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Recent evidence suggests that transforming growth factor alpha (TGF-α) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-α on enterocyte turnover and correlated it with epidermal-growth factor (EGF) receptor expression along the villus–crypt axis in a rat model of short bowel syndrome (SBS). Male rats were divided into three groups, sham rats underwent bowel transection (group A); SBS rats underwent a 75% bowel resection (group B); and SBS/TGF-α rats underwent bowel resection and were treated with TGF-α (75 μg/kg) (group C) from the seventh postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Villus tips, lateral villi and crypts were separated using laser capture microdissection. EGF receptor expression for each compartment was assessed by quantitative real-time PCR (Taqman). Statistical analysis was performed using one-way ANOVA test, with P < 0.05 considered statistically significant. Treatment with TGF-α resulted in a significant increase in all parameters of intestinal adaptation. EGF receptor expression in crypts significantly increased in SBS rats (vs sham rats) (0.035 ± 0.013 vs 0.010 ± 0.002 Log ng Total RNA/18 s) and was accompanied by a significant increase in enterocyte proliferation (169 ± 8 vs 138 ± 5 BrdU positive cells/per 10 crypts, P < 0.05) and decreased apoptosis following TGF-α administration (group C). A significant decrease in EGF receptor expression at the tip of the villus (0.005 ± 0.002 vs 0.029 ± 0.014 Log ng Total RNA/18 s) and in the lateral villus (0.003 ± 0.001 vs 0.028 ± 0.006 Log ng Total RNA/18 s) in SBS (group B) rats (vs sham, group A) was accompanied by increased cell apoptosis in these compartments following treatment with TGF-α (group C). In a rat model of SBS, TGF-α increased enterocyte proliferation and stimulated intestinal adaptation. The effect of TGF-α on enterocyte turnover is correlated with EGF receptor expression along the villus–crypt axis. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Laparoscopy has been associated with lower inflammatory responses. However, it has been postulated that minilaparotomy, in contrast to full laparotomy, is equally minimally invasive. Objective: The aim of this study was to investigate local, systemic, and distant organ immune responses after different surgical approaches to the abdominal cavity, such as minilaparotomy, full laparotomy, and laparoscopy, in a small animal model. Methods: Male Lewis rats received a permanent central venous catheter and were randomized to 4 groups (n = 6 per group). The animals were subjected to anesthesia alone (control), minilaparotomy (1 cm), full laparotomy (7 cm), or laparoscopy for 60 minutes. Blood was collected via the central venous catheter before as well as 1 hour and 6 hours after the start of intervention. Peritoneal and bronchoalveolar lavages, as well as heart puncture, were performed after 24 hours. Results: All surgical interventions led to a significant migration of polymorphonucleocytes into the abdominal cavity. Full laparotomy resulted in a significant increase in nitric oxide production by peritoneal macrophages as compared with control. Macrophage nitric oxide production after laparoscopy and minilaparotomy was not significantly different. A shift in the expression of OX-6 and CD54 was only detected after full laparotomy. Systemically, O2 − release by circulating mononuclear cells was significantly increased after minilaparotomy and full laparotomy, but not after laparoscopy. The systemic levels of IL6 were significantly accelerated only after full laparotomy, with a maximum after 6 hours. In the lungs, function of alveolar macrophages was not altered in any group. Conclusions: Any approach to the peritoneal cavity causes local inflammatory responses. Full laparotomy alters peritoneal macrophage functions more pronouncedly than does minilaparotomy or laparoscopy. Systemic inflammatory responses, such as free oxygen radical release, are significantly increased by both minilaparotomy and full laparotomy, whereas laparoscopy preserves systemic immune function. Our results may lead to further preference for the laparoscopic approach over minilaparotomy and full laparotomy. [Copyright &y& Elsevier]

Exclusive lower pole pelvi-ureteric junction obstruction (PUJO) in double collecting systems in children is a rare condition requiring reconstructive surgery. We report on the feasibility of laparoscopic transabdominal dismembered pyeloplasty in two cases. Two children with duplicated collecting systems presented with hydronephrosis of lower pole moiety due to exclusive PUJO. Isotope renography revealed impaired drainage of affected lower kidney pole. A four-trocar transabdominal technique was used. No stent was used in one patient with bilateral duplication (male, 6 years) while a 4 Fr. double-J stent was placed laparoscopically in another with unilateral duplication (male, 9 months). Both patients had uneventful laparoscopic transabdominal dismembered pyeloplasty. The operation time was 115 and 155 min, respectively, and was comparable to our previously reported patient series undergoing laparoscopic pyeloplasty for singular collecting systems. After a mean follow-up of 21 months (range 12-42), both patients were asymptomatic and showed improved pelvi-ureteric drainage on isotope renography and improved hydronephrosis on ultrasound scan. Laparoscopic transabdominal dismembered pyeloplasty is safe and effective in children with rare lower pole PUJO in double collecting systems. [ABSTRACT FROM AUTHOR]

Definitive medical treatment for benign recurrent intrahepatic cholestasis (BRIC) is not available and the significance of surgical treatment is a matter of debate. It has been postulated that BRIC may progress to progressive familial intrahepatic cholestasis (PFIC), which leads to liver insufficiency and cirrhosis. External biliary diversion represents an option for both conditions and we recently introduced a new laparoscopic technique for infants with PFIC. However, limited umbilical incision may interfere with creating a jejunal conduit by infraumbilical exteriorisation, in particular in obese adolescents. Therefore, we modified our technique by exteriorising a small bowel loop via the right midabdominal trocar incision at the position of the jejunostomy. The technique was used in a 17-year-old obese patient with BRIC. This is the first report on a patient with BRIC undergoing laparoscopic external biliary diversion. [ABSTRACT FROM AUTHOR]

The use of minimally invasive surgery (MIS) in pediatric patients has increased over the past decades. The process of mastering a new procedure is termed the learning curve, during which the ability to operate increases but poorer outcomes are produced. We aim to analyze the current evidence on learning curves in pediatric MIS and evaluate its impact on patient's clinical outcomes. A systematic literature search was performed for studies listed on PubMed that reported on the learning curve for MIS surgical procedures. Studies were included if they stated the number of procedures required to reach a consistency in outcomes or if they compared outcomes between early and late period of MIS experience regarding the endpoints operative time, conversions, and intra-/postoperative complications. A total of 22 articles reporting on 11 surgical procedures were included in the study. Most authors reported a significant decrease in operative time as well as peri- and postoperative complications with increasing experience of the surgeon. Complications ranged from minor to major, the latter being especially severe for patients receiving pyloromyotomy (5-7% higher risk of mucosal perforation), esophageal atresia repair (15% higher leakage rate and 19-77% higher stenosis rate), or Kasai portoenterostomy (26-35% more liver transplants in the first year after surgery) during the learning curve period. Pediatric MIS comes with a considerable learning curve that may have a significant impact on the patient's clinical outcomes. Efforts should be made to minimize the effect of the learning curve on the patients. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies demonstrated a release of toxic metals, e.g. nickel and chromium, from stainless steel bars used for minimally invasive repair of pectus excavatum (MIRPE). In the present study, we investigated the impact of titanium nitride coating on the metal release and exposure of MIRPE patients. Material and methods: We analyzed the courses of nickel and chromium levels in blood, urine and local tissue in patients undergoing MIRPE with a titanium nitride coated pectus bar between 03/2017 and 10/2018. Sample collection was scheduled prior to MIRPE, at defined postoperative time points and at bar removal. Additionally, we evaluated irritative symptoms. Results were compared to a control group who received uncoated stainless steel bars in a previous time period (03/2015–02/2017). Results: 12 patients received coated pectus bars (mean age 15.7 years). The control group included 28 patients. After implantation of a titanium nitride coated bar, significant increase in systemic nickel and chromium levels after one, two and three years was noted. In an interim analysis one year after MIRPE, we observed patients with coated bars to have significantly elevated trace metal values compared to the control group. This elevation persisted throughout the observation period. Tissue metal values were also significantly increased. Irritative symptoms occurred significantly more often in study patients compared to controls (50.0% vs. 14.3%). Conclusions: Coating of pectus bars with titanium nitride failed to reduce metal contamination after MIRPE. Instead, it resulted in a significant increase of trace metal levels after MIRPE, compared to patients with stainless steel bars, which may be explained by wear of the coating and inter-component mobilization processes. [ABSTRACT FROM AUTHOR]

Background: Inconsistent definitions of complications and unexpected events have limited accurate analysis of surgical outcomes. Perioperative outcome classifications currently used for adult patients have limitations when used for children. Methods: A multidisciplinary group of experts modified the Clavien--Dindo classification to increase its utility and accuracy in paediatric surgery cohorts. Organizational and management errors were considered in the novel Clavien--Madadi classification, which focuses on procedural invasiveness rather than anaesthetic management. Unexpected events were prospectively documented in a paediatric surgery cohort. Results of the Clavien--Dindo and Clavien--Madadi classifications were compared and correlated with procedure complexity. Results: Unexpected events were prospectively documented in a cohort of 17 502 children undergoing surgery between 2017 and 2021. The results of both classifications were highly correlated (ρ = 0.95), although the novel Clavien--Madadi classification identified 449 additional events (organizational and management errors) over the Clavien--Dindo classification, increasing the total number of events by 38 per cent (1605 versus 1158 events). The results of the novel system correlated significantly with the complexity of procedures in children (ρ = 0.756). Furthermore, grading of events > grade III according to the Clavien--Madadi classification showed a higher correlation with procedure complexity (ρ = 0.658) than the Clavien--Dindo classification (ρ = 0.198). Conclusion: The Clavien--Madadi classification is a tool for the detection of surgical and non-medical errors in paediatric surgery populations. Further validation in paediatric surgery populations is required before widespread use. [ABSTRACT FROM AUTHOR]

Severity grading systems for complications in surgical patients have been used since 1992. An increasing assessment of these instruments in pediatric surgery is also noticed, without their validation in children. To analyze the current practice, we performed a literature review with focus on the assessment and grading of complications. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies reporting on postoperative complications as a primary or secondary endpoint using a severity grading system were included. Definition for simple adverse events, classification systems used, and the time horizon of postoperative documentation were analyzed. A total of 566 articles were screened, of which 36 met the inclusion criteria. About 86.1% of the papers were retrospective and 13.9% prospective analyses. None of the studies were prospective-randomized trials. Twenty (55.6%) studies did not include a definition of adverse events, whereas the remaining 16 (44.4%) showed variations in their definitions. All studies applied the Clavien-Dindo classification, whereas five (13.9%) additionally used the Comprehensive Complication Index. One study compared alternative grading instruments with the Clavien-Dindo classification, without demonstrating the superiority of any classification in pediatric surgery. Twenty-two studies (61.1%) did not report the time horizon of perioperative complication documentation, while 8 studies (22.2%) used 30 days and 6 studies (16.7%) used 3 months of postoperative documentation. Definition and classification of postoperative complications are inconsistent in the pediatric surgical literature. Establishment of a standardized protocol is mandatory to accurately compare outcome data. [ABSTRACT FROM AUTHOR]

By this notice, the Editor and the Publisher of European Journal of Pediatric Surgery retract from publication the following article: Cevizci N, Dokucu A I, Baskin D, Karadağ C A, Sever N, Yalçin M, Bahadir E, Başak M. Virtual bronchoscopy as a dynamic modality in the diagnosis and treatment of suspected foreign body aspiration. Eur J Pediatr Surg 2008; 18: 398-401. Epub 2008 Nov 20. This retraction is due to substantial overlap of data, subject matter and illustrations with the following article: Ozkurt H, Bahadir E, Ucgul A, Altuna C, Basak M, Cevizci N M, Dokucu A I. Comparison of multidetector computed tomography-virtual bronchoscopy and conventional bronchoscopy in children with suspected foreign body aspiration. Emerg Radiol Epub 2008 Nov 19. We apologise to our readership. [ABSTRACT FROM AUTHOR]

Background:  Numerous studies from Asian countries, including large collectives, have reported excellent results after laparoscopic resection of choledochal malformation (CM). However, the role of laparoscopic CM resection is still controversial outside Asia. We aimed to analyze the outcome of laparoscopic CM resection in our institution and to compare our outcome with the data reported in the literature.Methods:  All patients who underwent laparoscopic CM resection in our pediatric surgical department from 2002 to 2019 were retrospectively analyzed for surgical details and postoperative complications, which were graded according to the Clavien-Dindo classification. A systematic literature search identified all reports on over 10 cases of laparoscopic pediatric CM resection and surgical details, follow-up, and complication rates were extracted.Results:  Fifty-seven patients (72% female) with a mean age of 3.6 + 4.1 years underwent laparoscopic CM resection in our department. Conversion rate was 30%. Total complication rate was 28%. The rate of major complications (Clavien-Dindo grade III or more) was 16% and included stricture of the biliodigestive or enteric anastomosis (n = 4), adhesive ileus (n = 3), portal vein thrombosis (n = 1), and recurrent cholangitis with consecutive liver transplantation (n = 1). With increasing experience, complication rates decreased. The majority of publications on laparoscopic CM resections originated from Asia (n = 36) and reported on low complication rates. In contrast, publications originating from non-Asian countries (n = 5) reported on higher complications following laparoscopic CM resection.Conclusion:  Our data indicate that laparoscopic CM resection can be safely performed. The learning curve in combination with the low incidence calls for a centralization of patients who undergo laparoscopic CM resection. There seems to be a discrepancy on complications rates reported from Asian and non-Asian countries following laparoscopic CM resection. [ABSTRACT FROM AUTHOR]

Background: Minimally-invasive repair of pectus excavatum (MIRPE) has been shown to be associated with high release of trace metals into patient's body. The aim of our study was to analyze the kinetics of metal contamination after MIRPE and after bar removal. Methods: We prospectively assessed nickel and chromium changes in blood, urine, and local tissue in patients undergoing MIRPE with stainless-steel bar(s). Baseline samples were taken prior to surgery, further samples were taken at six defined time points until 30 months after bar removal. Clinical symptoms were evaluated at the time of every sample collection. Results: 28 patients were included (mean age 16.4 years). At four weeks after MIRPE and persisting up to bar removal, we found significantly elevated trace metal levels in blood and urine. Tissue nickel and chromium levels were significantly elevated at the time of bar removal. After bar removal, the concentration of trace metal in urine and the concentration of chromium in plasma decreased gradually. In contrast, nickel levels in blood further increased. Five patients showed irritative symptoms after MIRPE, all symptomatic patients had elevated metal levels. Conclusions: Following MIRPE, we found a rapid systemic increase of nickel and chromium. Our data indicate that trace metal release could cause irritative symptoms. The prolonged elevated systemic nickel levels beyond bar removal necessitate further investigations of the long-term side effects of MIRPE. [ABSTRACT FROM AUTHOR]

Introduction:  In Germany, pediatric surgery is organized in a decentralized manner. A nationwide clinical registry does not exist. The aim of this research is to analyze the current status of pulmonary surgery in the country in respect of children and adolescents.Materials and Methods:  Claims data have been extracted from two health insurance databases representing 34% of the German population. Operative diagnoses and procedures, as well as patients' characteristics, were recorded from 2016 to 2019.Results:  The incidence of the four index diagnoses investigated matched the current literature in three of four entities. The main indications <8 years were congenital lung malformations (61%) and spontaneous pneumothorax at age 8 to 17 years (77%). Furthermore, 1,668 pediatric pulmonary procedures (0-17 years) were identified (668 pulmonary resections). Two age peaks were identified: 13% of patients were operated on before 1 year old and 50% of patients were between 15 and 17 years old. Video-assisted-thoracoscopic-surgery (VATS) for pulmonary resections was applied in 62% of cases. 96% of pulmonary resections in patients <1 year and 70% of pulmonary resections in children between 1 and 14 years were performed by pediatric surgeons. Of patients between 15 and 17 years old, only 14% were operated on in pediatric surgery. The estimated average pulmonary resection caseload was 3.2 cases per year and per institution for pediatric surgery and 1.5 for adult surgery.Conclusion:  Indications for pulmonary surgery in children arise from rare diagnoses. In total, 66% of lung resections are performed in patients <1 year and >14 years. The majority of lung resections are performed as VATS. Patients ≤14 years are predominantly operated on by pediatric surgeons. The accessibility of pediatric pulmonary surgery is acceptable, but there is a low caseload per center. [ABSTRACT FROM AUTHOR]

Background: After repair of esophageal atresia (EA), childhood survivors commonly present with digestive and respiratory morbidity, and around 55% have associated anomalies. Although it is known that these problems can reduce health-related quality of life in children with EA, less is understood about the impact on the family. We aimed to identify factors related to family impact in children with EA.Methods: One parent each of a child with EA (2-18 years) in 180 families from Sweden and Germany answered the PedsQL™ Family Impact Module as the dependent variable. The independent variables were the child's parent-reported health-related quality of life as measured by PedsQL™ 4.0, current symptoms, school situation, and parent/family characteristics together with child clinical data from the medical records.Results: Stepwise multivariable regression analysis showed a multifactorial model of the total family impact scores (R2 = 0.60), with independent factors being the child's overall generic health-related quality of life, school-absence ≥ 1/month, severe tracheomalacia, a family receiving carer's allowance, and a parent with no university/college education, p < 0.05. Logistic regression analysis showed that an increased number of symptoms in the child the preceding 4 weeks lowered the family impact scores; however, the child's feeding (R2 = 0.35) and digestive symptoms (R2 = 0.25) explained more in the variation of scores than the child's respiratory symptoms (R2 = 0.09), p < 0.0001.Conclusions: Family functioning may be a contributing factor to the maintenance of child health. The study findings suggest multifactorial explanations to family impact in children with EA, which are essential when optimizing the support to these families in clinical and psychosocial practice. Future research should explore experiences of family impact from all family members' perspectives and multicenter studies are warranted to understand better the effectiveness of psychosocial-educational interventions to families of children with EA. [ABSTRACT FROM AUTHOR]

T-cells have been demonstrated to modulate ischemia–reperfusion injury (IRI) in the kidney, lung, liver, and intestine. Whereas most T-cell subpopulations contribute primarily to the antigen-specific effector and memory phases of immunity, γδ-T-cells combine adaptive features with rapid, innate-like responses that can place them in the initiation phase of immune reactions. Therefore, we aimed to clarify the role of γδ-T-cells in intestinal IRI. Adult wild-type (WT) and γδ-T-cell-deficient mice were subjected to acute intestinal IRI. Gene expression of pro-inflammatory cytokines and influx of leukocyte subpopulations in the gut were assessed by qPCR and flow cytometry. Serum transaminases were measured as an indicator of distant organ IRI. Intestinal IRI led to increased influx of neutrophils, pro-inflammatory cytokine expression and LDH/ALT/AST elevation. Selective deficiency of γδ-T-cells significantly decreased pro-inflammatory cytokine levels and neutrophil infiltration in the gut following IRI compared to controls. Furthermore, γδ-T-cell deficiency resulted in decreased LDH and transaminases levels in sera, indicating amelioration of distant organ injury. Increasing evidence demonstrates a key role of T-cell subpopulations in IRI. We demonstrate that γδ-T-cell deficiency ameliorated pro-inflammatory cytokine production, neutrophil recruitment and distant organ injury. Thus, γδ-T-cells may be considered as mediators contributing to the inflammatory response in the acute phase of intestinal IRI. [ABSTRACT FROM AUTHOR]

Background: Intermittent work breaks are common in fields with high workload but not yet for surgeons during operations. We evaluated the effects of intraoperative breaks during complex laparoscopic surgery (5 min every half hour) on the surgeon. Methods: Fifty-one operations were randomized to a scheme with intraoperative breaks and release of the pneumoperitoneum (intermittent pneumoperitoneum (IPP)) or conventional conduct (CPP). Stress hormones and α-amylase were determined in the surgeon's saliva pre-, intra-, and postoperatively. Mental performance and error scores, musculoskeletal strain, and continuous ECG were secondary endpoints. Results: Regular intraoperative breaks did not prolong the operation (IPP vs. CPP group: 176 vs. 180 min, p > 0.05). The surgeon's cortisol levels during the operation were reduced by 22 ± 10.3% in the IPP vs. the CPP group ( p < 0.05). There were significantly fewer ( p < 0.05) intraoperative events in the IPP vs. the CPP group, which yielded higher α-amylase peaks. The pre- to postoperative increase in the error rates of the bp-concentration test was fourfold reduced in the IPP group ( p = 0.052). The relevant locomotive strain-scores were grossly reduced by IPP ( p < 0.001). Conclusions: Our data support the idea that work breaks during complex laparoscopic surgery can reduce psychological stress and preserve performance without prolongation of the operation time compared with the traditional work scheme. [ABSTRACT FROM AUTHOR]

Effective analgesia is essential for the success of fast-track (FT) pediatric surgery. Aim of the study was to achieve an optimal analgesia protocol for a comfortable postoperative course and early mobilization in children undergoing urological procedures. A prospective study of two analgesia concepts in a series of children undergoing laparoscopic pyeloplasty (LP) and nephrectomy (LN) was performed. Thirty-six consecutive patients received analgesia according to the protocol “Fast Track I” (FT I), 23 patients according to the modified analgesia protocol “Fast Track II” (FT II). Differences between the protocols were frequency of pain measurement, more frequent use of local anesthesia and higher dosage of Acetaminophen. End points were pain intensity, use of opioids and side effects. Data derived from the German reimbursement system (G-DRG) regarding lengths of hospital stay were compared. On the day of operation (6:00 p.m.), pain scores of patients using FT II were significantly lower than those using the FT I protocol (1.51 ± 0.4 FT II versus 3.8 ± 0.4 FT I, p = 0.001). Pain scores still tended to be lower in the FT II group on the first postoperative day (8:00 a.m.), but from that point on, the difference was not significant (1.52 ± 0.5 FT II versus 2.3 ± 0.4 FT I, p = 0.186). Hospital stay was short, compared to the German average, in both groups. The modified analgesia protocol FT II leads to earlier and more effective pain reduction, lower use of opioids and fewer side effects than the previously used protocol FT I. Hence, modification of analgesia in pediatric urology is essential. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate fast-track concepts in routine pediatric surgery in a university clinic over 1 year. Fast-track concepts were established for procedures requiring hospital admission in patients up to 15 years of age. Patients were studied prospectively from June 2006 to June 2007. Out of a total of 436 potentially suitable patients, 155 (36%) were finally treated following the protocols. The mean intensity of pain in children younger than 4 years (CHIPPS, 0–10) was 1.3 ± 1.5 the evening of the operation day and decreased to <1 at all other time points. The initial postoperative mean pain intensity in older children (Smiley/VAS, 1–10) was 3.7 ± 2.2 and decreased constantly thereafter. The mean hospital stay of fast-track patients was significantly shorter compared with German diagnosis-related group data (4.6 ± 2.9 versus 9.7 ± 3.8, p < 0.01). There were four (3%) readmissions for minor complications. At follow-up after 2 weeks, 95% of patients and parents judged fast-track care as excellent. Fast-track concepts are feasible in one third of pediatric patients undergoing routine in-hospital surgery. Fast-track pediatric surgery achieves accelerated convalescence, minimal hospital stay, and high patient and parent satisfaction. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine whether the association of seminal vesicle cyst (SVC) and renal anomaly in young children correlates with previously reported cases of SVCs in adolescent and adult patients, as congenital SVCs, although rare, are frequently described in association with ipsilateral renal agenesis, mainly in adolescent and adult patients, whereas reports on SVCs in younger children are sparse. PATIENTS AND METHODS We report on nine infants (median age 4 months) with congenital SVCs, all of them associated with ipsilateral dysplastic kidneys. All patients had ultrasonography of the renal system and voiding cysto-urethrography. Magnetic resonance imaging was used in two patients. RESULTS The SVCs were found incidentally during ultrasonography for the renal anomaly. Three patients had dysplastic and six had multicystic dysplastic kidneys. In previous reported adult cases of SVCs the most common associated renal anomaly was agenesis of the ipsilateral kidney (25 of 44 cases), whereas only one case of dysplastic kidney was reported. CONCLUSION As the appearance of renal agenesis might result from a former congenital dysplastic kidney, our findings indicate that cases of ipsilateral renal agenesis in adult patients with congenital SVCs might represent former dysplastic or multicystic dysplastic kidney. [ABSTRACT FROM AUTHOR]

Based on the hypothesis that autoimmunological factors coregulate the pathomechanism in biliary atresia (BA), adjuvant therapy with steroids has become routine, although its efficacy has never been proven. In 2010, a study on the advantages of budesonide compared to prednisolone in autoimmune hepatitis gave rise to experimental therapy using budesonide as an adjuvant BA treatment. Ninety-five BA patients prospectively received a budesonide 2 mg/dose rectal foam daily for three months (SG). A case-matched control group (CG: 81) was retrospectively recruited. The outcome measures were survival with native liver (SNL), determined at six months and two years after the Kasai procedure. The follow-up rate was 100%. At six months, SNL was statistically not different but became so after two years (SG: 54%; CG: 32%; p < 0.001). No steroid-related side effects were observed, except for eight patients with finally caught-up growth retardation. This study demonstrates for the first time a significantly longer survival with native liver in patients with BA after adjuvant therapy. However, indication, dosage, and duration of any budesonide application is not given in neonates with BA. Hence, we suggest extending the postoperative use of budesonide in a multicenter observational study with a clearly defined follow-up protocol, particularly in terms of potentially underestimated side effects. [ABSTRACT FROM AUTHOR]

Purpose: Recent evidence suggests that transforming growth factor-alpha (TGF-alpha) enhances enterocyte proliferation and exerts a gut trophic effect. The purpose of the present study was to evaluate the effect of TGF-alpha on enterocyte proliferation and intestinal recovery following methotrexate (MTX)-induced intestinal mucositis in rats and in Caco-2 cells.Methods: Nonpretreated Caco-2 cells and those pretreated with MTX were incubated with increasing concentrations of TGF-alpha. Cell proliferation was determined by FACS cytometry. Adult rats were divided into three groups: control rats treated with vehicle, MTX rats treated with one dose (20 microg/kg) of MTX given intraperitoneally, and MTX-TGF-alpha rats treated with one dose of MTX followed by two doses of TGF-alpha (75 microg/kg a day). Three days after MTX injection, rats were sacrificed. Intestinal mucosal damage (Park's score), mucosal structural changes, and enterocyte proliferation were measured at sacrifice. Western blotting was used to determine the level of extracellular signal-related kinase (ERK) protein, a marker of cell proliferation. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with P value less than 0.05 considered statistically significant.Results: The in vitro experiment demonstrated that treatment with TGF-alpha of Caco-2 cells resulted in a significant stimulation of cell proliferation in a dose-dependent manner. The in vivo experiment showed that treatment with TGF-alpha resulted in a significant increase in bowel and mucosal weight, DNA and protein content in jejunum and ileum, villus height in jejunum and ileum, crypt depth in ileum, and increased cell proliferation in jejunum and ileum compared to the MTX group. MTX-TGF-alpha rats also had a significantly lower intestinal injury score in ileum when compared to MTX animals. The increase in levels of cell proliferation in MTX-TGF-alpha rats corresponded with the increase in ERK protein levels in intestinal mucosa.Conclusion: Treatment with TGF-alpha prevents mucosal injury, enhances ERK-induced enterocyte proliferation, and improves intestinal recovery following MTX-induced intestinal mucositis in rats. These findings correlated with the observation that TGF-alpha also caused a significant stimulation of cell proliferation in a Caco-2 cell culture model treated with MTX. These observations may have significant implications for the treatment of patients on chemotherapy who develop severe mucositis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current study was to investigate effects of CO(2) atmosphere, mimicking conditions of the pneumoperitoneum during laparoscopy, on epigenetic conditions of Rassf1A and DCR2 oncogenes in neuroblastoma cells.Methods: SH-SY5Y neuroblastoma cells were exposed to 100% CO(2) for 4 h. Cells were lysed 4, 8 and 168 h after exposure. After methylation analysis of Rassf1A and DCR2 with polymerase chain reaction, results were compared to those of physiologically incubated neuroblastoma cells.Results: No significant changes were found after exposure to carbon dioxide compared to the control. Values of methylated Rassf1A were 12.6 +/- 1.1 versus 13.2 +/- 1.4 ng/microl in the controls, respectively (4 h after incubation), 12.6 +/- 1.2 versus 15.1 +/- 0.9 ng/microl (8 h) and 14.2 +/- 1.5 versus 11.7 +/- 1.3 ng/microl (168 h). DCR2 showed values of 4.6 +/- 0.5 versus 3.7 +/- 0.5 ng/microl (4 h), 3.8 +/- 0.5 versus 4.1 +/- 0.4 ng/microl (8 h) and 3.6 +/- 0.4 versus 3.8 +/- 0.5 ng/microl (168 h).Conclusion: Exposure of neuroblastoma cells to 100% CO(2) does not alter methylation of two prognostic relevant index genes. It seems therefore unlikely that effects on methylation levels within CO(2) pneumoperitoneum lead to epigenetic changes in neuroblastoma. [ABSTRACT FROM AUTHOR]

Summary: Background: Vascular clamping techniques are commonly used but so far the impact on pediatric liver surgery has not been investigated. The purpose of this study was to analyze pedicle clamping during pediatric liver resection in terms of hepato-cellular injury and blood loss. Methods: Sixty-seven children undergoing liver resection were analyzed retrospectively. Vascular clamping was used in 28 cases (PC group), in 39 the resection was performed without clamping (NPC group). Major hepatectomies (resection of more than three segments) were carried out in 88%, minor hepatectomies (resection of three and less segments) in 12% of patients. Twenty-six children underwent extended liver resection. Patient data, liver function tests (LFTs) and blood loss were analyzed statistically. Results: There were no significant differences in patient preoperative and postoperative data and LFTs between the groups. Within the NPC group the amount of administered fresh frozen plasma (FFP) in total and per kilogram (FFP/kg) was significantly higher (p=0.023 and 0.028) than in the PC group. For patients with extended liver resection, operation times were significantly longer (p=0.016) in the group without vascular clamping (NPCext). In the NPCext group significantly more children required packed red cells, FFP and FFP/kg. LFTs showed no significant differences in all children regardless of vascular clamping. Conclusions: For children undergoing liver resection, vascular clamping offers a blood saving surgical technique. Postoperative LFTs were not statistically different, regardless of vascular clamping. Pedicle clamping proved to be a safe method, not associated with an increase in perioperative complications. [Copyright &y& Elsevier]

Numerous human macrophage (mphi) subpopulations with different behavior have been identified in adults. It is well known that peritoneal mphi are activated by abdominal surgery and subsequently contribute to a systemic inflammatory response that leads to immune suppression, increased morbidity and mortality. Information on the role of pleural mphi in adults is scarce and information on their role in children is lacking. We investigated the behavior of pleural versus peritoneal mphi in children and adolescents. As a first step, we compared the cellular composition of the pleural and peritoneal surface in children and adolescents. Pleural and peritoneal lavages were performed in 21 patients undergoing non-contaminated laparoscopic and thoracoscopic surgical procedures. We observed a significantly higher percentage of mphi in the pleural compared to the peritoneal cavity with less lymphocytes, a small amount of polymorphonuclear cells (PMNs) and other cells. To further study the mphi inflammatory response, we measured the spontaneous and LPS triggered cytokine release of isolated pleural versus peritoneal mphi (IL-1beta, IL-6, and IL-10). The pattern of cytokine release was similar in both, pleural and peritoneal mphi. Directly after lavage, they showed a strong activation, with no difference between stimulated and non-stimulated cells. After 24 h resting, mphi of both compartments reacted to LPS with a similar significant increase in the cytokine release. In conclusion, our results demonstrate that pleural mphi represent the dominant cell population in the pleural cavity of the young. They show a similar inflammatory response as peritoneal mphi and should be considered to play a major role in the local inflammatory response to thoracic surgery. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive techniques are increasingly applied to children with malignant tumors. We showed previously that CO2 used for pneumoperitoneum modulates the function of macrophages and polymorphonuclear cells via direct effects and via acidification. Numerous in vitro and small animal model studies also confirmed an alteration of the behavior of several types of adult tumor cells by CO2. The impact of CO2 and other gases used for pneumoperitoneum on the behavior of various pediatric tumors has not yet been determined. Methods: Cell lines of neuroblastoma (IMR 32, SK-N-SH, Sy5y), lymphoma (Daudi), hepatoblastoma (Huh 6), hepatocellular carcinoma (Hep G2), and rhabdomyosarcoma (Te 671) were incubated for 2 h. Incubation was performed with 100% CO2, 100% helium, and 5% CO2 as control. Cell proliferation was determined by the MTT-assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] by actively growing cells to produce a blue formazan product. The MTT-assay was performed before, directly after incubation, and daily for 4 days. Vitality of the cells was determined by trypan blue. The extracellular pH during incubation was measured during gas exposition every 10 min using Bayer Rapid Lab 855. Results: CO2 for 2 h significantly decreased the proliferation of neuroblastoma, lymphoma, hepatoblastoma, and hepatocellular carcinoma cells. This decrease persisted over 4 days in neuroblastoma, lymphoma, and hepatocellular carcinoma cells. The CO2 had no impact on hepatoblastoma and rhabdomyosarcoma cells. Helium had a similar effect on neuroblastoma cells. After 4 days, a significant decrease of cell activity was found in two neuroblastoma cell lines and in hepatoblastoma cells. Helium had no effect on lymphoma and hepatocellular carcinoma cells. The extracellular pH was 6.2 during incubation with CO2, and 7.6 during incubation with helium. Conclusion: CO2 and helium may affect the proliferation of some pediatric tumor cell lines in vitro. However, some of these effects and the impact on the extracellular pH are differential. The role of pH modulation, hypoxia and direct effects of gases remain to be investigated before a general recommendation on the use of minimally invasive techniques in pediatric oncology can be given. [ABSTRACT FROM AUTHOR]

One hypothesis of the pathogenesis of biliary atresia (BA) is a virus-induced and immune-mediated injury to bile duct cells as mimicked in the rotavirus-induced murine model. This theory is supported by studies showing a predominant T helper cell response type 1-like phenotype of inflammation with increased interferon gamma-induced chemokines in the liver of humans and mice suffering from BA. Recent gene expression profiling studies using microarray analysis showed the induction of a proinflammatory state in human liver specimens with high analogies in extrahepatic biliary tissue of BA mice. The aim of the present study was a microarray analysis of gene expression in the liver of Balb/c mice, comparing infected mice that show the phenotype of BA versus infected mice without symptoms, thus trying to elucidate genes that are not related to the viral origin of this model, but to the specific pathogenesis of the clinical picture of BA. Fifteen mug of RNA, each of three BA-positive and three BA-negative mice, were pooled and comparatively hybridized to spotted cDNA microarrays containing 250 key genes with high relevance to immunological settings. We identified the 40 genes most differentially expressed in mice with and without BA. The majority of genes with higher expression in BA-positive mice encoded proinflammatory cytokines involved in the Th1 pathway, such as CCL2, CCL5, CCR5, CXCL10, CCL2, IL1F5 and in apoptosis, such as DDR3 and granzyme A and B. In this initial study of the molecular characterization of our RRV-induced BA mouse model system, we also found potential novel candidates important to BA etiology, such as growth hormone receptor and insulin-like growth factor. Of particular interest, very low expression of TIMD2 was observed in BA-positive mice. TIMD2 plays a critical role in the regulation of a Th2-type response through the inhibition of IFN gamma. [ABSTRACT FROM AUTHOR]

Background: The Clavien-Madadi classification is a novel instrument for the assessment and grading of unexpected events in pediatric surgery, based on the Clavien-Dindo classification. The system has been adjusted to better fit the pediatric population in a prospective single-center study. There is a need now to validate the Clavien-Madadi classification within an international expert network., Methods: A pediatric surgical working group created 19 case scenarios with unexpected events in a multi-staged process. Those were circulated within the European Reference Network of Inherited and Congenital Anomalies (ERNICA) and surgeons were instructed to rate the scenarios according to the Clavien-Madadi vs. Clavien-Dindo classification., Results: 59 surgeons from 12 European countries completed the questionnaire. Based on ratings of the case scenarios, the Clavien-Madadi classification showed significantly superior agreement rates of the respondents (85.9% vs 76.2%; p < 0.05) and was less frequently considered inaccurate for rating the pediatric population compared to Clavien-Dindo (2.1% vs 11.1%; p = 0.05). Fleiss' kappa analysis showed slightly higher strength of agreement using the Clavien-Madadi classification (0.74 vs 0.69). Additionally, intraclass correlation coefficient was slightly higher for the Clavien-Madadi compared to the Clavien-Dindo classification (ICC just 0.93 vs 0.89; ICC unjust 0.93 vs 0.89). More pediatric surgeons preferred the Clavien-Madadi classification for the case scenarios (43.0% vs 11.8%; p = 0.002) and advantages of the Clavien-Madadi were confirmed by 81.4% of the surgeons., Conclusion: The Clavien-Madadi classification is an accurate and reliable instrument for the grading of unexpected events in pediatric surgery. We therefore recommend its application in clinical and academic pediatric surgical practice., Level of Evidence: III., Competing Interests: Conflicts of interest None of the authors have any conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Procedure-related registries in general surgical practice offer a platform for prospective trials, the pooling of data, and detailed outcome analysis. Recommendations by the Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) collaboration and Outcome4Medicine have further improved the uniform reporting of complications and adverse events.In the pediatric surgical network, disease-specific registries for rare and inherited congenital anomalies are gaining importance, fostering international collaborations on studies of low-incidence diseases. However, to date, reporting of complications in the pediatric surgical registries has been inconsistent. Therefore, the European Reference Network for Rare Inherited and Congenital Anomalies (ERNICA) recently endorsed the validation of the first severity grading system for children. The planned reform of the European Paediatric Surgical Audit (EPSA) registry, which includes the implementation of the Clavien-Madadi classification, represents a further effort to establish uniform outcome reporting.This article provides an overview of experiences with surgical registries and complication reporting, along with the potential application of this knowledge to future pediatric surgical practice., Competing Interests: None declared., (Thieme. All rights reserved.)

Nowadays laparoscopic interventions enable the collection of resident macrophage populations out of the human cavities. We employed this technique to isolate pleural monocytes/macrophages from healthy young adults who underwent a correction of pectus excavatum. High quality CD14 + monocytes/macrophages (plMo/Mφ) were used for RNA-sequencing (RNA-seq) in comparison with human monocyte-derived macrophages (MDM) natural (MDM-0) or IL-4-polarized (MDM-IL4). Transcriptome analysis revealed 7166 and 7076 differentially expressed genes (DEGs) in plMo/Mφ relative to natural MDM-0 and polarized MDM-IL4, respectively. The gene set enrichment analysis, which was used to compare RNA-seq data from plMo/Mφ with single-cell (scRNA-seq) data online from human bronchial lavage macrophages, showed that plMo/Mφs are characterized by a high expression of genes belonging to the metallothionein (MT) family, and that the expression of these genes is significantly higher in plMo/Mφ than in MDM-0 or MDM-IL4. Our results provide additional insights on high MTs-expressing macrophage subsets, which seem to be present not only in bronchial lavage of healthy adults or in pleural exudates of lung cancer patients but also in pleural fluid of healthy young adults. Macrophage subsets expressing high MTs may have specific roles in lung defense, repair, and homeostasis, and require further investigations., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)