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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Jahrestagung der Vereinigung Westdeutscher Hals-Nasen-Ohren-Ärzte; 20190329-20190330; Neuss; DOC68 /20190206/
    Publication Date: 2019-02-07
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    Keywords: RADIATION-THERAPY ; chemotherapy ; EUROPEAN ORGANIZATION ; ADULT PATIENTS ; ANAPLASTIC OLIGODENDROGLIOMAS ; PROGRESSION-FREE SURVIVAL ; PHASE-III TRIAL ; oligoastrocytomas ; DIFFUSE ASTROCYTOMAS ; CODON 132 MUTATION ; IDH2 MUTATIONS
    Abstract: Purpose: To investigate whether TP53 mutation, 1p/19q codeletions, O(6)-methylguanylmethyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation predict natural course of disease or response to radiotherapy or chemotherapy or both in low-grade glioma patients. Experimental Design: Cohort A consisted of 89 patients with diffuse astrocytoma World Health Organization (WHO) grade II (n = 40), oligoastrocytoma (n = 23), or oligodendroglioma (n = 26) who did not receive radiotherapy or chemotherapy after first operation and were monitored until progression [progressive disease (PD); n 59] and beyond or until the end of follow-up (n = 30). Cohort B consisted of 50 patients with WHO grade II gliomas who received radiotherapy or chemotherapy at diagnosis. Tumors were analyzed for TP53 mutations, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutations. Results: Median progression-free survival (PFS) in cohort A was 4.1 years (95% CI: 3.1-5.1). No molecular marker was prognostic for PFS after surgery alone, using multivariate adjustment for histology, age, and extent of resection. IDH1 mutations were associated with prolonged survival from the diagnosis of PD in oligoastrocytomas (OA II)/oligodendrogliomas (O II) and with overall survival (OS) in all tumors. 1p/19q codeletion and IDH1 mutation were prognostic for PFS and OS in cohort B. Conclusions: None of the parameters are sensitive prognostic biomarkers in WHO grade II glioma patients who do not receive radiotherapy or chemotherapy after surgery. Limitations of this study include the selection of patients with favorable outcome, the nonrandomized allocation of treatment, and the insufficient sample size to distinguish between effects of radiotherapy versus chemotherapy. Regardless of histology, IDH1 mutation status is the strongest prognostic marker for OS.
    Type of Publication: Journal article published
    PubMed ID: 21558404
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  • 3
    Keywords: OUTCOMES ; ANOMALIES ; RECONSTRUCTION ; CHILDHOOD ; TERM-FOLLOW-UP ; ADOLESCENCE ; FERTILITY ; EPISPADIAS COMPLEX ; SOCIAL INTEGRATION ; PATIENTS BORN
    Abstract: BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) comprises a spectrum of congenital anomalies that represents the severe end of urorectal malformations, and has a profound impact on continence as well as sexual and renal functions. OBJECTIVE: The relation between severity of BEEC and its associated functional impairments, on one hand, and the resulting restrictions in quality of life and potential psychopathology determine the patients' outcome. It is important for improving further outcome to identify BEEC-related sources of distress in the long term. Genital function and sexuality becomes an important issue for adolescent and adult BEEC individuals. Hence, the present study focused on sexual function and psychological adaption in patients with BEEC. STUDY DESIGN: In a multicenter study 52 patients (13 females, 39 males) with classic bladder exstrophy (BE) with their bladders in use were assessed by a self-developed questionnaire about sexual function, and psychosexual and psychosocial outcome. The patients were born between 1948 and 1994 (median age 31 years). RESULTS: Twelve of 13 (92%) females and 25 of 39 (64%) males with classic BE had answered the questions on sexual function. Of these, 50% females and 92% males answered that they masturbated. Females had sexual intercourse more frequently. Six (50%) females affirmed dyspareunia whereas only two (8%) males reported pain during erection. Eight (67%) females specified having orgasms. Eighteen (72%) males were able to ejaculate. Two males and none of the females lived in a committed partnership (Figure). Two (15%) females and 13 (33%) males answered all psychosocial questions. The majority of these patients had concerns about satisfactory sexuality and lasting, happy partnerships. A minority of patients of both sexes were willing to answer psychosocial questions. Sexual activity and relationships of many adult BE patients seems to be impaired. Not surprisingly, sexual activity and awareness were different in males and females even in a multi-organ anomaly. DISCUSSION: To date, one of the main goals of the medical treatment of BEEC/BE patients is to enable normal sexual life and fertility. However, only a few outcome studies have focused on these issues with contradicting results, most of them not using standardized outcome measures. In accordance with other studies, our female BE patients have dyspareunia and most of our male BE patients were able to ejaculate. But the question of normal force of ejaculation, ejaculated volume, or semen analysis remains unanswered. Despite partial confirmation of previous findings, there is inconsistency referring to the outcome measured by the available studies. This might in part be explained by the fact that, other than this study, most previous studies are the result of single-institution experience. Thus, selection bias in the patient sampling due to different a clinical collective in different hospitals may be the consequence. Furthermore, patients' honesty and self-reflection in answering difficult questions regarding their sexual and cosmetic impairments is questionable. In addition, studies include a wide range of age groups and are connected with this life period. Fears and condition-specific anxieties might change over time. Hence, the strengths of this study are the nationwide and treating physician-independent data acquisition as well as the large sample size of adult patients with a very rare congenital malformation. Unfortunately, more detailed analyses on sexual function and current psychosocial situation, for example correlation of data with clinical symptoms such as continence status, was not possible as data were mainly not answered by patients. CONCLUSION: To improve the quality of life of patients with BEEC/BE, treatment and follow-up should emphasize physical but also psychological care in these patients. Physicians should further re-evaluate their preconceptions and should take care of the patients
    Type of Publication: Journal article published
    PubMed ID: 25986209
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 11; DOC061 /20150416/
    Publication Date: 2015-04-17
    Description: Einleitung: Im Rahmen der allermeisten Eingriffe ist eine Eröffnung und partielle Schädigung im Bereich der Bogengänge geeignet das Innenohrhörvermögen deutlich zu gefährden. In seltenen Fällen ist jedoch bei sofortigem Verschluss auch größerer Defekte des Labyrinths ein partieller Hörerhalt möglich. Methoden: Im vorliegenden Beitrag wird der Fall eines 16-jährigen Patienten beschrieben, bei dem ein ausgedehntes Cholesteatom des linken Felsenbeines vorlag. Ergebnisse: Im Rahmen der Operation zeigte sich eine Ausdehnung des Cholesteatoms weit nach medial und unter den hinteren Bogengang, so dass der Eingriff im ersten Schritt abgebrochen wurde. Nach erneuter ausführlicher Aufklärung über eine drohende Ertaubung, erfolgte dann im Rahmen eines zweiten Eingriffes die vollständige Entfernung des Cholesteatoms im Bereich des lateralen Bogengangs und des teilarodierten hinteren Bogengangs unter Monitoring des N. fazialis. Hier zeigte sich ein großer Knochensequester, unter dem das Cholesteatom weiter dem N. facialis folgend in den Bereich des inneren Gehörganges zog. Nach vollständiger Entfernung wurde der Bereich mit Perichondrium und Temporalismuskel obliteriert. Der Patient hatte bereits in der ersten Hörkontrolle einen Teilerhalt seiner Innenohrhörfunktion. Nunmehr ist der Patient seit über einem Jahr in der postoperativen Nachkontrolle und hat auf dem Ohr weiterhin ein sozial verwertbares Restgehör. Schlussfolgerung: Der Fall belegt eindrücklich, dass auch nach nahezu vollständiger Entfernung des Labyrinths ein nennenswerter Hörerhalt auf dem betroffenen Ohr gelingen kann.Der Erstautor gibt keinen Interessenkonflikt an.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 11; DOC178 /20150416/
    Publication Date: 2015-04-17
    Description: Einleitung: Goldstandard der OSAS-Therapie bei mittel- und schwergradigem OSAS ist die Versorgung mit CPAP. Ein Prädiktor für das OSAS ist die Adipositas, daher können gewichtsreduzierende Maßnahmen bis hin zur bariatrischen Operation eine adjuvante Behandlung im Therapiekonzept der mittel- bis schwergradiges OSA darstellen. Methoden: In der Studie konnten bis dato 9 Patienten mit CPAP-pflichtigem OSAS nach bariatrischer Chirurgie eingeschlossen werden. Der präoperative Durchschnitts-AHI lag bei 78/h. Prä- und postoperativ wurden der AHI, die CPAP-Pflichtigkeit, die Tagesmüdigkeit (ESS) und das Risiko für OSAS (Berlin-Q-Test) verglichen. Ergebnisse: Nach Stabilisierung des Gewichtsverlustes als Effekt einer bariatrischen Operation bei einem durchschnittlichen BMI von 46,4 kg/m2 war das schwergradige OSAS mit einem präoperativen Durchschnitts-AHI von 78/h und einer hochsuffizienten CPAP-Therapie mit 12,5 mbar postoperativ bei 6 der 9 Patienten nicht mehr nachweisbar. Es ergab sich ein durchschnittlicher postoperativer AHI von 7/h. Der ESS-Wert sank im Schnitt auf 3 Punkte.Fazit: Die Studie zeigt, daß bariatrisch erreichter Gewichtsverlust eine Reduktion des AHI bei deutlich adipösen Patienten erbringen kann. Zugleich mahnt diese Studie dazu, bariatrische Chirurgie nicht als Ersatz für suffiziente CPAP-Versorgung zu sehen, sondern als sinnvolle Ergänzung bei besonders adipösen Patienten zu erwägen und dabei eine Milderung der OSAS bis hin zur Heilung der OSAS bei stabilem Gewicht zu erwarten.Der Erstautor gibt keinen Interessenkonflikt an.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 6
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung; 20190509-20190511; Wien; DOC19oegu099 /20190408/
    Publication Date: 2019-04-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 7
    Keywords: RISK ; DEFECTS ; BIRTHS ; CLOACAL EXSTROPHY ; POSSIBLE ASSOCIATION
    Abstract: Objective To identify genetic and nongenetic risk factors that contribute to the severity of the bladder exstrophy-epispadias complex (BEEC). Study design Patients with BEEC from North America (n = 167) and Europe (n = 274) were included. The following data were collected: associated anomalies, parental age at conception, mode of conception, periconceptional folic acid supplementation, maternal risk factors during pregnancy, and environmental risk factors. The patients were divided into 3 subgroups according to phenotype severity: (i) mild, epispadias (n = 43); (ii) intermediate, classic bladder exstrophy (n = 366); and (iii) severe, cloacal exstrophy (n = 31). These subgroups then were compared with identify factors that contribute to phenotype severity. Results Males were overrepresented in all subgroups. A relatively high prevalence of cleft lip, with or without cleft palate, was observed. Maternal smoking and medical radiation during the first trimester were associated with the severe cloacal exstrophy phenotype. Compliance with periconceptional folic acid supplementation was associated with the mildest phenotype (epispadias). Conclusions Periconceptional folic acid supplementation appears to prevent the development of the severe phenotype of BEEC.
    Type of Publication: Journal article published
    PubMed ID: 21679965
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  • 8
    Keywords: GENES ; PROJECT ; OF-THE-LITERATURE ; FAMILIES ; EPISPADIAS COMPLEX BEEC ; imputation ; DYSREGULATION ; GUDMAP ; SALL1 ; PLAYS
    Abstract: Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed discovery and follow-up samples comprising 218 cases/865 controls and 78 trios in total, all of European descent. Our discovery sample identified a marker near SALL1, showing genome-wide significant association with CBE. However, analyses performed on follow-up samples did not add further support to these findings. We were also able to identify an association with CBE across our study samples (discovery: P = 8.88 x 10(-5); follow-up: P = 0.0025; combined: 1.09 x 10(-6)) in a highly conserved 32 kb intergenic region containing regulatory elements between WNT3 and WNT9B. Subsequent analyses in mice revealed expression for both genes in the genital region during stages relevant to the development of CBE in humans. Unfortunately, we were not able to replicate the suggestive signal for WNT3 and WNT9B in a sample that was enriched for non-CBE BEEC cases (P = 0.51). Our suggestive findings support the hypothesis that larger samples are warranted to identify association of common variation with CBE.
    Type of Publication: Journal article published
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  • 9
    Keywords: PROTEINS ; DIFFERENTIATION ; SONIC HEDGEHOG ; FAMILIES ; REQUIREMENT ; progenitor ; UPSTREAM ; MALFORMATIONS ; EPISPADIAS COMPLEX ; HOMEODOMAIN
    Abstract: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 x 10-12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region.
    Type of Publication: Journal article published
    PubMed ID: 25763902
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  • 10
    Abstract: Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to the brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and the interactions of disseminated metastatic cells with the brain microenvironment are largely unknown. To study the hallmarks of brain metastatic niche formation, we established a transplantable model of spontaneous melanoma brain metastasis in immunocompetent mice and developed molecular tools for quantitative detection of brain micrometastases. Here we demonstrate that micrometastases are associated with instigation of astrogliosis, neuroinflammation, and hyperpermeability of the blood-brain barrier. Furthermore, we show a functional role for astrocytes in facilitating initial growth of melanoma cells. Our findings suggest that astrogliosis, physiologically instigated as a brain tissue damage response, is hijacked by tumor cells to support metastatic growth. Studying spontaneous melanoma brain metastasis in a clinically relevant setting is the key to developing therapeutic approaches that may prevent brain metastatic relapse. Cancer Res; 76(15); 4359-71. (c)2016 AACR.
    Type of Publication: Journal article published
    PubMed ID: 27261506
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