B-cell-specific checkpoint molecules that regulate anti-tumour immunity.

The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth, we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice. The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1, encoded by Havcr1) and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden, selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses. Loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumour-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth.

Regulatory B cells: TIM-1, transplant tolerance, and rejection.

Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL-10 expression, but also utilizes additional regulatory mechanisms such as TGF-ß, FasL, IL-35, and TIGIT. Although Bregs are present in various subsets defined by phenotypic markers (including canonical B cell subsets), our understanding of Bregs has been limited by the lack of a broadly inclusive and specific phenotypic or transcriptional marker. TIM-1, a broad marker for Bregs first identified in transplant models, plays a major role in Breg maintenance and induction. Here, we expand on the role of TIM-1+  Bregs in immune tolerance and propose TIM-1 as a unifying marker for Bregs that utilize various inhibitory mechanisms in addition to IL-10. Further, this review provides an in-depth assessment of our understanding of Bregs in transplantation as elucidated in murine models and clinical studies. These studies highlight the major contribution of Bregs in preventing allograft rejection, and their ability to serve as highly predictive biomarkers for clinical transplant outcomes.

Utility of Enteral Contrast Protocols in Pediatric Adhesive Small Bowel Obstruction: A Prospective Multicenter Observational Study.

OBJECTIVE: Our objective was to determine the utility of enteral contrast-based protocols in the diagnosis and management of adhesive small bowel obstruction (ASBO) for children. BACKGROUND: Enteral contrast-based protocols for adults with ASBO are associated with decreased need for surgery and shorter hospitalization. Pediatric-specific data are limited. METHODS: We conducted a prospective observational study between October 2020 and December 2022 at nine children's hospitals who are members of the Western Pediatric Surgery Research Consortium. Inclusion criteria were children aged 1-20 years diagnosed with ASBO who underwent a trial of nonoperative management (NOM) at hospital admission. Comparisons were made between those children who received an enteral contrast challenge and those who did not. The primary outcome was need for surgery. RESULTS: We enrolled 136 children (71% male; median age: 12 y); 84 (62%) received an enteral contrast challenge. There was no difference in rate of operative intervention between the no contrast (34.6%) and contrast groups (36.9%; P=0.93). Eighty-seven (64%) were successfully managed nonoperatively with no difference in median length of stay (P=0.10) or rate of unplanned readmission (P=0.14). Among the 49 children who required an operation, there was no significant difference in time from admission to surgery or rate of small bowel resection based on prior contrast administration. CONCLUSIONS: The addition of enteral contrast-based protocols for management of pediatric ASBO does not decrease the likelihood of surgery or shorten hospitalization. Larger randomized studies may be needed to further define the role of radiologic contrast in the management of ASBO in children.

Management and Outcomes of Wilms Tumor With Suprarenal Intravascular Extension: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

Transitional B cell cytokines risk stratify early borderline rejection after renal transplantation.

Borderline rejection (BL) in renal transplantation is associated with decreased allograft survival, yet many patients with BL maintain stable graft function. Identifying patients with early BL at risk for shortened allograft survival would allow for timely targeted therapeutic intervention aimed at improving outcomes. 851/1187 patients transplanted between 2013-18 underwent early biopsy (0-4 mos). 217/851 (25%) had BL and were compared to 387/851 without significant inflammation (NI). Serial surveillance and for-cause biopsies and seven-year follow-up were used to evaluate histological and clinical progression. To identify high-risk patients, we examined clinical/histological parameters using regression and non-linear dimensionality reduction (tSNE) and a biomarker based on peripheral blood transitional-1 B cell (T1B) IL-10/TNFα ratio. Compared to NI, early BL was associated with increased progression to late acute rejection (AR; 5-12 mos), premature interstitial fibrosis and tubular atrophy (IFTA) and decreased seven-year graft survival. However, decreased graft survival was limited to BL patients who progressed to late AR or IFTA, and was not influenced by treatment. Although tSNE clustered patients into groups based on clinical factors, the ability of these factors to risk stratify BL patients was modest. In contrast, a low T1B IL-10/TNFα ratio at 3 months identified BL patients at high risk for progression to AR (ROC AUC 0.87) and poor 7-yr graft survival (52% vs. 92%, p=0.003), while BL patients with a high ratio had similar graft survival to patients with NI (91%, p=NS). Thus, progressive early allograft inflammation manifested as BL that progresses to late AR in the first post-transplant year represents a high-risk clinical state for poor allograft outcomes. Such high-risk status can be predicted by the T1B IL-10/TNFα ratio before irreversible scarring sets in, thus allowing timely risk stratification.

Multi-institutional assessment of the prevalence of neuroendocrine tumors in children undergoing laparoscopic appendectomy for acute appendicitis in the United States.

As non-operative management of acute appendicitis in children has become more common, missed incidental appendiceal pathology can be an unintended consequence. We assessed the prevalence of neuroendocrine tumors in appendectomy specimens from eight US children's hospitals from 2012 to 2021. The prevalence of neuroendocrine tumors (NET) was found to be 1:271, with a median age of 14 years and 62% female. Most tumors were small (median 6 mm; interquartile range [IQR]: 3-10), and no recurrence was noted during the follow-up period (median 22.5 months; IQR: 3-53). The possibility of delayed diagnosis of these tumors should be part of the discussion for non-operative management of pediatric acute appendicitis.

Outcome of Extracorporeal Cardiopulmonary Resuscitation in Pediatric Patients Without Congenital Cardiac Disease: Extracorporeal Life Support Organization Registry Study.

OBJECTIVES: To describe the use of extracorporeal cardiopulmonary resuscitation (ECPR) in pediatric patients without congenital heart disease (CHD) and identify associations with in-hospital mortality, with a specific focus on initial arrest rhythm. DESIGN: Retrospective cohort study using data from pediatric patients enrolled in Extracorporeal Life Support Organization (ELSO) registry between January 1, 2017, and December 31, 2019. SETTING: International, multicenter. PATIENTS: We included ECPR patients under 18 years old, and excluded those with CHD. Subgroup analysis of patients with initial arrest rhythm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 567 patients: neonates (12%), infants (27%), children between 1 and 5 years old (25%), and children over 5 years old (36%). The patient cohort included 51% males, 43% of White race, and 89% not obese. Most suffered respiratory disease (26%), followed by acquired cardiac disease (25%) and sepsis (12%). In-hospital mortality was 59%. We found that obesity (adjusted odds ratio [aOR], 2.28; 95% CI, 1.21-4.31) and traumatic injury (aOR, 6.94; 95% CI, 1.55-30.88) were associated with greater odds of in-hospital mortality. We also identified lower odds of death associated with White race (aOR, 0.64; 95% CI, 0.45-0.91), ventricular tachycardia (VT) as an initial arrest rhythm (aOR, 0.36; 95% CI, 0.16-0.78), return of spontaneous circulation before cannulation (aOR, 0.56; 95% CI, 0.35-0.9), and acquired cardiac disease (aOR, 0.43; 95% CI, 0.29-0.64). Respiratory disease was associated with greater odds of severe neurologic complications (aOR, 1.64; 95% CI, 1.06-2.54). CONCLUSIONS: In children without CHD undergoing ECPR, we found greater odds of in-hospital mortality were associated with either obesity or trauma. The ELSO dataset also showed that other variables were associated with lesser odds of mortality, including VT as an initial arrest rhythm. Prospective studies are needed to elucidate the reasons for these survival differences.

Inflammatory myofibroblastic tumor: A multi-institutional study from the Pediatric Surgical Oncology Research Collaborative.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

Incidence and management of pleural effusions in patients with Wilms tumor: A Pediatric Surgical Oncology Research Collaborative study.

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Post-Procedural Opioid Prescribing in Children: A Survey of the American Academy of Pediatrics.

INTRODUCTION: North America is in the midst of an opioid epidemic. The role of pediatric surgeons and other procedural specialists in this public health crisis remains unclear. There is likely considerable variation in the use of opioid and non-opioid analgesics, but the spectrum of practice is still uncertain. METHODS: We performed an online survey in July 2018 of the 2086 pediatric surgeons and proceduralists who were active members in the American Academy of Pediatrics. The survey inquired about practice environment, use of opioid and non-opioid pain medications, and attitudes towards the opioid epidemic. RESULTS: 178 specialists completed the survey for a response rate of 8.5%. Most respondents utilize oral acetaminophen (86%) and ibuprofen (80%) after procedures >75% of the time. Self-reported opioid prescribing increases with age after both outpatient and inpatient procedures (P < 0.001). Pediatric general surgeons prescribe opioids less frequently than other specialists, particularly after inpatient procedures. The majority of respondents (81%) believe that the opioid epidemic is a major problem but only 31% indicated that they have a major role to play. CONCLUSIONS: There is significant variation in opioid prescribing patterns as reported by pediatric surgeons and proceduralists. Guidelines are needed to standardize the use of non-opioid analgesics and decrease reliance on opioids for outpatient and inpatient procedures.

Regulatory and transitional B cells: potential biomarkers and therapeutic targets in organ transplantation.

PURPOSE OF THE REVIEW: Regulatory B cells (Bregs) play a prominent role in various disease settings. While progress has been hindered by the lack of a specific Breg marker, new findings highlight their role modulating the alloimmune response and promoting allograft survival. RECENT FINDINGS: Herein, we focus on the recent advances in Breg biology and their role in transplantation. We review studies showing that T-cell immunoglobulin and mucin domain 1 (TIM-1) is an inclusive and functional Breg marker in mice that may have human relevance. We highlight the utility of the B cell interleukin-10/tumor necrosis factor-alpha (IL-10/TNFα) ratio in identifying underlying immunological reactivity and predicting clinical outcomes in kidney transplantation. This may identify patients requiring more immunosuppression and provide insight into potential therapeutic approaches that can modulate the Breg: B effector cell (Beff) balance. SUMMARY: Emerging data support Bregs as potent modulators of immune responses in humans. Their ability to promote allograft survival must await development of approaches to expand Bregs in vitro/in vivo . The low IL-10/TNFα ratio reflecting decreased Breg/Beff balance, predicts acute rejection (AR) and poorer outcomes in renal transplantation. It remains to be determined whether this paradigm can be extended to other allografts and whether therapy aiming to correct the relative deficiency of Bregs will improve outcomes.

Retroperitoneal Sclerosing Lipogranuloma in an Adolescent With Congenital Atresia of the Inferior Vena Cava: Case Report and Literature Review.

Sclerosing lipogranuloma (SLG) in children is a rare, benign disease of unknown etiology suspected to be due to abnormal fatty tissue reaction. A 13-year-old girl presented with progressively worsening back pain. Cross-sectional imaging identified a retroperitoneal mass compressing the left ureter as well as infrarenal inferior vena cava atresia with extensive venous collaterals and chronic partially occlusive thromboses of the iliac veins. Surgical biopsy was consistent with SLG and it resolved spontaneously. SLG is typically a disease of adulthood but may be seen in children. The association between inferior vena cava atresia with venous thrombosis and development of SLG has not been reported previously.

Risk Factors for Inpatient Mortality in Patients Born with Gastroschisis in the United States.

OBJECTIVE: This study aimed to characterize risk factors for inpatient mortality in patients born with gastroschisis in a contemporary cohort. STUDY DESIGN: This was a retrospective cohort study of infants born with gastroschisis using the Kids' Inpatient Database 2016. Simple descriptive statistics were used to characterize the patients by demographics, and illness severity was estimated using the All-Patient Refined Diagnosis-Related Groups classification. Variables associated with an increased risk of mortality on univariate analysis were incorporated into a multivariable logistic regression model to generate adjusted odds ratios (aORs) for mortality. RESULTS: An estimated 1,990 patient with gastroschisis were born in 2016, with a 3.7% mortality rate during the initial hospitalization. Multivariable logistic regression demonstrated the following variables to be associated with an increased risk of inpatient mortality: black or Asian race compared with white (aOR: 2.6, 95% confidence interval [CI]: 1.1-6.1, p = 0.03 and aOR: 4.1, 95% CI: 1.3-13.3, p = 0.02, respectively), whereas private health insurance compared with government (aOR: 0.2; 95% CI: 0.2-0.8; p = 0.007) and exurban domicile compared with urban (aOR: 0.5; 95% CI: 0.2-0.9; p = 0.04) appeared to be associated with a decreased risk of inpatient mortality. CONCLUSION: Inpatient mortality for neonates with gastroschisis is relatively low. Even after correcting for illness severity, race, health insurance status, and domicile appear to play a role in mortality disparities. Opportunities may exist to further decrease mortality in at-risk populations.

Association of same-day discharge with hospital readmission after pediatric thyroidectomy.

BACKGROUND: Studies have demonstrated that same-day discharge (SDD) following thyroid resection is safe and feasible in adults but there are no similar studies in the pediatric age group. The purpose of this study is to evaluate the influence of SDD on 30-day readmission rates following thyroid surgery in pediatric patients. METHODS: This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database to evaluate 30-day readmission rates among patients < 19 years of age who underwent thyroid resection between 2012 and 2017. Patients excluded were those discharged more than 2 days after surgery. The main exposure variable was SDD and the primary outcome was 30-day readmission. Secondary outcomes included wound complications, unplanned reoperation and death. Patient characteristics were compared using chi-squared testing and odds ratios for readmission were calculated using multivariate logistic regression. RESULTS: Of the 1125 patients (79% female, median age 15 years), 122 (11%) were discharged on the day of surgery. Total or near-total thyroidectomy represented the majority of operations (714, 63.5%) and patients undergoing these operations were less likely to be discharged on the same day as surgery compared to those undergoing thyroid lobectomy (4.3 vs. 22.1%, P < 0.001). Twenty-nine patients were readmitted within 30 days (3 in the same day group, 26 in the later group). There was no difference in the odds of readmission between the two groups (adjusted odds ratio in SDD compared to later discharge 1.04 [95% CI 0.29-3.75, P = 0.96; readmission rate, 2.46 vs. 2.59%). Wound complications were reported in two patients, both in the later discharge group. CONCLUSION: Same-day discharge in pediatric patients undergoing thyroidectomy is not associated with an increase in 30-day readmissions or wound complications when compared to patients discharged 1 or 2 days after surgery. In selected patients, SDD may be an appropriate alternative to traditional overnight stay.

Antigen-dependent interactions between regulatory B cells and T cells at the T:B border inhibit subsequent T cell interactions with DCs.

IL-10+ regulatory B cells (Bregs) inhibit immune responses in various settings. While Bregs appear to inhibit inflammatory cytokine expression by CD4+ T cells and innate immune cells, their reported impact on CD8+ T cells is contradictory. Moreover, it remains unclear which effects of Bregs are direct versus indirect. Finally, the subanatomical localization of Breg suppressive function and the nature of their intercellular interactions remain unknown. Using novel tamoxifen-inducible B cell-specific IL-10 knockout mice, we found that Bregs inhibit CD8+ T cell proliferation and inhibit inflammatory cytokine expression by both CD4+ and CD8+ T cells. Sort-purified Bregs from IL-10-reporter mice were adoptively transferred into wild-type hosts and examined by live-cell imaging. Bregs localized to the T:B border, specifically entered the T cell zone, and made more frequent and longer contacts with both CD4+ and CD8+ T cells than did non-Bregs. These Breg:T cell interactions were antigen-specific and reduced subsequent T:DC contacts. Thus, Bregs inhibit T cells through direct cognate interactions that subsequently reduce DC:T cell interactions.

Predictive Model for Operative Intervention after Blunt Abdominal Trauma in Children with Equivocal CT Findings: A Pilot Study.

BACKGROUND: To study the clinical and radiologic factors predicting the need for surgical intervention after blunt abdominal trauma (BAT) in children with equivocal computed tomography (CT) scan findings. METHODS: We performed a retrospective review of the trauma database at our level I pediatric trauma center between 2011 and 2019. We selected patients with BAT and equivocal findings for surgical intervention on CT scan. We studied five factors: abdominal wall bruising (AWB), abdominal pain/tenderness (APT), thoracolumbar fracture, the presence of free fluid (FF), and the presence of solid organ injury, all previously reported in the literature to predict the need for operative intervention. We used t-test, the Kruskal-Wallis test and logistic regression to study the association of these factors with the need for operation in our pediatric cohort. RESULTS: Of 3044 blunt trauma patients, 288 had abdominal CT scans with 61 patients demonstrating equivocal findings. Operation was performed for 12 patients (19.7%) confirming surgically correctable traumatic injuries. The need for surgical intervention was significantly associated with the age of the patients (P = 0.03), the presence of APT (P = 0.001), AWB (P = 0.01), and FF (P = 0.04). The presence of thoracolumbar fracture and solid organ injury were not significantly associated with the need for operation. For the subset of 37 patients who were injured in a motor vehicle crash, five (13.5%) required surgical intervention, which was significantly associated with the presence of AWB (P = 0.04), APT (P = 0.01), and FF (P = 0.03). A predictive model that used these factors produced a receiver operating characteristic curve of 0.86. CONCLUSIONS: In cases of equivocal abdominal CT scan findings to evaluate BAT in children, the presence of abdominal wall tenderness, AWB, or FF may be significant factors predicting more accurately the need for operative intervention. A predictive model using the combination of clinical and image findings might determine with more certainty, the need for surgical intervention in children with BAT and equivocal CT findings. Validation on a larger multi-institutional data set should be done.

Systematic Review of Disparities in Care and Outcomes in Pediatric Appendectomy.

BACKGROUND: The impact of social, racial, and economic inequities on health and surgical outcomes for children is poorly described. METHODS: A systematic review using search terms related to disparities in care of pediatric appendicitis identified 20 titles and narrowed to 11 full texts. Nine retrospective studies were analyzed, representing 350,408 cases treated across the United States from 1983 to 2010. Outcomes included length of stay (LOS), appendiceal perforation rate (AP), laparoscopic versus open approach, and rate of misdiagnosis. RESULTS: The most frequently reported outcomes were LOS (six of nine studies) and AP (six of nine studies). AP was higher for young children (48% for <6 versus 25% for >10), those in rural settings (42% versus 26% in urban settings), and patients receiving care at children's hospitals (35% versus 22% at nonchildren's hospitals). Longer LOS was associated with young age in three studies (2-5 d for age <10 y versus 1-3 d for age >11 y), race in four studies (1.5-3 d for African American children versus 1-2 d for other races), and lower family income in two studies (2-4 d versus 1-3 d for highest income). Inequitable use of laparoscopy, time to surgery, and rates of misdiagnosis were also reported to be associated with age and race. CONCLUSIONS: Although limited, the existing literature suggests that social, racial, and economic inequalities impact management and outcomes in pediatric appendicitis. More studies are needed to better describe and mitigate disparities in the surgical care of children.

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study.

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.

Geospatial Mapping of Pediatric Surgical Capacity in North Kivu, Democratic Republic of Congo.

BACKGROUND: Despite recent attention to the provision of healthcare in low- and middle-income countries, improvements in access to surgical services have been disproportionately lagging. METHODS: This study analyzes the geographic variability in access to pediatric surgical services in the province of North Kivu, Democratic Republic of Congo (DRC). On-site data collection was conducted using the Global Assessment of Pediatric Surgery tool. Spatial distribution of providers was mapped using the Geographical Information System and open-sourced spatial data to determine distances traveled to access surgical care. RESULTS: Forty facilities were evaluated across 32 health zones; 68.9% of the provincial population was within 15 km of these facilities. Eleven facilities met a minimum World Health Organization safety score of 8; 48.1% of the population was within 15 km of corresponding facilities. The majority of children were treated by someone with specific pediatric surgery training in only 4 facilities; one facility had a trained pediatric anesthesia provider. Fifty-seven percent of the population was within 15 km of a facility with critical care and emergency medicine (EM) capabilities. There was one pediatric critical care provider and no pediatric EM providers identified within the province. Location-allocation assessment is needed to combine geographic area with potential for greatest impact and facility assessment. CONCLUSIONS: Limitations in access to surgical care in the DRC are multifactorial with poor resources, few formally trained surgical providers, and near-absent access to pediatric anesthesiologists. The study highlights the deficits in the capacity for surgical care while demonstrating a reproducible model for assessment and identification of ways to improve access to care.