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.

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.

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.

Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions.

The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

[Characteristics of group A patients according to the ABC classification for gastric cancer risk screening].

In the ABC classification for gastric cancer risk screening, group A (Helicobacter pylori infection-negative, pepsinogen [PG]-negative) patients are assumed to be at low risk, but some patients do have atrophic gastritis and H. pylori infection. This study aimed to identify the characteristics of group A patients. Healthy adults in Yamagata City who underwent barium radiography and ABC classification participated in the survey. Patient radiographs were randomly interspersed and reviewed by two gastroenterologists who were blinded to the H. pylori and PG statuses. Group A patients (n=1462) was subclassified as follows: atrophic gastritis group, 21.5%; intermediate group, 15.7%; and no atrophic gastritis group, 62.8%. Elderly subjects and those with H. pylori antibody titers of 3.0-9.9U/ml should be carefully evaluated while interpreting the results of the ABC classification for gastric cancer risk screening.

[Chylothorax in a patient with advanced gastric cancer and mediastinal lymph node metastasis causing thoracic duct obstruction].

We report the case of a 61-year-old female with advanced gastric cancer and mediastinal lymph node metastasis who developed chylothorax. The patient presented with cough, dyspnea and pain in the left lower limb, back, and hips. Her lower limb symptoms were attributed to cellulitis. Computed tomography revealed right-sided pleural effusion, multiple lymph node swelling, and thickening of the gastric wall. Following pleural aspiration, the effusion was identified to be chyle. Cytopathologically, numerous adenocarcinoma cells were detected in clumps, and subsequent esophagogastroduodenoscopy revealed type 3 gastric cancer. We diagnosed multiple lymph node metastases with pleural dissemination. Chemotherapy was administered; however, she eventually succumbed to disease progression. We suspected that the chylothorax resulted from the mediastinal lymph node metastasis that caused thoracic duct obstruction.

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.

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.

Difficulties in the treatment of intestinal amoebiasis in mentally disabled individuals at a rehabilitation institution for the intellectually impaired in Japan.

BACKGROUND: A mass Entamoeba histolytica infection recurred despite repeated treatments with metronidazole at a rehabilitation institution for individuals with intellectual impairments. METHODS: Diloxanide furoate was administered to improve intractable intestinal amoebiasis after a recurring amoebic infection that tends to occur via coprophagy in mentally disabled individuals infected with E. histolytica at an institution (the prevalence rate and positive serology rate were 38.2 and 67.1%, respectively). The therapeutic effect of the drugs was judged by microscopic stool examination and an E. histolytica antigen detection kit. RESULTS: The mass infection was eliminated through the administration of metronidazole and subsequent use of diloxanide furoate. CONCLUSIONS: Combination therapy successfully cured and prevented transmission of the mass E. histolytica infection at the institution.

Plasma level of granulocyte-colony stimulating factor during granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis.

BACKGROUND/AIMS: Cytapheresis with extra-corporeal circulation for ulcerative colitis is effective but its mechanisms are still unclear. Granulocytecolony stimulating factor (G-CSF) strongly mobilizes bone marrow-derived cells and serves as antiinflammatory factor. We investigated plasma levels of G-CSF during granulocyte and monocyte adsorptive apheresis (GCAP). METHODOLOGY: Nineteen cases of ulcerative colitis were measured plasma concentration of G-CSF during the first session of GCAP therapy. RESULTS: G-CSF were significantly increased in the column inflow at 30 min compared with the baseline (Wilcoxon test, p < 0.01), and also increased through the column (Wilcoxon test, p < 0.01). The ratio of the increase in the column outflow at 60 min was 1.5-fold compared with the baseline. However, we could not show a significant relation between G-CSF level and clinical efficacy. CONCLUSIONS: This is the first report concerning G-CSF during CAP. G-CSF is increased due to GCAP and appears to be a candidate which should be further investigated.

[A case of primary orbital adenocarcinoma responding to chemoradiation].

Primary orbital adenocarcinoma is very rare. There are not any reports about the treatment of this disease, except for surgery. We experienced a case of primary orbital adenocarcinoma, which we successfully treated by chemoradiation using 5-FU and cisplatin. It is very important to collect and record cases of rare diseases responding to certain chemotherapy regimens.

[Non pulsatile active bleeding from the gastrointestinal mucosa without ulceration during anticoagulation therapy -consideration on bleeding from angiodysplasia during anticoagulation therapy-].

We reported 3 cases of the uncommon type of persistent gastrointestinal bleeding during anticoagulation therapy due to cardiovascular disorders or collagen disease. Endoscopic observation showed non pulsatile active bleeding from apparently normal mucosa, without any ulcer or obvious vascularectasia. The outflow of bleeding was string-like and continuous. Based on previous reports, we considered the possibly of these cases unique bleeding angiodysplasia and angiodysplasia during anticoagulation therapy. The frequency of this type of bleeding may increase, as anticoagulation therapy has become more common. We should pay attention to such lesions when we treat gastrointestinal bleeding.

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.

A multi center study of granulocyte and monocyte adsorption apheresis therapy for ulcerative colitis-clinical efficacy and production of interleukin-1 receptor antagonist.

Granulocyte and monocyte adsorption apheresis (GCAP) is a useful strategy for intractable ulcerative colitis, but its mechanisms of therapy is not fully explained. Previously, depleting activated granulocytes and monocytes (GMs) and modifying product of proinflammatory cytokines had been proposed. In addition, activated GMs are releasing anti-inflammatory cytokines, interleukin-1 receptor antagonist (IL-1ra) that may contribute to the clinical efficacy of GCAP therapy. Hence, to investigate contribution of IL-1ra as well as to confirm clinical efficacy of this therapy based on clinical activity index (CAI), we performed a multicenter study. Twenty-five of 38 (65.8%) patients achieved remission state (CAI < or = 4) and two of 38 (5.3%) revealed clinical improvement. Almost effective cases significantly decreased CAI even at 3rd session of GCAP. Plasma level of IL-1ra from outflow of the GCAP column at 30 min was significantly increased rather than inflow. Median exact elevated level of IL-1ra was 221 pg/ml and median of increasing ratio was 1.6 times. Furthermore, the responsive patients, who well released the IL-1ra at outflow more than 100 pg/ml compared with inflow, tended to show clinical effectiveness. While, the increased ratio of IL-1ra in effective cases did not differ from ineffective cases, and there were no significant relationship with improvement of CAI score. These conflict results suggest that the increase of IL-1ra at outflow is not a direct factor to the clinical improvement, but the induction of clinical improvement is accompanied by the release of IL-1ra. The IL-1ra may be involved in the multiple steps for the improvement induced by GCAP.

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.

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.

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.

Effect of Cellulose Acetate Beads on Interleukin-23 Release.

Interleukin (IL)-23, which is released by activated monocytes and neutrophils, promotes production of high levels of IL-17 by T-helper 17 cells. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis using Adacolumn. Contact between blood and CA beads induces cytokine release; however, their inflammatory effects on IL-23 release are unclear. We aimed to clarify the effect of CA beads on IL-23 release in vitro. We incubated peripheral blood with and without CA beads and measured IL-23. Compared to blood samples incubated without CA beads, blood samples incubated with CA beads had significantly decreased amounts of IL-23. In conclusion, CA beads inhibited IL-23 release from adsorbed GMs. The biological effects of this decrease in IL-23 release during GM adsorption to CA beads need further clarification.

Effect of Cellulose Acetate Beads on the Release of Transforming Growth Factor-ß.

Transforming growth factor-ß (TGF-ß) is released by activated platelets and induces the differentiation of T-helper 17 from naïve T cells. Contact between blood and cellulose acetate (CA) beads induces cytokine release, although their inflammatory effects on TGF-ß release are unclear. We aimed to clarify the effect of CA beads on the release of TGF-ß in vitro. We incubated peripheral blood with and without CA beads and measured platelets and TGF-ß. Compared with blood samples incubated without beads, the platelet count and amount of TGF-ß significantly decreased in blood samples incubated with CA beads. In conclusion, CA beads inhibited the release of TGF-ß from adsorbed platelets. The biological effects of this reduction of TGF-ß release during platelet adsorption to CA beads need further clarification.

Characteristics of Small Bowel Polyps Detected in Cowden Syndrome by Capsule Endoscopy.

Cowden syndrome is an uncommon, autosomal dominant disease characterized by multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases are reportedly complicated by malignant diseases. Hamartomatous polyps occur throughout the gastrointestinal tract, the most common sites being the stomach, colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome; however, they are difficult to detect by conventional examination, including double-contrast X-ray study. Here, we report three cases of Cowden syndrome with small bowel polyps, which were detected by capsule endoscopy. The small bowel polyps of Cowden syndrome frequently occur at the oral end of the small bowel, especially in the duodenum and jejunum, and their color is similar to that of the surrounding mucosa; additionally, the polyps are relatively small (2-5 mm). Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome.