[Necessity for radiological examinations in children : Children in two levels]. / Notwendigkeit von radiologischen Untersuchungen bei Kindern : Das Kind in 2 Ebenen.

The diagnostics and treatment of pediatric skeletal trauma can be fundamentally different from adults. Based on in-house data the diagnostic approach to the most frequently encountered pediatric injury patterns is discussed. The necessity for a primary X­ray imaging or computed tomography examination is questioned. Both diagnostic methods cause stochastic radiation damage. Therefore, it is important to perform the safest examination for the child while injuries are correctly diagnosed.

Association of exercise-induced hyperinsulinaemic hypoglycaemia with MCT1-expressing insulinoma.

AIMS/HYPOTHESIS: Exercise-induced hyperinsulinism (EIHI) is a hypoglycaemic disorder characterised by inappropriate insulin secretion following anaerobic exercise or pyruvate load. Activating promoter mutations in the MCT1 gene (also known as SCLA16A1), coding for monocarboxylate transporter 1 (MCT1), were shown to associate with EIHI. Recently, transgenic Mct1 expression in pancreatic beta cells was shown to introduce EIHI symptoms in mice. To date, MCT1 has not been demonstrated in insulin-producing cells from an EIHI patient. METHODS: In vivo insulin secretion was studied during an exercise test before and after the resection of an insulinoma. The presence of MCT1 was analysed using immunohistochemistry followed by laser scanning microscopy, western blot analysis and real-time RT-PCR of MCT1. The presence of MCT1 protein was analysed in four additional insulinoma patients. RESULTS: Clinical testing revealed massive insulin secretion induced by anaerobic exercise preoperatively, but not postoperatively. MCT1 protein was not detected in the patient's normal islets. In contrast, immunoreactivity was clearly observed in the insulinoma tissue. Western blot analysis and real-time RT-PCR showed a four- to fivefold increase in MCT1 in the insulinoma tissue of the EIHI patient compared with human pancreatic islets. MCT1 protein was detected in three of four additional insulinomas. CONCLUSIONS/INTERPRETATION: We show for the first time that an MCT1-expressing insulinoma was associated with EIHI and that MCT1 might be present in most insulinomas. Our data suggest that MCT1 expression in human insulin-producing cells can lead to EIHI and warrant further studies on the role of MCT1 in human insulinoma patients.

Malignant pancreatic tumors in children and young adults: evaluation of 228 patients identified through the Surveillance, Epidemiology, and End Result (SEER) database.

BACKGROUND: Malignant pancreatic tumors are rare in young patients, few epidemiologic data are available. We reviewed prognostic factors and outcome of 228 patients <30 years with malignant pancreatic tumors identified through the U.S. National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) Public-use Database from 1973 to 2004. METHODS: Cases were grouped using the ICD-O-3. 5-year overall survival (OAS) was assessed by gender, ethnicity, SEER stage, and 5-year age intervals using univariate and Cox regression analysis. RESULTS: 228 patients with malignant pancreatic tumors were identified, resulting in an incidence of 0.46/million (100 carcinomas, 85 endocrine tumors, 8 solid pseudopapillary neoplasms (SPN), 11 pancreatoblastomas) in the USA. OAS was worse in males than females (37% vs. 55%, p=0.005). OAS according to stage was 87%, 68%, 21% for local (n=54), regional (n=42), distant metastatic disease (n=108), respectively. OAS of patients with carcinoma was 33%, endocrine tumors 58%, SPNs 88%, pancreatoblastomas 66%. Cox regression revealed stage (p=< 0.001), histology (p=< 0.001), age group (p=0.05) to be independent prognostic factors. CONCLUSION: Malignant pancreatic tumors are extremely rare in children and young adults. Entities change over the age groups towards more carcinomas with worse outcome in older patients. Tumor stage, histology and age group are important predictors for outcome. International collaboration is needed to learn more about pediatric pancreatic tumors.

Intraoperative sonography: a technique for localizing focal forms of congenital hyperinsulinism in the pancreas.

Congenital hyperinsulinism (CHI), syn. nesidioblastosis, is the most frequent cause of persistent, recurrent hypoglycemia in infancy. One third of patients show a single circumscribed focus. Enucleation of the focus and the removal of all affected ß-cells with preservation of healthy tissue is the treatment of choice. The intrapancreatic choledochus as well as the ductus pancreaticus major must remain intact. The diagnostic gold standard is 18F-DOPA-PET/CT. Intraoperative sonography is carried out to correctly visualize the focus preoperatively localized by PET/CT in situ during the operation. The enucleation of the focus was carried out 3 - 20 days after PET/CT in 5 patients at an age of 3.5 - 14 months. Intraoperative ultrasound was carried out with high-capacity devices of different manufacturers under use of broadband probes (9 - 14 MHz). The localization by intraoperative ultrasound was accurate in all 5 patients with focal CHI, with regard to the intraoperative localization as previously described by PET/CT and histology. D. choledochus and D. pancreaticus major were separated intraoperatively by ultrasound. 3 of 5 patients were cured by complete enucleation of the focus. Nevertheless, the entire intraoperative identification of the segmented focus is still problematic. Characteristic sonographic features of a CHI focus are: hypoechogenicity, variable homogeneous and inhomogenous texture, blurred, irregular limitation without capsule, filiform, lobular processes, and insular dispersal into the surrounding tissue. Intraoperative high-resolution sonography helps the pediatric surgeon to determine size, configuration and topography of a CHI focus.

Human Islets Exhibit Electrical Activity on Microelectrode Arrays (MEA).

This study demonstrates for the first time that the microelectrode array (MEA) technique allows analysis of electrical activity of islets isolated from human biopsies. We have shown before that this method, i.e., measuring beta cell electrical activity with extracellular electrodes, is a powerful tool to assess glucose responsiveness of isolated murine islets. In the present study, human islets were shown to exhibit glucose-dependent oscillatory electrical activity. The glucose responsiveness could be furthermore demonstrated by an increase of insulin secretion in response to glucose. Electrical activity was increased by tolbutamide and inhibited by diazoxide. In human islets bursts of electrical activity were markedly blunted by the Na(+) channel inhibitor tetrodotoxin which does not affect electrical activity in mouse islets. Thus, the MEA technique emerges as a powerful tool to decipher online the unique features of human islets.Additionally, this technique will enable research with human islets even if only a few islets are available and it will allow a fast and easy test of metabolic integrity of islets destined for transplantation.

Serum levels of end products of nitric oxide synthesis correlate positively with tumor necrosis factor alpha and negatively with body temperature in patients with postoperative abdominal sepsis.

Nitric oxide (NO) has been implicated as the principal mediator of the catecholamine resistant vasodilation in septic shock. In this pilot study, we wanted to know if the serum values of nitrite/nitrate (NO2/NO3), the stable endproducts of NO biosynthesis, are elevated in patients with septic shock. Furthermore, we investigated whether there is a correlation between NO2/NO3 serum levels and tumor necrosis factor alpha or interleukin 6. NO2/NO3 serum values were significantly elevated in septic patients compared to controls (72.1 +/- 6.1 vs. 35.7 +/- 9.2 microM, p < .001). There was a significant positive correlation between serum values of NO2/NO3 and tumor necrosis factor alpha (rs = 0.59, p < .001). In contrast, no correlation between NO2/NO3 and interleukin 6 was found. With the exception of body core temperature, which showed a negative correlation with NO2/NO3 levels, no clinical variable turned out to be significantly related to NO biosynthesis. These data indicate a potential role for NO in the clinical course of abdominal sepsis, but points out that more specific data has to be evaluated by prospective clinical studies in order to understand the complex pathophysiologic role of this novel mediator.

Impact of experimental peritonitis on bone marrow cell function.

BACKGROUND: The effects of abdominal sepsis on the regulation of cell turnover in bone marrow and on the function of hematopoietic stem cells were investigated. METHODS: In a new mouse model of abdominal sepsis (colon ascendens stent peritonitis [CASP]) the proliferation, apoptosis, and colony-forming capacity of bone marrow cells were determined. RESULTS: Both experimental peritonitis and sham surgery increased proliferation of bone marrow cells significantly (P < .01). Incubation with granulocyte-macrophage colony-stimulating factor but not granulocyte colony-stimulating factor further augmented proliferation of bone marrow cells from septic mice. In contrast to cell proliferation, bone marrow cell apoptosis was significantly (P < .001) increased in response to CASP but not to sham surgery. CASP surgery and treatment of normal bone marrow cells with lipopolysaccharide, tumor necrosis factor-alpha, interleukin 1 beta, and interferon gamma increased the number of apoptotic cells to a similar extent. Stem cell assays revealed that during the late phase of peritonitis the colony formation by granulocytic-monocytic precursors was increased, whereas mature erythroid colony-forming cells were suppressed. Incubation of normal bone marrow cells with lipopolysaccharide and cytokines showed similar effects. CONCLUSIONS: These results reveal differential effects of experimental peritonitis on various hematopoietic lineages and suggest a potential role of inflammatory mediators for the dysregulation of bone marrow cell function during abdominal sepsis.

Simultaneous pneumonectomy and esophagectomy for bronchial carcinoma.

Two cases of bronchial carcinoma with oesophageal involvement are presented. Both were treated by simultaneous pneumonectomy and oesophagectomy. The postoperative course of each patient was complicated by secondary infection of the pneumonectomy space. One patient expired from a recurrent intratracheal tumour on the 83rd postoperative day and the other remains tumour free 3 years after treatment. As few therapeutic alternatives exist for non small cell bronchial carcinoma, primary radical surgical treatment should be considered, even in advanced cases where the tumour invades the oesophagus.

Ceramide induces apoptosis in neuroblastoma cell cultures resistant to CD95 (Fas/APO-1)-mediated apoptosis.

BACKGROUND/PURPOSE: Spontaneous tumor regression is a well-known characteristic in neuroblastomas. Because preliminary reports have shown that regression may be caused by apoptosis (a lethal cascade mediated by the CD95 (APO-1/Fas)-receptor), we analyzed the expression of CD95-receptors in 5 human neuroblastoma cell lines. Ceramides (known stimuli of apoptosis downstream from the CD95-receptor complex) also were used to test whether apoptosis would be induced in neuroblastoma cell cultures resistant to CD95-mediated programmed cell death. METHODS: The expression of the CD95-receptor was assessed by flow cytometry after incubation with either fluorisothiocyanate-conjugated (FITC) anti-CD95-antibody (UB2) or CD95-ligand for 16 hours. Apoptotic cell death was detected via microscopy, cell viability testing (MTT, 3-[4,5 dimehylthiazole-2-yl]-2,5 diphenyltetrazoliumbromide), and flow cytometric analysis after propidium iodide staining of the DNA. RESULTS: CD95-receptor expression was found on all neuroblastoma cell lines. Stimulation of the CD95-receptor of the malignant glioblastoma cell line LN229 (positive control) with either anti-CD95-antibody or CD95-ligand induced apoptosis. Apoptosis was not seen, however, in any of the neuroblastoma cell lines when the CD95-receptor was stimulated with anti-CD95-antibody or the CD95-ligand. Significant apoptosis was detected in all neuroblastoma cell lines after the addition of 25 micromol/L C2- and C6-ceramide. CONCLUSIONS: CD95-receptors are present on neuroblastoma cell lines, and these cells are resistant to apoptosis stimulated by anti-CD95-antibody or CD95-ligand. Apoptosis is induced, however, when these cells are treated with ceramide. A signal blockage downstream from the CD95-receptor complex and upstream of ceramide may account for this finding, and the "cellular FLICE inhibitory protein" (cFLIP) may be primarily responsible.

[Mediators in septic shock: strategies of securing them and assessment of their causal significance]. / Mediatoren beim septischen Schock: Strategien zu ihrer Sicherung und zur Einschätzung ihrer kausalen Bedeutung.

More than 100 different mediators are discussed as being responsible for the progression of the septic shock syndrome. A new concept is described to establish the causal role of a single mediator by using a decision tree which excludes different non-causal associations (different kinds of bias and chance). By definition of several criteria and methodological standards, the published studies on mediator release/formation could be analysed and evaluated (meta-analysis). Furthermore, the classical concept of one cause--one disease (Koch-Dale) is extended to a concept of multiple determining factors. The role of a single mediator can be assessed quantitatively by notation of conditional probabilities in the presence of other causal factors. A mediator can be classified as a necessary, sufficient or contributory determinant in septic shock. Improved therapeutic concepts can be expected from this approach.

[The therapeutic results of programmed relaparotomy in diffuse peritonitis]. / Therapie-Ergebnisse der programmierten Relaparotomie bei der diffusen Peritonitis.

The therapeutical concept of programmed relaparotomy was performed in 184 patients with diffuse peritonitis from 4/1984 to 4/1991. Clinical results were prospectively documented and a total of 46 variables (e.g. risk factors, clinical parameters, laboratory tests, microbiological screenings, score systems) both univariate and multivariate were tested for prognostic significance. Total lethality rate was 26% (48/184 patients). If complete eradication of the source of infection was surgically achieved (150 patients/82%) lethality rate was only 9%. In contrast, lethality rate was 100% in patients with unsuccessful surgical focus eradication. Eradication of the source of infection during the first operation (104 patients/56%) resulted in a lethality rate of 6%, compared to 17% for patients who needed two or even more operations (46 patients/25%). Eradication of the source of infection during the first laparotomy ("focus eradication on time") was the most important prognostic parameters. Of further prognostic significance but with declining importance where serum-creatinine at the beginning of the treatment, patient's age (greater than less than 70 years) and preexistent hepatic disease.

[Development of pediatric surgery in the next 20 years]. / Entwicklung der Kinderchirurgie in den nächsten 20 Jahren.

Pediatric surgery focuses not on an anatomic region or organ system, but on the development of a growing human being according to age. Recently, a tendency to reduce and to downgrade pediatric surgery could be observed which is due to economic reasons and an alarming lack of trained surgeons. Just as 60 years ago, general surgeons continue to operate on infants and children. However, this is a step backwards and an anachronism. Children are not small adults and pediatric surgery can be distinguished from adult surgery in many aspects, such as the spectrum of surgical diseases, the congenital malformations and frequently the indications and techniques of surgery. Pediatric surgeons, however, by themselves should specialize in centers which are focused on rare and complex diseases. Pediatric surgery should not be separated in the hospital, but integrated in a network with general surgery, traumatology, pediatrics, neonatology and specialists of the other surgical disciplines. Strict patient age limitations are not compatible with the individuality of adolescents and should be avoided. A well-equipped clinic for pediatric surgery is expensive, but a mandatory investment in the future!

Interstitial cells of Cajal in the vermiform appendix in childhood.

BACKGROUND AND AIMS: The interstitial cells of Cajal (ICC) have not yet been investigated in the vermiform appendix. They are important for the peristalsis of the gastrointestinal tract and have been found to be altered in various motility disorders. Motor disturbance has been suggested as a possible contributor in the unclear etiology of appendicitis. We wanted to examine the distribution of the ICC in the vermiform appendix. Furthermore we investigated whether ICC are altered in persons with appendicitis. METHODS: We investigated the ICC distribution in 28 appendices of children using immunohistochemistry and anti-c-kit antibodies. Cells and processes were quantified in normal, acute and chronic inflamed appendices. RESULTS: IC(C)-CM and IC(C)-LM were found in the circular and longitudinal muscle layers, respectively. IC(C)-LM, however, were scarce and inhomogeneous in contrast to the IC(C)-CM. The functionally important subgroups of the colon, the IC(C)-SM and IC(C)-MP, however, could not be detected in the appendix with the used antibody. There was no difference in the distribution of detected ICC between normal and inflamed appendices. CONCLUSION: IC(C)-LM are altered and IC(C)-SM and IC(C)-MP are lost in the vermiform appendix with no differences between healthy and inflamed tissue and without a correlation to appendicitis. Thus, other factors must be considered in the etiology of appendicitis.

Laser resection of posterior urethral valves.

Laser resection (LR) of posterior urethral valves during infancy as early as possible after diagnosis appears to represent a safe and reliable method. In contrast to other procedures, LR allows valve ablation with thin cystoscopes and carries little risk, even in premature and newborn infants. Its application in seven children in the course of 2 years principally confirmed its suitability for use: it could be applied in all cases without any problems and led to extensive resection of the valve tissue and removal of the obstruction in all patients. The encouraging clinical findings were confirmed by control cystoscopies and micturating cystourethrograms. Complications arising from the method were not observed.

[Prognostic factors in diffuse peritonitis]. / Prognosefaktoren bei der diffusen Peritonitis.

In order to evaluate their prognostic relevance for survival 46 variables were submitted to univariate as well as multivariate analysis in a group of 184 patients with diffuse peritonitis. In the univariate analysis a significant correlation with the outcome was found for the following parameters: age greater than or equal to 70 years, preexisting hepatic or cardiac disease, no eradication of the primary source of infection at first laparotomy for peritonitis, cardiovascular instability, respiratory failure, hyperbilirubinemia, thrombocytopenia, elevated serum creatinine and diminished creatinine clearance at the beginning and proof of pseudomonas aeruginosa in the peritoneal exsudate and of candida albicans in the blood culture during the course of the peritonitis. In the multivariate analysis the surgical eradication of the primary source of infection at the first laparotomy for peritonitis, serum creatinine at the beginning of peritonitis, age greater than or equal to 70 years and a preexisting hepatic disease proved to be the independent variables with significant prognostic relevance for survival of the patients.

[Actuarial survival and prognostic factors of bronchial cancer]. / Uberlebenswahrscheinlichkeit und prognostische Faktoren des Bronchialkarzinoms.

A total of 1325 patients with bronchogenic carcinoma who were treated at the surgical clinic of the Technical University of Munich between 1981 and 1991 were enrolled in a prospective follow-up study. The 5-year actuarial survival rate of 605 patients with squamous cell carcinoma was 28.2%, of 288 patients with adenocarcinoma 38.0%, of 219 patients with small cell carcinoma 15.4%, of 74 patients with giant cell carcinoma 19.0%, and of 139 patients with other histologic findings 27.8%. In all, 680 patients (51.4%) underwent surgery. Diagnostic thoracotomy without resection was performed in 6.2% of cases. Lethality within 30 days was 1% for lobectomy, 7.3% for bilobectomy, and 7.7% for pneumonectomy including extended resections. The 5-year survival rates among the operated patients were 64.8% for T1N0M0 tumours, 49.4% for T2N0M0, 46.1% for T1N1M0, 43.4% for T2N1M0, 23.8% for T3 and 11.7% for T4. T1N0M0 adenocarcinoma was associated with a better prognosis than squamous cell carcinoma of the same early stage, with a 5-year survival rate of 82.2% vs 55.9%. The prognosis of patients with T3N2 was worse than that of patients with a T3-4 primary tumour but only N0-1 lymph node involvement (5-year survival rate 18.1% vs 31.7%). Stepwise logistic regression analysis identified tumour stage, therapy, and histologic result as the factors with the greatest impact on the prognosis. Adjuvant radiation after resection in patients with T2-3 adenocarcinoma or squamous cell carcinoma improved the prognosis by one tumour stage compared with patients who only underwent surgery. In conclusion, surgical therapy of bronchogenic carcinoma offers favourable survival rates with acceptable risk.(ABSTRACT TRUNCATED AT 250 WORDS)

[Respiratory burst and phagocytosis activity in patients with infection after surgical abdominal interventions]. / Respiratory burst und Phagozytoseaktivität bei Patienten mit Sepsis nach abdominalchirurgischen Eingriffen.

Phagocyte functions such as respiratory burst or phagocytic activity allow the determination of septic courses. Already in case of surgical stress a reduced constitutive generation of reactive oxygen metabolites could be shown, which is assumed to influence the outcome of following septic courses. The results of septic patients suggest that in spite of a functioning uptake of particles and germs (phagocytosis) a defect of intracellular killing (respiratory burst) exists.

[Causes of organ failure in infection]. / Ursachen des Organversagens bei Sepsis.

Causes of septic multiple organ failure are endotoxin induced mechanisms, exotoxin induced mechanisms and sepsis associated immunosuppression. Pharmacological intervention is limited. Therapy is restricted to aggressive surgical treatment in terms of eradication of the source of infection combined with supportive intensive care medicine. The prevention of systemic infections is mandatory. Approaches to new therapeutical concepts are outlined.