Notch Signaling Pathway in Pancreatobiliary Tumors.

Background and objectives: The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival. Materials and Methods: We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, n = 14), intrahepatic cholangiocarcinoma (iCC, n = 24), and extrahepatic cholangiocarcinoma (eCC, n = 22) cholangiocarcinomas via immunohistochemistry and ImageJ software-assisted analysis. An Immunohistochemistry (IHC)-score was determined by the percentage and intensity of stained (positive) cells (scale 0-7) and normal and malignant tissue was compared. In the IHC results, patients' (gender, age) and tumor (TNM Classification of Malignant Tumors, Union Internationale contre le Cancer (UICC) stages, grading, and lymphangitic carcinomatosa) characteristics were correlated to patient survival. Results: For eCC, the expression of CD44 (p = 0.043, IHC-score 3.94 vs. 3.54) and for iCC, the expression of CD44 (p = 0.026, IHC-score 4.04 vs. 3.48) and Notch1 (p < 0.001, IHC-score 2.87 vs. 1.78) was significantly higher in the tumor compared to non-malignant tissue. For PDAC, the expression of ADAM17 (p = 0.008, IHC-score 3.43 vs. 1.73), CD44 (p = 0.012, IHC-score 3.64 vs. 2.27), Notch1 (p = 0.012, IHC-score 2.21 vs. 0.64), and Notch4 (p = 0.008, IHC-score 2.86 vs. 0.91) was significantly higher in the tumor tissue. However, none of the analyzed Notch-signaling related components showed an association to patient survival. Conclusion: A significant overexpression of almost all studied components of the Notch signaling pathway can be found in the tumor tissue, however, without a significant influence on patient survival. Therefore, further studies are warranted to draw conclusions on Notch pathway's relevance for patient survival.

The significance of cerebrospinal fluid analysis in the differential diagnosis of 564 psychiatric patients: Multiple sclerosis is more common than autoimmune-encephalitis.

The analysis of cerebrospinal fluid (CSF) is an essential tool for the differential diagnosis of psychiatric disorders caused by autoimmune inflammation or infections. Clear guidelines for CSF analysis are limited and mainly available for schizophrenia and dementia. Thus, insights into CSF changes in psychiatric patients largely derive from research. We analyzed the clinical and CSF data of 564 psychiatric patients without pre-existing neurological diagnoses from March 1998 to April 2020. Primary aim was to detect previously undiagnosed neurological conditions as underlying cause for the psychiatric disorder. Following CSF analysis, 8 % of patients (47/564) were diagnosed with a neurological disorder. This was the case in 12.0 % (23/193) of patients with affective disorders, 7.2 % (19/262) of patients with schizophrenia, and 4.0 % (23/193) of patients with anxiety disorders. The predominant new diagnoses were multiple sclerosis (19/47) and autoimmune encephalitis (10/47). Abnormal CSF findings without any implications for further treatment were detected in 17.0 % (94/564) of patients. Our data indicates that CSF analysis in patients suffering from psychiatric disorders may uncover underlying organic causes, most commonly multiple sclerosis and autoimmune encephalitis. Our findings imply that the incorporation of CSF analysis in routine psychiatric assessments is potentially beneficial.