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Background: The pathology and management of breast masses in pediatric patients is markedly different than in adults. The vast majority of lesions in children and adolescents are benign, but the rare malignant breast masses require prompt recognition and treatment. Pediatric surgeons navigating clinical evaluation of these masses must balance preservation of the developing breast with appropriate diagnosis and surgical management., Methods: The current English language literature was queried for pediatric and adolescent breast masses. Identified manuscripts were reviewed and classified by level of evidence. Based on these results, as well as expert consensus, an algorithm regarding clinical workup and management was established., Results: Evaluation of pediatric breast masses begins with a thorough history and physical exam. Palpable masses should then be further characterized using an ultrasound-guided algorithm. In select cases, observation without surgical resection is appropriate. Surgical management of presumed benign lesions, when performed, should prioritize conserving developing breast tissue and the nipple areolar complex. Excisional biopsy is preferable to core needle biopsy when technically feasible. Surgical management of malignant lesions varies depending on the type of malignancy., Conclusion: Pediatric surgeons are often the first point of contact after identification of a breast mass in a pediatric or adolescent patient, and therefore play a critical role in management. Based on literature review and expert consensus, we propose an algorithm to guide pediatric surgeons in the diagnosis and treatment of these predominantly benign lesions. For the rare malignant lesions, a multi-disciplinary team approach is recommended to optimize patient care., (Copyright © 2024. Published by Elsevier Inc.)

Background: Historically, surgical biopsy (SB) for diagnosis of pediatric solid tumors was considered necessary to provide adequate tissue for histologic and molecular analysis. Less invasive biopsy techniques such as image-guided core needle biopsy (CNB), have shown comparable accuracy with decreased morbidity in some adult studies. However, data regarding the safety and efficacy of CNB in pediatric tumors is limited. This study's aim was to assess the overall rate of successful diagnosis and safety of CNB compared to SB in children with malignancies., Methods: A PRISMA compliant systematic review was performed in MEDLINE via PubMed, Embase and CINAHL Plus database searches from 2010 to 2023. Studies were included with relevance to the following clinical question: For children with concern for malignancy requiring biopsy for diagnosis, how does CNB compare to open or laparoscopic/thoracoscopic SB in terms of safety and diagnostic efficacy? Data for patients ≤21 years requiring biopsy for diagnosis of liver tumors, neuroblastoma (NB), soft tissue sarcoma (STS), and lymphoma were included., Results: Twenty-seven studies including 2477 patients met inclusion criteria, with 2065 undergoing CNB and 412 SB. Of the 2477 patients, 820 patients had NB, 307 liver tumors, 96 STS, 151 lymphoma, and 1103 patients were from studies that included multiple diagnoses. The average complication rate for CNB was 2.9% compared to 21.4% for SB (p < 0.001). Bleeding was the most common complication in both groups, but significantly higher after SB (22.1% vs 2.3%) (p < 0.001). CNB was diagnostic in 90.8% of patients compared to 98.8% who underwent SB (p < 0.001)., Conclusions: Rates of successful diagnosis were greater than 90% for both CNB and SB, though significantly higher for SB. Conversely, complication rates were close to ten times higher after SB compared to CNB. Given its relatively lower risk profile, CNB can be a safe and useful diagnostic tool for children with solid malignancies. Research focused on enhancing CNB's diagnostic accuracy while maintaining low morbidity should be further explored., Level of Evidence: Treatment study, Level III., Competing Interests: Declaration of competing interest The authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2022 UICC.)

Purpose: To assess the utility of preoperative venography in evaluating and managing patients with congenital portosystemic shunts (CPSSs)., Materials and Methods: A retrospective study was performed of 42 patients (62% female; median age, 4.1 years) diagnosed with a CPSS from 2005 to 2018. Preoperative venography (n = 39) and balloon occlusive pressure measurements (n = 33) within the mesenteric venous system guided treatment. Primary outcome was serum ammonia levels at 1 month after shunt closure. Management strategies included single (n = 12) or staged (n = 18) operative ligation, endovascular occlusion (n = 8), combined surgical and endovascular closure (n = 2), and observation (n = 2)., Results: At 1 month, serum ammonia levels decreased from 82.5 ± 10.3 μmol/L to 38.4 ± 4.6 μmol/L (P < .001). No difference was observed in the decrease between patients treated surgically or endovascularly (P = .91). Mean occluded to non-occluded pressure gradients were significantly lower for endovascular closure (5.3 ± 1.8 mmHg) than for surgical closure (12.3 ± 3.3 mmHg, P = .02). Shunts were classified as extrahepatic in 29 patients and as intrahepatic in 13 patients; all shunts demonstrated filling of the portal system with occlusive venography. Broad and short shunts were closed surgically; narrow and long shunts were closed endovascularly. Shunts were closed in a single session (n = 20) if the pressure gradient was less than 10 mmHg and the occluded mesenteric pressure was less than 25 mmHg., Conclusions: Preoperative venography delineates shunt morphology, and balloon occlusion simulates closure hemodynamics. This information is necessary to determine whether definitive closure should be performed through endovascular or surgical methods and whether closure should be performed in a single or staged setting., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Background: The presentation of appendicitis in pediatrics is variable, and diagnostic imaging is often used. Magnetic resonance imaging (MRI) is replacing computed tomography in some centers, particularly after a nondiagnostic ultrasound (NDUS). Nonetheless, MRI is not widely used in this setting because of cost, procedure time, institutional capacity, and high rates of negative scans. We hypothesized that the Alvarado Score (AS) could be used to determine the additive diagnostic value of MRI after an NDUS., Materials and Methods: Retrospective review of patients aged ≤18 y at a single tertiary care children's hospital who received an ultrasound for suspected appendicitis during 10 consecutive months in 2017. NDUS were defined as nonvisualization of the appendix or secondary signs without radiologic diagnosis. AS were retrospectively calculated from the electronic medical record. Primary outcomes were pathology-confirmed appendicitis, appendectomy, and perforation., Results: AS was determined for 352 patients out of 463 who met inclusion criteria (76%). Sixty-two percent had an NDUS, and 45% of these patients received MRI. Patients with high-risk AS were significantly more likely to have MRI diagnostic of appendicitis (P = 0.0015), and low-risk AS patients were more likely to have a negative or equivocal MRI (P = 0.0169). Twenty-one MRI scans were required per each additional diagnosis of appendicitis in patients with low AS after NDUS versus 4.2 in intermediate-risk AS patients and 2.1 in high-risk AS patients., Conclusions: Risk stratification with AS can help assess the additive diagnostic utility of MRI after NDUS. MRI may be overutilized for diagnosing acute appendicitis in pediatric patients with low-risk AS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fluid shear stress in the vasculature is the driving force for natural bypass growth, a fundamental endogenous mechanism to counteract the detrimental consequences of vascular occlusive disease, such as stroke or myocardial infarction. This process, referred to as "arteriogenesis," relies on local recruitment of leukocytes, which supply growth factors to preexisting collateral arterioles enabling them to grow. Although several mechanosensing proteins have been identified, the series of mechanotransduction events resulting in local leukocyte recruitment is not understood. In a mouse model of arteriogenesis (femoral artery ligation), we found that endothelial cells release RNA in response to increased fluid shear stress and that administration of RNase inhibitor blocking plasma RNases improved perfusion recovery. In contrast, treatment with bovine pancreatic RNase A or human recombinant RNase1 interfered with leukocyte recruitment and collateral artery growth. Our results indicated that extracellular RNA (eRNA) regulated leukocyte recruitment by engaging vascular endothelial growth factor receptor 2 (VEGFR2), which was confirmed by intravital microscopic studies in a murine cremaster model of inflammation. Moreover, we found that release of von Willebrand factor (VWF) as a result of shear stress is dependent on VEGFR2. Blocking VEGFR2, RNase application, or VWF deficiency interfered with platelet-neutrophil aggregate formation, which is essential for initiating the inflammatory process in arteriogenesis. Taken together, the results show that eRNA is released from endothelial cells in response to shear stress. We demonstrate this extracellular nucleic acid as a critical mediator of mechanotransduction by inducing the liberation of VWF, thereby initiating the multistep inflammatory process responsible for arteriogenesis., (© 2019 by The American Society of Hematology.)

Introduction: Surgical site infection is very uncommon after pyloromyotomy in children, and it is considered a "clean" procedure under the traditional wound classification system. This study aims to investigate prophylactic antibiotic administration for pyloromyotomy among children's hospitals in the USA., Methods: The Pediatric Health Information System (PHIS) database was retrospectively reviewed from 2014 to 2015 including all patients less than 1 year old who had a principal diagnosis of pyloric stenosis and underwent pyloromyotomy. Patient demographics, hospital length of stay, and perioperative antibiotic administration were extracted., Results: A total of 4206 patients met study criteria. Most patients were male (84%) and Caucasian (70%). The median age at admission was 32 days (IQR 24-44 days), and median length of stay was 2 days (IQR 1-2 days). Antibiotics were administered perioperatively in 2153 (51%) patients with marked variation among children's hospitals. Antibiotics were given to more than 10% of patients in more than 90% of hospitals, and only two of 49 hospitals gave no antibiotic prophylaxis., Conclusions: This study has shown that at several tertiary-level children's hospitals in the USA, antibiotic prophylaxis is administered for pyloromyotomy, a "clean" procedure. This highlights the need for standardization of care and more effective antibiotic stewardship in pediatric surgery.

Background: The utility of mechanical bowel preparation (MBP) to minimize infectious complications in elective colorectal surgery is contentious. Though data is scarce in children, adult studies suggest a benefit to MBP when administered with oral antibiotics (OAB)., Methods: After IRB approval, the Pediatric Health Information System (PHIS) was queried for young children undergoing elective colon surgery from 2011 to 2014. Patients were divided into: no bowel preparation (Group 1), MBP (Group 2), and MBP plus OAB (Group 3). Statistical significance was determined using univariate and multivariate analysis with GEE models accounting for clustering by hospital., Results: One thousand five hundred eighty-one patients met study criteria: 63.7% in Group 1, 27.1% in Group 2, and 9.2% in Group 3. Surgical complication rate was higher in Group 1 (23.3%) compared to Groups 2 and 3 (14.2% and 15.5%; P<0.001). However, median length of stay was shorter in Group 1 (4, IQR 4days) compared to Group 2 (5, IQR 3) and Group 3 (6, IQR 3) (P<0.001). 30-day readmission rates were similar. In multivariate analysis compared to patients in Group 1, the odds of surgical complications were 0.72 (95% CI 0.40-1.29, P=0.28) with MBP alone (Group 2), 1.79 (95% CI 1.28-2.52, P=0.0008) with MBP+OAB (Group 3), and 1.13 (95% CI 0.81-1.58, P=0.46) for the aggregate Group 2 plus 3., Conclusion: Utilization of bowel preparation in children is variable across children's hospitals nationally, and the benefit is unclear. Given the discrepancy with adult literature, a three-armed pediatric-specific randomized controlled trial is warranted., Level of Evidence: Level III treatment study - retrospective comparative study., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system., Methods: From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis., Results: 137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143)., Conclusion: The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

Midkine is a pleiotropic factor, which is involved in angiogenesis. However, its mode of action in this process is still ill defined. The function of midkine in arteriogenesis, the growth of natural bypasses from pre-existing collateral arteries, compensating for the loss of an occluded artery has never been investigated. Arteriogenesis is an inflammatory process, which relies on the proliferation of endothelial cells and smooth muscle cells. We show that midkine deficiency strikingly interferes with the proliferation of endothelial cells in arteriogenesis, thereby interfering with the process of collateral artery growth. We identified midkine to be responsible for increased plasma levels of vascular endothelial growth factor A (VEGFA), necessary and sufficient to promote endothelial cell proliferation in growing collaterals. Mechanistically, we demonstrate that leukocyte domiciled midkine mediates increased plasma levels of VEGFA relevant for upregulation of endothelial nitric oxide synthase 1 and 3, necessary for proper endothelial cell proliferation, and that non-leukocyte domiciled midkine additionally improves vasodilation. The data provided on the role of midkine in endothelial proliferation are likely to be relevant for both, the process of arteriogenesis and angiogenesis. Moreover, our data might help to estimate the therapeutic effect of clinically applied VEGFA in patients with vascular occlusive diseases., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit(+)/CXCR-4(+) cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

l-Arginine is the common substrate for nitric oxide synthases (NOS) and arginase. Whereas the contribution of NOS to collateral artery growth (arteriogenesis) has been demonstrated, the functional role of arginase remains to be elucidated and was topic of the present study. Arteriogenesis was induced in mice by ligation of the femoral artery. Laser Doppler perfusion measurements demonstrated a significant reduction in arteriogenesis in mice treated with the arginase inhibitor nor-NOHA (N(ω)-hydroxy-nor-arginine). Accompanying in vitro results on murine primary arterial endothelial cells and smooth muscle cells revealed that nor-NOHA treatment interfered with cell proliferation and resulted in increased nitrate/nitrite levels, indicative for increased NO production. Immuno-histological analyses on tissue samples demonstrated that nor-NOHA administration caused a significant reduction in M2 macrophage accumulation around growing collateral arteries. Gene expression studies on isolated growing collaterals evidenced that nor-NOHA treatment abolished the differential expression of Icam1 (intercellular adhesion molecule 1). From our data we conclude that arginase activity is essential for arteriogenesis by promoting perivascular M2 macrophage accumulation as well as arterial cell proliferation.

Purpose: The objective of this study is to compare outcomes for pediatric patients undergoing laparoscopic appendectomy (LA) performed either (1) using an endostapler (ES) to divide the appendix and mesoappendix or (2) using endoloops (ELs) to close the appendiceal stump and electrocautery to divide the mesoappendix., Methods: We conducted a retrospective chart review of all patients who underwent LA for suspected appendicitis 4 years at a free standing children's hospital. The use of EL and ES was compared separately in patients with perforated and nonperforated appendicitis. We compared patient characteristics and outcomes., Results: There were no significant differences in rate of postoperative abscess, rate of subsequent small bowel obstruction requiring operation or rate of intraperitoneal hematoma between the ES and EL groups for both nonperforated and perforated appendectomy cases. Superficial wound infection was more common in the nonperforated EL group (17/309, 5.5%) than in the nonperforated ES group (2/235, 0.9%; p = 0.007). Operative time for the EL technique (52.2 ± 15.8 minutes; p = 0.047) was shorter than for the ES technique (58 ± 23.2 minutes) for patients with perforated appendicitis., Conclusion: EL stump closure and mesoappendix cauterization during LA is safe and effective in children with appendicitis, including perforated appendicitis., (Georg Thieme Verlag KG Stuttgart · New York.)

Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.

Background: Gastrostomy tube placement is associated with frequent postoperative complications. The aims of this study were to 1) determine the incidence of postoperative gastrostomy complications and 2) determine if patient demographics, comorbidities, or operative technique could predict these complications., Methods: A retrospective review was conducted on children who underwent gastrostomy tube placement from June 2006 through August 2009. Patient demographics, comorbidities, operative technique, health care visits, and complications were collected. Data were analyzed by chi-squared analysis (P < 0.05 significant)., Results: One hundred and fifty-nine patients were evaluated, with the majority of patients <5 years of age (129/159). Ninety-four patients underwent open gastrostomy, 31 laparoscopic gastrostomy, and 34 laparoscopic-assisted gastrostomy. Granulation tissue was the most common postoperative complication, occurring in 58% of patients (93/159). The majority of patients with granulation tissue had full resolution by the fourth postoperative month. Tube dislodgement was the second most common complication, occurring 69 times in 44 of the patients (28%) and resulting in 59 emergency department (ED) visits. Overall, gastrostomy complications resulted in 100 ED and 462 clinic visits. Ninety-three percent (93/100) of ED visits resulted in discharge home from the ED. Gender, age, insurance status, and operative technique were not predictive of complications., Conclusions: Granulation tissue and tube dislodgement are the most common complications after gastrostomy placement in children. Gender, age, insurance status, and operative technique were not predictive of complications. Emergency department utilization is high in children with gastrostomy tubes.

Background: Although nonoperative management is an accepted practice for most adults with focal nodular hyperplasia (FNH), questions remain about the safety and feasibility of this strategy in children. Our aim was to review the clinical features of children with FNH and determine current management patterns., Methods: We reviewed records of all children and adolescents with FNH managed at our institution from 1999 to 2009 and performed a MEDLINE search to identify all published cases of FNH in the pediatric population., Results: A total of 172 patients with FNH were identified, including 11 at our institution. The median age at diagnosis was 8.7 years and 66% were female. Median tumor size was 6 cm, and 25% had multiple lesions. Thirty-six percent were symptomatic at presentation. Twenty-four percent had a history of malignancy. Management included resection (61%), biopsy followed by observation (21%), and observation alone (18%). Indications for resection included symptoms (48%), inability to rule out malignancy (24%), tumor growth (15%), and biopsy-proven concurrent malignancy (9%)., Conclusions: Although FNH is a benign lesion that is typically managed nonoperatively in adults, most children with FNH currently undergo resection because of symptoms, increasing size, or inability to confidently rule out malignancy., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: Although initial nonoperative management of focal, perforated appendicitis in children is increasingly practiced, the need for subsequent interval appendectomy remains debated. We hypothesized that cost comparison would favor continued nonoperative management over routine interval appendectomy., Methods: Decision tree analysis was used to compare continued nonoperative management with routine interval appendectomy after initial success with nonoperative management of perforated appendicitis. Outcome probabilities were obtained from literature review and cost estimates from the Kid's Inpatient Database. Sensitivity analyses were performed on the 2 most influential variables in the model, the probability of successful nonoperative management and the costs associated with successful observation. Monte Carlo simulation was performed using the range of cost estimates., Results: Costs for continued nonoperative observation were estimated at $3080.78 as compared to $5034.58 for the interval appendectomy. Sensitivity analysis confirms a cost savings for nonoperative management as long as the likelihood of successful observation exceeds 60%. As the cost of nonoperative management increased, the required probability for its success also increased. Using wide distributions for both probability estimates as well as costs, Monte Carlo simulation favored continued observation in 75% of scenarios., Conclusion: Continued nonoperative management has a cost advantage over routine interval appendectomy after initial success with conservative management in children with focal, perforated appendicitis., (Copyright © 2010 Elsevier Inc. All rights reserved.)

AU-rich elements (AREs) are located in the 3' untranslated region (3' UTR) of their host genes and tightly regulate mRNA degradation and expression. Examples for this kind of regulation are the human proto-oncogene c-fos and the cytokine TNFalpha. Despite large effort in this field, the exact mechanism of ARE-mediated mRNA turnover remains unclear. In this work we analysed the effects of c-fos- and TNFalpha AREs on mRNA abundance and protein expression of selected human cDNAs in the yeast Pichia pastoris. This yeast is exceedingly well known for its excellent protein production capacity; however, ARE-like mechanisms have not been studied in this yeast to date. Interestingly, we observed both stabilizing and destabilizing effects of the c-fos ARE, whereas the TNFalpha ARE has a destabilizing or expression-reducing function in all tested cDNAs. Based on this observation, we introduced a number of single-point mutations upstream of the introduced c-fos ARE into the 3' UTR of a single cDNA in order to demonstrate the importance of ARE-flanking sequences for their own regulation. In conclusion, we illustrate that the analysis of ARE-mediated effects on mRNA abundance and protein expression of a reporter depends on the sequence of the reporter itself as well as the ARE-surrounding sequences within the 3' UTR. For this reason, we question whether already established reporter constructs in other cellular systems display the true type of regulation of the tested AREs for its original host gene. Finally, we propose that AREs should be analysed in their native sequence context.

An association between oxcarbazepine therapy and hepatic adenoma (HA) has been documented in animal models but not observed in humans. The authors report a case of a 16-year-old girl on oxcarbazepine therapy for seizure disorder who presented with a giant HA. Pathology of the HA was notable for marked periductal fibrosis and glycoprotein inclusions in the nontumor liver. The patient was not on oral contraceptives and has no other known risk factors for HA.