Validation of the Clavien-Madadi Classification for Unexpected Events in Pediatric Surgery: A Collaborative ERNICA Project.

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 (ICCjust 0.93 vs 0.89; ICCunjust 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.

Titanium nitride coating of pectus bar increases metal contamination after minimally-invasive repair of pectus excavatum.

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.

Implementation and validation of a novel instrument for the grading of unexpected events in paediatric surgery: Clavien-Madadi classification.

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.

Surgical management of large tracheoesophageal fistula in infants after button battery ingestion.

OBJECTIVES: In recent years, an increase in severe and even fatal outcomes related to oesophageal or airway button battery (BB) ingestion by infants and small children has been reported. Extensive tissue necrosis caused by lodged BB can lead to major complications, including tracheoesophageal fistula (TEF). In these instances, best treatment remains controversial. While small defects may warrant a conservative approach, surgery often remains inevitable in highly complex cases with large TEF. We present a series of small children that underwent successful surgical management by a multidisciplinary team in our institution. METHODS: This is a retrospective analysis of n = 4 patients <18 months undergoing TEF repair from 2018 to 2021. RESULTS: Surgical repair under extracorporeal membrane oxygenation (ECMO) support was feasible in n = 4 patients by reconstructing the trachea with decellularized aortic homografts that were buttressed with pedicled latissimus dorsi muscle flaps. While direct oesophageal repair was feasible in 1 patient, 3 required esophagogastrostomy and secondary repair. The procedure was completed successfully in all 4 children with no mortality and acceptable morbidity. CONCLUSIONS: Tracheo-oesophageal repair after BB ingestion remains challenging and is associated with major morbidity. Bioprosthetic materials in conjunction with the interposition of vascularized tissue flaps between trachea and oesophagus appear to be a valid approach to manage severe cases.

Definition, Documentation, and Classification of Complications in Pediatric Surgical Literature-A Plea for Standardization.

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.

Pleural CD14+ monocytes/macrophages of healthy adolescents show a high expression of metallothionein family genes.

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.

Nickel contamination after minimally-invasive repair of pectus excavatum persists after bar removal.

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.

Accumulation of Postoperative Unexpected Events Assessed by the Comprehensive Complication Index® as Prognostic Outcome Parameters for Kasai Procedure.

Introduction The Kasai procedure in children with biliary atresia (BA) is associated with several complications in the short-term. The Comprehensive Complication Index (CCI®) is a validated metric in adult surgery for the analysis of complications and morbidity in surgical patients. We aimed to analyze the CCI® for the first time in BA infants and to correlate its association with outcomes. Material and Methods We conducted a retrospective review of medical records of infants with type III BA undergoing the Kasai procedure between January 2011 and December 2021 at our institution. All unexpected events were ranked according to the Clavien−Dindo classification, and the CCI® per patient was subsequently calculated. Clavien−Dindo grades, individual events, CCI®, and total event numbers per patient were correlated with one- and two-year outcomes post-surgery. Results A total of 131 events were identified in 101 patients (ranging 0−11 per patient). Forty-four Grade I (33.6%), 67 Grade II (51.1%), 18 Grade III (13.7%), and two sentinel events [>Grade IV] (1.5%) were documented according to Clavien−Dindo, including one death in a cardiac-associated BA patient. None of the complications significantly correlated with a poor outcome. Sixty-three (62.4%) CCI® scores were calculated (range 0−100). The mean CCI® score during the in-patient treatment post-surgery was significantly higher in patients with a poorer outcome than patients with native liver survival at one- and two-year follow-up (22.7 ± 21.7 vs. 13.2 ± 18.1; p = 0.02). Conclusion Not the severity of complications, but the accumulation of numerous events related to Kasai procedure were associated with a poorer outcome. Therefore, the CCI® is an excellent instrument for the postoperative morbidity assessment of BA patients.

The Role of Laparoscopic Treatment of Choledochal Malformation in Europe: A Single-Center Experience and Review of the Literature.

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.

Controversies in Choledochal Malformation in Children: An International Survey among Pediatric Hepatobiliary Surgeons and Gastroenterologists.

BACKGROUND: While congenital choledochal malformation (CCM) is relatively well known within the pediatric surgical and pediatric gastroenterological communities, many controversies and questions remain. METHODS: In this paper, we will discuss the results of an international Delphi survey among members of the European Reference Network RARE-LIVER and of the faculty of the Biliary Atresia and Related Diseases (BARD) network to identify the most common practices as well as controversies regarding diagnosis, treatment and follow-up of this still enigmatic disease. RESULTS: Twenty-two individual respondents completed the survey. While there seems to be agreement on the definitions of CCM, preoperative workup, surgical approach and follow-up still vary considerably. The mainstay of treatment remains the removal of the entire extrahepatic biliary tract, clearance of debris both proximally and distally, followed by reconstruction with (according to 86% of respondents) a Roux-en-Y hepaticojejunostomy. Nonetheless, both laparoscopic and robotic-assisted resections are gaining ground with the suggestion that this might be facilitated by concentration of care and resources in specialized centers. However, long-term outcomes are still lacking. CONCLUSIONS: As even post-surgical CCM has to be considered as having premalignant potential, follow-up should be well-organized and continued into adulthood. This seems to be lacking in many centers. International cooperation for both benchmarking and research is paramount to improving care for this rare disease.

Centralization of Biliary Atresia: Has Germany Learned Its Lessons?

INTRODUCTION: The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade. MATERIALS AND METHODS: In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany. RESULT: Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001-2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001-2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001-2005 [p = 0.5]). Compared with the 2001-2005 analysis, all criteria showed improvement but the differences are statistically not significant. CONCLUSION: Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction.

Laparoscopic versus Open Pediatric Surgery: Three Decades of Comparative Studies.

INTRODUCTION: Despite its wide acceptance, the superiority of laparoscopic versus open pediatric surgery has remained controversial. There is still a call for well-founded evidence. We reviewed the literature on studies published in the last three decades and dealing with advantages and disadvantages of laparoscopy compared to open surgery. MATERIALS AND METHODS: Studies comparing laparoscopic versus open abdominal procedures in children were searched in PubMed/MEDLINE. Reports on upper and lower gastrointestinal as hepatobiliary surgery and on surgery of pancreas and spleen were included. Advantages and disadvantages of laparoscopic surgery were analyzed for different types of procedures. Complications were categorized using the Clavien-Dindo classification. RESULTS: A total of 239 studies dealing with 19 types of procedures and outcomes in 929,157 patients were analyzed. We identified 26 randomized controlled trials (10.8%) and 213 comparative studies (89.2%). The most frequently reported advantage of laparoscopy was shorter hospital stay in 60.4% of studies. Longer operative time was the most frequently reported disadvantage of laparoscopy in 52.7% of studies. Clavien-Dindo grade I to III complications (mild-moderate) were less frequently identified in laparoscopic compared to open procedures (80.3% of studies). Grade-IV complications (severe) were less frequently reported after laparoscopic versus open appendectomy for perforated appendicitis and more frequently after laparoscopic Kasai's portoenterostomy. We identified a decreased frequency of reporting on advantages after laparoscopy and increased reporting on disadvantages for all surgery types over the decades. CONCLUSION: Laparoscopic compared with open pediatric surgery seems to be beneficial in most types of procedures. The number of randomized controlled trials (RCTs) remains limited. However, the number of reports on disadvantages increased during the past decades.

Kasai Procedure in Patients Older Than 90 Days: Worth a Cut.

INTRODUCTION: Age at Kasai portoenterostomy (KPE) has been identified as a predictive factor for native-liver survival in patients with biliary atresia (BA). Outcomes of pediatric liver transplantation (LT) have improved over recent years. It has been proposed to consider primary LT as a treatment option for late-presenting BA infants instead of attempting KPE. We present our experience with patients older than 90 days undergoing KPE. MATERIALS AND METHODS: A retrospective chart review of patients with BA undergoing KPE at our institution between January 2010 and December 2020 was performed. Patients 90 days and older at the time of surgery were included. Patients' characteristics, perioperative data, and follow-up results were collected. Eleven patients matched the inclusion criteria. Mean age at KPE was 108 days (range: 90-133 days). RESULTS: Postoperative jaundice clearance (bilirubin < 2 mg/dL) at 2-year follow-up was achieved in three patients (27%). Eight patients (73%) received a liver transplant at a mean of 626 days (range: 57-2,109 days) after KPE. Four patients (36%) were transplanted within 12 months post-KPE. Two patients died 237 and 139 days after KPE due to disease-related complications. One patient is still alive with his native liver, currently 10 years old. CONCLUSION: Even when performed at an advanced age, KPE can help prolong native-liver survival in BA patients and offers an important bridge to transplant. In our opinion, it continues to represent a viable primary treatment option for late-presenting infants with BA.

Adjuvant Therapy with Budesonide Post-Kasai Reduces the Need for Liver Transplantation in Biliary Atresia.

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.

Province-Wide Stool Color Card Screening for Biliary Atresia in Lower-Saxony: Experiences with Passive Distribution Strategies and Results.

BACKGROUND: Stool color card (SCC) screenings for biliary atresia (BA) have shown to improve Kasai timing and outcome significantly. Both obligatory and non-obligatory screenings with passive distribution strategies have proven to be effective. Therefore, we have initiated a voluntary SCC program and aim to describe our experience. METHODS: Since 2017 we supply all maternity wards in Lower-Saxony with SCC. Attending pediatricians and parents of BA infants were contacted via questionnaires and asked for their evaluation of the SCC screening. RESULTS: 85.2% of attending pediatricians support the SCC screening, but only 78.1% considered the initiative useful. In their clinical routine, only 67% of visiting parents report to have received an SCC at the maternity hospital. In the group of parents of BA infants, only 54% (7/13) had received an SCC. Out of those seven parents, only one had referred their child to a children's hospital based on pathological SCC results. The lack of SCC education in the maternity hospitals was made responsible by parents. Within three years, only one infant with BA was identified through the SCC. CONCLUSIONS: Our voluntary SCC screening shows serious limitations with inacceptable distribution of SCCs and low acceptance of attending pediatricians. SCC programs in decentralized health care systems without educational campaigns, standardized diagnostic and treatment algorithms and the definition of reference centers are additional burdens for local health care providers without the promised benefit.

Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia.

BACKGROUND: Biliary atresia (BA) is a neonatal cholangiopathy characterized by progressive destruction of the biliary system resulting in liver cirrhosis. Residual bile drainage can temporarily be achieved through Kasai portoenterostomy (KPE) and some children show long-term survival with their native liver. However, most children eventually require liver transplantation (LTX). As several growth factors (GF) and chemokines have been shown to promote fibrogenesis in the liver, we assessed whether GF are predictive for the course of disease. MATERIAL AND METHODS: Liver and sera samples were collected from 49 infants with BA during KPE. Levels of 13 different GF were measured by multiplex immunoassay. Patient outcomes were stratified into favorable (bilirubin < 20 µmol/L at 2-year follow-up) and unfavorable (LTX). GF levels were compared between groups by a t-test, correlation coefficients were calculated, and principal component analyses performed. RESULTS: Twenty-two patients showed a favorable and 27 an unfavorable disease course. No relation of GF and outcome could be established. In both groups, high levels of SDF-1alpha/CXCL12 (1473.0 ± 497.5 pg/mL), FGF2 (301.2 ± 207.8 pg/mL), and VEGF-a (209.0 ± 146.4 pg/mL) levels were measured within the liver, followed (in descending order) by PDGF-bb, LIF, GM-CSF, BDNF, VEGF-d, beta-NGF, IL-7, SCF, PIGF-1, and EGF. Serum marker levels showed much higher mean variation compared to hepatic values and no correlation to the protein microenvironment in the liver. CONCLUSIONS: Our study demonstrates high amounts of GF in livers from infants with BA at KPE, but no correlation to the outcome or serum values could be established. Our data suggest that local or systemic GF levels are unsuitable for prediction of the disease course. Collectively, we conclude that in BA the degree of proliferative activity caused by GF is a dismissible factor for the further course of disease.

Severity grading of unexpected events in paediatric surgery: evaluation of five classification systems and the Comprehensive Complication Index (CCI®).

BACKGROUND: Postoperative adverse events may be associated with substantial morbidity and mortality. Numerous severity grading systems for these events have been introduced and validated but have not yet been systematically applied in paediatric surgery. This study aimed to analyse the advantages and disadvantages of these classifications in a paediatric cohort. METHODS: Unexpected events associated with interventional or organizational problems in the department of paediatric surgery during 2017-2020 were prospectively documented daily for all children. Events were classified according to the Clavien-Dindo grading system during monthly morbidity and mortality conferences. All events were also classified according to five additional grading systems: T92, contracted Accordion, expanded Accordion, Memorial Sloan Kettering Cancer Center, and Comprehensive Complication Index (CCI)®. RESULTS: Of 6296 patients, 673 (10.7 per cent) developed adverse events and 240 (35.7 per cent) had multiple events. Overall, 1253 adverse events were identified; of these, 574 (45.2 per cent) were associated with surgical or medical interventions and 679 (54.8 per cent) included organizational problems. The grading systems demonstrated high overall correlation (rpears = 0.9), with minor differences in sentinel events. The Clavien-Dindo classification offered the most detailed assessment. However, these details had only limited additional value. The CCI® scores were correlated with other grading systems (rpears = 0.9) and were useful in analysing multiple events within individual patients. CONCLUSION: Grading systems demonstrated similar scoring patterns for minor and sentinel events, with none being superior for unexpected events in children. However, the CCI® can be a major improvement in assessing morbidity in patients with multiple events. Its use is therefore recommended in prospective studies on paediatric surgery.

The Intestinal Flora at Kasai Procedure in Children with Biliary Atresia Appears Not to Affect Postoperative Cholangitis.

INTRODUCTION: Evidence supports long-term oral antibiotic prophylaxis to prevent cholangitis after Kasai procedure. Data regarding perioperative intravenous prophylaxis are lacking. Ascending pathogens from the intestine are made responsible for recurrent cholangitis. Therefore, we analyzed the flora in the upper jejunum during the Kasai procedure and their potential impact on postoperative cholangitis. MATERIALS AND METHODS: In 26 patients, swabs were taken at the bowel prepared for the Roux-en-Y-loop. Our postoperative protocol includes intravenous third-generation cephalosporins for 2 weeks and rectal steroids starting at day 4. Cholangitis was defined as the postoperative reappearance of acholic stools or increase of serum bilirubin in combination with fevers or increase of inflammatory parameters. In this scenario, Tazocin was administered for another 2 weeks. RESULTS: Swabs remained sterile in nine patients (34.6%). In 17 patients (65.4%), gram-positive and gram-negative pathogens were identified; all belonging to physiological intestinal flora. A total of 96.2% pathogens were covered by the antibiotic prophylaxis. The cholangitis incidence was 55.6% in the sterile cohort, and 23.5% in the gram-positive and gram-negative cohort (p = 0.06). In the cholangitis cohort, no significant differences were detected for the age at Kasai and the pre- and postoperative total bilirubin. CONCLUSION: We found that our antibiotic regiment covered bacteria in the upper gastrointestinal (GI) tract in the majority of our patients at the time of Kasai. Nonetheless, a significant proportion of patients developed signs of cholangitis. There was no higher rate of cholangitis in patients with resistant bacteria. Thus, our data do not support the hypothesis of extended postoperative intravenous antibiotics to prevent ascending cholangitis.

Choledochal Cysts Resected during Childhood Show No Mutations of KRAS and BRAF as Early Markers of Malignancy in Cholangiocytes.

INTRODUCTION: In patients with choledochal cysts (CDC), a hyperplasia-dysplasia-carcinoma sequence can lead to biliary tract malignancy. The limited data available suggest that the risk decreases considerably after excision in childhood. We analyzed samples of resected CDC from pediatric patients histologically and performed mutational analysis of the proto-oncogenes KRAS and BRAF as early markers of malignant alteration in cholangiocytes. MATERIALS AND METHODS: After institutional review board approval, patients undergoing resection for CDC in our center from 2011 to 2019 were retrospectively identified. Histopathological reports were searched for inflammation and endothelial alteration. Cases with sufficient tissue specimen were tested for KRAS codon 12/13 and BRAF codon 600 mutations by pyrosequencing. RESULTS: In total, 42 patients underwent resection for choledochal cyst in the study period. Median age at surgery was 2.4 years (range = 18 days-18 years). Histopathological analysis showed no malignancy, but various degrees of inflammation or fibrosis in approximately 50% of the patients and in all age groups. Sufficient tissue for mutation analysis was available for 22 cases, all of which tested negative for KRAS or BRAF mutation. CONCLUSION: In our series, chronic inflammatory changes were frequently present in CDC of infants and children. However, the lack of KRAS and BRAF mutations suggests that no malignant changes have been initiated in this group of European patients undergoing early resection.