Search

Apical-out enteroids mimic the in vivo environment well due to their accessible apical surface and mucus layer, making them an ideal model for studying the impact of (bioactive) food compounds. Generated human ileal apical-out enteroids showed a fucose-containing mucus layer surrounding the apical brush border on their exposure side, indicating their physiological relevance. Effects on the mucosal epithelium of antibacterial prenylated phenolics (glabridin, licochalcone A, and glycycoumarin) from licorice roots were investigated for cytotoxicity, cell viability, barrier integrity, and biotransformation. At concentrations up to 500 μg mL -1 , licochalcone A and glycycoumarin did not significantly affect apical-out enteroids, with cytotoxicities of -6 ± 2 and -2 ± 2% and cell viabilities of 77 ± 22 and 77 ± 13%, respectively ( p > 0.05). Conversely, 500 μg mL -1 glabridin induced significant cytotoxicity (31 ± 25%, p < 0.05) and reduced cell viability (21 ± 14%, p < 0.01). Apical-out enteroids revealed differential sensitivities to prenylated phenolics not observed in apical-in enteroids and Caco-2 cells. Both enteroid models showed phase II biotransformation but differed in the extent of glucuronide conversion. The apical mucus layer of apical-out enteroids likely contributed to these differential interactions, potentially due to differences in electrostatic repulsion. This study underscores the relevance of 3D apical-out enteroid models and highlights the promise of prenylated phenolics for antimicrobial applications.

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs < 50 mm compared to HCAs ≥ 50 mm. Changes in final postoperative diagnosis were assessed. We performed a retrospective study that included patients who underwent resection for (suspected) HCAs in the Netherlands from 2014 to 2019. Indication for resection was analyzed and stratified for small (<50 mm) and large (≥50 mm) tumors. Logistic regression analysis was performed on factors influencing change in tumor diagnosis. Out of 222 patients who underwent surgery, 44 (20%) patients had a tumor <50 mm. Median age was 46 (interquartile range [IQR], 33-56) years in patients with small tumors and 37 (IQR, 31-46) years in patients with large tumors ( p  = 0.016). Patients with small tumors were more frequently men (21% vs. 5%, p  = 0.002). Main indications for resection in patients with small tumors were suspicion of (pre)malignancy (55%), (previous) bleeding (14%), and male sex (11%). Patients with large tumors received operations because of tumor size >50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p  < 0.01), male sex (aOR, 3.7; p  = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p  = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of the American Association for the Study of Liver Diseases.)

Fatty acid amides (FAAs), conjugates of fatty acids with ethanolamine, mono-amine neurotransmitters or amino acids are a class of molecules that display diverse functional roles in different cells and tissues. Recently we reported that one of the serotonin-fatty acid conjugates, docosahexaenoyl serotonin (DHA-5-HT), previously found in gut tissue of mouse and pig, attenuates the IL-23-IL-17 signaling axis in LPS-stimulated mice macrophages. However, its presence and effects in humans remained to be elucidated. Here, we report for the first time its identification in human intestinal (colon) tissue, along with a series of related N-acyl serotonins. Furthermore, we tested these fatty acid conjugates for their ability to inhibit the release of IL-17 and CCL-20 by stimulated human peripheral blood mononuclear cells (PBMCs). Serotonin conjugates with palmitic acid (PA-5-HT), stearic acid (SA-5-HT) and oleic acid (OA-5-HT) were detected in higher levels than arachidonoyl serotonin (AA-5-HT) and DHA-5-HT, while eicosapentaenoyl serotonin (EPA-5-HT) could not be quantified. Among these, DHA-5-HT was the most potent in inhibiting IL-17 and CCL-20, typical Th17 pro-inflammatory mediators, by Concanavalin A (ConA)-stimulated human PBMCs. These results underline the idea that DHA-5-HT is a gut-specific endogenously produced mediator with the capacity to modulate the IL-17/Th17 signaling response. Our findings may be of relevance in relation to intestinal inflammatory diseases like Crohn's disease and Ulcerative colitis., (Copyright © 2017. Published by Elsevier B.V.)

Background: Because mortality and morbidity of pancreatic surgery have decreased to acceptable levels, the complex question arises whether pancreatic resection should be performed in patients with preoperatively doubtful resectable pancreatic cancer., Methods: Perioperative parameters and outcome of 80 patients who underwent a microscopically incomplete (R1) resection were compared with those of 90 patients who underwent a bypass for locally advanced disease for pancreatic adenocarcinoma. All patients initially underwent exploratory laparotomy with the intention to perform a resection. Quality of life was assessed by analyzing readmissions and their indications., Results: Groups were similar with respect to age, presenting symptoms, and preoperative health status. Tumors were significantly larger in the bypass group (3.5 cm vs 2.9 cm, P < .01). Hospital mortality was comparable: zero after R1 resection and 2% after bypass. Of all severe complications, only intra-abdominal hemorrhage occurred significantly more frequently after resection (10% vs 2%; P = .03). Hospital stay after resection was significantly longer than after bypass (16 vs 10 days; P < .01). Survival was significantly longer after R1 resection (15.8 vs 9.5 months, P < .01). Sixty-one percent of patients were readmitted for a total of 215 admissions, equally distributed between groups. After R1 resection, 0.58% of the total survival time after initial discharge was spent in the hospital, after bypass, 0.69%, which was not significantly different., Conclusions: R1 pancreatic resection and bypass for locally advanced disease can be performed with comparable low mortality and morbidity rates. Readmission rates are also comparable between groups and time spent in the hospital after initial discharge is low. Because resection offers adequate palliation in pancreatic cancer, a more aggressive surgical approach in patients who are found to have a doubtfully resectable tumor could be advocated, even if only an R1 resection can be achieved.

Between January 1997 and February 2000, 101 fine-needle pancreatic aspirates were obtained. After a cytologic diagnosis was made, possible molecular alterations were determined on the 94 aspirates with adequate tissue using a molecular panel (K-ras, p53, and DPC4 [MAD4] genes). The 94 aspirates were categorized as follows: diagnostic of adenocarcinoma, 48 (51%); atypical (suggestive of but not diagnostic of adenocarcinoma), 19 (20%); negative for adenocarcinoma, 25 (2 7%); diagnostic of a neoplasm other than adenocarcinoma, 2 (2%). Clinical follow-up revealed that 3 patients (12%) with negative cytologic diagnoses and 12 patients (63%) with atypical cytologic diagnoses had adenocarcinoma. Of 63 with a final diagnosis of adenocarcinoma, 42 (67%) had an alteration in at least 1 of the genes analyzed. In contrast, only 2 (6%) of 31 patients without adenocarcinoma had an alteration in 1 gene on the panel. Overall, the molecular analyses supported the diagnosis of adenocarcinoma in 6 (32%) of 19 aspirates originally diagnosed as atypical by cytology alone. A molecular panel that includes the K-ras, p53, and DPC4 (MAD4) genes correlates with and can supplement traditional cytologic diagnosis of pancreatic fine-needle aspirates.

Despite several advances in our basic understanding and in the clinical management of pancreatic cancer, virtually all patients who will be diagnosed with pancreatic cancer will die from this disease. The high mortality of pancreatic cancer is predominantly because of diagnosis at an advanced stage of disease and a lack of effective treatments. We used the Gene Logic Inc. BioExpress platform and Affymetrix GeneChip arrays to identify genes differentially expressed in pancreatic cancer. cDNA was prepared from samples of normal pancreas (n = 11), normal gastrointestinal mucosa (n = 22), resected pancreas cancer tissues (n = 14), and pancreas cancer cell lines (n = 8), and was hybridized to the complete Affymetrix Human Genome U95 GeneChip set (arrays U95 A, B, C, D, and E) for simultaneous analysis of 60,000 cDNA fragments, with 12,000 fragments covering full-length genes and 48,000 fragments covering expressed sequence tags (ESTs). Genes expressed at levels at least fivefold greater in the pancreatic cancers ascompared to normal tissues were identified. Serial analysis of gene expression (SAGE) libraries (http://www.ncbi.nlm.nih.gov/SAGE/) of two normal pancreatic ductal cell cultures (HX and H126) were used to exclude genes expressed in the normal ducts (more than five tags per library). Differential expression of selected candidate genes was validated by immunohistochemical analysis (n = 3), by in situ hybridization (n = 1), and by reverse transcriptase-polymerase chain reaction (n = 8). One hundred eighty fragments were identified as having fivefold or greater expression levels in pancreas cancer specimens as compared to normal tissue, of which 124 corresponded to known genes and 56 to ESTs. Of these 124 fragments, 10 genes were represented by two or more fragments, resulting in 107 known genes identified as differentially expressed in pancreatic cancer. An additional 10 genes were expressed in the SAGE libraries of normal pancreatic duct epithelium, and were excluded from further analysis. A literature search indicated that 28 of the remaining 97 genes have been reported in association with pancreatic cancer, validating this approach. The remaining 69 genes have not been implicated in pancreatic cancer before, and have immediate potential as novel therapeutic targets and tumor markers of pancreatic cancer.