Decreased Abundance of Genus Slackia in Individuals With Obesity and Colorectal Adenoma.

Background and Aims: The increasing prevalence of obesity has significantly contributed to the global burden of colorectal cancer and the precancerous colorectal adenoma (CRA). Gut microbiota vary at each stage of colorectal carcinogenesis and participate in energy homeostasis. Elucidating gut microbiotal characteristics in obesity-related CRA may help prevent and treat colorectal tumors; however, this remains unclarified. Therefore, this study investigated the gut microbiota profile of patients with obesity-related CRA. Methods: This hospital setting-based cross-sectional study included 113 participants (66 [without CRA control group] and 37 [with CRA group]; each group was divided into obese and nonobese groups) who underwent screening colonoscopy between June 2019 and January 2020. Gut microbiota were analyzed using 16S rRNA and polymerase chain reaction techniques and the data compared between the aforementioned groups. Results: No between-group difference was observed in the diversity index; however, α diversity was the lowest in the obese CRA group. The CRA group had significantly higher and lower numbers of 26 and 17 genera, respectively. Genus Slackia was significantly lower in the obese CRA group than in the nonobese CRA group. Multivariate analysis of the quartiles according to genus Slackia relative abundance rates revealed that the first quartile was an independent risk factor for CRA (odds ratio, 3.57; 95% confidence interval 1.19-10.7). The proportion of equol reductase-positive participants was lowest in the obese CRA group (P = .04). Multivariate odds ratio for CRA was 5.46 (95% confidence interval 1.35-22.0) for genus Slackia and equol reductase-negative participants. Conclusion: Decreased abundance of genus Slackia and absence of equol reductase potentially influence obesity-related CRA development.

Low serum pancreatic amylase levels as a novel latent risk factor for colorectal adenoma in non-alcohol drinkers.

BACKGROUND AND AIM: Obesity, insulin resistance, and metabolic alterations increase the risk of colorectal cancer and adenoma (CRA). Non-alcoholic fatty liver disease (NAFLD) or pancreatic disease (NAFPD) shares many risk factors with CRA that may have significant roles in its development; however, the relationship between CRA and NAFLD/NAFPD remains unclear. METHODS: This cross-sectional study recruited 712 eligible participants without current drinking who had undergone total colonoscopy as part of a health checkup. These participants were classified into a CRA group (n = 236) and a control group (n = 439), which consisted of individuals without CRA and a history of polyp resection. NAFLD and NAFPD were diagnosed based on abdominal ultrasonography findings. RESULTS: Non-alcoholic fatty liver disease was observed more frequently in individuals with CRA than in the control group (55.9% vs 41.6%, P < 0.01). There was no significant association between NAFPD and CRA; however, serum pancreatic amylase (P-amylase) levels were significantly lower in individuals with CRA. Although NAFLD was one of the factors increasing the presence of CRA (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.07-2.10), low P-amylase levels were significantly associated with the presence of CRA (OR, 1.73; 95% CI, 1.04-2.88) independent of age, sex, current smoking, obesity, metabolic alterations including insulin resistance, and NAFLD. CONCLUSIONS: Low serum P-amylase levels were a possible independent risk factor for CRA in the present study. The latent pancreatic exocrine-endocrine-gut relationship was considered a novel pathway involved in obesity-related CRA development, in non-alcoholic individuals.

Characteristics of the gut microbiome profile in obese patients with colorectal cancer.

BACKGROUND AND AIM: Obesity affects the gut microbiome, which in turn increases the risk for colorectal cancer. Several studies have shown the mechanisms by which some bacteria may influence the development of colorectal cancer; however, gut microbiome characteristics in obese patients with colorectal cancer remain unclear. Therefore, this study evaluated their gut microbiome profile and its relationship with metabolic markers. METHODS: The study assessed fecal samples from 36 consecutive patients with colorectal cancer and 38 controls without colorectal cancer. To identify microbiotic variations between patients with colorectal cancer and controls, as well as between nonobese and obese individuals, 16S rRNA gene amplicon sequencing was performed. RESULTS: Principal coordinate analysis showed significant differences in the overall structure of the microbiome among the study groups. The α-diversity, assessed by the Chao1 index or Shannon index, was higher in patients with colorectal cancer versus controls. The relative abundance of the genera Enterococcus, Capnocytophaga, and Polaribacter was significantly altered in obese patients with colorectal cancer, whose serum low-density lipoprotein concentrations were positively correlated with the abundance of the genus Enterococcus; among the most abundant species was Enterococcus faecalis, observed at lower levels in obese versus nonobese patients. CONCLUSIONS: This study demonstrated several compositional alterations of the gut microbiome in patients with colorectal cancer and showed that a reduced presence of E. faecalis may be associated with obesity-related colorectal cancer development. The gut microbiome may provide novel insights into the potential mechanisms in obesity-related colorectal carcinogenesis.

Physiological heating augments the anti-inflammatory reactions during granulocyte/monocyte apheresis: A in vitro study.

Granulocyte and monocyte adsorptive apheresis (GMA), an effective therapy for inflammatory disorders, exerts an anti-inflammatory influence by utilizing the biological reaction between blood and cellulose acetate (CA) beads, which are the carriers of the GMA column. Although the biological reaction has an optimum temperature, blood contacts the CA beads below body temperature as GMA is performed in an extracorporeal circulation system. We investigated various soluble factors in blood treated with CA beads at 25°C and 37°C. Here, the optimal temperature for IL-1 receptor antagonist (IL-1ra) release induced by CA beads was 37°C, and IL-6 production from monocytic cells was inhibited by the addition of plasma prepared from the CA bead-treated blood at 37°C, rather than at 25°C. These results indicated that physiological heating of the apheresis carrier augmented the anti-inflammatory reaction in vitro. Thus, heating during GMA may be a new approach for augmenting clinical efficacy.

Association between High Levels of Circulating Chemerin and Colorectal Adenoma in Men.

BACKGROUND: Obesity and metabolic syndrome are considered the risk factors of colorectal adenoma (CRA) and colorectal cancer (CRC). Chemerin is a novel adipocytokine associated with the development of gastric cancer, esophageal cancer, hepatocellular carcinoma, and CRC. However, the relationship between chemerin levels and CRA remains unclear. OBJECTIVE: This study is aimed at investigating the -association between serum chemerin levels and the development of CRA. METHODS: We conducted a total colonoscopy-based cross-sectional case-control study of 80 male patients with CRA and 80 male age-matched control individuals without CRA, according to their endoscopic findings. Serum chemerin concentrations were measured using a sandwich enzyme-linked immunosorbent assay kit, and the OR of CRA was calculated via logistic regression analysis. RESULTS: The mean serum chemerin level of the CRA group was significantly higher than that of the control group (7.9 ± 0.41 vs. 5.16 ± 0.34 ng/mL, p < 0.001). Serum chemerin level was positively correlated to the development of CRA (r = 0.34). Multivariate logistic regression analysis revealed that a high chemerin level was independently associated with the development of CRA (OR 2.82, 95% CI 1.39-5.72). CONCLUSIONS: Our findings indicated that increased serum chemerin levels are positively associated with the presence of CRA in men. Chemerin may play an important role in the development of CRA.

Esophageal intramural pseudodiverticulosis complicated with severe stricture requiring surgical resection.

Esophageal intramural pseudodiverticulosis (EIPD) is an uncommon benign disorder leading to esophageal strictures. The etiology remains unknown; however, anti-fungal treatments or endoscopic balloon dilation can improve early esophageal strictures and these rarely require surgical treatment. We report a case of a 46-year-old male with a 6 cm-long esophageal stricture due to EIPD, which did not improve following treatment with an anti-fungal agent, eventually causing aspiration pneumonia. Therefore, we performed a thoraco-laparoscopic esophagectomy, and his symptoms were improved after surgery. This case suggests that a surgical treatment should be considered in patients with extensive, severe strictures attributable to EIPD.

Adsorption of Soluble Immunoglobulin-Type Adhesion Molecules to Cellulose Acetate Beads.

Circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) are elevated in patients with inflammatory bowel disease. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis (GMA). We investigated the effect of CA beads on sICAM-1 and sVCAM-1 plasma concentrations in vitro. Because GM adsorption to CA beads increased with a rise in the incubation temperature in our previous study, peripheral blood was incubated with and without CA beads at 5, 25, 37, or 43 °C and plasma sICAM-1 and sVCAM-1 was measured. The sICAM-1 and sVCAM-1 concentrations in samples incubated with CA beads were significantly lower than those without CA beads at all four temperatures. However, no significant differences were observed both sICAM-1 and sVCAM-1 plasma levels at the four different temperatures after incubation with CA beads. These results suggest that independent of incubation temperature, sICAM-1 and sVCAM-1 are likely to adsorb CA beads. These molecules may be a new index for predicting the therapeutic effects of GMA.

Impaired Secretion of Glucagon-Like Peptide 1 in Patients with Colorectal Adenoma after an Oral Glucose Load.

BACKGROUND/AIMS: Obesity and insulin resistance are associated with an increased risk of colorectal adenoma (CRA). Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis through its amplification of insulin secretion in response to oral nutrients; however, its role in human CRA remains unknown. We investigated oral glucose-mediated GLP-1 secretion in patients with adenoma. METHODS: We performed a case-control study of 15 nondiabetic patients with pathologically diagnosed CRA and 10 age-matched healthy controls without adenoma. Plasma concentrations of active GLP-1 were measured during a 75 g oral glucose tolerance test. RESULTS: Mean waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR) values, the total areas under the curve (AUC) of glucose and insulin were significantly higher in patients with CRA than in controls. The total AUC of GLP-1 (p = 0.01) was lower in patients with CRA than in controls. Moreover, the total AUC of GLP-1 showed a negative correlation with WC, total AUC of glucose, and HOMA-IR. Multiple linear regression analyses revealed that the total AUC of GLP-1 was independently correlated with the number and maximum size of CRAs. CONCLUSION: GLP-1 could actively participate in the development of CRA in humans, particularly in patients with metabolic syndrome.

Effect of Temperature on Granulocyte and Monocyte Adsorption to Cellulose Acetate Beads.

Granulocyte and monocyte (GM) adsorptive apheresis (GMA) is an effective therapy for inflammatory disorders including inflammatory bowel disease (IBD). During GMA, the blood of a patient with IBD passes through a column to contact cellulose acetate (CA) beads at a temperature below body temperature, likely close to room temperature. Here we investigated the effect of temperature on GM adsorption to CA beads in vitro. We incubated peripheral blood with and without CA beads at 5°C, 25°C, 37°C, and 43°C and calculated the ratios of adsorbed GMs. The ratios of adsorbed GMs increased as the temperature was raised. Additionally, we measured complement activation fragment concentrations. C3a and C5a concentrations also increased as the temperature was raised, and C5a concentrations had a positive correlation with the ratios of adsorbed GMs. These results suggest that warming the column during GMA might increase GM adsorption to CA beads, thereby enhancing the clinical efficacy of GMA.

Diagnosis and treatment of eosinophilic esophagitis in clinical practice.

Eosinophilic esophagitis (EoE) is a chronic and abnormal Th2 type immunological response characterized by intense eosinophilic inflammation localized within the esophagus. This leads to esophageal dysfunction and remodeling accompanied by subepithelial fibrosis. Recently, EoE has been recognized as one of the major causes of dysphagia or food impaction in adults. The prevalence of EoE has been increasing over the past several decades, particularly in Western countries. EoE should be differentiated from secondary esophageal eosinophilia (EE) in gastroesophageal reflux disease (GERD) and eosinophilic gastroenteritis, involving the entire gastrointestinal tract. EoE is an uncommon condition in Asia compared with Western countries. With the growing interest and awareness of this condition during the past decade, reports of this disease are increasingly emerging in Asian countries including Japan. Typical EoE does not respond to proton pump inhibitor (PPI) therapy according to the current Western diagnostic guidelines. However, some cases of EE exhibit symptomatic relief and histological improvement in response to PPI [i.e., PPI-responsive esophageal eosinophilia (PPI-REE)]. The understanding of the clinical manifestations and unique endoscopic images of EoE, differences and similarities between GERD, PPI-REE, and EoE will all serve as the differential diagnosis. Further knowledge of the indications and efficacy of PPI therapy and topical steroid therapy will also aid in the management of these diseases. In this article, we will review the current diagnosis and treatment of EoE in clinical practice.