed late in the period of maturation.

Unilateral cryptorchidism is frequently accompanied by infertility. Uncertainty exists as to whether the infertility is a genetic effect or is related to an autoimmune reaction to the elevated testis. The effects of unilateral cryptorchidism were evaluated in 50 mice by surgically elevating the left testicle of 21-day-old mice into the abdomen (AT). A sham operation was performed on the left testicle of 50 control mice (SHT). The temperature of the abdominal testes measured 2.5 degrees C higher than the scrotal testes. The testes were removed from both sides at 1, 2, 3, 4 and 6 weeks postoperation. After testicular weights were recorded, seminiferous tubule diameters were measured, and germinal epithelium maturity was graded histologically using a modified Johnson testicular biopsy score. Progressive abnormal changes were seen in the contralateral descended testicles of AT as compared to SHT. By 3 weeks, though testicular weight changes were similar, mean seminiferous tubule diameter was smaller (P less than .001), and the germinal epithelium was less mature (P less than .001). These changes persisted through the sixth week. By changing the physiologic environment of one testicle, we have induced alterations in the histologic appearance of the contralateral testicle during the period of normal maturation.