Prognostic Significance of Tumor and Inflammatory Markers in Disease-Free and Overall Survival Duration in Colonic Adenocarcinoma Patients.

Introduction Colorectal carcinoma (CRC) continues to be a major global health concern, contributing substantially to cancer incidence and mortality. Colonic adenocarcinoma, a common subtype of CRC, is influenced by various prognostic factors, including tumor stage, histopathological characteristics, and tumor markers. Despite their routine use in clinical settings, the prognostic value of traditional tumor markers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and others, is still under debate. In this study, we aim to analyze the tumor markers' prognostic significance in our CRC patients in terms of disease-free survival and overall survival. Methods A retrospective study was conducted on 71 patients who underwent surgery for colonic adenocarcinoma between January 1, 2018, and January 1, 2024. Data on patient demographics, recurrence rates, survival times, and tumor marker levels (CEA, CA 19-9, CA 125, AFP, and CRP to albumin ratio (CAR)), disease-free survival duration (DFS), and overall survival durations (OS) were collected and analyzed. Statistical analyses included Pearson and Spearman correlation coefficients, the Mann-Whitney U test, ROC curve analysis, and Kaplan-Meier survival analysis. Results The study found that elevated CAR and CA 125 levels were significantly associated with higher mortality and recurrence rates, whereas elevated CEA levels were strongly predictive of recurrence. Receiver operating characteristic (ROC) analysis identified optimal cutoff values for these markers, with CEA ≥ 47.145, CA 125 ≥ 15.85, and CAR ≥ 6.796 demonstrating high specificity and predictive value for recurrence. Kaplan-Meier analysis revealed that patients with CEA < 47.145 had a significantly longer DFS (67.7 months) compared to those with CEA ≥ 47.145 (24 months, p < 0.001). Similarly, patients with CA 125 < 15.85 and CAR < 6.796 showed longer DFS compared to those with higher values. Overall survival analysis also highlighted that patients with CA 125 < 21.71 and CAR < 4.09 had better survival outcomes, with significant differences of 26 and 10 months, respectively (p < 0.001 and p = 0.001). Conclusion Tumor markers, such as CEA, CA 125, and CAR, hold significant prognostic value in colonic adenocarcinoma, with higher levels correlating with poorer outcomes. These findings underscore the importance of integrating tumor markers into clinical decision-making to optimize treatment strategies and improve patient survival. Future research should focus on standardizing the use of these markers and exploring novel biomarkers for enhanced prognostication.

Advances in Colon-Targeted Drug Delivery Systems: Innovative Strategies for Treating Colonic Disorders and Prospects for the Future.

Colon-specific targeting delivery systems have drawn a great deal of attention because they represent potential vehicles for treating colonic disorders like diverticulitis, colitis, salmonellosis, Crohn's disease, etc. with less systemic adverse effects as well as for the better oral delivery of many therapeutics that are prone to enzymatic and acidic deterioration in the upper GI tract. Smart polymeric delivery systems in particular have been investigated as "intelligent" delivery systems capable of releasing entrapped pharmaceuticals at the proper time & site of action in response to certain physiological stimuli. The creation of novel polymers & crosslinkers with improved biodegradability and biocompatibility would expand and enhance applications now in use. The development of polymeric systems could result in more precise and programmable drug delivery/therapies. In addition, newer advancements have led to the development of numerous ground-breaking techniques for directing a medication molecule to the colon. This review highlighted formulation techniques pH-dependent, time-dependent, enzyme sensitive, magnetically dependent, ligand-receptor mediated, and microflora-activated systems. Moreover, several methods have been put forth that make use of the innovative idea of such delivery systems, and mechanisms in which the release of drugs is regulated by pH and time as well as pH and the colon's bacteria.

Development of an infant colon simulating in vitro model, I-TIM-2, to study the effects of modulation strategies on the infant gut microbiome composition and function.

The early life stages are critical for the development of the gut microbiome. Variables such as antibiotics exposure, birth-mode via Cesarean section, and formula feeding are associated with disruptions in microbiome development and are related to adverse health effects later in life. Studying the effects of microbiome-modulating strategies in infants is challenged by appropriate ethical constraints. Therefore, we developed I-TIM-2, an infant in vitro colonic model based on the validated, computer-controlled, dynamic model of the colon, TIM-2. The system, consisting of four separate compartments, was inoculated with feces from four healthy, primarily breastfed infants, displaying distinctive microbiome profiles. For each infant's fecal sample, a 96-h experiment was performed, with two compartments receiving an infant diet adapted medium and two compartments additionally receiving five human milk oligosaccharides (HMOs) in physiological concentrations and proportions. Bacterial composition was determined by shotgun metagenomics and qPCR. Concentrations of short-chain fatty acids (SCFAs) and HMOs were determined by LC-MS. Microbial diversity and high amounts of inoculum-derived species were preserved in the model throughout each experiment. Microbiome composition and SCFA concentrations were consistent with published data from infants. HMOs strongly modulated the microbiome composition by stimulating relative proportions of Bifidobacterium. This affected the metabolic output and resulted in an increased production of acetic and formic acid, characteristic of bifidobacterial HMO metabolism. In conclusion, these data demonstrate the development of a valid model to study the dynamics and modulations of the infant gut microbiome and metabolome.IMPORTANCEThe infant gut microbiome is intricately linked to the health of its host. This is partly mediated through the bacterial production of metabolites that interact with the host cells. Human milk shapes the establishment of the infant gut microbiome as it contains human milk sugars that select for primarily bifidobacteria. The establishment can be disrupted by modern interventions such as formula feeding. This can alter the microbiome composition and metabolite production profile, which can affect the host. In this article, we set up an infant in vitro colonic model to study microbiome interactions and functions. In this model, we investigated the effects of human milk sugars and their promotion of bifidobacteria at the expense of other bacteria. The model is an ideal system to assess the effects of various modulating strategies on the infant gut microbiome and its interactions with its host.

Ogilvie syndrome with caecal perforation following cesarean section: a rare case report from Jordan.

Introduction: Ogilvie syndrome is a rare condition characterized by acute colonic dilation. In 1948, H. Ogilvie first described it in medical literature. Its incidence is estimated at 100 cases per 100 000 per year in the US. Both abdominal distention and pain are considered major symptoms. Presentation of case: A 32-year-old woman, 36+1 weeks pregnant, experienced labour pain and was admitted to the hospital. Upon examination, she was in labour, but the foetus was in a breech position, necessitating a caesarean section. After 36 h later, she returned to the emergency department with severe, 1-day-old diffuse abdominal pain, accompanied by moderate bilious vomiting and significant abdominal distension. Abdominal CT with contrast revealed pneumoperitoneum, abdominal wall emphysema, and pneumatosis intestinalis involving the caecum and ascending colon, suggesting bowel necrosis. Emergency laparotomy revealed a caecal perforation, which was closed surgically without resection. Clinical discussion: Ogilvie syndrome is more common in males but can occur in females for several reasons, including pregnancy, caesarean section, pelvic surgeries, and trauma. Several factors contribute to the occurrence of this syndrome, such as pelvic fractures and cardiac events. Surgery may be required if there is suspicion of bowel perforation or ischaemia. Conclusion: OS is a rare condition in women, often seen after childbirth or pelvic surgery, with an unclear cause but believed to be related to autonomic nervous system imbalance. Patients with abdominal pain and distension, without evidence of obstruction, should be evaluated for pseudo-obstruction using abdominal pelvic CT, and treatment may involve conservative measures, medication, and colonoscopic decompression.

From evidence to practice: real-world insights into outpatient management of acute uncomplicated diverticulitis.

BACKGROUND: Diverticulitis is experiencing a significant increase in prevalence and its widespread in-hospital management results in a high burden on healthcare systems worldwide. This study compared inpatient and outpatient approach of acute non-complicated diverticulitis using a non-selected population in a real-world setting. METHODS: This observational retrospective study included all consecutive patients from two Portuguese institutions diagnosed between January 2017 and December 2021 with non-complicated diverticulitis according to the modified Hinchey Classification. The primary endpoints were to identify criteria for inpatient treatment and compare the outcomes on the basis of the treatment regimen. The secondary endpoints were to determine the predictive factors for clinical outcomes, focusing on treatment failure, pain recurrence, and the need for elective surgery following the initial episode. RESULTS: A total of 688 patients were included in this study, 437 treated as outpatients and 251 hospitalized. Inpatient management was significantly associated with higher preadmission American society of anesthesiologists (ASA) score (p = 0.004), fever (p = 0.030), leukocytosis (p < 0.001), and elevated C-reactive protein (CRP) (p < 0.001). No significant association was found between failure of conservative treatment and patient's age, ASA score, baseline CRP, presence of systemic inflammatory response syndrome (SIRS), and inpatient or outpatient treatment regimen. Pain recurrence was significantly associated with higher CRP levels (p = 0.049), inpatient treatment regime (p = 0.009) and post index episode mesalazine prescription (p = 0.006). Moreover, the need for elective surgery was significantly associated with the presence of previous episodes (p = 0.004) and pain recurrence (p < 0.001). CONCLUSIONS: The majority of patients with uncomplicated diverticulitis of the left colon experience successful conservative approach and can be safely managed in an ambulatory setting. Neither treatment failure, recurrence of pain, or need for posterior elective surgery are associated with outpatient treatment regimen.

Colonic torsion and volvulus in dogs is associated with a low mortality rate and good long-term outcome.

OBJECTIVE: To describe clinical findings, complications, and short- and long-term outcomes associated with colonic torsion and volvulus in dogs. ANIMALS: 28 client-owned dogs. CLINICAL PRESENTATION: Multi-institutional, retrospective study. Medical records were searched for dogs of any age, body weight, sex, and breed that underwent surgery for colonic torsion and volvulus. Collected data included signalment, previous history, preoperative findings, time until surgery, intraoperative findings, postoperative complications, length of hospitalization, survival to discharge, and outcomes. RESULTS: 28 dogs were included. Thirteen of 28 dogs (46.4%) had preexisting gastrointestinal conditions. Nine of 28 dogs (32.1%) had a gastropexy performed prior to presentation. Ten dogs (35.7%) were found to have a resolution of colonic torsion and volvulus at the time of the surgery. All but 1 dog (27 of 28 [96.4%]) survived to discharge. Two dogs died during the postoperative period, yielding a mortality rate of 7.1%. Postoperative complications were noted in 9 dogs (9 of 28 [32.1%]). Long-term follow-up information was available in 16 of 28 dogs (57%). Among 16 dogs with at least 6 months' follow-up, all dogs (16 of 16 [100%]) were alive at 6 months postoperatively. Two dogs developed mesenteric torsion after the initial surgery. CLINICAL RELEVANCE: Dogs with colonic torsion and volvulus undergoing surgery can have an excellent survival-to-discharge ratio with a low mortality rate. Surgeons should not be prompted to euthanize or assume a guarded prognosis solely on the basis of the intraoperative appearance of the bowel and should consider all factors prior to making decisions. Owners should be informed of the risk of developing further torsional diseases after surgery.

Characterising and preventing the gut microbiota's inactivation of trifluridine, a colorectal cancer drug.

The gut microbiome can metabolise hundreds of drugs, potentially affecting their bioavailability and pharmacological effect. As most gut bacteria reside in the colon, drugs that reach the colon in significant proportions may be most impacted by microbiome metabolism. In this study the anti-colorectal cancer drug trifluridine was used as a model drug for characterising metabolism by the colonic microbiota, identifying correlations between bacterial species and individuals' rates of microbiome drug inactivation, and developing strategies to prevent drug inactivation following targeted colonic delivery. High performance liquid chromatography and ultra-high performance liquid chromatography coupled with high resolution tandem mass spectrometry demonstrated trifluridine's variable and multi-route metabolism by the faecal microbiota sourced from six healthy humans. Here, four drug metabolites were linked to the microbiome for the first time. Metagenomic sequencing of the human microbiota samples revealed their composition, which facilitated prediction of individual donors' microbial trifluridine inactivation. Notably, the abundance of Clostridium perfringens strongly correlated with the extent of trifluridine inactivation by microbiota samples after 2 hours (R2 = 0.8966). Finally, several strategies were trialled for the prevention of microbial trifluridine metabolism. It was shown that uridine, a safe and well-tolerated molecule, significantly reduced the microbiota's metabolism of trifluridine by acting as a competitive enzyme inhibitor. Further, uridine was found to provide prebiotic effects. The findings in this study greatly expand knowledge on trifluridine's interactions with the gut microbiome and provide valuable insights for investigating the microbiome metabolism of other drugs. The results demonstrate how protection strategies could enhance the colonic stability of microbiome-sensitive drugs.

Denoising method for colonic pressure signals based on improved wavelet threshold.

The colonic peristaltic pressure signal is helpful for the diagnosis of intestinal diseases, but it is difficult to reflect the real situation of colonic peristalsis due to the interference of various factors. To solve this problem, an improved wavelet threshold denoising method based on discrete wavelet transform is proposed in this paper. This algorithm can effectively extract colonic peristaltic pressure signals and filter out noise. Firstly, a threshold function with three shape adjustment factors is constructed to give the function continuity and better flexibility. Then, a threshold calculation method based on different decomposition levels is designed. By adjusting the three preset shape factors, an appropriate threshold function is determined, and denoising of colonic pressure signals is achieved through hierarchical thresholding. In addition, the experimental analysis of bumps signal verifies that the proposed denoising method has good reliability and stability when dealing with non-stationary signals. Finally, the denoising performance of the proposed method was validated using colonic pressure signals. The experimental results indicate that, compared to other methods, this approach performs better in denoising and extracting colonic peristaltic pressure signals, aiding in further identification and treatment of colonic peristalsis disorders.

Frailty in elderly patients with acute colonic diverticulitis is associated with worse in-hospital outcomes: a nationwide analysis.

Background: Frailty has been identified as an independent predictor of mortality in the elderly. We investigated the effects of frailty status on in-hospital outcomes of acute colonic diverticulitis (ACD) in the elderly, using the Hospital Frailty Risk Score. Methods: We used the National Inpatient Sample (NIS) databases from 2016-2020 to identify patients aged ≥75 years hospitalized with ACD. Using a 1:1 matching method, we created propensity-matched cohorts of frail (Hospital Frailty Risk Score ≥5) and non-frail (Hospital Frailty Risk Score ≤4) patients within the ACD population. Results: We identified 53.3% ACD patients as frail. We matched 21,720 frail ACD patients to an equal number of non-frail ACD patients using propensity score matching. Frail patients exhibited significantly higher mortality rates, longer hospital stays, and greater median inpatient costs. Frail patients also experienced a greater number of complications, including abscess formation, intestinal perforation, gastrointestinal fistula formation, sepsis without shock, sepsis with shock, acute kidney injury, hypovolemic or hemorrhagic shock, need for blood transfusion, cardiac arrest, and need for intensive care (all P-values <0.001). Additionally, frail patients underwent open colectomy and colostomy procedures more frequently, while laparoscopic colectomies were performed less frequently (all P-values <0.001). Conclusions: In this nationwide analysis, frailty in ACD is strongly associated with worse mortality, longer hospital stays and higher costs, as well as a greater incidence of local and systemic complications. Furthermore, frailty is linked to a greater need for open colectomy and colostomy procedures.

Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy.

BACKGROUND: Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. OBJECTIVE: We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis. DESIGN: Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results. RESULTS: Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11+ epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer. CONCLUSION: Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.

Risk Factors for Postoperative Major Morbidity, Anastomotic Leakage, Re-Surgery and Mortality in Patients with Colonic Perforation.

Background/Objectives: This study aimed to determine the risk factors associated with postoperative major morbidity, anastomotic/suture leakage, re-surgery and mortality in patients undergoing emergency surgery for colonic perforation. Methods: A total of 204 adult patients treated surgically for colonic perforation from 2016 to 2021 at the University Hospital Erlangen were included in a retrospective analysis. Patient demographics and pre-, intra- and postoperative parameters were obtained and evaluated among various outcome groups (in-hospital major morbidity, anastomotic/suture leakage, re-surgery and 90-day mortality). Results: Postoperative in-hospital major morbidity, anastomotic/suture leakage, need of re-surgery and 90-day mortality occurred in 45%, 12%, 25% and 12% of the included patients, respectively. Independent risk factors for in-hospital major morbidity were identified and included the presence of any comorbidity, a significantly reduced preoperative general condition, the localization of perforation in the right hemicolon and the need for an intraoperative blood transfusion. The only independent risk factor for anastomotic/suture leakage was the presence of any comorbidity, whereas no independent risk factors for re-surgery were found. An age > 65 years, a significantly reduced preoperative general condition and the need for an intraoperative blood transfusion were independent risk factors for 90-day mortality. Conclusions: Our study identified risk factors impacting postoperative outcomes in patients undergoing emergency surgery for colonic perforation. These patients should receive enhanced postoperative care and may benefit from individualized and targeted therapeutic approaches.

A Pressure Sensing Device to Assist in Colonoscopic Procedures to Prevent Perforation-A Case Study.

Colonoscopy has a limited field of view because it relies solely on a small camera attached to the end of the scope and a screen displayed on a monitor. Consequently, the quality and safety of diagnosis and treatment depend on the experience and skills of the gastroenterologist. When a novice attempts to insert the colonoscope during the procedure, excessive pressure can sometimes be applied to the colon wall. This pressure can cause a medical accident known as colonic perforation, which the physician should prevent. We propose an assisting device that senses the pressure applied to the colon wall, analyzes the risk of perforation, and warns the physician in real time. Flexible pressure sensors are attached to the surface of the colonoscope shaft. These sensors measure pressure signals during a colonoscopy procedure. A simple signal processor is used to collect and process the pressure signals. In the experiment, a colonoscope equipped with the proposed device was inserted into a simulated colon made from a colon extracted from a pig. The processed data were visually communicated to the gastroenterologist via displays and light-emitting diodes (LEDs). The device helps the physician continuously monitor and prevent excessive pressure on the colon wall. In this experiment, the device appropriately generated and delivered warnings to help the physicians prevent colonic perforation. In the future, the device is to be improved, and more experiments will be performed in live swine models or humans to confirm its efficacy and safety.

Somatostatin Peptides Prevent Increased Human Colonic Epithelial Permeability Induced by Hypoxia.

Mesenteric ischemia increases gut permeability and bacterial translocation. In human colon, chemical hypoxia induced by 2,4-dinitrophenol (DNP) activates basolateral intermediate conductance K+ (IK) channels (designated KCa3.1 or KCNN4) and increases paracellular shunt conductance/permeability (GS), but whether this leads to increased macromolecule permeability is unclear. Somatostatin (SOM) inhibits IK channels and prevents hypoxia-induced increases in GS. Thus, we examined whether octreotide (OCT), a synthetic SOM analogue, prevents hypoxia-induced increases GS in human colon and hypoxia-induced increases in total epithelial conductance (GT) and permeability to FITC-dextran 4000 (FITC) in rat colon. The effects of serosal SOM and OCT on increases in GS induced by 100 µM DNP were compared in isolated human colon. The effects of OCT on DNP-induced increases in GT and transepithelial FITC movement were evaluated in isolated rat distal colon. GS in DNP-treated human colon was 52% greater than in controls (P = 0.003). GS was similar when 2 µM SOM was added after or before DNP treatment, in both cases being less (P <0.05) than with DNP alone. 0.2 µM OCT was equally effective preventing hypoxia-induced increases in GS, whether added after or before DNP treatment. In rat distal colon, DNP significantly increased GT by 18% (P = 0.016) and mucosa-to-serosa FITC movement by 43% (P = 0.01), and 0.2 µM OCT pre-treatment completely prevented these changes. We conclude that OCT prevents hypoxia-induced increases in paracellular/macromolecule permeability and speculate it may limit ischemia-induced gut hyperpermeability during abdominal surgery, thereby reducing bacterial/bacterial toxin translocation and sepsis.

Oat ß-(1 → 3, 1 → 4)-d-glucan alleviates food allergy-induced colonic injury in mice by increasing Lachnospiraceae abundance and butyrate production.

Oat ß-(1 â†’ 3, 1 â†’ 4)-d-glucan (OBG), a linear polysaccharide primarily found in oat bran, has been demonstrated to possess immunomodulatory properties and regulate gut microbiota. This study aimed to investigate the impact of low molecular weight (Mw) OBG (155.2 kDa) on colonic injury and allergic symptoms induced by food allergy (FA), and to explore its potential mechanism. In Experiment 1, results indicated that oral OBG improved colonic inflammation and epithelial barrier, and significantly relieved allergy symptoms. Importantly, the OBG supplement altered the gut microbiota composition, particularly increasing the abundance of Lachnospiraceae and its genera, and promoted the production of short-chain fatty acids, especially butyrate. However, in Experiment 2, the gut microbial depletion eliminated these protective effects of OBG on the colon in allergic mice. Further, in Experiment 3, fecal microbiota transplantation and sterile fecal filtrate transfer directly validated the role of OBG-mediated gut microbiota and its metabolites in relieving FA and its induced colonic injury. Our findings suggest that low Mw OBG can alleviate FA-induced colonic damage by increasing Lachnospiraceae abundance and butyrate production, and provide novel insights into the health benefits and mechanisms of dietary polysaccharide intervention for FA.

Safety and efficacy of autologous blood tattooing for preoperative colonic localization: a comparative study with conventional India ink tattooing.

BACKGROUND: India ink has been a popular choice for a tattooing agent in preoperative endoscopic localization but often results in unfavorable effects. Subsequently, autologous blood tattooing has arisen as an alternative option. Due to the limited availability of comparative studies on the matter, we conducted a study to compare the perioperative outcomes associated with India ink tattooing versus autologous blood tattooing. METHODS: A total of 96 patients who underwent minimally invasive surgical procedures for left-sided colonic neoplasm following preoperative endoscopic localization were included in the study. These patients were categorized into two groups: 36 patients who received India ink tattooing and 60 patients who underwent autologous blood tattooing. The perioperative outcomes including procedure-related outcomes and postoperative outcomes were compared between the two groups. RESULTS: There was no significant difference in visibility and spillage of tattooing agent between India ink group and autologous blood group. However, India ink group showed a higher incidence of post-tattooing fever, higher level of postoperative C-reactive protein level, longer time to first flatus, resumption of surgical soft diet, and duration of hospital stay, and a higher occurrence of postoperative complications including ileus and surgical site infection compared with the autologous blood group. In the multivariate analysis, India ink tattooing was significantly associated with the occurrence of postoperative complications. In the subgroup analysis involving patients with intraperitoneal spillage, the autologous blood group demonstrated significantly favorable perioperative outcomes compared with India ink group. CONCLUSIONS: Autologous blood tattooing demonstrated comparable visibility and enhanced safety, establishing it as a potential alternative to India ink for preoperative endoscopic localization.

Bacterial lipopolysaccharide inhibits free thiamin uptake along the intestinal tract via interference with membrane expression of thiamin transporters-1 & -2.

This study examined the effect of exposure of small and large intestinal epithelial cells to the bacterial lipopolysaccharide (LPS) on uptake of free form of vitamin B1, i.e., thiamin. The intestinal tract encounters two sources of thiamin: diet and the gut microbiota. Absorption of thiamin in both the small and large intestine occurs via a carrier-mediated process that involves thiamin transporters-1 & -2 (THTR-1 & -2). Complementary in vitro (human duodenal epithelial HuTu-80 cells and human colonic epithelial NCM460 cells), in vivo (mice), and ex vivo (human primary differentiated enteroid and colonoid monolayers) models were used. The results showed that exposure to LPS causes a significant inhibition in carrier-mediated [3H]-thiamin uptake by small and large intestinal epithelia, with no change in levels of expression of THTR-1& -2 mRNAs and their total cellular proteins. However, a significant decrease in the fractions of the THTR-1& -2 proteins that are expressed at the cell membranes of these epithelial cells was observed. These effects of LPS appeared to involve a protein kinase A (PKA) signaling pathway as activating this pathway caused a reversal in the inhibition of thiamin uptake and level of expression of its transporters at the cell membrane. These findings demonstrate that exposure of gut epithelia to LPS (a situation that occurs under different pathological conditions) leads to inhibition in thiamin uptake due to a decrease in level of expression of its transporters at the cell membrane that is likely mediated via a PKA-signaling pathway.

Gastrointestinal digestion of yerba mate, rosemary and green tea extracts and their subsequent colonic fermentation by human, pig or rat inocula.

Polyphenolic compounds are common constituents of human and animal diets and undergo extensive metabolism by the gut microbiota before entering circulation. In order to compare the transformations of polyphenols from yerba mate, rosemary, and green tea extracts in the gastrointestinal tract, simulated gastrointestinal digestion coupled with colonic fermentation were used. For enhancing the comparative character of the investigation, colonic fermentation was performed with human, pig and rat intestinal microbiota. Chemical analysis was performed using a HPLC system coupled to a diode-array detector and mass spectrometer. Gastrointestinal digestion diminished the total amount of phenolics in the rosemary and green tea extracts by 27.5 and 59.2 %, respectively. These reductions occurred mainly at the expense of the major constituents of these extracts, namely rosmarinic acid (-45.7 %) and epigalocatechin gallate (-60.6 %). The yerba mate extract was practically not affected in terms of total phenolics, but several conversions and isomerizations occurred (e.g., 30 % of trans-3-O-caffeoylquinic acid was converted into the cis form). The polyphenolics of the yerba mate extract were also the least decomposed by the microbiota of all three species, especially in the case of the human one (-10.8 %). In contrast, the human microbiota transformed the polyphenolics of the rosemary and green extracts by 95.9 and 88.2 %, respectively. The yerba mate-extract had its contents in cis 3-O-caffeoylquinic acid diminished by 78 % by the human microbiota relative to the gastrointestinal digestion, but the content of 5-O-caffeoylquinic acid (also a chlorogenic acid), was increased by 22.2 %. The latter phenomenon did not occur with the rat and pig microbiota. The pronounced interspecies differences indicate the need for considerable caution when translating the results of experiments on the effects of polyphenolics performed in rats, or even pigs, to humans.

Amphicrine carcinoma of the right colon, a report of a case and review of literature.

Mixed neuroendocrine and non-neuroendocrine neoplasms, recently recognized in the WHO classification as (MiNEN), are rare tumors of the gastrointestinal tract. These tumors are composed of two distinct cellular components; a well- or poorly differentiated neuroendocrine tumor and a non-neuroendocrine tumor, usually in the form of an adenocarcinoma, either admixed with or adjacent to one another. A rarer phenotype is a tumor in which the endocrine and epithelial cell features occur within the same cell; i.e. amphicrine carcinoma. Herein, we report the case of an 80-year-old female patient who presented with melena, and who, on biopsy was diagnosed as amphicrine carcinoma that was mismatch repair deficient (MMRd) with loss of MLH1/PMS2 nuclear expression by immunohistochemistry. The histological and immunohistochemical findings of this rare entity are presented with review of pertinent literature.

Morphological and functional features of the colonic mucus barrier in patients with symptomatic uncomplicated diverticular disease and acute uncomplicated diverticulitis.

OBJECTIVE: Aim: The purpose was to identify the morphological and functional features of the colonic mucus barrier in patients with symptomatic uncomplicated diverticular disease and acute uncomplicated diverticulitis. PATIENTS AND METHODS: Materials and Methods: In the research, three groups were formed. Group 1 included fragments of the mucous membrane of the large intestine, which were collected from 12 people during autopsies. The results of autopsies and histological examination of the material did not reveal any gastrointestinal pathology. Group 2 included biopsies of the mucous membrane of the large intestine from the area of the diverticulum of 34 patients with symptomatic uncomplicated diverticular disease. Group 3 included biopsies of the mucous membrane of the large intestine of 26 patients with acute uncomplicated diverticulitis. Histological (hematoxylin and eosin staining), histochemical (PAS reaction) and immunohistochemical (mouse monoclonal antibodies to Mucin 2 (MUC2) and Mucin 4 (MUC4)) staining methods were used. A morphometric study was also carried out. RESULTS: Results: In patients with diverticular disease, the authors identified disturbances in the morphofunctional state of the mucus barrier of the colon, the structure and function of goblet cells contained in its mucous membrane, characterized by a decrease in the thickness of the mucus layer covering the surface of the mucous membrane; a decrease in the size and number of goblet cells with a decrease in their mucus-producing ability; a change in the mucin profile, characterized by a violation of the content of MUC2 and MUC4. These changes were greatest in patients with acute uncomplicated diverticulitis compared with patients with symptomatic uncomplicated diverticular disease. CONCLUSION: Conclusions: The identified disturbances in the morphofunctional state of the mucus barrier of the colon, structural and functional changes in goblet cells may be one of the mechanisms for the development of acute uncomplicated diverticulitis and symptomatic uncomplicated diverticular disease.