[Congenital pulmonary malformations : Diagnosis and treatment]. / Kongenitale Lungenfehlbildungen : Diagnostik und Therapie.

PERFORMANCE: Congenital pulmonary malformations (CPM) are rare and can be associated with high morbidity. Clinical presentation, diagnostic procedures, imaging, and therapy of CPM are discussed. ACHIEVEMENTS: Today, most CPM can be diagnosed prenatally by ultrasound. Postnatally, respiratory symptoms up to respiratory failure and recurrent lower respiratory tract infection are typical findings. Due to low diagnostic accuracy of chest x­ray in CPM, all children with prenatal diagnosis of CPM or postnatally suspected CPM should undergo cross-sectional imaging. PRACTICAL RECOMMENDATIONS: Based on imaging alone, the various subtypes of CPM cannot be definitively differentiated, which is why histological confirmation remains the gold standard. Surgical resection is the standard of care with minimally invasive procedures increasingly being employed. In certain situations, a watch-and-wait approach is possible.

Continuous intra-gastral monitoring of intra-abdominal pressure in critically ill children: a validation study.

BACKGROUND: In critically ill children, detection of intra-abdominal hypertension (IAH > 10 mmHg) and abdominal compartment syndrome (ACS = IAH + organ dysfunction) is paramount and usually monitored through intra-vesical pressures (IVP) as current standard. IVP, however, carries important disadvantages, being time-consuming, discontinuous, with infection risk through observer-dependent manipulation, and ill-defined for catheter sizes. Therefore, we sought to validate air-capsule-based measurement of intra-gastric pressure (ACM-IGP). METHODS: We prospectively compared ACM-IGP with IVP both in vivo and in vitro (water column), according to Abdominal-Compartment-Society validation criteria. We controlled for patient age, admission diagnosis, gastric filling/propulsive medication, respiratory status, sedation levels and transurethral catheters, all influencing intra-abdominal pressure (IAP). RESULTS: In tertiary care PICU setting, finally, n = 97 children were enrolled (median age, 1.3 years [range 0 days-17 years], LOS-PICU 8.0 [1-332] days, PRISM-III-Score 13 [0-35]). In n = 2.770 measurements pairs, median IAP was 6.7 [0.9-23.0] mmHg, n = 38 (39%) children suffered from IAH > 10 mmHg, n = 4 from ACS. In vitro against water column, ACM-IGP correlated perfectly (r2 0.99, mean bias - 0.1 ± 0.5 mmHg, limits of agreement (LOA) - 1.1/+ 0.9, percentage error [PE] 12%) as compared with IVP (r2 0.98, bias + 0.7 ± 0.6 mmHg, LOA - 0.5/+ 1.9, PE 15%). With larger IVP catheters at higher pressure levels, IVP underestimated pressures against water column. In vivo, agreement between either technique was strong (r2 0.95, bias 0.3 ± 0.8 mmHg, LOA - 1.3/+ 1.9 mmHg, PE 23%). No impact of predefined control variables on measurement agreement was observed. CONCLUSIONS: In a large PICU population with high IAH prevalence, ACM-IGP agreed favourably with IVP. More widespread usage of ACM-IGP may improve detection rates of ACS in critically ill children. Trial registration WHO-ICTRP-No. DRKS00006556 (German Clinical Trial Register). Registered 12th September 2014, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00006556.

The prevalence and role of coping strategies in the nutritional intake of children born with esophageal atresia: a condition-specific approach.

This study describes results of a condition-specific approach to the assessment of coping strategies in nutritional intake situations used by children with esophageal atresia. One hundred three families of children 2-17 years old with esophageal atresia participated (94% response rate). Following standardized focus groups with 30 families, nine coping items were developed, reflecting nine different coping strategies in nutritional intake situations. The coping items were pilot tested by 73 new families and evaluated for feasibility, validity, and reliability. The families also completed a validated condition-specific quality-of-life questionnaire for children with esophageal atresia, which included the scale Eating-Quality-of-life. Data were analyzed using descriptives, between-group analysis, and Spearman's rho (P < 0.05). Altogether, the coping items were feasible, valid, and reliable. Items reflecting problem-focused strategies revealed that 89% of 2-17 years old 'recognized their responsibility' and managed nutritional intake problems on their own, 79% 'tried to solve their feeding problems' testing different solutions, 79% took a 'confronting approach' to do what peers did in eating situations, and 54% 'sought other people's support'. Items reflecting emotion-focused strategies showed that 86% of the children 'accepted' their feeding difficulties, 68% 'reappraised feeding difficulties into positive outcomes' such as to eat only when food tasted good. Moreover, 63% of the children 'avoided' nutritional intake situations, 29% 'expressed worry or fear' when faced with these situations, while 25% 'distanced' themselves from eating problems by hiding or throwing away food. The children's use of coping strategies were mostly related to the existence of digestive symptoms (P < 0.05). Positive and negative coping strategies were identified. Of particular note was a correlation cluster of the so-called disengagement strategies 'avoidance', 'expression of emotional concerns' and 'distancing'. These strategies were negatively correlated with Eating-Quality-of-Life. Conversely, taking a 'confronting approach' correlated positively with Eating-Quality-of-life (P < 0.05). Hence, most children with esophageal atresia employ various coping strategies in nutritional intake situations. A good Eating-Quality-of-life may be positively affected by treating digestive morbidity and encouraging children to take an active approach to their eating problems rather than using disengagement coping.

[Biliary atresia and congenital cholestatic syndromes : Characteristics before, after and during transition]. / Gallengangatresie und angeborene Cholestasesyndrome : Besonderheiten vor, nach und während der Transition.

BACKGROUND: A growing number of patients with biliary atresia and congenital cholestatic syndromes are reaching adulthood. These patients often have a number of typical medical features, including specific characteristics of liver transplantation medicine. OBJECTIVE: What are the special features in the care of adults suffering from liver diseases with manifestation in childhood and adolescence, both before and after liver transplantation (LTX). How does the progression of individual diseases differ depending on age at manifestation? What are specific aspects following pediatric LTX? PATIENTS AND METHODS: Evaluation and discussion of existing guidelines and recommendations of the individual disciplines and professional societies as well as the current literature. Joint discussion of the recommendations between disciplines (gastroenterology, pediatric gastroenterology, surgery). Inclusion of center-specific experiences with transition from existing transition outpatient departments and training. RESULTS: The recommendations are presented specifically for each disease. Special features in individual diseases after LTX are also discussed. Diagnosis-independent general treatment concepts for cholestasis and chronic liver disease are presented. CONCLUSION: Patients with biliary atresia and congenital cholestatic syndromes have a life-long chronic liver disease with and without LTX and require specific medical care. The patients benefit from the pooling of expertise in the individual disciplines.

Development and pilot-testing of a condition-specific instrument to assess the quality-of-life in children and adolescents born with esophageal atresia.

The survival rate of children with esophageal atresia has today reached 95%. However, children are at risk of chronic morbidity related to esophageal and respiratory dysfunction, and associated anomalies. This study describes the pilot testing of a condition-specific health-related quality-of-life instrument for children with esophageal atresia in Sweden and Germany, using a patient-derived development approach consistent with international guidelines. Following a literature review, standardized focus groups were conducted with 30 Swedish families of children with esophageal atresia aged 2-17 years. The results were used for item generation of two age-specific pilot questionnaire versions. These were then translated from Swedish into German with considerations of linguistic and semantical perspectives. The 30-item pilot questionnaire for children aged 2-7 years was completed by 34 families (parent report), and the 50-item pilot questionnaire for children aged 8-17 years was completed by 52 families (51 child report, 52 parent report), with an overall response rate of 96% in the total sample. Based on predefined psychometric criteria, poorly performing items were removed, resulting in an 18-item version with three domains (Eating, Physical health and treatment, Social isolation and stress,) for children aged 2-7 years and a 26-item version with four domains (Eating, Social relationships, Body perception, and Health and well-being) for children aged 8-17 years. Both versions demonstrated good internal consistency reliability and acceptable convergent and known-groups validity for the total scores. The study identified specific health-related quality-of-life domains for pediatric patients with esophageal atresia, highlighting issues that are important for follow-up care. After field testing in a larger patient sample, this instrument can be used to enhance the evaluation of pediatric surgical care.

Acupuncture in posttonsillectomy pain : A prospective, double-blinded, randomized, controlled trial.

BACKGROUND: Postoperative swallowing pain is one of the most unpleasant after-effects of tonsillectomy. During recent years, the demand for alternatives to drug-based pain therapy has continued to grow, although the topic has received little research attention until now. MATERIALS AND METHODS: A total of 46 patients were randomized into verum acupuncture, control acupuncture, and drug-based treatment groups. All patients received nonsteroidal antirheumatic drugs (NSAIDs). One hour after drug intake, the verum group also received acupuncture according to classical acupuncture rules (S34, S44 and PC5). The control group had acupuncture needles placed at nonspecific acupuncture points in the midaxillary line. Acupuncture was performed by a blinded acupuncturist, who had learnt exclusively these techniques in the run up to the study. Patients were asked to evaluate their pain before, and at intervals of 20 min, 1 h, 2 h, and 3 h after drug intake/acupuncture treatment using a visual analog scale (VAS). RESULTS: The analgesic effect of acupuncture was significant up to 3 hours in the verum group (p < 0.05). The analgesic effect in the control acupuncture group was significant for up to 1 h after acupuncture (p < 0.05). With reference to the time point before acupuncture, the differences between both acupuncture groups and the drug group were significant (p < 0.01) over the whole time. CONCLUSION: Acupuncture is an effective complement to NSAIDs in the treatment of posttonsillectomy pain. Particularly patients with allergies, drug intolerance, or reduced response to the commonly administered drugs may benefit from acupuncture.

[Acupuncture in posttonsillectomy pain : A prospective double-blind randomized controlled trial. German version]. / Einsatz von Akupunktur bei Posttonsillektomieschmerz : Eine prospektive, randomisierte und kontrollierte Doppelblindstudie.

BACKGROUND: Postoperative swallowing pain is one of the most unpleasant after-effects of tonsillectomy. During recent years, the demand for alternatives to drug-based pain therapy has continued to grow, although the topic has received little research attention until now. MATERIALS AND METHODS: A total of 46 patients were randomized into verum acupuncture, control acupuncture, and drug-based treatment groups. All patients received nonsteroidal antirheumatic drugs (NSAIDs). One hour after drug intake, the verum group also received acupuncture according to classical acupuncture rules (S34, S44 and PC5). The control group had acupuncture needles placed at nonspecific acupuncture points in the midaxillary line. Acupuncture was performed by a blinded acupuncturist, who had learnt exclusively these techniques in the run up to the study. Patients were asked to evaluate their pain before, and at intervals of 20 min, 1 h, 2 h, and 3 h after drug intake/acupuncture treatment using a visual analog scale (VAS). RESULTS: The analgesic effect of acupuncture was significant up to 3 hours in the verum group (p < 0.05). The analgesic effect in the control acupuncture group was significant for up to 1 h after acupuncture (p < 0.05). With reference to the time point before acupuncture, the differences between both acupuncture groups and the drug group were significant (p < 0.01) over the whole time. CONCLUSION: Acupuncture is an effective complement to NSAIDs in the treatment of posttonsillectomy pain. Particularly patients with allergies, drug intolerance, or reduced response to the commonly administered drugs may benefit from acupuncture.

[Ethical conflicts in pediatric surgery: high-performance medicine and the economical environment]. / Ethische Konflikte in der Kinderchirurgie : Hochleistungsmedizin und ökonomische Rahmenbedingungen.

BACKGROUND: Healthcare is increasingly influenced by economical constraints which can lead to ethical conflicts for surgeons. The aim of the study was to investigate the incidence of these conflicts and the coping strategies of surgeons. METHODS: A prospective, standardized staff survey in an academic pediatric surgical department was performed over a period of 4 weeks. The types of conflict and solution strategies were determined. The agreement with given statements was determined using a 5-point Likert scale. RESULTS: In 155 returned questionnaires 74 ethical conflicts were identified. Most conflicts concerned decisions relating to diagnosis-related groups (DRG) which were economically based. To resolve the ethical conflict surgeons decided to the detriment of patients in 73  % and to the economical benefit in 72 %. In 8  % a medical disadvantage for the patient was noted and in 62  % a disadvantage for patient comfort was seen. Surgeons were highly dissatisfied with the conflict solutions (2.3/5). CONCLUSIONS: Economical considerations cause ethical conflicts in the daily routine in pediatric surgery. Decisions are made to the benefit of the hospital and cause a decrease in patient comfort. Political solutions for this problem are required in the interest of all those involved.

COUP-TFII gene expression is upregulated in embryonic pleuroperitoneal folds in the nitrofen-induced congenital diaphragmatic hernia rat model.

INTRODUCTION: The nitrofen model of congenital diaphragmatic hernia (CDH) creates a Bochdalek-type diaphragmatic defect and has been widely used to investigate the pathogenesis of CDH. However, the exact pathogenesis of the diaphragmatic defect in this model is still poorly understood. Chicken ovalbumin upstream promotor-transcription factor II (COUP-TFII) is expressed in the embryonic pleuroperitoneal folds (PPF) in the early stage of development and in the diaphragm in the late days of gestation. COUP-TFII is known to be a strong repressor of the retinoid signaling pathway (RSP), which plays an important role in diaphragm development. Furthermore, it has been recently shown that COUP-TFII is upregulated during early gestation in the nitrofen-induced hypoplastic lung. We designed this study to investigate the hypothesis that COUP-TFII gene expression is upregulated during early diaphragmatic development in the PPF. MATERIAL AND METHODS: Timed pregnant rats were exposed to either olive oil (Control) or nitrofen (CDH) on day 9 of gestation (D9). Fetuses were sacrificed on D13, D18 or D21. The PPF was dissected from D13 fetuses using laser capture microdissection. Diaphragms were dissected from D18 and D21 fetuses under the dissection microscope. The relative mRNA expression levels of COUP-TFII were determined using real-time PCR. Immunohistochemistry was performed to evaluate diaphragmatic protein expression and the distribution of COUP-TFII.Results On D13, gene expression levels of COUP-TFII in the PPF were significantly increased in the CDH group (82.93 ± 11.85) compared to Controls (46.22 ± 8.09; p < 0.05), whereas there were no differences at later time points. The immunoreactivity of diaphragmatic COUP-TFII was markedly increased in the PPF in the CDH group compared to controls on D13. No difference in immunoreactivity was observed on D18 and D21. CONCLUSION: Upregulation of COUP-II gene expression in the PPF may contribute to the diaphragmatic defect in the nitrofen CDH model by inhibiting the RSP.

Failure to report ethical approval and informed consent in paediatric surgical publications.

INTRODUCTION: Medical research involving human subjects must follow ethical standards as outlined in the Declaration of Helsinki of the World Medical Association. The 3 journals J Ped Surg, Eur J Pediatr Surg and Pediatr Surg Int all require authors' statements regarding ethical approval and the patient or guardian informed consent for studies involving human subjects. It has previously been reported that ethical approval and informed consent is not documented in a considerable proportion of publications in other journals. The aim of this study was to investigate whether ethical approval and informed consent was documented in a consecutive series of publications involving human subjects in the 3 paediatric surgical journals. MATERIAL AND METHODS: All articles involving human subjects or material published in the print and online issues of J Ped Surg, Eur J Pediatr Surg and Pediatr Surg Int in 2010 were systematically reviewed as to whether ethics committee or institutional review board approval and patient or guardian consent to participate in the study was reported. Publications were categorised into prospective studies, retrospective studies, description of new methods and case reports. RESULTS: 579 articles were included in the study (324 J Ped Surg, 103 Eur J Pediatr Surg and 153 Pediatr Surg Int). In case reports (n=142), the lowest level of documentation of ethical approval (1.4%) and informed consent (1%) was observed. The remaining 437 original articles reported ethical approval in 54% of publications (prospective studies 66%, retrospective studies 59%, new methods 27%). Informed consent was documented in 16% of the original articles (prospective studies 50%, retrospective studies 17%, new methods 14%). Detailed investigation of the different journals revealed the highest rate of reporting of ethical approval for J Pediatr Surg (71%), followed by Eur J Pediatr Surg (43%), and Pediatr Surg Int (24%). Patient or guardian informed consent was reported in 15% of the publications in J Pediatr Surg and Pediatr Surg Int, respectively, and in 24% of the papers published in Eur J Pediatr Surg. CONCLUSION: Adherence to ethical principles in paediatric surgical research should be improved. Information on ethical approval and informed consent should be included in all manuscripts accepted for publication. Editors should consider establishing a specific online template asking authors for the necessary information during the submission process.

IGFBP-4 gene overexpression in the nitrofen-induced hypoplastic lung.

PURPOSE: The precise mechanism of pulmonary hypoplasia (HP) associated with congenital diaphragmatic hernia (CDH) remains unclear. Insulin-like growth factors (IGFs) play an essential role in fetal lung development through IGF receptors (IGFRs) by regulating cellular proliferation, differentiation and survival. It has been reported that the expression of genes involved in IGF-IGFR signaling is altered in the nitrofen-induced hypoplastic lung during the later stages of lung development. IGF-binding proteins (IGFBPs) control bioavailability, activity and disruption of IGFs through the high affinity IGFBP/IGF complexes. IGFBP-4 is a key inhibitor of IGF-IGFR signaling-mediated cell proliferation. It has been revealed that cell proliferation in fetal lung fibroblasts is inhibited by increased IGFBP-4 production. We hypothesized that IGFBP-4 gene expression is increased during the later stages of lung development in the nitrofen-induced CDH lung. METHODS: Pregnant Sprague-Dawley rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. Fetuses were harvested by cesarean section on D18 and D21. Fetal lungs were divided into 3 groups: control, nitrofen without CDH [CDH(-)] and nitrofen with CDH [CDH(+)] (n=24 at each time point). Relative mRNA levels of IGFBP-4 were determined using real-time RT-PCR. Immunohistochemistry was performed to evaluate the protein expression of IGFBP-4. RESULTS: The relative expression levels of IGFBP-4 mRNA were significantly increased in CDH(-) and CDH(+) groups on D18 and D21 compared to controls. Immunohistochemistry showed increased IGFBP-4 expression in mesenchymal compartments on D18 and D21 in hypoplastic lungs compared to controls. CONCLUSION: Overexpression of pulmonary IGFBP-4 during the later stages of lung development may contribute to pulmonary hypoplasia in the nitrofen-induced CDH model by inhibiting IGF-mediated cell proliferation.

Downregulation of FGFRL1 contributes to the development of the diaphragmatic defect in the nitrofen model of congenital diaphragmatic hernia.

INTRODUCTION: The nitrofen model of Congenital Diaphragmatic Hernia (CDH) displays a diaphragmatic defect of the Bochdalek-type and has been widely used to investigate the pathogenesis of CDH. However, the exact pathomechanism of the diaphragmatic defect is still poorly understood. Fibroblast growth factor (FGF) receptor-like 1 (FGFRL1), a member of the FGF receptor family, plays a key role in physiological diaphragmatic development. FGFRL1 is expressed in the fetal diaphragm at low levels in early gestation and its expression steadily increases, becoming most pronounced in later gestational stages. It has been reported that FGFRL1 homozygous null mice have thin, partially amuscular diaphragms and die at birth due to respiratory failure. The aim of this study was to investigate the hypothesis that FGFRL1 gene expression in the diaphragm is downregulated during the later gestational stages in the nitrofen CDH model. MATERIAL AND METHODS: Timed pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9 of gestation (D9). Cesarean section was performed on D18 or D21. Fetal diaphragms (n=40) were micro-dissected and divided into CDH group and controls. Total RNA was extracted from the diaphragms and the mRNA levels of FGFRL1 were determined using real-time PCR. Immunohistochemistry was performed to evaluate diaphragmatic protein expression of FGFRL1. Student's t-test and Mann-Whitney test were used, where appropriate. Statistical significance was considered for p<0.05. RESULTS: Relative mRNA expression levels of FGFRL1 were significantly decreased in the CDH group compared to controls on D18 (3.63 ± 1.65 vs. 6.04 ± 3.12, p<0.05) and D21 (1.36 ± 1.01 vs. 2.57 ± 1.34, p<0.05). Immunoreactivity of FGFRL1 was markedly decreased in the diaphragms of the CDH group compared to controls on D18 and D21. CONCLUSION: Our data provide strong evidence that downregulation of the FGFRL1 gene during the late stages of gestation may contribute to the development of the diaphragmatic defect in nitrofen-induced CDH.

Down-regulation of lung Kruppel-like factor in the nitrofen-induced hypoplastic lung.

INTRODUCTION: Pulmonary hypoplasia is a primary cause of high morbidity and mortality in neonates with Congenital Diaphragmatic Hernia (CDH). However, the precise pathogenesis of PH associated with CDH is still not clearly understood. It has been recently reported that lung Kruppel-like factor (LKLF), a member of the Kruppel-like factor family of transcription factors, is predominantly expressed in lungs and plays an important role in lung morphogenesis and functional maturation. It has been reported that homozygous deletion of LKLF gene in mice results in reduced lung morphogenesis. It is further reported that chimeric mice derived from LKLF (-/-) embryonic stem cells exhibit delayed lung development especially in the later gestational stages. We therefore designed this study to test the hypothesis that the LKLF gene is down-regulated during later stages of lung development in nitrofen-induced hypoplastic lungs. MATERIAL AND METHODS: Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into 3 groups:control, nitrofen without CDH(CDH(-)) and nitrofen with CDH(CDH(+)) (n=24 for each group). Real-time RT-PCR analysis was performed to investigate pulmonary gene expression levels of LKLF. Differences between the 3 groups at each time point were tested statistically and significance was accepted at p<0.05. Immunohistochemistry was also performed to evaluate LKLF protein expression and distribution. RESULTS: The relative mRNA expression levels of LKLF on D18 and D21 were significantly decreased (p<0.01) in CDH(-) and CDH(+) groups compared to controls. The gene expression levels of LKLF on D15 did not differ significantly between the nitrofen group and controls. Immunohistochemical study showed strong LKLF immunoreactivity on D18 and D21 in nitrofen-induced hypoplastic lung compared to controls, whereas no difference was seen on D15. CONCLUSIONS: Our results provide evidence for the first time that LKLF is down-regulated in the later stages of lung development in nitrofen-induced hypoplastic lungs. These data suggest that the down-regulation of LKLF during this critical period of lung morphogenesis may impair lung development and maturation, resulting in pulmonary hypoplasia in the nitrofen CDH model.

Working and training conditions of residents in pediatric surgery: a nationwide survey in Germany.

PURPOSE: As in other surgical specialties, increasing concern has been expressed worldwide about the shortage of trainees in pediatric surgery training programs. We performed a nationwide survey to investigate the current situation in Germany. METHODS: An internet-based nationwide survey comprising 36 questions on training conditions in pediatric surgery was linked to the homepage of the German Society of Pediatric Surgery from June to September 2008. Statements on the following aspects were evaluated by responding residents using a scale from 1 (I do not agree at all) to 5 (I fully agree): workplace, cooperation with colleagues, head of the department, cooperation with other specialties, training and research conditions. A median value of 3 indicated an unsatisfactory assessment, with at least 50% of respondents giving an indifferent or negative response. RESULTS: 70 questionnaires were completed. Some of the evaluations revealed problematic areas. In particular, statements regarding working hours revealed dissatisfaction among the responding doctors. The median value accorded the statement "I am satisfied with the current working time regulation" was 2.9. With regard to departmental heads, some criticisms were directed against a perceived lack of soft skills. According to the respondents, their involvement in decision-making processes was insufficient ("We are involved in decision-making processes affecting our working conditions" - median value 2.4). Residents were also dissatisfied with the feedback they received for their work ("I get enough feedback regarding my achievement" - median value 2.6). Another problem area was career development ("I will finish my specialist training in time" - median value 2.9). However, these points did not affect overall satisfaction. CONCLUSIONS: Trainee satisfaction with regulations on working hours is low. Despite a general satisfaction with all fields appraised, improvements in various individual areas, e. g., the attitude of departmental heads and strategies of career development, are necessary.

Laparoscopy for suspected appendicitis in children: May a macroscopically normal appendix be left in situ?

BACKGROUND/PURPOSE: An appendix which appears macroscopically normal is found in 10%-20% of laparoscopic explorations for suspected appendicitis. The appropriate surgical strategy for these cases is a matter of debate. We analysed a consecutive series of children in whom an inconspicuous appendix was left in situ. MATERIAL AND METHODS: Laparoscopic exploration was performed in 188 consecutive children with suspected appendicitis and an expected need for immediate operation from 2002 to 2006. Our concept included laparoscopic appendectomy in patients with macroscopic signs of inflammation. Normal appearing appendices were left in situ. All patients with a remaining appendix underwent follow-up. Major endpoints were defined as postoperative complications, re-operations for abdominal symptoms, hospital admissions and consultations with medical doctors during the follow-up period. In addition, other symptoms and well-being were assessed. RESULTS: The appendix appeared macroscopically normal in 21 (11%) of the 188 patients (mean age 11.7 years (+/-4.2); 11 f, 10 m), and was therefore left in situ. The immediate postoperative course was uneventful in all patients with a mean hospital stay of 2.7 (+/-1.2) days. During the follow-up period (mean of 25 (+/-17) months), 18 patients (86%) did not or only rarely (< or = 2 times) consult a medical doctor for abdominal symptoms. Three patients (14%) reported more than 2 consultations. No patient was readmitted to hospital or operated for acute appendicitis. At the last follow-up, 20 patients (95%) were entirely symptom-free. One patient complained about persisting right lower quadrant pain, but refused further diagnostic procedures or interventions. CONCLUSION: According to our results, a macroscopically inconspicuous appendix may be left in situ in patients undergoing laparoscopy for suspected appendicitis. However, this conclusion is based on a small number of patients and larger series are mandatory.

Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML).

The important cell cycle regulatory gene p15(INK4b) has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15(INK4b) gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5' region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.