Die operative Versorgung der sekundären Coxarthrose bei kongenitaler Hüftluxation (Crowe TypIV)

Zusammenfassung: Operationsziel: Ziel der Therapie ist die mechanische und funktionelle Stabilisation einer hohen Hüftluxation bei dysplasiebedingter Coxarthrose mittels endoprothetischem Ersatz. Indikationen: Hüftdysplasie im Erwachsenenalter. Fortgeschrittene symptomatische Coxarthrose. Hohe Hüftluxation gemäß CroweIII/IV. Symptomatische Beinlängendifferenz. Kontraindikationen: Zerebrospinale Dysfunktionen. Muskeldystrophien. Manifeste Störung des Knochenmetabolismus. Infektion. Immunsupprimierte Patienten. Operationstechnik: Seitenlage (variabel). Gerade laterale Inzision über dem Trochanter major und Eingehen zwischen dem Vorderrand des M.gluteus maximus und dem Hinterrand des M.gluteus medius, dem sog. Gibson-Intervall. Darstellen des N.ischiadicus und permanente Kontrolle desselben, um hier bei jeglichen Manipulationen, vor allem bei der Reposition des Femurs, einen Traktionsschaden aufgrund erhöhter Spannung zu vermeiden. Trochanter-Flip-Osteotomie und Darstellen der Gelenkkapsel zwischen M.piriformis und M.gluteus minimus. Aufgrund des Hochstands des Femurs kann hier die Identifikation der anatomischen Landmarken erschwert sein. Schrittweise Z-förmige Kapsulektomie der elongierten Kapsel und Darstellen der Primärpfanne, die häufig aufgrund der langzeitigen Luxation des Femurkopfs nur rudimentär ausgebildet ist. Lokalisation des Pfannengrunds bzw. der Tränenfigur. Aufraspeln der Pfanne und Implantation der mit der Pfannengröße konformen Hakendachschale. Fixation der Pfanne je nach Halt und Knochenqualität mit 3-5Schrauben. Resektion des proximalen Femurs je nach Spannung der Weichteile bis auf Höhe oder sogar unter das Niveau des Trochanter minor. Anschließend Aufraspeln des Femurs und unter steter Spannungskontrolle des N.ischiadicus Reposition des Femurs in die Hüftpfanne; je nach Spannung des N.ischiadicus und der umgebenden Weichteile erfolgt eine Nachresektion des proximalen Femurs. Anfrischen des proximalen Femurs mit dem Meißel zur besseren Konsolidation des Trochanter-major-Fragments. Refixation des Trochanters mittels Cerclage, wobei die Muskulatur des M.gluteus medius an seinem Ursprung am Os ilium oder am muskulotendinösen Übergang am Trochanterfragment etwas mobilisiert werden muss, um den Trochanter major wieder distal am proximalen Femur refixieren zu können. Weiterbehandlung: Während der Hospitalisierung regelmäßige Behandlung auf der passiven Bewegungsschiene mit maximal 70° Flexion. Keine aktive Abduktion, keine passive Adduktion über die Mittellinie, kein Heben des gestreckten Beins, 10-15kg Teilbelastung an zwei Unterarmgehstöcken während 8Wochen. Je nach Compliance des Patienten und intraoperativer Stabilität der Prothese trägt der Patient eine Antiluxationsbandage (in Bern Hohmann-Bandage) für die ersten 6-8Wochen postoperativ. Anschließend erste klinische und radiologische Nachkontrolle und je nach Konsolidation des Trochanter major schrittweiser Übergang zur Vollbelastung. Thromboseprophylaxe bis zur Vollbelastung. Ergebnisse: Im beobachteten Zeitraum von 1998-2012 erfolgten insgesamt 28Hüftprothesenimplantationen bei hoher Hüftluxation im Erwachsenenalter im Stadium CroweIV, die mit einer Hakendachschale und einer femoralen Verkürzungsosteotomie behandelt wurden. Aktuell liegen von 14Patienten nach 8 ± 1,2Jahren (3,5-12Jahren) klinische Nachuntersuchungen vor. In diesem mittleren Beobachtungszeitraum zeigten sich gemäß Merle-d'Aubigné-Score bei 86 % der operierten Patienten Verbesserungen. Gute bis exzellente Resultate wurden in 71 % der Fälle erreicht. Langzeitergebnisse (< 10Jahre) stehen bis dato noch au

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors

Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients

Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations

Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. T-distributed stochastic neighbor-embedding (t-SNE) and hierarchical clustering analysis of these 102 cases against 158 reference cases from 12 glioma reference classes revealed that a subset of 83 of these tumors share a common DNA methylation profile that is distinct from the reference classes. These 83 tumors were thus denominated DNA methylation class anaplastic astrocytoma with piloid features (MC AAP). The 19 remaining tumors were distributed amongst the reference classes, with additional testing confirming the molecular diagnosis in most cases. Median age of patients with MC AAP was 41.5 years. The most frequent localization was the posterior fossa (74%). Deletions of CDKN2A/B (66/83, 80%), MAPK pathway gene alterations (49/65, 75%, most frequently affecting NF1, followed by BRAF and FGFR1) and mutations of ATRX or loss of ATRX expression (33/74, 45%) were the most common molecular alterations. All tumors were IDH1/2 wildtype. The MGMT promoter was methylated in 38/83 tumors (45%). Outcome analysis confirmed an unfavorable clinical course in comparison to PA, but better than IDH wildtype glioblastoma. In conclusion, we show that a subset of histologically defined anaplastic pilocytic astrocytomas forms a separate DNA methylation cluster, harbors recurrent alterations in MAPK pathway genes in combination with alterations of CDKN2A/B and ATRX, affects patients who are on average older than those diagnosed with PA and has an intermediate clinical outcome

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology