Pathologe最新文献

Paediatric acute liver failure (PALF; also fulminant hepatic failure, fulminant hepatitis) is a critical clinical syndrome that is characterised by a sudden, rapid deterioration and disease progression in a usually previously healthy child. The pathogenesis is an advanced degree of hepatocellular necrosis that exceeds the rate of hepatocyte regeneration. The diagnostic criteria of PALF (modelled on adult criteria) were developed by the "Pediatric Acute Liver Failure (PALF) Study Group" (NIH). The rule of the liver biopsy in PALF is controversial and in some cases contraindicated (coagulopathic state). In addition, extensive necrosis is a common finding in PALFs but may not be predictive of the overall outcome (transplantation versus continuous treatment) due to sampling issues. There are, however, some histological patterns that offer a degree of specificity that can be carefully considered in the overall clinical picture. The histopathologists will be part of a multidisciplinary team and can contribute to the diagnostic and prognostic pathway.The aetiologies of PALF are numerous and depend on age and geographical region. For all age groups the main causes can be divided into infectious, immunological, metabolic and toxin drug related. Rarer causes include circulatory disorders and malignancies. In the paediatric group, up to 30-50% of causes leading to PALF remain unknown.

Over the last few decades, various models have been established within gastroenterological research that have significantly contributed to a better understanding of the (patho)physiological processes of various gastrointestinal (GI) diseases (inflammation, organ injuries, carcinomas). This review will focus on such models including genetically engineered mouse models (GEMMs), xenografts, and organoid-based culture systems. GEMMs laid the foundation for successful modeling of such diseases. These have the decisive advantage that diseases can be assessed in their physiological environment and thus allow the examination of cell-cell communications of various cell types (epithelium, fibroblast, immune cells). However, the discrepancy between the genetic background of mice and humans reflected a pivotal disadvantage that could at least partially be circumvented by transplanting human cells into immunocompromised host animals. The time-consuming and labor-intensive generation of such xenograft models, however, considerably limits their usefulness for timely preclinical drug screenings. Thus, novel organoid-based human cell culture systems from adult stem cells or pluripotent stem cells are a promising human tool for modeling GI diseases. The first results already show their usefulness in the regulation of adult tissue homeostasis, regeneration, and tumor development. In addition, this system can be easily established in clinical diagnostics and thus enables real-time ex vivo pharmacotyping to develop personalized therapy strategies, particularly for cancer patients.

Background: Bladder cancer ranks among the top ten most common tumor types worldwide and represents a growing healthcare problem, accounting for a large part of total healthcare costs. Chemotherapy is effective in a subset of patients, while causing severe side effects. Tumor pathogenesis and drug resistance mechanisms are largely unknown. Precision medicine is failing in bladder cancer, as bladder tumors are genetically and molecularly very heterogeneous. Currently, therapeutic decision-making depends on assessing a single fragment of surgically acquired tumor tissue.

Objective: New preclinical model systems for bladder cancer are indispensable for developing therapeutic strategies tailored to individual patient and tumor characteristics. Organoids are small 3D tissue cultures that simulate small-size organs "in a dish" and tumoroids are a special type of cancer organoid (i.e., malignant tissue).

Materials and methods: Since 2016, we have collaborated with the renowned Hubrecht Institute to provide proof of concept of tissue-based bladder tumoroids mimicking parental tumors. We have developed a living biobank containing bladder organoids and tumoroids grown from over 50 patient samples, which reflect crucial aspects of bladder cancer pathogenesis.

Results: Histological and immunofluorescence analysis indicated that the heterogeneity and subclassification of tumoroids mimicked those of corresponding parental tumor samples. Thus, urothelial tumoroids mimic crucial aspects of bladder cancer pathogenesis.

Conclusion: Research with urothelial tumoroids will open up new avenues for bladder cancer pathogenesis and drug-resistance research as well as for precision medicine approaches.

Background: Autopsies are an important tool for understanding novel diseases, including COVID-19.

Materials and methods: The German Registry of COVID-19 Autopsies (DeRegCOVID) was established and launched in April 2020. DeRegCOVID acts as the electronic backbone of the German Network for Autopsies in Pandemics (DEFEAT PANDEMIcs), which started in September 2020.

Results: The results of DeRegCOVID and DEFEAT PANDEMIcs are characterized by an unprecedented collaboration of more than 35 university and non-university autopsy centers linking pathological, neuropathological, and forensic medicine institutes. DeRegCOVID has evolved, adapted to new challenges, and currently contains the largest international autopsy dataset. After only a short period of operation, more than 80 publications have been produced, which have contributed to the understanding of the pathogenesis of COVID-19, e.g., through the discovery of thromboembolic events, multiorgan tropism, and NeuroCovid-19. The autopsy centers have carried out extensive educational work and, beyond the scientific gain in knowledge, have explained to politicians and the general public the essential role of autopsies in pandemic management. To further develop autopsy-driven research, a continuation of DEFEAT PANDEMIcs was conceived, the National Autopsy Network (NATON).

Conclusions: The registry and network, in which all interested centers can participate, have demonstrated the value of networked medical research and the high value of autopsy for medicine.