TY - THES A1 - Stanescu, Angela T1 - Fieber und Neutropenie bei krebskranken Kindern - prognostische Faktoren und Therapie T1 - Fever and neutropenia in children with cancer - prognostic parameters and therapy N2 - Onkologische Patienten sind während der Phase der Chemotherapie-bedingten Knochenmarkdepression besonders durch Infektionen bedroht. Da bisher keine Parameter bekannt sind, die eine schwerwiegende bakterielle Infektion zu Beginn einer Fieberepisode von anderen Fieberursachen sicher differenziert, werden diese Patienten bei Fieber und Neutropenie trotz der damit verbundenen Nachteile und Risiken, wie z.B. mögliche Resistenzbildung, Toxizität der Antibiotika, Risiko nosokomialer Infektionen, psychische Belastung der kleinen Patienten und deren Eltern, sofort stationär aufgenommen und intravenös mit Antibiotika behandelt. In der vorliegenden Studie wurde der diagnostische Wert der Interleukine 6 und –8 für die Früherkennung schwerer Infektionen bei pädiatrischen Patienten mit Fieber und Chemotherapie-bedingter Neutropenie untersucht und mit dem diagnostischen Wert des CrP verglichen. In einem Beobachtungszeitraum von 15 Monaten wurden in 128 Fieberepisoden bei 55 Patienten mit einem breiten Spektrum onkologischer Grunderkrankungen die Konzentrationen der Parameter an den ersten Fiebertagen bestimmt. Neben 95 FUO-Episoden wurden sechs bakterielle Infektionen mit gram-negativem Erreger, 19 bakterielle Infektionen mit gram-positivem Erreger, drei Pilzinfektionen und fünf klinisch dokumentierte Infektionen behandelt. Es zeigten sich signifikant höhere IL-6 und IL-8 Konzentrationen am ersten Fiebertag bei Infektionen mit gram-negativen Bakterien, S.aureus und Pilzen, also bei potentiell schwerer verlaufenden Infektionen als bei FUO, S.epidermidis- und klinisch dokumentierten Infektionen. Schwere Infektionen konnten mit einer deutlich höheren Sensitivität und Spezifität von anderen Fieberursachen durch die Interleukine als durch das CrP unterschieden werden. Die Interleukine-6 und –8 könnten im Gegensatz zum CrP eine wertvolle Hilfe in der Frühdiagnostik von schwerwiegenden Infektionen bei pädiatrischen Patienten mit chemotherapiebedingter Neutropenie und Fieber sein. Die in dieser Arbeit dargestellten Ergebnisse müssen jedoch vor einem routinemäßigen Einsatz im Klinikalltag in großen, prospektiven Studien validiert werden. Ein weiteres Ziel dieser Studie war, den Therapieerfolg einer initialen Monotherapie mit Imipenem/Cilastat zur Behandlung von Kindern mit Fieber und Chemotherapie-bedingter Neutropenie zu untersuchen und mit dem Therapieerfolg einer initialen Therapie mit einer Ceftazidim/Teicoplanin Kombination zu vergleichen. In insgesamt 106 auswertbaren Fieberepisoden wurde 54 mal initial mit der Monotherapie und 52 mal initial mit der Kombinationstherapie behandelt. Die antibiotische Therapie wurde nach einer Mindestdauer von 72 Stunden beendet, wenn der Patient 24 Stunden fieberfrei war und die Kriterien für FUO erfüllt waren, d.h., kein Erreger nachgewiesen werden konnte und keine weiteren klinischen Zeichen einer Infektion bestanden. Keiner der Patienten verstarb infolge einer Infektion. Rund die Hälfte der Patienten entfieberten in beiden Therapiegruppen innerhalb von drei Tagen unter der Initialtherapie. Beide Therapiegruppen unterschieden sich nicht signifikant hinsichtlich der Therapiedauer, der Fieberdauer und hinsichtlich der Rezidivhäufigkeit und waren damit gleich effektiv. Lediglich bei den Infektionen mit gram-positiven Eregern zeigte sich erwartungsgemäß, dass die initiale Kombinationstherapie aufgrund des Teicoplaninanteils zu einer rascheren Entfieberung führte. Alle Patienten, die initial mit der Imipenemmonotherapie behandelt wurden, konnten nach Eintreffen des Antibiogramms erfolgreich behandelt werden. Glykopeptide sind Reserveantibiotika, die möglichst gezielt und sparsam eingesetzt werden sollten, um einer Resistenzbildung vorzubeugen. In dieser Studie konnte gezeigt werden, dass auch der verzögerte Einsatz von Teicoplanin in der Folgetherapie bzw. in Kenntnis des Antibiogramms den Therapieerfolg nicht signifikant vermindert und dadurch keine bedrohliche Situation für einen Patienten entstand. Vorteile einer Monotherapie sind außerdem eine potentiell geringere Toxizitiät, und ein potentiell geringerer Kosten- und Personalaufwand. Wir ziehen aus den genannten Gründen eine initiale Monotherapie mit Imipenem einer initialen Therapie mit einer Ceftazidim/Teicoplanin Kombination vor. Nach frühzeitiger Beendigung der antibiotischen Therapie bei Patienten mit FUO unabhängig von der Granulozytenzahl im Blutbild kam es zu keiner Häufung von Rezidiven. Mit dieser Praxis könnte sich nicht nur das Risiko einer Resistenzbildung senken lassen. Ein verkürzter stationärer Aufenthalt verbessert die Lebensqualität der Patienten, nicht zuletzt bedeutet dies auch einen geringeren Kosten- und Personalaufwand. N2 - Febrile Neutropenia in Pediatric Cancer Patients - Prognostic Factors and Therapeutic Interventions Infectious complications represent a significant cause of morbidity and mortality in children with cancer undergoing chemotherapy. In most cases, fever is an important, early indication of serious infection. Discrimination between serious and inconsequential infection in febrile neutropenic patients at the time of presentation is difficult. It is the standard of care that all febrile patients with neutropenia receive systemic antibacterial therapy, primarily because of the deleterious effects of withholding therapy until confirming a diagnosis. Although the paradigm of treating all patients with neutropenia with broad-spectrum antibiotics at the first sign of fever has drastically reduced morbidity and nearly eliminated mortality, currently nearly two-thirds of children are treated without having a source of the fever identified. Neutropenic children with fever are hospitalized, which results in disruption of family life and in high costs. In addition, extended time in the hospital also subjects children to a higher risk of nosocomial infections with resistant organisms. Recently, attention has focused on identifying serum markers of the immunologic response that may be useful for therapeutic interventions. For example, increases in circulating levels of the cytokines IL-6 and IL-8 are apparent early in the course of infection, whereas the increase of the widely used C-reactive protein (CrP) is delayed. In this study, the diagnostic usefulness of IL-6 and IL-8 as an early marker for serious infection in febrile neutropenic children was investigated and the results were compared with the diagnostic value of CrP. Circulating levels of IL-6, IL-8 and CrP were measured in 128 episodes of fever and neutropenia among 55 patients at the time of admission and 24 hours later. Based on micobiological and clinical data, each episode of fever was retrospectively assigned to either fever of unknow orign (FUO) (n=95), documented infection with gram-negative organism (n=6), documented infection with gram-positive organism (n=19), fungal infection (n=3), or clinical documented infection (n=5). The highest levels of IL-6 and IL-8 were measured in children who were diagnosed with bacteremia due to gram-negative organisms. These levels were significantly higher than those measured in patients with neutropenia who had bacteremia due to gram-positive pathogens, FUO or clinically documented infection. In contrast, measured levels of CrP displayed a broad overlap among the different groups. Levels of IL-6 and IL-8, measured at the time of admission, predicted serious infections with high sensitivity and specificity. The results, however, require confirmation in large, prospective studies before use for stratification of antibiotic therapy. As a second part of the study, efficacy and safety of two different antibiotic regimens (imipenem monotherapy and combination therapy with ceftazidime/teicoplanin) were assessed as initial therapy for febrile neutropenic children. In episodes of FUO, treatment regiment allowed discontinuation of antibiotics regardless of absolute neutrophil count or evidence of bone marrow recovery as long as patients were afebrile for at least 24 hours and had been treated for a minimum of 72 hours. Hundred-and-six episodes of febrile neutropenia occurred in 56 patients. In 54 episodes, children received imipenem monotherapy, whereas the combination therapy was given in 52 febrile episodes. No death or major complication occurred. None of the patients had to be rehospitalized for recurrent fever or infection. Duration of fever and duration of therapy did not differ significantly between both treatment regimens. In children with FUO, short-term antibiotic therapy with discontinuation of intravenous antibiotics regardless of the neutrophil count or evidence of bone marrow recovery seems safe and effective, and may improve the quality of life for patients. However, for each antibiotic regimen for febrile neutropenic patients, the local pattern of resistance of pathogens has to be evaluated. KW - Fieber KW - Neutropenie KW - IL-6 KW - IL-8 KW - CrP KW - Therapie KW - fever KW - neutropenia KW - IL-6 KW - IL-8 KW - CrP KW - therapy Y1 - 2005 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-12150 ER - TY - JOUR A1 - Riedmeier, Maria A1 - Decarolis, Boris A1 - Haubitz, Imme A1 - Müller, Sophie A1 - Uttinger, Konstantin A1 - Börner, Kevin A1 - Reibetanz, Joachim A1 - Wiegering, Armin A1 - Härtel, Christoph A1 - Schlegel, Paul-Gerhardt A1 - Fassnacht, Martin A1 - Wiegering, Verena T1 - Adrenocortical carcinoma in childhood: a systematic review JF - Cancers N2 - Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81% — local recurrence, 19% (n = 65) — distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies. KW - pediatric adrenocortical cancer KW - pediatric adrenocortical adenoma KW - pediatric adrenocortical tumor KW - prognostic factors KW - therapy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248507 SN - 2072-6694 VL - 13 IS - 21 ER - TY - JOUR A1 - Uttinger, Konstantin L. A1 - Riedmeier, Maria A1 - Reibetanz, Joachim A1 - Meyer, Thomas A1 - Germer, Christoph Thomas A1 - Fassnacht, Martin A1 - Wiegering, Armin A1 - Wiegering, Verena T1 - Adrenalectomies in children and adolescents in Germany – a diagnose related groups based analysis from 2009-2017 JF - Frontiers in Endocrinology N2 - Background Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome. Methods This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included. Results A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1%). The majority of patients were between 0 and 5 years old (52% overall), while 11.1% were between 6 and 11 and 38.8% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29% of all cases with the majority of affected patients being 12 years or older. 15% were not defined regarding tumor behavior. Overall complication rate was 27% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different “low volume” hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different “high volume” hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications. Conclusion Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals. KW - pediatric KW - neuroblastoma – diagnosis KW - therapy KW - adrenocortical adenocarcinoma KW - outcome KW - volume KW - adrenalectomia Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282280 SN - 1664-2392 VL - 13 ER - TY - JOUR A1 - Wiegering, Verena A1 - Riedmeier, Maria A1 - Thompson, Lester D. R. A1 - Virgone, Calogero A1 - Redlich, Antje A1 - Kuhlen, Michaela A1 - Gultekin, Melis A1 - Yalcin, Bilgehan A1 - Decarolis, Boris A1 - Härtel, Christoph A1 - Schlegel, Paul-Gerhardt A1 - Fassnacht, Martin A1 - Timmermann, Beate T1 - Radiotherapy for pediatric adrenocortical carcinoma - Review of the literature JF - Clinical and Translational Radiation Oncology N2 - Background and purpose Pediatric adrenocortical carcinoma (pACC) is a rare disease with poor prognosis. Publications on radiotherapy (RT) are scarce. This review summarizes the current data on RT for pACC and possibly provides first evidence to justify its use in this setting. Materials and methods We searched the PubMed and Embase database for manuscripts regarding RT for pACC. Results We included 17 manuscripts reporting on 76 patients treated with RT, after screening 2961 references and 269 full articles. In addition, we added data of 4 unreported pACC patients treated by co-authors. All reports based on retrospective data. Median age at first diagnosis was 11.1 years (70% female); 78% of patients presented with hormonal activity. RT was mostly performed for curative intent (78%). 88% of RT were administered during primary therapy. The site of RT was predominantly the local tumor bed (76%). Doses of RT ranged from 15 to 62 Gy (median 50 Gy). Information on target volumes or fractionation were lacking. Median follow-up was 6,9 years and 64% of the patients died of disease, with 33% alive without disease. In 16 of 48 patients with available follow-up data after adjuvant RT (33%) no recurrence was reported and in 3 of 9 patients palliative RT seemed to induce some benefit for the patient. Conclusions Our first systematic review on RT for pACC provides too few data for any general recommendation, but adjuvant RT in patients with high risk might be considered. International collaborative studies are urgently needed to establish better evidence on the role of RT in this rare malignancy. KW - pediatric adrenocortical cancer KW - pediatric adrenocortical carcinoma KW - pediatric adrenocortical tumor KW - radiotherapy KW - therapy KW - treatment Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300472 VL - 35 ER -