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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.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.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).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.

BACKGROUND Pediatric non-central nervous system (CNS) malignant rhabdoid tumors (MRTs) are rare and aggressive malignancies without standard treatment strategies. The National Cancer Database (NCDB) was utilized to describe the incidence, characteristics, treatment strategies, and outcomes in pediatric patients. METHODS Patients

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.

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.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.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.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.

The purpose of this study was to analyze a nationwide database of malpractice lawsuits involving pediatric surgical patients to identify contributing factors in liability claims.Using the CRICO (Controlled Risk Insurance Company Strategies' Comparative Benchmarking System) database, malpractice claims involving patients ≤18 y old were reviewed from 2008 to 2017. Data were analyzed using descriptive statistics and logistic regression.Of the 844 claims, 76% of the patients were older than age 5. While the average total indemnity paid was $544,325, cases with claimants1-year-old accounted for 24% of the total indemnity paid, with an average of $1,135,240 per claimant. The most frequently named responsible services were Orthopedics (34%), General Surgery (15%), and Otolaryngology (11%). Fracture or dislocation, appendectomy, skin/breast surgery, arthroscopy, and tonsillectomy/adenoidectomy were among the frequently involved procedures for the cohort of cases. The most common contributing factors for the top procedures involve issues surrounding patient assessment, technical performance, and communication. Cases with a contributing factor of failure to appreciate and reconcile relevant sign/symptom/test results were associated with a higher likelihood of payment (OR 6.6, P 0.05). Issues surrounding the selection of therapy also led to an increased likelihood of an indemnity payment (OR 2.8, P 0.05).Malpractice claims related to pediatric surgical procedures involve a wide range of specialties. Patient evaluations, technical performance, and communication are modifiable factors to improve surgical care in children. The contributing factors assigned to each procedure may represent an opportunity for focused improvement to improve patient outcomes.

Purpose Current investigational priorities in the treatment of favorable histology Wilms tumor (FHWT) center on accurate staging and risk-stratification. The extent of lymph node (LN) sampling has not been clearly defined; its importance cannot be overstated as it guides adjuvant therapy. The identification of a minimum LN yield to minimize the risk of harboring occult metastatic disease could help development of surgical guidelines. This study focuses on using the beta-binomial distribution to estimate the risk of occult metastatic disease in patients with FHWT. Materials & methods The National Cancer Database was queried for patients with unilateral FHWT from 2004 to 2013. Data were used to characterize nodal positivity for patients who underwent surgery and had ≥ 1 positive LN and ≥ 2 LNs examined. The probability of missing a positive LN (i.e., false negative) for a given LN yield was calculated using an empirical estimation and the beta-binomial model. Patients were then stratified by tumor size. Results 422 patients met study criteria. To limit the chance of missing a positive LN to ≤ 10%, the empirical estimation and beta-binomial model estimated that 6 and 10 LNs needed to be sampled, respectively. Tumor size did not influence the result. Internal validation showed little variation to maintain a false negative rate ≤ 10%. Conclusions Using mathematical modeling, it appears that the desired LN yield in FHWT to reduce the risk of false-negative LN sampling to ≤ 10% is between 6 and 10. The current analysis represents an objective attempt to determine the desired surgical approach to LN sampling to accurately stage patients with FHWT. Level of evidence II

Pediatric non-central nervous system (CNS) malignant rhabdoid tumors (MRTs) are rare and aggressive malignancies without standard treatment strategies. The National Cancer Database (NCDB) was utilized to describe the incidence, characteristics, treatment strategies, and outcomes in pediatric patients.Patients18 years of age and diagnosed with non-CNS MRTs were analyzed from the NCDB from 2004 to 2014. Log-rank tests compared differences in Kaplan-Meier survival distributions. Univariate and multivariable Cox proportional hazard regression models identified predictors of mortality.Overall, 202 patients were identified. Soft tissue tumors were most common and metastatic disease was present at diagnosis in 34.2% of patients. The 1- and 5-year overall survival (OS) rates were 48.8% and 35.9%, respectively. Multivariable analysis revealed that age1 year and the presence of metastasis were negative prognostic indicators (p = 0.058). The 1- and 5-year OS rates were 59.9% and 46.5%, respectively, for patients who received surgical intervention (n = 143) compared with 12.3% and 7.4%, respectively, for those treated nonoperatively (n = 59; p 0.01). Surgical resection was associated with improved outcomes on univariate analysis, although it was no longer an independent predictor of survival on multivariate analysis (p = 0.18). In the cohort of surgical patients, the presence of residual disease trended towards clinically significant worse outcomes (p = 0.13).Patients with non-CNS MRTs who were diagnosed in infancy and had metastatic disease had worse survival outcomes. Although surgical resection was associated with improved survival in non-CNS MRTs, it was not independently associated with survival on multivariate analysis. Efforts to improve survival may instead depend on improving chemotherapeutic strategies and developing targeted therapies.

Background To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD). Methods Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected. Results Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival. Conclusion This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.

Purpose Canada is the second largest country in the world, with most of the population located in the southern-most portion of its geography. We sought to define the relative distribution of pediatric surgeons to potential pediatric patients using data from the Canadian census. Methods The 2011 Canadian Census and a convenience sample of current Canadian pediatric surgeons were used to calculate straight-line distances between pediatric surgeon postal code centroids and census dissemination block centroids. Results Currently, there are 74 practicing pediatric surgeons in Canada; 493,345 populated census blocks were identified, and 7,752,075 children were enumerated. The median (IQR) kilometers to the closest pediatric surgeon was 27.99 (11.35, 85.47) kilometers, and 22.7% of Canadian children lived more than 100 km from care. Nearly 13% of children lived greater than 200 km from the nearest pediatric surgeon. Conclusion More than 1.7 million Canadian children, nearly one quarter of all Canadian children, live greater than 100 km from the closest pediatric surgeon. This identifies a disparate group of patients who do not have an equal access-to-care as compared to others in the country. Level of Evidence Level IV.

Background The purpose of this study was to evaluate safety, technical success, and clinical outcomes of treatment for venous malformations using n-BCA glue embolization immediately prior to excision. Sixty three patients (22 male, 41 female; mean age 12 years (range 1–25)) who underwent 70 procedures for extremity and trunk venous malformations were reviewed. Indications for treatment included pain (100%), swelling (22%), and diminished range of motion (16%). Thirty seven patients (59%) had undergone prior stand-alone interventional or surgical treatment but were persistently symptomatic. Safety, technical and clinical success were retrospectively assessed. Results Embolization was technically successful in 100% of patients. Mean lesion size was 3.0 × 2.9 × 5.7 cm. Three patients (5%) underwent planned, second stage procedures for lesions intentionally not treated at the first procedure. Four patients (6%) underwent an unplanned, second stage procedure for residual disease after the primary operation. Mean and median follow-up duration were 18 and 17 months, respectively (range 3 to 35 months). Symptomatic improvement was achieved in 58 patients (92%), of whom 41 (65%) reported complete elimination of pain. There were no recognized instances of nontarget embolization or other complications of the interventional procedure. One patient required additional surgery for wound dehiscence and one patient developed an abscess requiring incision and drainage. Minor surgical complications included surgical site skin infections (n = 5) and numbness (n = 1). Mean and median surgical blood loss volumes were 131 mL and 10 mL, respectively. One patient required perioperative blood transfusion. Conclusions Extremity and truncal venous malformations can be safely and effectively treated in a single-stage fashion using glue embolization immediately preceding excision.

Background/purpose Pediatric testicular tumors are rare, constituting only 1% of all pediatric solid tumors. Single-institution studies addressing pediatric testicular tumors published to date have been limited in the number of patients. Methods We utilized the National Cancer Data Base (1998–2012) to review all prepubescent patients (≤12 years old) with testicular neoplasms. Demographics, tumor characteristics, treatment modalities, and outcomes were abstracted. Results A total of 479 patients were identified, with a median age of 3 years (IQR 0–4) at diagnosis. 67% of cases were diagnosed by 3 years of age. Yolk sac tumors were the most common histology (202 patients, 42.2%). Most tumors were diagnosed at a low stage. Resection was performed in 465 boys, with 75% having undergone radical orchiectomies. Chemotherapy was utilized in 28% of cases and radiotherapy in 7%. With mean follow-up of 5.6 years, mortality rate was 3%. No difference in mortality was noted based on histology or extent of surgical resection. Conclusions This series of prepubertal testicular tumors is the largest yet reported and highlights the patient demographics, tumor characteristics, treatment modalities and outcomes for these tumors. Type of study Prognosis study Level of evidence II.

Standard of care for unilateral nephroblastoma includes total nephrectomy (TN) with nodal sampling. We sought to compare the outcomes of TN and partial nephrectomy (PN). We performed a retrospective cohort study of TN and PN for nephroblastoma using the National Cancer Data Base. The outcomes included nodal sampling frequency, margin status, and survival. Categorical and continuous data were evaluated with χ2 and t tests, respectively ( P < 0.05). Generalized linear models evaluated nodal sampling and margin status. Cox regression compared survival. In total, 235 patients underwent PN and 3572 had TN. TN patients were 50 per cent more likely to undergo nodal sampling (RR: 1.47, 95% CI 1.30–1.66). There was no difference in margin status (RR: 0.91, 95% CI 0.65–1.28) or overall survival (HR 1.57; 95% CI 0.78–3.19). This study reports the largest review of patients with PN for unilateral nephroblastoma. PN patients had less nodal sampling but similar margin involvement and overall survival.

Multimodal therapy is the standard treatment for pediatric rhabdomyosarcoma, but for adolescents and young adults (AYAs: ages 15-39) and older adults with rhabdomyosarcoma, the use of adjuvant therapy is variable, and survival is greatly decreased compared with younger patients.All patients with rhabdomyosarcoma who had a curative operative were identified from the 1998-2012 National Cancer Database. Regression analyses identified independent factors relating to receipt of multimodal therapy (resection + chemotherapy + radiation) and the influence of multimodal therapy on 5-year overall survival.Of 2,312 patients, 44% were pediatric (age 15 years), 22% AYA (ages 15-39), and 34% adult (age ≥ 40 years). Adults received multimodal therapy least often (pediatric: 62%, AYA: 46%, adults: 24%; P .001), even after controlling for demographic characteristics, tumor features, and stage. In the entire cohort, multimodal therapy was associated with a decreased risk of death within 5 years (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.84), with similar findings after stratification by age (pediatric: HR 0.64, 95% CI 0.48-0.85; AYA: HR 0.72, 95% CI 0.55-0.95; adult: HR 0.74, 95% CI 0.58-0.93). In AYAs only, black and Hispanic patients had an increased risk of death within 5 years (black patients: HR 1.64, 95% CI 1.14-2.37; Hispanic patients: HR 1.62, 95% CI 1.11-2.36).This first large national study suggests that multimodal therapy is independently associated with improved survival for both AYAs and adults with rhabdomyosarcoma, similar to pediatric patients, but multimodal therapy is appreciably underused. Implementation of multimodal therapy for all patients could potentially improve overall outcomes of patients with rhabdomyosarcoma.

Multisystem inflammatory syndrome in children (MIS-C) is an identified complication of the COVID-19 infection. A common presentation of both COVID-19 and MIS-C is acute abdominal pain, sometimes mimicking appendicitis. We report two cases of patients initially diagnosed with appendicitis who either presented with or developed signs of shock and were found to have MIS-C. An 8-year-old girl who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) presented with fever, abdominal pain, and shock with ultrasound findings consistent with acute appendicitis. After being treated for MIS-C, she underwent appendectomy and improved. Final pathology was consistent with acute appendicitis. A 9-year-old girl who tested negative for COVID RT-PCR presented with uncomplicated appendicitis and underwent laparoscopic appendectomy, but developed post-operative fever and shock. Antibody testing was positive and she responded to treatment for MIS-C. Histology showed lymphohistiocytic inflammation within the muscularis propria, mesoappendix and serosa without the typical neutrophil-rich inflammation and mucosal involvement of acute appendicitis. The diagnosis was MIS-C, not appendicitis. Given the new reality of the COVID-19 pandemic, pediatric surgeons must be aware of MIS-C as a possible diagnosis and should understand the diagnostic criteria and current treatment guidelines.

Background: Tunneled central venous catheters (CVC) were developed five decades ago. Since then, several clinician-inventors have created a variety of catheters with different functions. Indeed, many catheters have been named after their inventor. Many have wondered who the inventors were of each catheter, and what specifically inspired their inventions. Many of these compelling stories have yet to be told. Data source: A literature review of common catheters and personal communication with inventors. Only first person accounts from inventors or those close to the invention were used. Conclusions: CVCs are now essential devices that have saved countless lives. Though the inventors have earned the honor of naming their catheters, it may be reasonable to consider more consistent terminology to describe these catheters to avoid confusion.

Well-differentiated thyroid cancer is the most common endocrine malignancy in children. Adult literature has demonstrated socioeconomic disparities in patients undergoing thyroidectomy, but the effects of socioeconomic status on the management of pediatric well-differentiated thyroid cancer remains poorly understood.Patients ≤21 years of age with well-differentiated thyroid cancer remains were reviewed from the National Cancer Data Base. Three socioeconomic surrogate variables were identified: insurance type, median income, and educational quartile. Tumor characteristics, diagnostic intervals, and clinical outcomes were compared within each socioeconomic surrogate variable.A total of 9,585 children with well-differentiated thyroid cancer remains were reviewed. In multivariate analysis, lower income, lower educational quartile, and insurance status were associated with higher stage at diagnosis. Furthermore, lower income quartile was associated with a longer time from diagnosis to treatment (P .002). Similarly, uninsured children had a longer time from diagnosis to treatment (28 days) compared with those with government (19 days) or private (18 days) insurance (P .001). Despite being diagnosed at a higher stage and having a longer time interval between diagnosis and treatment, there was no significant difference in either overall survival or rates of unplanned readmissions based on any of the socioeconomic surrogate variables.Children from lower income families and those lacking insurance experienced a longer period from diagnosis to treatment of their well-differentiated thyroid cancer remains. These patients also presented with higher stage disease. These data suggest a delay in care for children from low-income families. Although these findings did not translate into worse outcomes for well-differentiated thyroid cancer remains, future efforts should focus on reducing these differences.

The following is the conference proceeding of the Second Ein Debate from the 48th Annual Meeting of the Canadian Association of Paediatric Surgeons held in Vancouver, BC, from September 22 to 24, 2016. The three main topics for debate, as prepared by the members of the CAPS Ethics Committee, are: 1. Regionalization of care: pros and cons, 2. Innovation in clinical care: ethical considerations, and 3. Surgeon well-being: caring for the caregiver. The authors of this paper, as participants in the debate, were assigned their positions at random. Therefore, the opinions they express within this summary might not reflect their own viewpoints. In the first discussion, arguments for and against the regionalization of pediatric surgical care are discussed, primarily in the context of a case of BA. In the pro argument, the evidence and lessons learned from different European countries are explored as well as different models to provide the best BA care outside of large teaching centers. In the counterargument, the author explains how regionalization of care could be detrimental for the patient, the family, the regional center, and for the health care system in general. In the debate on surgical innovation the authors define surgical innovation. They review the pertinent ethical principles, explore a model for its implementation, and the role of the institution at which the innovation is proposed. In the third section, surgeon well-being is examined, and recent literature on surgeon resiliency and burnout both at the attending and resident level is reviewed.

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

Pediatric breast malignancies are rare, and descriptions in the literature are limited. The purpose of our study was to compare pediatric and adult breast malignancy. We performed a retrospective cohort study using the National Cancer Data Base comparing patients ≤21 years to those >21 years at diagnosis (1998–2012). Generalized linear models estimated differences in demographic, tumor, and treatment characteristics. Cox regression was used to compare overall survival. Of 1,999,181 cases of invasive breast malignancies, 477 (0.02%) occurred in patients ≤21 years. Ninety-nine percent of adult patients had invasive carcinoma compared with 64.8% of pediatric patients with the remaining patients having sarcoma, malignant phyllodes, or malignancy not otherwise specified (p

We sought to compare the presentation, management, and outcomes in gastric adenocarcinoma cancer for pediatric and adult patients.Using the 2004 to 2014 National Cancer Database (NCDB), patients ≤21 years (pediatric) were retrospectively compared to21 years (adult). Chi-squared tests were used to compare categorical variables, and Cox regression was used to estimate hazard ratios (HR) for survival differences.Of the 129,024 gastric adenocarcinoma cases identified, 129 (0.10%) occurred in pediatric patients. Pediatric cases presented with more advanced disease, including poorly differentiated tumors (81% vs 65%, p = 0.006) and stage 4 disease (56% vs 41%, p = 0.002). Signet ring adenocarcinoma comprised 45% of cases in the pediatric group as compared to 20% of cases in the adults (P 0.001). Similar proportions in both groups underwent surgery. However, near-total gastrectomy was more common in the pediatric group (16% vs 6%, p 0.001). The proportions of patients with negative margins, nodal examination, and presence of positive nodes were similar. There was no overall survival difference between the two age groups (HR 0.92, 95% Confidence interval 0.73-1.15).While gastric adenocarcinoma in pediatric patients present with a more advanced stage and poorly differentiated tumors compared to adults, survival appears to be comparable.Retrospective cohort study.III.

Background Solid pseudopapillary neoplasms (SPPNs) comprise the majority of pediatric pancreatic neoplasms. We queried the National Cancer Database to compare pediatric and adult patients with SSPNs to examine differences in demographics, tumor characteristics, treatment, and overall survival. We aimed to determine if survival differences existed between adult and pediatric patients with SPPN. Methods The National Cancer Database (2004-2014) was reviewed, and patients were stratified by age at diagnosis: pediatric (≤21 y) and adult (≥22 y). Demographics, comorbidities, tumor characteristics, diagnostic periods, treatments, and survival rates were compared using pooled variance t-tests and chi-square, followed by multivariate Cox proportional hazard model (α = 0.05). Log-rank test was used to compare survival. Results A total of 468 patients were analyzed and categorized according to age group. Four hundred and fourteen patients were included in the survival analysis. The pediatric patients were primarily female, Caucasian, had no comorbidities, and presented with stage I disease. Race/ethnicity, gender, socioeconomic status, comorbidities, and disease stage at presentation were similar between the groups. There was no difference in time to initiation of therapy or to surgical intervention. No significant difference was found in type of surgical resection, chemotherapy, or radiotherapy utilization. Despite the similarities between groups, comparison of overall survival demonstrated improved survival of pediatric SPPN compared with adult SPPN in every pathologic stage. Conclusions These results suggest that pediatric and adult SPPNs are similar with regards to demographics, tumor characteristics, and treatment modalities. However, survival was better in children with SPPNs, which may be due to differences in tumor biology and may serve for risk stratification of prognosis.

Background The purpose of this study was to evaluate the frequency and characteristics of surgical protocol violations (SPVs) among children undergoing surgery for renal tumors who were enrolled on the Children's Oncology Group (COG) renal tumor biology and classification study AREN03B2. Methods AREN03B2 was opened in February 2006, and as on March 31, 2013, there were 3,664 eligible patients. The surgical review forms for 3,536 patients with unilateral disease were centrally reviewed for SPVs. The frequency, type, number of violations, institutional prevalence, and quartiles for SPVs were assessed. Results Of the 3,536 patients, there were a total of 505 with at least one SPV (564 total SPVs reported), for an overall incidence of 14.28%. The types of SPVs included a lack of lymph node sampling in 365 (64.7%), avoidable spill in 61 (10.8%), biopsy immediately before nephrectomy in 89 (15.8%), an incorrect abdominal incision in 32 (5.7%), and unnecessary resection of organs in 17 (3.0%). The SPVs occurred in 163 of 215 participating institutions (75.8%). For centers with at least one SPV, the mean number of SPVs reported was 3.10 ± 2.39 (mean ± standard deviation). The incidence of protocol violation per institution ranged from 0 to 67%. Centers with an average of ≤1 case/year had an incidence of SPVs of 12.2 ± 3.8%, those with an average of >1 to 0.05). Conclusions SPVs that potentially result in additional exposure to chemotherapy and radiation therapy are not uncommon in children undergoing resection of renal malignancies.

The overwhelming majority of ovarian cysts in pediatric and adolescent girls are physiologic; however, large simple and complex ovarian lesions often require surgical intervention due to the increased risk of neoplasia. In this review article, we discuss the preoperative evaluation and intraoperative management of large ovarian neoplasms. We review the current literature regarding long term ovarian function and fertility, rates of recurrence and residual disease, and novel surgical approaches. Managing large ovarian neoplasms in the pediatric and adolescent population requires careful preoperative and intraoperative care to optimally resect neoplasia while maximizing fertility and minimizing pain.

Central venous catheters (CVCs) are routinely filled with a heparin lock while not in use to avoid thrombus formation near the tip. However, heparin leakage is known to occur, and the lock effectiveness remains in question. It was recently shown that convective fluxes from the blood flow in the host vein transport the majority of locking solution away from the tip of hemodialysis catheters immediately after instillation. Combined with the low diffusivity of heparin, this results in concentrations of heparin at the catheter tip that are orders of magnitude lower than at instillation for the majority of the interdialytic phase, diminishing the antithrombotic effectiveness of the lock. In this study, heparin losses from three different CVCs with different tip designs are measured in a pulsatile flow loop. Planar laser-induced fluorescence and particle image velocimetry measurements of heparin concentration and fluid velocity are recorded downstream of the catheters and combined to evaluate heparin losses from each of the different catheter designs. Additionally, locking solution losses are measured from one catheter (Hickman) subjected to three different flow conditions. Heparin losses are shown to depend weakly on flow condition but be highly dependent on catheter design. Convective losses from the Hickman catheter, with no side holes, are minimal (1-2%), although losses from the other two catheter types, both with a number of side holes, are significantly higher (7%). These results indicate the potential to maintain a high concentration of locking solution during the interdialytic phase with proper catheter design, particularly focusing on side hole distribution and shape.

Standard of care for unilateral nephroblastoma includes total nephrectomy (TN) with nodal sampling. We sought to compare the outcomes of TN and partial nephrectomy (PN). We performed a retrospective cohort study of TN and PN for nephroblastoma using the National Cancer Data Base. The outcomes included nodal sampling frequency, margin status, and survival. Categorical and continuous data were evaluated with χ2 and t tests, respectively (P0.05). Generalized linear models evaluated nodal sampling and margin status. Cox regression compared survival. In total, 235 patients underwent PN and 3572 had TN. TN patients were 50 per cent more likely to undergo nodal sampling (RR: 1.47, 95% CI 1.30-1.66). There was no difference in margin status (RR: 0.91, 95% CI 0.65-1.28) or overall survival (HR 1.57; 95% CI 0.78-3.19). This study reports the largest review of patients with PN for unilateral nephroblastoma. PN patients had less nodal sampling but similar margin involvement and overall survival.

Central venous catheters (CVCs), placed in the Superior Vena Cava (SVC) for hemodialysis or chemotherapy, are routinely filled while not in use with heparin, an anticoagulant, to maintain patency and prevent thrombus formation at the catheter tip. The heparin-locking procedure, however, places the patient at risk for systemic bleeding, as heparin is known to leak from the catheter into the blood stream. We provide evidence from detailed in-vitro experiments that shows the driving mechanism behind heparin leakage to be convective-diffusive transport due to the pulsatile flow surrounding the catheter. This novel mechanism is supported by experimental planar laser induced fluorescence (PLIF) and particle image velocimetry (PIV) measurements of flow velocity and heparin transport from a CVC placed inside a model SVC inside a pulsatile flow loop. The results predict an initial, fast (< 10s), convection-dominated phase that rapidly depletes the concentration of heparin in the near-tip region, the region of the catheter with side holes. This is followed by a slow, diffusion-limited phase inside the catheter lumen, where the concentration is still high, that is insufficient at replenishing the lost heparin concentration in the near-tip region. The results presented here, which are consistent with previous in vivo estimates of 24-hour leakage rates, predict that the concentration of heparin in the near-tip region is essentially zero for the majority of the interdialytic phase, rendering the heparin locking procedure ineffective.

Adjuvant endocrine therapy (AET) has been shown to reduce the risk of second breast cancer events in women with ductal carcinoma in situ (DCIS). There is no population-level evaluation of AET use in DCIS patients after standardized reporting of estrogen receptor (ER) status in cancer registries in 2004. We conducted a retrospective cohort study of women with DCIS in the National Cancer Data Base between 2005 and 2012. Patient, tumor, and treatment characteristics as well as temporal trends associated with receipt of AET were evaluated by generalized linear regression. Among 206,255 DCIS patients, 36.5 % received AET. Fewer than half of ER-positive patients (n = 62,146, 46.4 %) received AET, with a modest but significant increase over time (43.6 % in 2005 to 47.5 % in 2012; unadjusted p trend

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.

Background Malignant ovarian germ cell tumors (MOGCTs) are a rare form of ovarian malignancy. Socioeconomic status (SES) has been shown to affect survival in several gynecologic cancers. We examined whether SES impacted survival in adolescent and young adults (AYAs) with MOGCT. Materials and methods The National Cancer Data Base was used to identify AYAs (aged 15-39 years) with MOGCT from 1998 to 2012. Three SES surrogate variables identified were as follows: insurance type, income quartile, and education quartile. Pooled variance t-tests and chi-square tests were used to compare tumor characteristics, the time from diagnosis to staging/treatment, and clinical outcome variables for each SES surrogate variable, while controlling for age and race/ethnicity in a multivariate model. Kaplan–Meier survival estimates were calculated using the log-rank test. Results A total of 3125 AYAs with MOGCT were identified. Subjects with lower SES measures had higher overall stage and T-stage MOGCTs at presentation. There was no significant difference in the time to staging/treatment, extent of surgery, or use of chemotherapy by SES. Subjects from a lower education background, from a lower income quartile, and without insurance had decreased survival ( P ≤ 0.02 for all). Controlling for overall stage and T-stage, the difference in survival was no longer significant. Conclusions AYAs with MOGCT from lower SES backgrounds presented with more advanced stage disease. Further studies that focus on the underlying reasons for this difference are needed to address these disparities.

Adrenal masses arise from the adrenal medulla or the adrenal cortex. Adrenal medullary lesions in children include relatively common neuroblastomas and rare pheochromocytomas. Adrenocortical tumors (ACTs) are rare in children and it is difficult to distinguish benign from malignant lesions in the absence of metastatic disease. ACTs differ substantially in clinical characteristics and biologic behavior from similar tumors in adults and from adrenal medullary tumors. ACTs in children are typically hormonally active and it is normally possible to make the diagnosis by the combination of history, physical examination, laboratory studies, and cross-sectional imaging. Complete surgical resection is critical for successful treatment of ACTs, as adjuvant treatment has only limited effectiveness. Although the earlier literature indicated that children with ACTs had a relatively poor prognosis, recent work suggests an improved outlook.

Background In many cancers, racial and socioeconomic disparities exist regarding the extent of surgery. For ovarian dysgerminoma, fertility-sparing (FS) surgery is recommended whenever possible. The aim of this study was to investigate rates of FS versus non–fertility-sparing (NFS) procedures for stage I ovarian dysgerminoma in adolescents and young adults (AYAs) by ethnicity/race and socioeconomic status. Materials and methods The National Cancer Data Base was queried for patients with ovarian dysgerminoma from 1998 to 2012. After selecting patients aged 15-39 y with stage I disease, a multivariate regression analysis was performed, and rates of FS and NFS procedures were compared, first according to ethnicity/race, and then by socioeconomic surrogate variables. Results Among the 687 AYAs with stage I ovarian dysgerminoma, there was no significant difference in rates of FS and NFS procedures based on ethnicity/race alone (P = 0.17), but there was a significant difference in procedure type for all three socioeconomic surrogates. The uninsured had higher NFS rates (30%) than those with government (21%) or private (19%) insurance (P = 0.036). Those in the poorest ZIP codes had almost twice the rate of NFS procedures (31%) compared with those in the most affluent ZIP codes (17%). For those in the least-educated regions, 24% underwent NFS procedures compared to 14% in the most-educated areas (P = 0.027). Conclusions AYAs with stage I ovarian dysgerminoma in lower socioeconomic groups were more likely to undergo NFS procedures than those in higher socioeconomic groups, but there was no difference in rates of FS versus NFS procedures by ethnicity/race. Approaches aimed at reducing socioeconomic disparities require further examination.

To describe secular trends in operative experience for surgical trainees across an extended period using the most comprehensive data available, the Accreditation Council for Graduate Medical Education (ACGME) case logs.Some experts have expressed concern that current trainees are inadequately prepared for independent practice. One frequently mentioned factor is whether duty hours' restrictions (DHR) implemented in 2003 and 2004 contributed by reducing time spent in the operating room.A dataset was generated from annual ACGME reports. Operative volume for total major cases (TMC), defined categories, and four index laparoscopic procedures was evaluated.TMC dropped after implementation of DHR but rebounded after a transition period (949 vs 946 cases, P = nonsignificance). Abdominal cases increased from 22% of overall cases to 31%. Alimentary cases increased from 21% to 26%. Trauma and vascular surgery substantially decreased. For trauma, this drop took place well before DHR. The decrease in vascular surgery also began before DHR but continued afterward as well: 148 cases/resident in the late 1990s to 107 currently.Although total operative volume rebounded after implementation of DHR, diversity of operative experienced narrowed. The combined increase in alimentary and abdominal cases is nearly 13%, over a half-year's worth of operating in 5-year training programs. Bedrock general surgery cases-trauma, vascular, pediatrics, and breast-decreased. Laparoscopic operations have steadily increased. If the competence of current graduates has, in fact, diminished. Our analysis suggests that operative volume is not the problem. Rather, changing disease processes, subspecialization, reductions in resident autonomy, and technical innovation challenge how today's general surgeons are trained.

CT and MRI are both used for abdominal staging of pediatric renal tumors. The diagnostic performance of the two modalities for local and regional staging of renal tumors has not been systematically evaluated. To compare the diagnostic performance of CT and MRI for local staging of pediatric renal tumors. The study population was derived from the AREN03B2 study of the Children’s Oncology Group. Baseline abdominal imaging performed with both CT and MRI within 30 days of nephrectomy was available for retrospective review in 82 renal tumor cases. Each case was evaluated for capsular penetration, lymph node metastasis, tumor thrombus, preoperative tumor rupture, and synchronous contralateral lesions. The surgical and pathological findings at central review were the reference standard. The sensitivity of CT and MRI for detecting capsular penetration was 68.6% and 62.9%, respectively (P = 0.73), while specificity was 86.5% and 83.8% (P = 1.0). The sensitivity of CT and MRI for detecting lymph node metastasis was 76.5% and 52.9% (P = 0.22), and specificity was 90.4% and 92.3% (P = 1.0). Synchronous contralateral lesions were identified by CT in 4/9 cases and by MRI in 7/9 cases. CT and MRI have similar diagnostic performance for detection of lymph node metastasis and capsular penetration. MR detected more contralateral synchronous lesions; however these were present in a very small number of cases. Either modality can be used for initial loco–regional staging of pediatric renal tumors.

The Children's Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology, pathology, and the surgical procedure to determine appropriate risk-based therapy. The purpose of this study was to determine the inter-rater reliability of the surgical reviews.Of the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood vessel involvement, spill, rupture, and lymph node involvement was selected for analysis. The surgical assessment was then performed independently by two blinded surgical reviewers and compared to the original assessment, which had been completed by another of the committee surgeons. Variables assessed included surgeon-determined local tumor stage, overall disease stage, type of renal procedure performed, presence of tumor rupture, occurrence of intraoperative tumor spill, blood vessel involvement, presence of peritoneal implants, and interpretation of residual disease. Inter-rater reliability was measured using the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value).Local tumor stage correlated in all 3 reviews except in one case (Kappa=0.9775, p0.001). Similarly, overall disease stage had excellent correlation (0.9422, p0.001). There was strong correlation for type of renal procedure (0.8357, p0.001), presence of tumor rupture (0.6858, p0.001), intraoperative tumor spill (0.6493, p0.001), and blood vessel involvement (0.6470, p0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753, p0.001) and interpretation of residual disease status (0.5310, p0.001).The inter-rater reliability of the surgical review is high based on the great consistency in the 3 independent review results. This analysis provides validation and establishes precedent for real-time central surgical review to determine treatment assignment in a risk-based stratagem for multimodal cancer therapy.

BACKGROUND The management of pediatric melanoma (PM) has largely been extrapolated from adult data. However, the behavior of PM appears to differ from its adult counterparts. Therefore, an international PM registry was created and analyzed. METHODS Twelve institutions contributed deidentified clinicopathologic and outcome data for patients diagnosed with PM from 1953 through 2008. RESULTS Overall survival (OS) data were reported for 365 patients with invasive PM who had adequate follow-up data. The mean age of the patients was 16 years (range 1 year-21 years). The 10-year OS rate, 80.6%, tended to vary by patient age: 100% for those aged birth to 10 years, 69.7% for those aged > 10 years to 15 years, and 79.5% for those aged > 15 years to 20 years (P = .147). Patients with melanomas measuring ≤ 1 mm had a favorable prognosis (10-year OS rate of 97%), whereas survival was lower but similar for patients with melanomas measuring > 1 mm to 2 mm, > 2 mm to 4 mm, and > 4 mm (70%, 78%, and 80%, respectively; P = .0077). Ulceration and lymph node metastasis were found to be correlated with worse survival (P = .022 and P = .017, respectively). The 10-year OS rate was 94.1% for patients with American Joint Committee on Cancer stage I disease, 79.6% for those with stage II disease, and 77.1% for patients with stage III disease (P 10 years. Further analyses are needed to probe for potential biological and behavioral differences in pediatric versus adult melanoma. Cancer 2013;119:4012–4019. © 2013 American Cancer Society.

Background Though the volume-outcome relationship has been well-established in adults, low mortality rates and small sample sizes have precluded definitive demonstration in children. This study compares treatment-specific factors for children with nephroblastoma at high (HVC) versus low volume centers (LVC). Methods We performed a retrospective cohort study comparing patients ≤18years with unilateral nephroblastoma treated at HVCs and LVCs using the National Cancer Data Base (1998–2012). Definitions of HVCs included performing above the median, the upper two quartiles, and the highest decile of nephroblastoma resections. Outcomes included nodal sampling, margin status, time to chemotherapy and radiation, and survival. Statistical analyses included χ 2 , t-tests, generalized linear, and Cox regression models (p Results Of 2911 patients from 210 centers, 1443 (49.6%) were treated at HVCs. There was no difference in frequency of preoperative biopsy or days to radiation (p>0.05). High volume centers were more likely to perform nodal sampling (RR 1.04, 95%CI 1.01–1.08) and had fewer days to chemotherapy (RR 0.80, 95%CI 0.69–0.93). Five-year survival was similar (HVC: 0.93, 95%CI 0.92–0.94; LVC: 0.93, 95%CI 0.91–0.94). Conclusions HVCs were more likely to perform nodal sampling and had fewer days to chemotherapy. There was no difference in days to radiation or survival between centers. Level of evidence Level II (retrospective prognosis study).

BackgroundSurgery resident education is based on experiential training, which is influenced by changes in clinical management strategies, technical and technologic advances, and administrative regulations. Trauma care has been exposed to each of these factors, prompting concerns about resident experience in operative trauma. The current study analyzed the reported volume of operative trauma for the last two decades; to our knowledge, this is the first evaluation of nationwide trends during such an extended time line.MethodsThe Accreditation Council for Graduate Medical Education (ACGME) database of operative logs was queried from academic year (AY) 1989-1990 to 2009-2010 to identify shifts in trauma operative experience. Annual case log data for each cohort of graduating surgery residents were combined into approximately 5-year blocks, designated Period I (AY1989-1990 to AY1993-1994), Period II (AY1994-1995 to AY1998-1999), Period III (AY1999-2000 to AY2002-2003), and Period IV (AY2003-2004 to AY2009-2010). The latter two periods were delineated by the year in which duty hour restrictions were implemented.ResultsOverall general surgery caseload increased from Period I to Period II (p < 0.001), remained stable from Period II to Period III, and decreased from Period III to Period IV (p < 0.001). However, for ACGME-designated trauma cases, there were significant declines from Period I to Period II (75.5 vs. 54.5 cases, p < 0.001) and Period II to Period III (54.5 vs. 39.3 cases, p < 0.001) but no difference between Period III and Period IV (39.3 vs. 39.4 cases). Graduating residents in Period I performed, on average, 31 intra-abdominal trauma operations, including approximately five spleen and four liver operations. Residents in Period IV performed 17 intra-abdominal trauma operations, including three spleen and approximately two liver operations.ConclusionRecent general surgery trainees perform fewer trauma operations than previous trainees. The majority of this decline occurred before implementation of work-hour restrictions. Although these changes reflect concurrent changes in management of trauma, surgical educators must meet the challenge of training residents in procedures less frequently performed.Level of evidenceEpidemiologic study, level III; therapeutic study, level IV.