-
Asian Journal of Surgery Jun 2024
PubMed: 38926063
DOI: 10.1016/j.asjsur.2024.05.301 -
Pathology Jun 2024Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and...
HNF6 and HNF4α expression in adenocarcinomas of the liver, pancreaticobiliary tract, and gastrointestinal tract: an immunohistochemical study of 480 adenocarcinomas of the digestive system.
Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and humans. However, little is known about the prevalence of HNF6 and HNF4α expression in carcinomas of the hepatobiliary tract and pancreas. We aimed to reveal the diagnostic utility of HNF6 and HNF4α immunolabelling in adenocarcinomas of these organs. We investigated HNF6 and HNF4α expression by immunohistochemistry using a total of 480 adenocarcinomas of the digestive system, including 282 of the hepatobiliary tract and pancreas and 198 of the gastrointestinal tract. HNF6 expression was primarily restricted to intrahepatic cholangiocarcinomas (CCs) (63%, n=80) and gallbladder adenocarcinomas (43%, n=88), among others. Notably, small duct intrahepatic CCs almost invariably expressed HNF6 (90%, n=42), showing stark contrast to a low prevalence in large duct intrahepatic CCs (10%, n=21; p<0.0001). HNF6 expression was infrequent in extrahepatic CCs (9%, n=55) and pancreatic ductal adenocarcinomas (7%, n=58), and it was rare in adenocarcinomas of the gastrointestinal tract [oesophagus/oesophagogastric junction (EGJ) (2%, n=45), stomach (2%, n=86), duodenum (0%, n=25), and colorectum (0%, n=42)]. In contrast, HNF4α was widely expressed among adenocarcinomas of the digestive system, including intrahepatic CCs (88%), extrahepatic CCs (94%), adenocarcinomas of the gallbladder (98%), pancreas (98%), oesophagus/EGJ (96%), stomach (98%), duodenum (80%), and colorectum (100%). HNF6 was frequently expressed in and almost restricted to intrahepatic CCs of small duct type and gallbladder adenocarcinomas, while HNF4α was expressed throughout adenocarcinomas of the digestive system. HNF6 immunolabelling may be useful in distinguishing small duct intrahepatic CCs from other types of CC as well as metastatic gastrointestinal adenocarcinomas.
PubMed: 38926048
DOI: 10.1016/j.pathol.2024.03.010 -
Surgery For Obesity and Related... May 2024Metabolic and Bariatric Surgery (MBS) is the most effective management for patients with obesity and weight-related medical conditions. Duodenal switch (DS) is a recent...
BACKGROUND
Metabolic and Bariatric Surgery (MBS) is the most effective management for patients with obesity and weight-related medical conditions. Duodenal switch (DS) is a recent MBS procedure with increasing attention in recent years, however the risk of anastomotic or staple line leaks and the lack of efficient surgical expertise hinders the procedure from becoming fully adopted.
OBJECTIVES
To determine the 30-day predictors of leaks following DS and explore their association with other 30-day postoperative complications.
SETTING
Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database.
METHODS
Patients who underwent a primary biliopancreatic diversion with DS or single-anastomosis duodenoileostomy with sleeve procedure, categorized as DS, were assessed for 30-day leaks. A multivariable logistic regression was constructed to identify the predictors of leaks. The assessment of postoperative complications arising from leaks was also performed.
RESULTS
A total of 21,839 DS patients were included, of which 177 (.8%) experienced leaks within 30 postoperative days. The most significant predictor of leaks was steroid immunosuppressive use (adjusted odds ratio [aOR] = 3.01, 95% confidence interval [CI] [1.56-5.13], P < .001) and age, with each decade of life associated with a 26% increase in risk (aOR = 1.26, 95% CI [1.09-1.45], P = .001). Operative length was also associated with leaks, with every additional 30 minutes increasing the odds of a leak by 23% (aOR = 1.23, 95% CI [1.18-1.29], P < .001). The occurrence of leaks was correlated with postoperative septic shock (Crude Odds Ratio [COR] = 280.99 [152.60-517.39]) and unplanned intensive care unit (ICU) admissions (COR = 79.04 [56.99-109.59]). Additionally, mortality rates increased 17-fold with the incidence of leaks (COR = 17.64 [7.41-41.99]).
CONCLUSIONS
Leaks following DS are a serious postoperative complication with significant risk factors of steroid use, prolonged operative time and advanced age. Leaks are also associated with other severe complications, highlighting the need for early diagnosis and intervention along with additional studies to further validate our results.
PubMed: 38926021
DOI: 10.1016/j.soard.2024.05.012 -
Journal of Clinical and Experimental... 2024Duodenal type follicular lymphoma (DFL), a rare entity of follicular lymphoma (FL), is clinically indolent and is characterized by a low histological grade compared with...
Duodenal type follicular lymphoma (DFL), a rare entity of follicular lymphoma (FL), is clinically indolent and is characterized by a low histological grade compared with nodal follicular lymphoma (NFL). Our previous reports revealed that DFL shares characteristics of both NFL and mucosa-associated lymphoid tissue (MALT) lymphoma in terms of clinical and biological aspects, suggesting its pathogenesis may involve antigenic stimulation. In contrast to NFL, the genomic methylation status of DFL is still challenging. Here, we determined the methylation profiles of DNAs from patients with DFL (n = 12), NFL (n = 10), duodenal reactive lymphoid hyperplasia (D-RLH) (n = 7), nodal reactive lymphoid hyperplasia (N-RLH) (n = 5), and duodenal samples from normal subjects (NDU) (n = 5) using methylation specific PCR of targets previously identified in MALT lymphoma (CDKN2B/P15, CDKN2A/P16, CDKN2C/P18, MGMT, hMLH-1, TP73, DAPK, HCAD). DAPK1 was frequently methylated in DFL (9/12; 75%), NFL (9/10; 90%), and D-RLH (5/7; 71%). CDKN2B/P15 sequences were methylated in six DFL samples and in only one NFL sample. Immunohistochemical analysis showed that p15 expression inversely correlated with methylation status. Genes encoding other cyclin-dependent kinase inhibitors (CDKN2A/P16, CDKN2C/P18) were not methylated in DFL samples. Methylation of the genes of interest was not detected in DNAs from D-RLH, except for DAPK1, and the difference in the extent of methylation between NDU and D-RLH was statistically significant (P = 0.013). Our results suggest that D-RLH serves as a reservoir for the development of DFL and that methylation of CDKN2B/P15 plays an important role in this process.
Topics: Humans; Lymphoma, Follicular; Death-Associated Protein Kinases; DNA Methylation; Male; Pseudolymphoma; Female; Middle Aged; Cyclin-Dependent Kinase Inhibitor p15; Aged; Duodenal Neoplasms; Adult
PubMed: 38925973
DOI: 10.3960/jslrt.24020 -
Biological & Pharmaceutical Bulletin 2024A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from...
A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from the outer environment. The intercellular spaces between adjacent epithelial cells are sealed by bicellular and tricellular tight junctions (TJs). Although one strategy for enhancing intestinal drug absorption is to modulate these TJs, comprehensive gene (mRNA) expression analysis of the TJs components has never been fully carried out in humans. In this study, we used human biopsy samples of normal-appearing mucosa showing no endoscopically visible inflammation collected from the duodenum, jejunum, ileum, colon, and rectum to examine the mRNA expression profiles of TJ components, including occludin and tricellulin and members of the claudin family, zonula occludens family, junctional adhesion molecule (JAM) family, and angulin family. Levels of claudin-3, -4, -7, -8, and -23 expression became more elevated in each segment along the intestinal tract from the upper segments to the lower segments, as did levels of angulin-1 and -2 expression. In contrast, expression of claudin-2 and -15 was decreased in the large intestine compared to the small intestine. Levels of occludin, tricellulin, and JAM-B and -C expression were unchanged throughout the intestine. Considering their segment specificity, claudin-8, claudin-15, and angulin-2 appear to be targets for the development of permeation enhancers in the rectum, small intestine, and large intestine, respectively. These data on heterogenous expression profiles of intestinal TJ components will be useful for the development of safe and efficient intestinal permeation enhancers.
Topics: Humans; Tight Junctions; Intestinal Mucosa; MARVEL Domain Containing 2 Protein; Claudins; Occludin; Male; Adult; Middle Aged; Female; RNA, Messenger; Gene Expression; Aged
PubMed: 38925921
DOI: 10.1248/bpb.b23-00927 -
Journal of Advanced Research Jun 2024During lactation, dairy cattle's digestive tract requires significant adaptations to meet the increased nutrient demands for milk production. As we attempt to improve...
During lactation, dairy cattle's digestive tract requires significant adaptations to meet the increased nutrient demands for milk production. As we attempt to improve milk-related traits through selective pressure, it is crucial to understand the biological functions of the epithelia of the rumen, small intestine, and colonic tissues in response to changes in physiological state driven by changes in nutrient demands for milk synthesis. In this study, we obtained a total of 108 transcriptome profiles from three tissues (epithelia of the colon, duodenum, and rumen) of five Holstein cows, spanning eight time points from the early, mid, late lactation periods to the dry period. On average 97.06% of reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We analyzed 27,607 gene expression patterns at multiple periods, enabling direct comparisons within and among tissues during different lactation stages, including early and peak lactation. We identified 1645, 813, and 2187 stage-specific genes in the colon, duodenum, and rumen, respectively, which were enriched for common or specific biological functions among different tissues. Time series analysis categorized the expressed genes within each tissue into four clusters. Furthermore, when the three tissues were analyzed collectively, 36 clusters of similarly expressed genes were identified. By integrating other comprehensive approaches such as gene co-expression analyses, functional enrichment, and cell type deconvolution, we gained profound insights into cattle lactation, revealing tissue-specific characteristics of the gastrointestinal tract and shedding light on the intricate molecular adaptations involved in nutrient absorption, immune regulation, and cellular processes for milk synthesis during lactation.
PubMed: 38925453
DOI: 10.1016/j.jare.2024.06.020 -
Endoscopy Dec 2024
Topics: Humans; Hamartoma; Brunner Glands; Duodenal Diseases; Male; Female; Duodenoscopy; Middle Aged
PubMed: 38925166
DOI: 10.1055/a-2336-3268 -
Cell Calcium Jun 2024The primary role of pancreatic ductal HCO secretion is to prevent premature activation of digestive enzymes and to provide a vehicle for the delivery of enzymes to the... (Review)
Review
The primary role of pancreatic ductal HCO secretion is to prevent premature activation of digestive enzymes and to provide a vehicle for the delivery of enzymes to the duodenum. In addition, HCOis responsible for the neutralization of gastric juice and protect against the formation of protein plugs and viscous mucus. Due to this multifaceted role of HCO in the pancreas, its altered functioning can greatly contribute to the development of various exocrine diseases. It is well known that the exocrine and endocrine pancreas interact lively with each other, but not all details of this relationship are known. An interesting finding of a recent study by Jo-Watanabe et al. is that the G protein-coupled oestrogen receptor, GPR30, which is expressed in the endocrine pancreas, can be also activated by HCO. This raises the possibility that ductal cells play a key role not only in the exocrine pancreas, but presumably also in endocrine function through HCO secretion.
PubMed: 38924880
DOI: 10.1016/j.ceca.2024.102922 -
Journal of the National Cancer Institute Jun 2024The microbiome has been associated with chemotherapy and immune checkpoint inhibitor (ICI) efficacy. How this pertains to resectable esophageal carcinoma (EC) is...
BACKGROUND
The microbiome has been associated with chemotherapy and immune checkpoint inhibitor (ICI) efficacy. How this pertains to resectable esophageal carcinoma (EC) is unknown. Our aim was to identify microbial signatures in resectable EC associated with response to neoadjuvant chemoradiotherapy (nCRT) with or without ICI.
METHODS
From two prospectively collected EC cohorts (n = 172 in total) treated with nCRT alone (n = 132) or a combination of nCRT and ICI (n = 40), fecal samples were available at baseline, during treatment, and pre-surgery. Additionally, in the ICI treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor and duodenal DNA were extracted for 16S rRNA sequencing. Associations were investigated between microbiome composition pathological complete response (pCR) and progression-free survival (PFS).
RESULTS
There was a significant shift in the microbiota profile of the fecal, tumor and duodenal microbiota over time. In the total cohort, patients with a pCR had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment, p = 0.036. Pre-surgery, lower alpha diversity (<4.12) was related to worse PFS, log-rank p = 0.025. Baseline tumor biopsies of patients with short PFS had more Fusobacterium. A low baseline duodenal alpha diversity (<3.96) was associated with worse PFS, log-rank p = 0.012.
CONCLUSIONS
Lower intestinal alpha diversity was associated with worse response and survival of EC patients. In tumor biopsies Fusobacterium was more abundant in patients with poor PFS. After further mechanistic validation, these findings may aid in response prediction and the design of novel microbiome modulating treatments for EC patients.
PubMed: 38924513
DOI: 10.1093/jnci/djae153 -
Veterinary Medicine and Science Jul 2024The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to...
BACKGROUND
The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to promoting growth of young ruminants. This study investigated effects of guanidino acetic acid (GAA) and rumen-protected betaine (RPB) supplementation on growth, dietary nutrient digestion and GAA metabolism in the small intestine of sheep.
METHODS
Eighteen healthy Kazakh rams (27.46 ± 0.10 kg of body weight and 3-month old) were categorized into control, test group I and test group II, which were fed a basal diet, 1500 mg/kg GAA and 1500 mg/kg GAA + 600 mg/kg RPB, respectively.
RESULTS
Compared with control group, test group II had increased (p < 0.05) average daily gain, plasma creatine level, ether extract (EE) and phosphorus digestibility on day 30. On day 60, the EE apparent digestibility, jugular venous plasma GAA, GAA content in the duodenal mucosa and GAA content in the jejunal and ileal mucosa of test group II were higher (p < 0.05) than other groups. Transcriptome analysis revealed that the differentially expressed genes (DEGs) involved in the duodenal pathways of oxidative phosphorylation and non-alcoholic fatty liver disease were significantly altered in test group II versus test group I (p < 0.05). Moreover, in the jejunum, the MAPK signalling pathway, complement and coagulation cascade and B-cell receptor signalling pathway were significantly enriched, with ATPase, solute carrier transporter protein, DHFR, SI, GCK, ACACA and FASN being the significantly DEGs (p < 0.05).
CONCLUSION
Dietary supplementation of RPB on top of GAA in sheep diets may promote sheep growth and development by improving the body's energy, amino acid, glucose and lipid metabolism capacity.
Topics: Animals; Dietary Supplements; Betaine; Animal Feed; Diet; Male; Digestion; Creatine; Glycine; Sheep; Sheep, Domestic; Animal Nutritional Physiological Phenomena; Random Allocation; Nutrients
PubMed: 38923734
DOI: 10.1002/vms3.1470