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Purpose: Lower intestinal venous malformations are rare anomalies resulting from errors in vascular morphogenesis. These lesions may cause significant chronic and acute gastrointestinal hemorrhage. Venous malformations are unresponsive to angiogenesis inhibitors. Though these anomalies are generally incompletely resectable due to diffuse pelvic and mesenteric involvement, we sought to abate bleeding by excluding the lesion from the gastrointestinal lumen. Methods: Three patients with circumferential transmural venous malformations of the colorectum, pelvis and mesentery were identified. Imaging findings were similar among the patients, and included circumferential septated bright signal on T-2 weighted MRI, contrast enhancement, and multiple phleboliths, seen best on CT. The lesion extended from the anus to the splenic flexure in two patients and throughout the entire colorectum in the other. Each had daily hematochezia for many years and required transfusions (estimated over 100 units in one case) and chronic iron therapy. Though bleeding began in early childhood in each patient, no therapy was successful until ages 7,24, and 45. Colectomy, anorectal mucosectomy (through the pelvic venous malformation), and endorectal pull-through and anastomosis was performed (coloanal in two and ileoanal in one). Results: Bleeding has been essentially eradicated in all three patients with 5 to 52 month follow-up. One patient received a three unit transfusion intraoperatively and the other two received none. The most recently operated patient, who has residual venous malformation in the remaining 1 cm of anal mucosa, has some mild difficulty with fecal control if her diet results in loose stool. Conclusion: Colectomy with mucosectomy and endorectal pull-through should be considered for diffuse venous malformations of the colorectum prior to the development of large transfusion requirements., SJ Fishman MD, FAAP; RC Shamberger MD, FAAP; V Fox MD, PE Burrows MD; Children's Hospital, Boston, MA [...]

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., (© 2024 UICC.)

Background: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields., Methods: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test., Results: Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR., Conclusions: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SGD has received travel expenses from Loxo, Roche, and Salarius and consulting fees from Amgen, Bayer, and Jazz. TIY receives in-kind software support from MIM software to support a multicenter pediatric registry. Prior Presentation: Presented in part at the 64th Annual Meeting of the American Society for Radiation Oncology, San Antonio, TX, October 23–26, 2022., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Children with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and range of development delays) syndrome are predisposed to Wilms tumor (WT) and intrinsic kidney disease. Using the comprehensive International WAGR Syndrome Association (IWSA) survey of children with WAGR syndrome, we analyzed tumor characteristics, treatment and congenital risk factors, and kidney function in children with WAGR and WT., Methods: Descriptive statistics were utilized including demographics, treatment strategies, and patient outcomes. Comparisons were made between patients with WAGR and WT to those with WAGR alone. A multivariable logistic regression was completed for risk of developing WT and to identify predictors of chronic kidney disease (CKD)., Results: Sixty-four of 145 children with WAGR developed WT (44.1%). Three relapsed and one died. CKD developed in five children with WAGR without WT (5/81, 6.2%), and in 34 with WAGR and WT (34/64, 28.3%). Children with WAGR and WT were younger (p = .017), and had a greater association with CKD than WAGR children without WT (p < .0001). Two children with WT required hemodialysis, and one underwent kidney transplantation. By univariate analysis, CKD at any stage was associated with complete nephrectomy for the WT surgery (p < .0001), chemotherapy duration greater than 12 months, and three-drug therapy. Upon multivariate analysis, prior nephrectomy was the only significant variable (p = .0002)., Conclusions: Epidemiological analysis of children with WAGR demonstrated favorable oncologic outcomes, but high rate of early CKD in those who developed WT. Further study of the use of nephron-sparing surgery in children with WAGR and strategies to delay or treat early CKD are needed., (© 2024 Wiley Periodicals LLC.)

Introduction: The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials., Methods: Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed., Results: Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months., Conclusion: Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed., (© 2024 Wiley Periodicals LLC.)

Children with renal masses require surgical management to provide accurate surgical staging and skilled resection of the tumor. This document includes evidence-based recommendations for pediatric surgeons regarding the resection, staging, and proper nodal basin evaluation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Neuroblastoma (NB) is the most common solid extracranial malignancy of childhood with an incidence of 1 per 100,000 in the United States compromising approximately 10 % of childhood cancer. Unfortunately, patients with high-risk NG continue to have long-term survival less than 50 %. Both Children's Oncology Group and the International Society of Paediatric Oncology have demonstrated the important role of surgery in the treatment of high-risk NB. Herein, we compose the results of an extensive literature review as well as expert opinion from leaders in pediatric surgical oncology, to present the critical elements of effective surgery for high-risk neuroblastoma., (Copyright © 2023. Published by Elsevier Inc.)

The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care., (© 2022 Wiley Periodicals LLC.)

Background: It is uncertain whether the presence of autoimmune thyroiditis (AIT) increases the risk of thyroid cancer in children with thyroid nodules. This study evaluated the association between AIT and thyroid cancer in pediatric patients with thyroid nodules. Methods: A cross-sectional study was performed of pediatric patients (<19 years old) with a thyroid nodule (≥1 cm) who underwent fine-needle aspiration in an academic pediatric thyroid center. AIT was defined by the presence of thyroid autoantibodies or diffusely heterogeneous sonographic echotexture. The primary outcome was diagnosis of thyroid cancer. The association of AIT with thyroid cancer was evaluated with univariable and multivariable logistic regression. Associations of AIT with subject and nodule characteristics were also assessed. Results: Four hundred fifty-eight thyroid nodules in 385 patients (81% female) were evaluated at a median age of 15.5 years (interquartile range 13.5-17.0). Thyroid cancer was present in 108 nodules (24%). AIT was present in 95 subjects (25%) and was independently associated with an increased risk of thyroid cancer (multivariable odds ratio [OR] 2.19, 95% confidence interval [CI] 1.32-3.62). Thyroid cancer was also independently associated with younger age, nodule size, and solitary nodules, but was not associated with serum thyrotropin concentration. AIT was not associated with the likelihood of subjects undergoing thyroid surgery ( p  = 0.17). AIT was less commonly associated with follicular thyroid carcinoma than with papillary thyroid carcinoma (OR 0.22, CI 0.05-1.06). Among papillary thyroid carcinomas, AIT was strongly associated with the diffuse sclerosing variant (OR 4.74, CI 1.33-16.9). AIT was not associated with the extent of local, regional, or distant disease at thyroid cancer diagnosis. Conclusions: AIT is independently associated with an increased risk of thyroid cancer in children with thyroid nodules. These findings suggest that the evaluation of thyroid autoantibodies and thyroid echotexture may inform thyroid cancer risk assessment and surgical decision-making in children with thyroid nodules.

Background: An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy of limited duration and tailoring postoperative therapy based on histopathologic response. The authors report outcomes based on postoperative histopathologic responses., Methods: Patients with BWT received treatment with vincristine, dactinomycin, and doxorubicin for 6 or 12 weeks followed by surgery. Postoperative therapy was prescribed based on the highest risk tumor according to the International Society of Pediatric Oncology classification and the Children's Oncology Group staging system., Results: Analyses were performed on data from 180 evaluable children. The 4-year event-free survival (EFS) and overall survival (OS) rates were 81% (95% CI, 74%-87%) and 95% (95% CI, 91%-99%), respectively. Seven patients who had completely necrotic tumors had a 4-year EFS rate of 100%. Of 118 patients who had tumors with intermediate-risk histopathology, the 4-year EFS and OS rates were 82% (95% CI, 74%-90%) and 97% (95% CI, 94%-100%), respectively. Fourteen patients who had blastemal-type tumors had 4-year EFS and OS rates of 79% (95% CI, 56%-100%) and 93% (95% CI, 79%-100%), respectively. Eighteen patients who had diffuse anaplasia had 4-year EFS and OS rates of 61% (95% CI, 35%-88%) and 72% (95% CI, 47%-97%), respectively; and the 4-year EFS and OS rates of 7 patients who had focal anaplasia were 71% (95% CI, 38%-100%) and 100%, respectively. There was no difference in the outcomes of patients who had different histopathologic subtypes within the intermediate-risk group (P = .54)., Conclusions: A risk-adapted treatment approach for BWT results in excellent outcomes. This approach was not successful in improving the outcome of patients who had diffuse anaplasia., (© 2022 American Cancer Society.)

Introduction: Diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) represents a unique category of nephroblastomatosis. Treatment has ranged from observation to multiple regimens of chemotherapy. Wilms tumors (WTs) develop in 100% of untreated patients and between 32 and 52% of treated patients. Renal preservation rates have not been previously reported. An aim of the Children's Oncology Group (COG) study AREN0534 was to prospectively evaluate the efficacy of chemotherapy in preserving renal units and preventing WT development in children with DHPLN., Methods: Patients were enrolled through the COG protocol AREN03B2 with central radiological review. DHPLN was defined as the cortical surface of the kidney being composed of hyperplastic rests, with the entire nephrogenic zone involved, and with a thick rind capping all of one or both kidneys. Treatment was with vincristine and dactinomycin (regimen EE4A), with cross-sectional imaging at weeks 6 and 12. If the patient's disease was stable or decreasing, treatment was continued for 19 weeks. Renal preservation, WT development rates at 1 year, and overall survival (OS) are reported., Results: Nine patients were enrolled (five females and four males), with a median age at enrollment of 10.22 months (range 2.92-29.11). One patient who was enrolled was deemed unevaluable because they did not meet the radiological criteria for DHPLN, resulting in eight evaluable patients. These eight patients had DHPLN confirmed via radiological criteria (all bilateral). Initial chemotherapy was EE4A for all eight patients, with seven of eight patients starting chemotherapy without tissue diagnosis.One patient who had an upfront partial nephrectomy was found to have DHPLN in the specimen and was subsequently treated with EE4A. All patients remained alive, with a median follow-up of 6.6 years (range 4.5-9.1). No patients were anephric; 14 of 16 kidneys were functioning (87.5%). Six of eight patients (75%) did not have WT on therapy, but two of these patients relapsed within 6 months of stopping therapy; both had favorable histology WT. One patient who was diagnosed with WT on therapy relapsed at 12 months (one of eight [12.5%]) and developed anaplastic histology., Conclusions: Chemotherapy for patients with DHPLN was effective in preserving kidney function. Five-year OS is excellent, however the ideal type and duration of chemotherapy to prevent WT development remains elusive., (© 2022. Society of Surgical Oncology.)

As curricular emphasis on anatomy in undergraduate medical education continues to evolve, new approaches to anatomical education are urgently needed to prepare medical students for residency. A surgical anatomy class was designed for third- and fourth-year medical students to explore important anatomical relationships by performing realistic surgical procedures on anatomical donors. Under the guidance of both surgeons and anatomists, students in this month-long elective course explored key anatomical relationships through performing surgical approaches, with the secondary benefit of practicing basic surgical techniques. Procedures, such as left nephrectomy, first rib resection for thoracic outlet syndrome, and carotid endarterectomy, were adapted from those used clinically by multiple surgical subspecialties. This viewpoint commentary highlights perspectives from students and instructors that suggest the value of a surgical approach to anatomical education for medical students preparing for procedure-oriented residencies, with the goals of: (1) describing the elective at the authors' institution, (2) promoting similar efforts across different institutions, and (3) encouraging future qualitative and quantitative studies of similar pedagogic efforts., (© 2020 American Association for Anatomy.)

Background: A primary objective of Children's Oncology Group study AREN0534 (Treatment for Patients With Multicentric or Bilaterally Predisposed, Unilateral Wilms Tumor) was to facilitate partial nephrectomy in 25% of children with bilaterally predisposed unilateral tumors (Wilms tumor/aniridia/genitourinary anomalies/range of developmental delays [WAGR] syndrome; and multifocal and overgrowth syndromes). The purpose of this prospective study was to achieve excellent event-free survival (EFS) and overall survival (OS) while preserving renal tissue through preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response., Methods: The treating institution identified whether a predisposition syndrome existed. Patients underwent a central review of imaging studies through the biology and classification study AREN03B2 and then were eligible to enroll on AREN0534. Patients were treated with induction chemotherapy determined by localized or metastatic disease on imaging (and histology if a biopsy had been undertaken). Surgery was based on radiographic response at 6 or 12 weeks. Further chemotherapy was determined by histology. Patients who had stage III or IV disease with favorable histology received radiotherapy as well as those who had stage I through IV anaplasia., Results: In total, 34 patients were evaluable, including 13 males and 21 females with a mean age at diagnosis of 2.79 years (range, 0.49-8.78 years). The median follow-up was 4.49 years (range, 1.67-8.01 years). The underlying diagnosis included Beckwith-Wiedemann syndrome in 9 patients, hemihypertrophy in 9 patients, multicentric tumors in 10 patients, WAGR syndrome in 2 patients, a solitary kidney in 2 patients, Denys-Drash syndrome in 1 patient, and Simpson-Golabi-Behmel syndrome in 1 patient. The 4-year EFS and OS rates were 94% (95% CI, 85.2%-100%) and 100%, respectively. Two patients relapsed (1 tumor bed, 1 abdomen), and none had disease progression during induction. According to Response Evaluation Criteria in Solid Tumor 1.1 criteria, radiographic responses included a complete response in 2 patients, a partial response in 21 patients, stable disease in 11 patients, and progressive disease in 0 patients. Posttherapy histologic classification was low-risk in 13 patients (including the 2 complete responders), intermediate-risk in 15 patients, and high-risk in 6 patients (1 focal anaplasia and 5 blastemal subtype). Prenephrectomy chemotherapy facilitated renal preservation in 22 of 34 patients (65%)., Conclusions: A standardized approach of preoperative chemotherapy, surgical resection within 12 weeks, and histology-based postoperative chemotherapy results in excellent EFS, OS, and preservation of renal parenchyma., (© 2020 American Cancer Society.)

Medullary thyroid carcinoma (MTC) is most commonly associated with RET gene mutations. ALK fusions have rarely been described, although not previously in pediatrics and not previously partnered with CCDC6 in MTC or any other cancer. A 10-year-old boy with progressive stridor was found to have metastatic MTC, including lung, lymph node, and adrenal metastases. Baseline calcitonin was 6703 pg/mL. While molecular testing was pending, he was treated empirically with the investigational selective RET inhibitor, LOXO-292, without improvement. Molecular testing revealed a novel CCDC6 - ALK fusion. His therapy was changed to crizotinib and then to alectinib for improved tolerability. Calcitonin decreased to 663 pg/mL after 6 days of ALK inhibition. He remains on alectinib with ongoing response. A novel CCDC6 - ALK fusion has now been implicated in a pediatric case of metastatic MTC. This fusion has profound clinical sensitivity to ALK inhibitors. This report expands the spectrum of ALK fusions seen in MTC, including the first pediatric case of ALK translocated MTC. This novel fusion with CCDC6 has not previously been reported in other human cancers. Given the dramatic response to ALK inhibition in this case, identifying patients with ALK fusion MTC has important therapeutic implications.

Purpose: In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy., Methods: Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies., Results: LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease ( P = .042), and 61.3% for patients with stage III/IV disease ( P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%)., Conclusion: Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

This study compared outcomes following total (TS) or partial splenectomy (PS) among patients with hereditary spherocytosis. Seventy-nine patients (TS = 33, PS = 46) were identified. The follow-up period was longer after PS (59.6 vs. 24.9 months, p  < .001). Long-term adverse events occurred more frequently following PS (50% vs. 29%, p  = .001). Anemia, jaundice, and fatigue recurred in six patients with PS, leading to five completion splenectomies. Hemoglobin was not different between PS and TS by 5 years post-procedure (12.3 vs. 13.4 g/dL, p  = .25). Both PS and TS ameliorate symptoms and improve hematologic parameters. The rate of secondary surgery following PS should be considered when planning the initial surgical procedure.

Background: Vedolizumab is a biologic, which inhibits leukocyte adhesion in the gut and is used to treat ulcerative colitis (UC) and Crohn's disease (CD). Little is known of the surgical outcomes in patients treated with vedolizumab. We reviewed the postoperative complications in a cohort of pediatric UC and CD patients treated with vedolizumab., Methods: We identified pediatric UC and CD patients treated with vedolizumab at our institution from 2014 to 2016. We compared postoperative outcomes in the vedolizumab exposed group to a cohort of vedolizumab naïve patients who required diverting ileostomy., Results: Of the 31 patients who were treated with vedolizumab, 13 patients required surgery. Eight of 13 (62%) vedolizumab exposed patients had a postoperative complication, including mucocutaneous separation at the stoma (3), readmission for pain/dehydration (2), bowel obstruction at the ostomy, and intraoperative colonic perforation. In comparison, four of 16 (25%) vedolizumab naive patients had a postoperative complication, including readmission for ileus and for high stoma output with mucocutaneous separation. p=0.07., Conclusions: At our institution, patients treated with vedolizumab prior to surgery have a high prevalence of postoperative complications, notably mucocutaneous separation of the stoma. A prospective, multicenter study is needed to determine if these observed complications are attributable to vedolizumab., Level of Evidence: Level III., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children's Oncology Group protocol AREN0532. Methods From October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status ( P < .01) and absence of LOH 1p or 16q ( P < .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). Conclusion Most patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.

Fanconi-Bickel syndrome is a rare autosomal recessive disorder due to mutations in the facilitative glucose transporter 2 ( GLUT2 or SLC2A2) gene resulting in excessive glycogen storage predominantly in the liver and kidney. Previous case reports of this condition have described liver biopsies with glycogen storage and variable steatosis and/or fibrosis. Unlike in other types of glycogen storage disease, hepatocellular adenomas and carcinomas have not been described to date in this syndrome. A 6-year-old boy with consanguineous parents had short stature, poorly controlled rickets, hepatosplenomegaly, and renal tubular dysfunction clinically consistent with Fanconi-Bickel Syndrome. Sequencing of the SLC2A2 gene showed a homozygous variant of unknown significance [c.474A > C (p.Arg158Ser)] causing a missense mutation in an evolutionarily conserved residue. An incidental single hepatic lesion was discovered on imaging, and subsequent resection showed a 2.6 cm well-differentiated hepatocellular carcinoma with moderate atypia, diffuse immunoreactivity for glypican-3, and nuclear b-catenin, and with focal complete loss of the reticulin framework. The non-neoplastic liver showed marked glycogen accumulation with mild periportal fibrosis, rare bridging fibrosis, and no regenerative or adenomatous nodules. By electron microscopy, tumor cells had pleomorphic nuclei, prominent nucleoli, and scant cytoplasm with numerous mitochondria. Well-developed canaliculi were occasionally seen. The non-neoplastic liver showed glycogenosis with abundant cytoplasmic free (non-membrane bound) glycogen. Hepatocellular carcinoma should be considered as a possible complication of Fanconi-Bickel syndrome. This well differentiated carcinoma did not appear to be associated with hepatic adenomatosis as has been described in some hepatocellular carcinomas associated with other hepatic glycogen storage disorders. The nuclear beta-catenin immunoreactivity indicates a role for the Wnt signaling pathway in the pathogenesis of this tumor.

Objective: The Children's Oncology Group study AREN0534 aimed to improve event-free survival (EFS) and overall survival (OS) while preserving renal tissue by intensifying preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response., Background: No prospective therapeutic clinic trials in children with bilateral Wilms tumors (BWT) exist. Historical outcomes for this group were poor and often involved prolonged chemotherapy; on NWTS-5, 4-year EFS for all children with BWT was 56%., Methods: Patients were enrolled and imaging studies were centrally reviewed to assess for bilateral renal lesions. They were treated with 3-drug induction chemotherapy (vincristine, dactinomycin, and doxorubicin) for 6 or 12 weeks based on radiographic response followed by surgery and further chemotherapy determined by histology. Radiation therapy was provided for postchemotherapy stage III and IV disease., Results: One hundred eighty-nine of 208 patients were evaluable. Four-year EFS and OS were 82.1% (95% CI: 73.5%-90.8%) and 94.9% (95% CI: 90.1%-99.7%. Twenty-three patients relapsed and 7 had disease progression. After induction chemotherapy 163 of 189 (84.0%) underwent definitive surgical treatment in at least 1 kidney by 12 weeks and 39% retained parts of both kidneys. Surgical approaches included: unilateral total nephrectomy with contralateral partial nephrectomy (48%), bilateral partial nephrectomy (35%), unilateral total nephrectomy (10.5%), unilateral partial nephrectomy (4%), and bilateral total nephrectomies (2.5%)., Conclusion: This treatment approach including standardized 3-drug preoperative chemotherapy, surgical resection within 12 weeks of diagnosis and response and histology-based postoperative therapy improved EFS and OS and preservation of renal parenchyma compared with historical outcomes for children with BWT.

Objective: To determine if observation alone after nephrectomy in very low-risk Wilms tumor (defined as stage I favorable histology Wilms tumors with nephrectomy weight <550g and age at diagnosis <2 years) results in satisfactory event-free survival and overall survival, and to correlate relapse with biomarkers., Patients and Methods: The AREN0532 study enrolled patients with very low-risk Wilms tumor confirmed by central review of pathology, diagnostic imaging, and surgical reports. After nephrectomy, patients were followed without adjuvant chemotherapy. Evaluable tumors were analyzed for WT1mutation, 1p and 16q copy loss, 1q copy gain, and 11p15 imprinting. The study was powered to detect a reduction in 4-year EFS from 87% to 75% and overall survival from 95% to 88%., Results: A total of 116 eligible patients enrolled with a median follow up of 80 months (range: 5-97 months). Twelve patients relapsed. Estimated 4-year event-free survival was 89.7% (95% confidence interval 84.1-95.2%) and overall survival was 100%. First sites of relapse were lung (n = 5), tumor bed (n = 4), and abdomen (n = 2), with one metachronous tumor in the contralateral kidney (n = 1) at a median time of 4.3 months for those who relapsed (range 2.3-44 months). The presence of intralobar (P = 0.46) or perilobar rests (P = 1.0) were not associated with relapse (P = 0.16). 1q gain, 1p and 16q loss, and WT1 mutation status were not associated with relapse. 11p15 methylation status was associated relapse (20% relapse with loss of heterozygosity, 25% with loss of imprinting, and 3.3% relapse with retention of the normal imprinting (P = 0.011))., Conclusions: Most patients meeting very low-risk criteria can be safely managed by nephrectomy alone with resultant reduced exposure to chemotherapy. Expansion of an observation alone strategy for low-risk Wilms tumor incorporating both clinical features and biomarkers should be considered.

Context: Most thyroid nodules are benign and their accurate identification can avoid unnecessary procedures. In adult patients, documentation of nodule autonomy is accepted as reassurance of benign histology and as justification to forgo biopsy or thyroidectomy. In contrast, the negative predictive value of nodule autonomy in children is uncertain. Some recent publications recommend surgical resection as initial management, but few address the degree of TSH suppression or the specific scintigraphic criteria used to diagnose autonomy., Objective: The objective of the study was to study the presenting features and cancer risk of children with autonomous nodules., Design and Setting: Medical records of all 31 children diagnosed with autonomous nodules at our center from 2003 to 2014 were retrospectively reviewed., Patients and Results: All children met full diagnostic criteria for autonomous nodules, defined by both autonomous 123 I uptake into the nodule and the suppression of uptake in the normal thyroid parenchyma on scintigraphy performed during hypothyrotropinemia. The median age of presentation was 15 years (range 3-18 y) with a female to male ratio of 15:1. Fifty-eight percent of patients had solitary nodules and 42% had multiple nodules. The median size of each patient's largest autonomous nodule was 39 mm (range 18-67 mm). Most of the children in this series (68%) had diagnostic biopsies and/or operative pathology of their largest autonomous nodule, which showed benign cytology or histology in all cases., Conclusions: In this pediatric series, the cancer rate observed in biopsied or resected autonomous nodules was 0%. Whereas larger studies are needed to confirm our findings, these results agree with earlier reports suggesting that thyroid cancer is rare in rigorously defined autonomous nodules and support that conservative management may be offered to selected children who meet strict diagnostic criteria for autonomous nodules, deferring definitive therapies until adulthood when the risks of thyroidectomy and 131 I ablation are lower.

Objectives: Infliximab (IFX) has become a mainstay of therapy for children with Crohn disease (CD). Despite medical advances, many children with CD, however, still require operative interventions. The risk of complications following resection in children treated with IFX remains largely unknown. We compare surgical outcomes stratified by IFX therapy in a cohort of children with CD who require bowel resection., Methods: We reviewed the postoperative complications in 123 children with CD who underwent bowel resection with primary anastomosis at our institution between 1977 and 2011. Demographics, medications, types of operations, and inpatient courses were analyzed. Complications and length of stay were compared based on medical therapy., Results: Overall, the postoperative complication rate was 13%. Of the 123 surgical cases, 24 children had received IFX before their operation. In the children treated with IFX, we identified 3 major complications, including anastomotic leak, acute renal failure, and intraabdominal abscess. There were 9 major complications in the non-IFX group, including infections (2), intraabdominal abscesses (2), bowel obstruction, shock, supraventricular tachycardia, phlegmon, and anastomotic stricture. No significant differences in complication rates or postoperative lengths of stay were identified between those who did or did not receive IFX., Conclusions: In this cohort, surgical procedures in children and young adults treated with IFX were not associated with an increased number of complications or prolonged length of stay. Given that postoperative complications are infrequent in children, larger multicenter studies may be required to determine whether IFX therapy increases the risk of surgical complications in pediatric CD.

Background: Medical organizations have increased interest in identifying and improving behaviors that threaten team performance and patient safety. Three hundred and sixty degree evaluations of surgeons were performed at 8 academically affiliated hospitals with a common Code of Excellence. We evaluate participant perceptions and make recommendations for future use., Study Design: Three hundred and eighty-five surgeons in a variety of specialties underwent 360-degree evaluations, with a median of 29 reviewers each (interquartile range 23 to 36). Beginning 6 months after evaluation, surgeons, department heads, and reviewers completed follow-up surveys evaluating accuracy of feedback, willingness to participate in repeat evaluations, and behavior change., Results: Survey response rate was 31% for surgeons (118 of 385), 59% for department heads (10 of 17), and 36% for reviewers (1,042 of 2,928). Eighty-seven percent of surgeons (95% CI, 75%-94%) agreed that reviewers provided accurate feedback. Similarly, 80% of department heads believed the feedback accurately reflected performance of surgeons within their department. Sixty percent of surgeon respondents (95% CI, 49%-75%) reported making changes to their practice based on feedback received. Seventy percent of reviewers (95% CI, 69%-74%) believed the evaluation process was valuable, with 82% (95% CI, 79%-84%) willing to participate in future 360-degree reviews. Thirty-two percent of reviewers (95% CI, 29%-35%) reported perceiving behavior change in surgeons., Conclusions: Three hundred and sixty degree evaluations can provide a practical, systematic, and subjectively accurate assessment of surgeon performance without undue reviewer burden. The process was found to result in beneficial behavior change, according to surgeons and their coworkers., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Ewing sarcoma require local primary tumor control with surgery, radiation, or both. The optimal choice of local control for overall and local disease control remains unclear., Methods: Patients with localized Ewing sarcoma of bone who were treated on 3 consecutive protocols with standard-dose, 5-drug chemotherapy every 3 weeks were included (n=465). Propensity scores were used to control for differences between local control groups by constructing multivariate models to assess the impact of local control type on clinical endpoints (event-free survival [EFS], overall survival, local failure, and distant failure) independent of differences in their propensity to receive each local control type., Results: Patients who underwent surgery were younger (P=.02) and had more appendicular tumors (P<.001). Compared with surgery, radiation had higher unadjusted risks of any event (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.18-2.44), death (HR, 1.84; 95% CI, 1.18-2.85), and local failure (HR, 2.57; 95% CI, 1.37-4.83). On multivariate analysis, compared with surgery, radiation had a higher risk of local failure (HR, 2.41; 95% CI, 1.24-4.68), although there were no significant differences in EFS (HR, 1.42; 95% CI, 0.94-2.14), overall survival (HR, 1.37; 95% CI, 0.83-2.26), or distant failure (HR, 1.13; 95% CI, 0.70-1.84) between local control groups., Conclusions: In this large group of similarly treated patients, choice of the mode of local control was not related significantly to EFS, overall survival, or distant failure, although the risk of local failure was greater for radiation compared with surgery. These data support surgical resection when appropriate, whereas radiotherapy remains a reasonable alternative in selected patients., (© 2014 American Cancer Society.)

Background: Despite advances in medical therapies, many children with Crohn's disease (CD) will require bowel resection. Although previous registry studies have attempted to identify risk factors for surgery, the effect of immunomodulators and biologics (IMB) on surgical indications has not been well characterized., Methods: We reviewed a series of 125 children with CD who underwent bowel resection with reanastomosis between 1977 and 2011 and were followed up for at least 6 months. We compared patients who underwent surgery for perforating disease (abscess or internal fistula) and patients who were operated on for medically refractory or fibrostenosing disease. Between these 2 groups, we examined medications received before surgery. Other demographic and disease-specific covariates were examined., Results: Of the 82 patients who received IMB before surgery, only 19 patients (23%) required surgery for a perforating complication of CD, whereas 63 patients (77%) required surgery for strictures or medically refractory disease. In contrast, of the 43 patients who did not receive IMB preoperatively, 20 patients (45%) developed a perforating complication and 23 patients (53%) required surgery for strictures or refractory disease. These differences across groups were significant, with a lower rate of operation for perforating disease among patients receiving preoperative IMB therapy (P = 0.007)., Conclusions: In our surgical cohort, children with CD who were treated with IMB were less likely to have surgery for perforating disease. This finding raises the possibility that the administration of IMB in children who require surgery may be associated with a difference in disease behavior.

Importance: Juvenile myasthenia gravis (MG) is a relatively rare autoimmune disorder. The comparative efficacy of plasmapheresis (PLEX) vs immunoglobulin as maintenance therapy is unclear for this childhood disease., Objective: To determine whether PLEX or intravenous immunoglobulin (IVIG) therapy is more effective as maintenance therapy in this disease., Design, Setting, and Participants: This retrospective analysis over a 33-year period involved 54 children and adolescents with juvenile MG at a specialized neuromuscular clinic and electromyography laboratory at a tertiary care academic pediatric hospital., Interventions: Plasmapheresis and IVIG., Main Outcomes and Measures: Response to treatment was measured by both improvement in objective physical examination findings and the patients’ reported improvement in symptoms and functional abilities., Results: Subjective and objective outcomes correlated well. Both PLEX and IVIG had high response rates. Of the 27 patients with generalized juvenile MG receiving PLEX, IVIG, or both treatments, 7 of 7 patients treated with PLEX alone responded, 5 of 10 patients treated with IVIG alone responded, and 9 of 10 patients who received both responded. There was a significant difference in response rates between patients who received PLEX vs IVIG (P = .04). The youngest age at which PLEX was initiated via peripheral venous access was 9 years, while the youngest child who received IVIG was 9 months old. Thymectomy was performed in 17 children, of whom 11 experienced significant postoperative improvement., Conclusions and Relevance: This study provides class III evidence that PLEX and IVIG both have high response rates as maintenance therapies and are reasonable therapeutic options for juvenile MG. Plasmapheresis may have a more consistent response rate than IVIG in this setting. These findings will provide some guidance regarding the approach to therapy for juvenile MG, especially as the results differ somewhat from those of studies focusing on adult MG.

In a retrospective analysis of childhood thyroid nodules, 18% were radiographic incidentalomas and 41% were discovered by a clinician's palpation; 40% were discovered by patients' families. The latter group had the largest nodules and highest rates of thyroid cancer metastasis, suggesting opportunities for earlier detection through annual well-child visits., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Intra-operative tumor spill increases the risk of local recurrence of Wilms tumor, and adversely impacts relapse-free (RFS) and overall survival (OS) rates., Methods: Surgical checklists, operative notes, institutional pathology reports, central pathology review and flow sheets of 602 patients registered between August 1986 and September 1994 on National Wilms Tumor Study-4 as randomized, followed or switched and coded as Final Stage II, favorable histology (FH) were reviewed. RFS and OS were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated using the Cox model and tested for statistical significance by the log-rank test., Results: Four hundred ninety-nine patients were found after review to have Stage II, FH Wilms tumor. The 8-year RFS percentages were 85.0% (95% confidence interval (CI): 81.1%, 88.1%) for those with no spill compared to 75.7% (65.8%, 83.2%) for those with spill. The 8-year OS percentages were 95.6% (93.1%, 97.3%) for those with no spill compared to 90.3% (82.2%, 94.9%) for those with spill. The HR for relapse among those with spill was 1.55 ((95%CI: 0.97,2.51), P = 0.067) and the HR for death was 1.94 ((0.92,4.09), P = 0.077)., Conclusions: RFS and OS were lower for patients who had intra-operative tumor spill. The majority of NWTS Stage II, FH patients with intra-operative tumor spill have an overall excellent outcome when treated with two drug chemotherapy (vincristine and actinomycin D) and no abdominal irradiation., (© 2013 Wiley Periodicals, Inc.)

Background: A multicenter study of pectus excavatum was described previously. This report presents our final results., Study Design: Patients treated surgically at 11 centers were followed prospectively. Each underwent a preoperative evaluation with CT scan, pulmonary function tests, and body image survey. Data were collected about associated conditions, complications, and perioperative pain. One year after treatment, patients underwent repeat chest CT scan, pulmonary function tests, and body image survey. A subset of 50 underwent exercise pulmonary function testing., Results: Of 327 patients, 284 underwent Nuss procedure and 43 underwent open procedure without mortality. Of 182 patients with complete follow-up (56%), 18% had late complications, similarly distributed, including substernal bar displacement in 7% and wound infection in 2%. Mean initial CT scan index of 4.4 improved to 3.0 post operation (severe >3.2, normal = 2.5). Computed tomography index improved at the deepest point (xiphoid) and also upper and middle sternum. Pulmonary function tests improved (forced vital capacity from 88% to 93%, forced expiratory volume in 1 second from 87% to 90%, and total lung capacity from 94% to 100% of predicted (p < 0.001 for each). VO2 max during peak exercise increased by 10.1% (p = 0.015) and O2 pulse by 19% (p = 0.007) in 20 subjects who completed both pre- and postoperative exercise tests., Conclusions: There is significant improvement in lung function at rest and in VO2 max and O2 pulse after surgical correction of pectus excavatum, with CT index >3.2. Operative correction significantly reduces CT index and markedly improves the shape of the entire chest, and can be performed safely in a variety of centers., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Nephrectomy with lymph node sampling is the recommended treatment for children with unilateral Wilms tumor under the Children's Oncology Group protocols. Using radiological assessment, we determined the feasibility of performing partial nephrectomy in a select group of patients with very low risk unilateral Wilms tumor., Materials and Methods: We reviewed imaging studies of 60 patients with a mean age of less than 2 years with very low risk unilateral Wilms tumor (mean weight less than 550 gm) to assess the feasibility of partial nephrectomy. We evaluated percentage of salvageable parenchyma, tumor location and anatomical features preventing a nephron sparing approach., Results: A linear relationship exists between tumor weight and computerized tomography estimated tumor volume. Mean tumor weight in the study population was 315 gm. Partial nephrectomy was deemed feasible in only 5 of 60 patients (8%)., Conclusions: When considering a select population with very low risk unilateral Wilms tumor (lower volume tumor), only a small percentage of nonpretreated patients are candidates for nephron sparing surgery., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Context: Thyroid cancer is the most common endocrine malignancy, but due to its rare occurrence in the pediatric population, the cancer risk of childhood thyroid nodules is incompletely defined, and optimal management of children with suspected nodules is debated., Objective: The aim was to study the presenting features and cancer risk of sporadic childhood thyroid nodules using a standardized clinical assessment and management plan., Design and Setting: Boston Children's Hospital and Brigham and Women's Hospital collaborated to create a multidisciplinary pediatric thyroid nodule clinic and implement a standardized assessment plan. Upon referral for a suspected nodule, serum TSH was measured and hypothyrotropinemic patients underwent (123)I scintigraphy. All others underwent thyroid ultrasonography, and if this confirmed nodule(s) ≥ 1 cm, ultrasound-guided fine-needle aspiration was performed. Medical records were retrospectively reviewed and compared to a control population of 2582 adults evaluated by identical methods., Patients and Results: Of 300 consecutive children referred for the initial evaluation of suspected thyroid nodules from 1997 to 2011, 17 were diagnosed with autonomous nodules by scintigraphy. Neck ultrasonography performed in the remainder revealed that biopsy was unnecessary in over half, either by documenting only sub-centimeter nodules or showing that no nodule was present. A total of 125 children met criteria for thyroid biopsy, which was performed without complication. Their rate of cancer was 22%, significantly higher than the adult rate of 14% (P = .02)., Conclusions: Neck ultrasonography and biopsy were key to the evaluation of children with suspected thyroid nodules. Although the relative cancer prevalence of sonographically confirmed nodules ≥ 1 cm is higher in pediatric patients than adults, most children referred for suspected nodules have benign conditions, and efforts to avoid unnecessary surgery in this majority are warranted.

Purpose: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome., Methods: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy., Results: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially in 194 patients (5.2%). Of the adrenal glands removed, 68 (4.4%) contained tumor. Adrenal involvement was more common in patients with stage 3 (9.8%) than stage 2 disease (1.9%; p < 0.0001). After controlling for stage and histopathology, five-year EFS was similar whether or not the adrenal gland was removed (p = 0.48), or involved with tumor (p = 0.81); however, intraoperative spill rates were higher in patients undergoing adrenalectomy (26.1% vs 15.5%, p < 0.0001), likely due to larger tumor size or technical factors. No patient had clinical evidence of adrenal insufficiency or tumor recurrence in the adrenal gland during follow-up (median 9.9 years)., Conclusions: Sparing the adrenal gland during nephrectomy for unilateral Wilms tumor was not associated with a higher incidence of intraoperative spill and was associated with a similar oncologic outcome, on a per-stage basis, with cases where the adrenal was removed. Thus, adrenalectomy should not be considered mandatory during radical nephrectomy for Wilms tumor., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Laparoscopic techniques have been applied to restorative proctocolectomy since the early 2000's. We have employed a technique for laparoscopic-assisted total proctocolectomy (TPC) and ileal pouch anal anastomosis (IPAA) for the treatment of children with ulcerative colitis (UC)., Methods: We retrospectively reviewed 68 laparoscopic-assisted TPCs and 39 open TPCs performed at our institution for UC between January 1997 and February 2011. Case duration, postoperative length of stay, and complications of the two groups were compared, and multivariable analysis was applied., Results: The two groups were comparable with respect to gender, age, and postoperative length of stay. Total abdominal colectomy (TAC) duration was significantly longer in the laparoscopic-assisted group (P < .001). Complications were similar in the laparoscopic and open group, although small bowel obstruction (SBO) was significantly less frequent in the laparoscopic group (log-rank test = 8.88, P = .003). Kaplan-Meier estimated freedom from SBO at 1 year follow-up is 99% for patients treated laparoscopically (95% CI: 98%-100%) and 76% for those undergoing an open surgical approach (95% CI: 64%-88%)., Conclusions: The significantly lower SBO rate, low complication rates, and equivalent length of stay favor use of the laparoscopic-assisted approach for TPC and IPAA in children., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: The primary purpose of this study was to investigate the relationship between Pediatric Ulcerative Colitis Activity Index (PUCAI) and operative management. We also specifically evaluated those patients receiving tacrolimus for their disease., Methods: A retrospective review (1/06-1/11) identified ulcerative colitis patients (≤21 years old) undergoing restorative proctocolectomy with rectal mucosectomy and ileal pouch-anal anastomosis. Main outcomes included pre-operative PUCAI, combined versus staged procedure, and postoperative complications. Patients receiving tacrolimus within 3 months of surgical intervention were identified. PUCAI at tacrolimus induction and medication side effects were also noted., Results: Sixty patients were identified. Forty-two (70%) underwent combined and 18 (30%) had staged procedures. Pre-operative PUCAI was lower for combined versus staged patients (p = < 0.001). Furthermore, a higher pre-operative PUCAI strongly correlated with the likelihood of undergoing a staged procedure (p < 0.001). Forty-four patients (73%) received tacrolimus. Significant improvement in their PUCAI was noted from induction to pre-operative evaluation (p < 0.001). Minor and reversible side effects occurred in 46% of patients receiving tacrolimus, but complication rates were not significantly different., Conclusions: There is a very strong correlation between the PUCAI and the likelihood of undergoing a staged procedure. A significant improvement in PUCAI occurs following preoperative tacrolimus therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Stage III designation in NWTS-5 (National Wilms Tumor Study-5) was determined by four pathologic criteria: positive lymph nodes (LNs), peritoneal implants, residual disease, and tumor rupture. The objective of this study was to determine the prognostic significance of each of the stage III criteria., Patients and Methods: Children with stage III Wilms tumor (WT) treated in NWTS-5 were assessed for event-free (EFS) and overall survival (OS). Sites of relapse and molecular status of tumors are reported. EFS and OS are reported 8 years after diagnosis., Results: There were 569 patients with local stage III favorable-histology (FH) WT in this analysis, of whom 109 had overall stage IV disease. LN involvement alone was the most frequent criterion for stage III designation (38%), followed by microscopic residual disease alone (20%), microscopic residual disease and LN involvement (14%), and spill or soilage alone (9%). The 8-year EFS and OS estimates for all patients with local stage III FHWT were 82% and 91%, respectively. Multivariate analysis demonstrated that both LN involvement (relative risk, 1.89; P = .005) and microscopic residual disease (relative risk, 1.87; P = .007) were predictive of EFS, and OS results were similar. There was no apparent difference in pattern of relapse according to stage III subtype. The rate of loss of heterozygosity was higher (6%) for those with positive LNs than for those without (2%; P = .05)., Conclusion: LN involvement and microscopic residual are the stage III criteria highly predictive of EFS and OS for patients with stage III FHWT. It is possible that in future studies, patients with different stage III criteria may receive different therapies.

Background: Laparoscopic techniques have been applied to restorative proctocolectomy since the early 2000s. We have employed a technique for laparoscopic-assisted total proctocolectomy (TPC) and ileal pouch anal anastomosis (IPAA) for the treatment of children with ulcerative colitis (UC)., Methods: A total of 68 children underwent laparoscopic-assisted TPCs at our institution from June 2003 to February 2011. The patients ranged from 5 to 22 years of age. We progressively modified our surgical approach in positioning, equipment use, and operative technique., Results: A total of 68 children underwent laparoscopic-assisted TPC within the 8-year time period. Two major complications occurred (2/68=3%) consisting of 1 duodenal injury and 1 small bowel injury. There were 6 minor complications (6/68=9%), including 5 stoma revisions and 1 port site hernia. There were no superficial wound infections. There were no reported cases of pouch fistulas, anastomotic breakdown, or neurovascular injuries., Conclusions: Our surgical technique is safe and effective in treating children with UC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To demonstrate that expectant observation of young infants with small adrenal masses would result in excellent event-free and overall survival., Background: Neuroblastoma is the most common malignant tumor in infants, and in young infants, 90% of neuroblastomas are located in the adrenal gland. Although surgical resection is standard therapy, multiple observations suggest that expectant observation could be a safe alternative for infants younger than 6 months who have small adrenal masses., Methods: A prospective study of infants younger than 6 months with small adrenal masses and no evidence of spreading beyond the primary tumor was performed at participating Children's Oncology Group institutions. Parents could choose observation or immediate surgical resection. Serial abdominal sonograms and urinary vanillylmandelic acid and homovanillic acid measurements were performed during a 90-week interval. Infants experiencing a 50% increase in the volume of the mass, urine catecholamine values, or an increase in the homovanillic acid to vanillylmandelic acid ratio greater than 2, were referred for surgical resection., Results: Eighty-seven eligible patients were enrolled: 83 elected observation and 4 chose immediate surgery. Sixteen observational patients ultimately had surgery; 8 had International Neuroblastoma Staging System stage 1 neuroblastoma, 2 had higher staged neuroblastoma (2B and 4S), 2 had low-grade adrenocortical neoplasm, 2 had adrenal hemorrhage, and 2 had extralobar pulmonary sequestration. The 2 patients with adrenocortical tumors were resected because of a more than 50% increase in tumor volume. The 3-year event-free survival for a neuroblastoma event was 97.7 ± 2.2% within the entire cohort of patients (n = 87). The 3-year overall survival was 100%, with a median follow-up of 3.2 years. Eighty-one percent of patients on the observation arm were spared resection., Conclusions: Expectant observation of infants younger than 6 months with small adrenal masses led to excellent event-free survival and overall survival while avoiding surgical intervention in a large majority of the patients.

Background: In high-risk neuroblastoma patients, response to induction chemotherapy is emerging as an important determinant of overall survival. We sought to determine whether histological changes in the primary tumor following induction therapy could be used as a marker of response., Procedure: Second-look primary tumor specimens from 43 patients were reviewed according to specific morphological features., Results: In the majority, induction therapy resulted in a shift from an intermediate/high to low mitosis-karyorrhexis index (MKI) (P = 0.0009) and from undifferentiated/poorly differentiated to differentiating tumors (P < 0.0001). Following induction therapy, persistence of intermediate/high tumor MKI and ≥90% persistent neuroblastic cells were predictive of a poor outcome (P = 0.001 and 0.03, respectively). Less than 10% tumor necrosis was associated with a trend towards lower survival., Conclusions: High proliferative activity in the primary tumor following induction therapy portends a poor outcome in patients with high-risk neuroblastoma. If confirmed in a larger cohort, tumor histology at second-look surgery could be used to define a subset of very high risk patients who would benefit from alternative therapies prior to myeloablative dose-intensive transplant., (Copyright © 2011 Wiley Periodicals, Inc.)