Background: Perihilar cholangiocarcinoma (pCCA) is characterised by poor outcomes. Early diagnosis is essential for patient survival. The peptide galanin (GAL) and its receptors GAL_1–3 are expressed in various tumours. Detailed characterisation of the GAL system in pCCA is lacking. Our study sought to characterise GAL and GAL_1–3 receptor (GAL_1–3–R) expression in the healthy human bile duct, in cholestasis and pCCA. Methods: Immunohistochemical staining was performed in healthy controls (n = 5) and in the peritumoural tissues (with and without cholestasis) (n = 20) and tumour tissues of pCCA patients (n = 33) using validated antibodies. The score values of GAL and GAL_1–3–R expression were calculated and statistically evaluated. Results: GAL and GAL₁–R were expressed in various bile duct cell types. GAL₂–R was only slightly but still expressed in almost all the examined tissues, and GAL₃–R specifically in cholangiocytes and capillaries. In a small pCCA patient cohort (n = 18), high GAL expression correlated with good survival, whereas high GAL₃–R correlated with poor survival. Conclusions: Our in-depth characterisation of the GAL system in the healthy human biliary duct and pCCA in a small patient cohort revealed that GAL and GAL₃–R expression in tumour cells of pCCA patients could potentially represent suitable biomarkers for survival.

Endoscopic submucosal dissection (ESD) is an effective treatment of early esophageal adenocarcinomas (EACs). The decision of ESD over esophagectomy is based on clinical evaluation of tumor depth and invasion. On a molecular level, tumor invasion is strongly associated with epithelial-to-mesenchymal transition (EMT). Here, we investigated whether localized ESD-resected and surgically resected EAC samples displayed different expression profiles of EMT protein and microRNA markers and whether these different expression profiles were able to retrospectively discriminate localized and surgically resected samples. By doing this, we aimed to evaluate whether preoperative measurement of EMT marker expression might support the decision regarding ESD over surgery. The results showed that ESD-resected samples displayed an epithelial expression profile, i.e., high expression of epithelial protein markers, whereas surgically resected samples displayed high expression of mesenchymal markers. In addition, the anti-EMT microRNA-205 was significantly more expressed in ESD-resected samples, whereas we found no significant differences in the expression levels of microRNA-200 family members. Furthermore, in our retrospective approach, we have demonstrated that measurement of selected EMT markers and microRNA-205 has significant discrimination power to distinguish ESD-resected and surgically resected samples. We suggest that the assessment of EMT status of EAC samples on a molecular level may support clinical evaluation regarding the applicability of ESD.

The bile duct transports bile fluid from the liver to the gallbladder and small intestine. It contains bioactive peptides, including galanin (GAL) and its receptors (GAL_1-3-R). Spexin (SPX), a member of the GAL peptide family, activates GAL₂-R and GAL₃-R. Its expression in perihilar bile ducts or in perihilar cholangiocarcinoma (pCCA), the most common biliary cancer, is largely unknown. This study investigated SPX expression in healthy, cholestatic, and malignant bile duct tissues. Immunohistochemistry was used to evaluate SPX in healthy (n = 4), peritumoral (PIT) (n = 23) and pCCA (n = 34) tissues. Score values of SPX expression were calculated and statistically analyzed. In healthy and PIT tissues with or without cholestasis, SPX expression was predominantly observed in cholangiocytes and nerve fibers. In pCCA, tumor cells also expressed SPX. SPX levels were similar across healthy, peritumoral, and cholangiocytes/tumor cells. In a small pCCA patient cohort (n = 19), SPX expression did not correlate with tumor grade or patient survival (p = 0.0838). The substantial expression of SPX in cholangiocytes and nerve fibers in the bile duct indicates that SPX contributes via galaninergic signaling to gall bladder function. The presence of SPX in submucosal nerve fibers suggests a neuromodulatory role, possibly involving bile duct motility. SPX expression did not correlate with survival in pCCA, whereas previous findings on GAL suggest a prognostic value. This highlights the need for joint studies of SPX and GAL in larger cohorts.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a five-year survival rate of 6%, yet the underlying causes remain poorly understood. The neuropeptide galanin (GAL) and its three receptors (GAL_1-3-R) are known to modulate tumor biology. This study characterizes the expression patterns of the GAL system in healthy and diseased pancreas to evaluate its potential as a biomarker for disease progression. Immunohistochemical staining for GAL and GAL_1-3-R was performed on tissue samples from healthy controls (n = 10), pancreatitis (n = 10), and PDAC (n = 34). Immunoreactive scores were quantified across histological compartments and were correlated with TNM stage, perineural invasion, and Union for International Cancer Control classification. GAL was widely expressed, with significant upregulation in lobular ducts and nerve bundles of PDAC compared to controls. Intra-neural GAL expression in PDAC positively correlated with advanced nodal stages and perineural invasion. In pancreatitis, GAL₁-R expression was selectively increased in lobular ducts. Although GAL₂-R expression peaked in endocrine cells, intra-neural GAL₂-R was significantly downregulated in PDAC compared to healthy tissue, with further decreases in advanced stages. GAL₃-R was predominantly localized to ducts and acini, showing higher expression in PDAC endocrine compartments than in pancreatitis or healthy tissue. Our findings demonstrate significant remodeling of the galaninergic system during pancreatic inflammation and carcinogenesis. Stage-dependent intra-neural GAL increases correlate with nodal involvement and perineural invasion, suggesting its potential as a prognostic biomarker for tumor aggressiveness. Progressive intra-neural GAL₂-R loss in PDAC may limit receptor-agonist therapy efficacy, necessitating receptor-status screening for personalized patient stratification in future clinical applications.

Background: Altered body composition is common in patients undergoing major hepatopancreaticobiliary (HPB) surgery and may be associated with increased postoperative morbidity. Conventional markers such as body mass index (BMI) and serum albumin have limited sensitivity for detecting early nutritional changes. Bioelectrical impedance analysis (BIA) provides an objective assessment of body composition, and phase angle (PA) may serve as a proxy for cellular status. Methods: This single-center retrospective observational cohort study included 73 patients undergoing major HPB surgery. Preoperative BIA-derived variables included resistance (R), reactance (Xc), PA, fat-free mass index (FFMI), fat mass index (FMI), and the Body Composition Chart (BCC). Nutritional Risk Screening 2002 (NRS 2002), serum albumin, and prealbumin were assessed preoperatively. BIA-derived data were compared with published healthy reference data. Postoperative complications were graded according to the Clavien–Dindo classification. Results: Patients demonstrated significant alterations in BIA-derived variables compared with healthy controls. Xc and PA were significantly reduced across all analyzable/matched sex and BMI strata (all p < 0.05). The median PA in the surgical cohort was 4.3° and significantly lower than reference values for both female and male patients (p < 0.001). FFMI and FMI distributions indicated a high prevalence of adverse body composition phenotypes, including low fat-free mass and increased adiposity. In multivariable Firth penalized logistic regression, a BCC classification outside the green reference zone (odds ratio (OR) 3.32, 95% confidence interval (CI) 1.04–12.87, p = 0.043) and higher Eastern Cooperative Oncology Group (ECOG) performance status (OR 2.07, 95% CI 1.08–4.24, p = 0.028) were independently associated with severe postoperative complications. Conclusions: Patients undergoing major HPB surgery frequently present with relevant preoperative nutritional and cellular impairments that are not adequately identified by BMI and serum albumin. Incorporation of BIA into routine preoperative assessment may improve risk stratification and support targeted nutritional optimization in this high-risk surgical population.