Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

Endoscopic ultrasonography and small‐bowel endoscopy: Present and future

Over the last decade, impressive technological advances have occurred in ultrasonography and small‐bowel endoscopy. Nowadays, endoscopic ultrasonography is an essential diagnostic tool and a therapeutic weapon for pancreatobiliary disorders. Capsule endoscopy and device‐assisted enteroscopy have quickly become the reference standard for the diagnosis of small‐bowel luminal diseases, thereby leading to radical changes in diagnostic and therapeutic pathways. We herein provide an up‐to‐date overview of the latest advances in endoscopic ultrasonography and small‐bowel endoscopy, focusing on the emerging paradigms and technological innovations that might improve clinical practice in the near future.     

Bloqueio do plano do eretor da espinha com técnica de múltiplos cateteres para esofagectomia aberta: relato de caso

Background and objective

Erector spinae plane block is a valid technique to provide simultaneously analgesia for combined thoracic and abdominal surgery.

EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

Quo vadis haemapheresis. Current developments in haemapheresis.

The techniques of haemapheresis originated in the development of centrifugal devices separating cells from plasma and later on plasma from cells. Subsequently membrane filtration was developed allowing for plasma-cell separation. The unspecificity of therapeutic plasma exchange led to the development of secondary plasma separation technologies being specific, semi-selective or selective such as adsorption, filtration or precipitation. In contrast on-line differential separation of cells is still under development. Whereas erythrocytapheresis, granulocytapheresis, lymphocytapheresis and stem cell apheresis are technically advanced, monocytapheresis may need further improvement. Also, indications such as erythrocytapheresis for the treatment of polycythaemia vera or photopheresis though being clinically effective and of considerable importance for an appropriate disease control are to some extent under debate as being either too costly or without sufficient understanding of the mechanism. Other forms of cell therapy are under development. Rheohaemapheresis as the most advanced technology of extracorporeal haemorheotherapy is a rapidly developing approach contributing to the treatment of microcirculatory diseases and tissue repair. Whereas the control of a considerable number of (auto-) antibody mediated diseases is beyond discussion, the indication of apheresis therapy for immune complex mediated diseases is quite often still under debate. Detoxification for artificial liver support advanced considerably during the last years, whereas conclusions on the efficacy of septicaemia treatment are debatable indeed. LDL-apheresis initiated in 1981 as immune apheresis is well established since 24 years, other semi-selective or unspecific procedures, allowing for the elimination of LDL-cholesterol among other plasma components are also being used. Correspondingly Lp(a) apheresis is available as a specific, highly efficient elimination procedure superior to techniques which also eliminate Lp(a). Quality control systems, more economical technologies as for instance by increasing automation, influencing the over-interpretation of evidence based medicine especially in patients with rare diseases without treatment alternative, more insight into the need of controlled clinical trials or alternatively improved diagnostic procedures are among others tools ways to expand the application of haemapheresis so far applied in cardiology, dermatology, haematology, immunology, nephrology, neurology, ophthalmology, otology, paediatrics, rheumatology, surgery and transfusion medicine.     

Proliferating pilomatricoma

We report on 9 patients with pilomatricomas that showed unusual histopathologic features. Our patients were mainly elderly individuals (age range 42 to 88 years; mean age 70.1 years) who presented solitary cutaneous nodules situated on the head and neck (7 neoplasms), upper arm (1 neoplasm), and back (1 neoplasm). All the lesions were treated by simple excision. Follow-up data available in 7 of the 9 patients (mean follow-up, 17 months) revealed local recurrences in 1 patient whose lesion recurred 3 times. No lymph node involvement or distant metastases were recorded in any of our cases. Histopathologically, most neoplasms were characterized by a relatively large lesion in the clermis that in some cases showed extension to the subcutis. Each lesion was predominantly composed of a lobular proliferation of basaloid cells in association with adjacent focal areas containing eosinophilic, cornified material with shadow cells. In some cases, relatively large areas of shadow cells were present, whereas, in others only small foci of shadows cells were observed. Cytomorphologically, the basaloid cells showed features of matrical and supramatrical cells of a normal hair follicle and exhibited variable nuclear atypia and mitotic figures. The overall architectural pattern of the neoplasms was different from that of large fully developed stereotypical pilomatricomas that maintain a cystic character with basaloid cells predominantly aligned at the periphery. Based on the histopathologic findings, namely the presence of a large, lobular proliferation of basaloid cells in association with small to large foci of shadow cells, we interpreted these neoplasms to be a distinctive proliferative variant of pilomatricoma and propose the designation "proliferating pilomatricoma." Proliferating pilomatricomas should be differentiated from the recently described matricoma, basal-cell carcinoma with matrical differentiation, and matrical carcinoma (pilomatrical carcinoma).     

Radiusköpfchenfrakturen

Trauma und Berufskrankheit - Zusammenfassung Die angemessene Behandlung der Radiusköpfchenfrakturen erfolgt nach korrekter Klassifikation unter Berücksichtigung von Begleitverletzungen...