[Histo- and molecular pathology in gastroenteropancreatic neuroendocrine neoplasms]. / Histo- und Molekularpathologie bei gastroenteropankreatischen neuroendokrinen Neoplasien.

Neuroendocrine neoplasms are classified according to the WHO classification based on morphological criteria into neuroendocrine tumors, neuroendocrine carcinomas, and mixed neuroendocrine-non-neuroendocrine neoplasms. Neuroendocrine tumors are well differentiated neoplasms and show characteristic site-specific histological and molecular features, which is important for their clinical management. In cases dealing with metastasis, pathology often can help to identify the primary tumors using a small immunohistochemical marker panel. Neuroendocrine carcinomas are poorly differentiated neoplasms. They are subdivided into neuroendocrine carcinomas of small cell and large cell type. The molecular profile of neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms shows a close relationship to conventional adenocarcinomas with site-specific features. Molecular analysis of neuroendocrine carcinomas and neuroendocrine-non-neuroendocrine neoplasms are not yet fully integrated in daily diagnostics and are mainly performed in the context of precision oncology.

Changes in hormones of the thyroid axis after tracheostomy and their influence on regeneration in patients with head and neck cancer: A prospective study.

This prospective study aimed to compare and evaluate changes in hormones of the thyroid axis affected by tracheostomy due to surgical treatment in patients with oral cancer. The patients were evaluated with regard to serum levels of the thyroid axis - free T3/triiodothyronine (fT3) and free T4/thyroxine (fT4), as well as thyroid-stimulating hormone (TSH) - at fixed perioperative time points: during the tumor staging about 1 week before operation, immediately before and within 6 h after operation, 2 days after operation, and about 10 days after operation. Additionally, data on the patients' characteristics (age, gender), relevant secondary diagnoses, duration of ventilation in the intensive care unit, and perioperative complications were obtained and analyzed. In total, 51 patients with an average age of 68.29 years (±11.82) were included. Analyses of thyroid hormones directly before and after tracheostomy showed a significant postoperative decrease in circulating TSH (p = 0.005) and fT3 (p < 0.001), whilst a significant increase in fT4 values (p < 0.001) was found. Nine patients showed perioperative complications, such as infection, emphysema, or requiring a revision operation. Eleven patients were diagnosed with a cardiac problem or suffered from agitation after operation. Within the limitations of the study it seems that hormonal changes following tracheostomy in critically ill patients should be monitored and thyroid hormone adjustment should be taken into account because the latter might lead to lower mortality and morbidity during hospitalization in these patients. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00023942.

Role of wnt5a in Metabolic Inflammation in Humans.

Context: Common nutrition-associated diseases like obesity and type 2 diabetes are linked to chronic low-grade inflammation. The secreted glycopeptide wingless-type mouse mammary tumor virus integration site family member 5a (wnt5a) has been implicated in metabolic inflammation in rodent models, suggesting a potential treatment target. Data on the role of wnt5a in human physiology have yielded conflicting results. Objective: Serum concentrations of wnt5a were measured in a cross-sectional cohort of 896 people to gain deeper insights into wnt5a physiology. Design: Serum concentrations of wnt5a were measured by ELISA and related to several phenotyping and genotyping data. In vitro experiments were performed in THP-1 macrophages to examine potential molecular mechanisms. Results: Wnt5a levels were significantly positively correlated to IL-6 and triglyceride levels. In subjects with diabetes, wnt5a levels were elevated and significantly correlated with fasting plasma glucose concentrations. Although wnt5a levels were not influenced by common single-nucleotide polymorphisms in the human wnt5a gene, environmental factors significantly altered wnt5a concentrations, as follows: (1) wnt5a levels were reduced in subjects with high nutritional load of the long-chain eicosatetraenoic acid independent of the total caloric intake and overall composition of the macronutrients, and (2) wnt5a levels were lower in humans with a high gut microbiome α diversity. In vitro experiments revealed that stimulation of the IL-6 receptor or the long-chain fatty acid receptor GPR40 directly affected wnt5a expression in human macrophages. Conclusion: Our data suggest that wnt5a is important in linking inflammation to metabolism. The nutrition and the microbiome might be interesting targets to prevent and/or treat wnt5a-mediated metabolic inflammation.