Withholding Urinary Catheters in Children Receiving Patient-Controlled Analgesia for Appendicitis.

BACKGROUND: In some institutions, urinary catheters (UCs) have been placed in all patients receiving opioid patient-controlled analgesia (PCA) because of the increased incidence of urinary retention. Our institutional data demonstrated no UC replacements in 48 children who had PCA for perforated appendicitis who had their catheters removed before discontinuation of the PCA. As part of a quality improvement initiative, we discontinued the practice of requiring UC with PCA for perforated appendicitis. MATERIALS AND METHODS: A prospective list of patients with perforated appendicitis was maintained. Data were gathered regarding 60 consecutive patients. UC placement was allowed for specific indications including urinary retention and surgeon discretion. RESULTS: Sixteen patients (27%) received a UC with 14 of these being placed in the operating room (OR). Two UCs were placed outside the OR for urinary retention. Patients who underwent UC placement in the OR weighed significantly more than those who did not (33 versus 42 kg, P = 0.05). No patients required replacement of the catheter once removed. There were no postoperative urinary tract infections. Median PCA duration was 68 h (50, 98) for patients with UC placed in the OR compared with 60 h (47, 78) (P = 0.42). Median postoperative length of stay for patients with UC placed in the OR was 95 h (76, 140) compared with 90 h (70, 113) (P = 0.09). CONCLUSIONS: UC can be withheld from patients with perforated appendicitis who are placed on PCA with a very low placement rate. UC placement at time of operation did not lengthen time receiving PCA or length of stay.

Genetic and chromosomal alterations in Kenyan Wilms Tumor.

Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub-Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub-Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment-resistant biology compromises survival further. To explore the biologic composition of Kenyan WT (KWT), we completed a next generation sequencing analysis targeting 10 WT-associated genes and evaluated whole-genome copy number variation. The study cohort was comprised of 44 KWT patients and their specimens. Fourteen children are confirmed dead at 2 years and 11 remain lost to follow-up despite multiple tracing attempts. TP53 was mutated most commonly in 11 KWT specimens (25%), CTNNB1 in 10 (23%), MYCN in 8 (18%), AMER1 in 5 (11%), WT1 and TOP2A in 4 (9%), and IGF2 in 3 (7%). Loss of heterozygosity (LOH) at 17p, which covers TP53, was detected in 18% of specimens examined. Copy number gain at 1q, a poor prognostic indicator of WT biology in developed countries, was detected in 32% of KWT analyzed, and 89% of these children are deceased. Similarly, LOH at 11q was detected in 32% of KWT, and 80% of these patients are deceased. From this genomic analysis, KWT biology appears uniquely aggressive and treatment-resistant.

Risk factors for abandonment of Wilms tumor therapy in Kenya.

BACKGROUND: Survival from Wilms tumor (WT) in sub-Saharan Africa remains dismal as a result of on-therapy mortality and treatment abandonment. Review of patients diagnosed from 2008 to 2011 in our Kenyan Wilms Tumor Registry showed a loss to follow up (LTFU) rate approaching 50%. The purpose of this study was to trace those LTFU, estimate the survival rate, and identify risk factors for treatment abandonment. PROCEDURE: We administered a comprehensive survey to parents of patients with WT at the two largest referral hospitals in Kenya to identify barriers to care. We also telephoned families who had abandoned care to determine vital status and identify risk factors for treatment abandonment. RESULTS: Of 136 registered patients, 77 were confirmed dead (56.7%), 38 remained alive (27.9%), and the vital status of 21 patients remains unknown (15.4%). After contacting 33 of the patients who either abandoned curative treatment (n = 34) or did not attend off-therapy visits (n = 20), the best estimate of 2-year overall survival of patients with WT in Kenya approaches 36%. Sixty-three percent of parents misunderstood treatment plans and 55% encountered financial barriers. When asked how to increase comfort with the child's treatment, 27% of parents volunteered improving inefficient services and 26% volunteered reducing drug-unavailability. CONCLUSIONS: Treatment abandonment remains a significant problem contributing to increased mortality from WT in developing countries. This multi-center survey identified the barriers to treatment completion from the parental perspective to be lack of education about WT and treatment, financial constraints, need for quality improvement, and drug-unavailability. Pediatr Blood Cancer 2015;62:252-256. © 2014 Wiley Periodicals, Inc.

Adjuvant radiation therapy increases disease-free survival in stage IB Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. Adjuvant radiation increases survival in advanced stages, but efficacy in stage I disease is unknown. A retrospective review included all patients treated for stage I MCC during a 15-year period at Vanderbilt University Medical Center. Among 42 patients, 26 (62%) had a negative sentinel lymph node biopsy (stage IA) and 16 (38%) had clinically negative lymph nodes (stage IB) at the time of resection. Analysis using Cox regression revealed that higher stage and absence of adjuvant radiation are associated with increased disease recurrence (hazard ratio, 6.29; P=0.003 and hazard ratio, 4.69; P=0.013, respectively). Controlling for stage, radiation therapy significantly increased disease-free survival among patients with stage IB disease (P=0.0026) in a log-rank test comparing Kaplan-Meier curves. These findings support adjuvant radiation therapy in stage IB MCC patients with clinically negative lymph nodes who do not undergo sentinel lymph node biopsy.

Molecular characterization of Wilms' tumor from a resource-constrained region of sub-Saharan Africa.

Sub-Saharan African children have an increased incidence of Wilms' tumor (WT) and experience alarmingly poor outcomes. Although these outcomes are largely due to inadequate therapy, we hypothesized that WT from this region exhibits features of biological aggressiveness that may warrant broader implementation of high-risk therapeutic protocols. We evaluated 15 Kenyan WT (KWT) for features of aggressive disease (blastemal predominance and Ki67/cellular proliferation) and treatment resistance (anaplasia and p53 immunopositivity). To explore the additional biological features of KWT, we determined the mutational status of the CTNNB1/ß-catenin and WT1 genes and performed immunostaining for markers of Wnt pathway activation (ß-catenin) and nephronic progenitor cell self-renewal (WT1, CITED1 and SIX2). We characterized the proteome of KWT using imaging mass spectrometry (IMS). The results were compared to histology- and age-matched North American WT (NAWT) controls. For patients with KWT, blastemal predominance was noted in 53.3% and anaplasia in 13%. We detected increased loss to follow-up (p = 0.028), disease relapse (p = 0.044), mortality (p = 0.001) and nuclear unrest (p = 0.001) in patients with KWT compared to controls. KWT and NAWT showed similar Ki67/cellular proliferation. We detected an increased proportion of epithelial nuclear ß-catenin in KWT (p = 0.013). All 15 KWT specimens were found to harbor wild-type CTNNB1/ß-catenin, and one contained a WT1 nonsense mutation. WT1 was detected by immunostaining in 100% of KWT, CITED1 in 80% and SIX2 in 80%. IMS revealed a molecular signature unique to KWT that was distinct from NAWT. The African WT specimens appear to express markers of adverse clinical behavior and treatment resistance and may require alternative therapies or implementation of high-risk treatment protocols.

Associations between pediatric choledochal cysts, biliary atresia, and congenital cardiac anomalies.

BACKGROUND: In our institutional experience treating pediatric choledochal cysts over the past 12 y, we noted that seven of 32 patients (21.9%) had comorbid congenital cardiac anomalies. This association has not been previously described other than in isolated case reports. We aimed to quantify this association on a national level. MATERIALS AND METHODS: We queried the 2009 Healthcare Cost and Utilization Project Kids' Inpatient Database. We identified patients with a diagnosis of choledochal cyst (ICD-9-CM 75169, 75162, and 75160) or biliary atresia (75161). We defined cardiac anomalies using the Clinical Classification Software code (CCS 213). Comorbid choledochal cysts or biliary atresia and congenital cardiac anomalies were quantified in both infant (<12 mo) and child (1-18 y) subpopulations. RESULTS: Of 1646 estimated discharges for patients with choledochal cysts, 506 (30.7%) were for patients who also had congenital cardiac anomalies, compared with 2.6% in the general hospitalized population (χ(2); P < 0.001). The frequency of congenital cardiac anomalies was lower in 1973 hospitalizations for biliary atresia (13.8%) than in those for patients with choledochal cysts (χ(2); P < 0.001). We detected cardiac anomalies in 44.9% of choledochal cyst hospitalizations for infants <12 mo (versus 3.44% general hospitalized population; χ(2); P < 0.001), but in 6.9% of children ages 1-18 y (versus 1.3% general hospitalized population; χ(2); P < 0.001). CONCLUSIONS: We observed a strong association between pediatric choledochal cysts and congenital cardiac anomalies that commonly manifests in infancy. When choledochal cysts are diagnosed either prenatally or in infancy, we suggest echocardiographic screening for cardiac anomalies, which may affect the timing of surgery and anesthetic planning.

Volume-outcome effects for children undergoing resection of renal malignancies.

INTRODUCTION: Adults undergoing oncologic resections at low-volume centers experience increased perioperative morbidity and mortality. The volume-outcome effect has not been extensively studied in pediatric oncologic resections. METHODS: To clarify volume-outcome effects in pediatric oncologic resections, we analyzed resection of renal malignancies in children less than 15 y of age. We conducted a cross-sectional analysis of hospital discharges included in the health care utilization project kids' inpatient database from 1997 to 2009, examining in-hospital operative complications, length of stay (LOS), and inflation-adjusted hospital charges. Hospital volume was expressed as low (n = 1-2), medium (n = 3-4), and high (n > 4) annual volume of resections. RESULTS: One thousand five hundred thirty-eight patients underwent renal malignancy resection. Of these, 527 patients had resection in low-, 422 in medium-, and 589 in high-volume hospitals. Relative to low-volume hospitals, those resected in medium-volume hospitals had an odds ratio of 0.62 (95% confidence interval 0.39-0.99, P = 0.046) for operative complication and those in high-volume hospitals had an odds ratio of 1.02 (95% confidence interval 0.63-1.65, P = 0.95). There was no detectable association with LOS (P = 0.113) or inflation-adjusted charges (P = 0.331). CONCLUSIONS: The number of complications, total charges, and LOS attributable to resection of a childhood renal malignancy did not differ among high-, medium-, or low-operative volume hospitals, although oncologic outcomes could not be determined because of the limited nature of this administrative database.

Castleman disease in a pediatric liver transplant recipient: a case report and literature review.

Castleman disease is a rare hematologic disorder, closely linked to the HHV-8, and most commonly observed in immunocompromised individuals. Thirteen months following a liver transplant for CPS-1 defect, a 15-month-old boy presented with fevers, anemia, and growth retardation. Abdominal CT scan showed splenomegaly and generalized lymphadenopathy. Histology of chest wall lymph nodes revealed a mixed CD3+ T-cell and CD20+ B-cell population with atretic germinal centers consistent with multicentric Castleman disease. Qualitative DNA PCR detected HHV-8 in the resected lymph node and in the blood, supporting the diagnosis. Immunosuppression was tapered, and he was transitioned from tacrolimus to sirolimus. His graft function remained stable, and repeat imaging showed regression of the lymphadenopathy. The child is living one yr after Castleman disease diagnosis with a well-functioning graft. Castleman disease is a potential complication of solid organ transplant and HHV-8 infection. Reduction in immunosuppression and switch to sirolimus may be an effective strategy to treat this condition.

Concordance of imaging modalities and cost minimization in the diagnosis of pediatric choledochal cysts.

PURPOSE: Given evolving imaging technologies, we noted significant variation in the diagnostic evaluation of pediatric choledochal cysts (CDC). To streamline the diagnostic approach to CDC, and minimize associated expenses, we compared typing accuracy and costs of ultrasound (US), intraoperative cholangiography (IOC), and magnetic resonance cholangiopancreatography (MRCP). METHODS: Records of 30 consecutive pediatric CDC patients were reviewed. Blinded to all clinical data, two pediatric radiologists reviewed all US, MRCPs, and IOCs to type CDCs according to the Todani classification. When compared with pathologic findings, the concordance between and accuracy of each diagnostic test were determined. Inflation-adjusted procedure charges and collections for imaging modalities were analyzed. RESULTS: Mean typing accuracy overlapped for US, IOC, and MRCP. Inter-rater reliability was 87 % for US (κ = 0.77), 80 % for IOC (κ = 0.62), and 60 % for MRCP (κ = 0.37). MRCP procedure charges ($1204.69) and collections ($420.85) exceeded IOC and US combined ($264.80 charges, p = 0.0002; $93.40 collections, p = 0.0021). CONCLUSION: Our data support the use of US alone in the diagnosis of pediatric CDC when no intrahepatic biliary ductal dilatation is visualized. However, when dilated intrahepatic ducts are encountered on US, MRCP should be utilized to distinguish a type I from a type IV CDC, which may alter the operative approach.

Race disparities in Wilms tumor incidence and biology.

BACKGROUND: Wilms tumor (WT) is thought to arise in children of Black African ancestry with greater frequency than in Whites. To clarify the biological basis for race disparities in WT, we first verified that Black children residing in Tennessee have an increased incidence of WT, and second, established molecular profiles in WT that are specific to race. MATERIALS AND METHODS: To assess race disparities in WT epidemiology, the Tennessee Cancer Registry (TCR) was queried for all in-state patients less than 20 y of age and registered between 1999 and 2008. To explore race disparities in WT biology, six Black and four White WT specimens acquired in Tennessee were analyzed using imaging mass spectrometry (IMS). RESULTS: TCR data show that Black children are over-represented among WT patients (29%) relative to all other childhood cancers (18.5%; P = 0.01). WT ranked the fifth most common cancer diagnosis among Blacks, but ninth among Whites. The diagnosis of WT occurred 79% more frequently among Blacks (n = 28) than Whites (n = 69; P = 0.01), and proportionally more Blacks tended to present with distant disease. Although overall survival from WT was not statistically different between Blacks (92.9%) and Whites (94.0%), Black males showed the lowest survival (85%; P = 0.21). IMS analysis identified peptide spectra from both WT blastema and stroma that independently classify specimens according to race with greater than 80% accuracy. CONCLUSIONS: In Tennessee, Black children appear more susceptible than Whites to develop WT. Race-specific molecular profiles can be determined that may help to clarify pathways of Wilms tumorigenesis and the biological basis for race disparities in WT incidence and biology.

A practical guide for short-term pediatric surgery global volunteers.

INTRODUCTION: The tremendous need for increasing the quantity and quality of global pediatric surgical care in underserved areas has been well documented. Concomitantly there has been a significant increase in interest by pediatric surgeons in helping to relieve this problem through surgical volunteerism. The intent of the article is to serve as a practical guide for pediatric surgeons contemplating or planning a short-term global volunteer endeavor. METHODS: The article is based on the authors' personal experiences and on the published experiences of other volunteers. FINDINGS: The following aspects of volunteerism are discussed: ethical considerations, where and how to go, what and whom to take with you, what to expect in your volunteer locale, and what to do and what to avoid in order to enhance the volunteer experience. CONCLUSIONS: The points discussed in this guide will hopefully make the volunteer activity one that results in greatly improved immediate and long term surgical care for children and improves the chances that the activity will be a meaningful, pleasant, and productive experience for both the volunteer and the host physician.

Race disparities in peptide profiles of North American and Kenyan Wilms tumor specimens.

BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide and arises in children of black African ancestry with greater frequency and severity than other race groups. A biologic basis for this pediatric cancer disparity has not been previously determined. We hypothesized that unique molecular fingerprints might underlie the variable incidence and distinct disease characteristics of WT observed between race groups. STUDY DESIGN: To evaluate molecular disparities between WTs of different race groups, the Children's Oncology Group provided 80 favorable histology specimens divided evenly between black and white patients and matched for disease characteristics. As a surrogate of black sub-Saharan African patients, we also analyzed 18 Kenyan WT specimens. Tissues were probed for peptide profiles using matrix-assisted laser desorption ionization time of flight imaging mass spectrometry. To control for histologic variability within and between specimens, cellular regions were analyzed separately as triphasic (containing blastema, epithelia, and stroma), blastema only, and stroma only. Data were queried using ClinProTools and statistically analyzed. RESULTS: Peptide profiles, detected in triphasic WT regions, recognized race with good accuracy, which increased for blastema- or stroma-only regions. Peptide profiles from North American WTs differed between black and white race groups but were far more similar in composition than Kenyan specimens. Individual peptides were identified that also associated with WT patient and disease characteristics (eg, treatment failure and stage). Statistically significant peptide fragments were used to sequence proteins, revealing specific cellular signaling pathways and candidate drug targets. CONCLUSIONS: Wilms tumor specimens arising among different race groups show unique molecular fingerprints that could explain disparate incidences and biologic behavior and that could reveal novel therapeutic targets.

Wilms tumor survival in Kenya.

PURPOSE: Survival from Wilms Tumor (WT) exceeds 90% at 5 years in developed nations, whereas at last report, 2-year event-free survival (EFS) in Kenya reached only 35%. To clarify factors linked to these poor outcomes in Kenya, we established a comprehensive web-based WT registry, comprised of patients from the four primary hospitals treating childhood cancers. MATERIALS AND METHODS: WT patients diagnosed between January 2008 and January 2012 were identified. Files were abstracted for demographic characteristics, treatment regimens, and enrollment in the Kenyan National Hospital Insurance Fund (NHIF). Children under 15 years of age having both a primary kidney tumor on imaging and concordant histology consistent with WT were included. RESULTS: Two-year event-free survival (EFS) was 52.7% for all patients (n=133), although loss to follow up (LTFU) was 50%. For the 33 patients who completed all scheduled standard therapy, 2-year EFS was 94%. Patients enrolled in NHIF tended to complete more standard therapy and had a lower hazard of death (Cox 0.192, p < 0.001). CONCLUSION: Survival of Kenyan WT patients has increased slightly since last report. Notably, WT patients completing all phases of standard therapy experienced 2-year survival approaching the benchmarks of developed nations. Efforts in Kenya should be made to enhance compliance with WT treatment through NHIF enrollment.

Assessing gonadal function after childhood ovarian surgery.

PURPOSE: We aimed to assess the late effects of ovarian salvage or oophorectomy on gonadal function and fertility as measured by menstrual regularity. METHODS: We performed a 10-year retrospective review of females aged 20 years or younger who required surgery to treat an ovarian disorder. A mail survey was distributed to these patients to evaluate the effects of ovarian surgery on menarche, menstrual regularity, and pregnancy. RESULTS: A total of 180 females had surgery to treat an ovarian disorder. Eighty-six of these underwent unilateral oophorectomy (48%), whereas 94 (52%) had an ovary sparing procedure. Eighty-one patients (45%) returned completed surveys. Of the respondents, 44 had oophorectomy, and 37 had ovarian salvage. Ages of menarche were similar between surgical groups. Symptoms of menstrual irregularity differed most significantly according to painful menses (oophorectomy, 27.3%; salvage, 59.5%; P < .04). Interestingly, continuation of regular menses after surgery was higher in the oophorectomy group (oophorectomy, 70%; salvage, 15%; P = .013). CONCLUSIONS: Unilateral oophorectomy does not appear to impair late gonadal function when compared with ovarian salvage. Surprisingly, oophorectomy appears to maintain more normal ovarian activity as estimated by menstrual regularity. Oophorectomy may be performed without apparent adverse effect on gonadal activity.