Clinical presentation and therapeutic outcome of patients with jackhammer esophagus-a multicenter cohort study in Japan.

BACKGROUND: Jackhammer esophagus (JE) is a hypercontractile esophageal motility disorder diagnosed using high-resolution manometry (HRM). We sought to determine the clinical presentation and therapeutic data of patients with JE in Japan. METHODS: The study included patients with JE, diagnosed through HRM performed for suspicious esophageal motility disorders. Demographics, esophagogastroduodenoscopy, radiology, and therapy data were collected from patient charts. RESULTS: Among the 4,412 HRM tests performed, 89 patients (61.6 ± 13.4 years; 64 males, 25 females) were diagnosed with JE (2.0%). Dysphagia was the most frequent symptom (80%), followed by chest pain (40%) and heartburn (25%). Esophagogastroduodenoscopy showed abnormal findings in 32% of patients: corkscrew/rosary beads appearance in 26%, narrowing in 11%. Eosinophilic infiltration (> 15 eosinophils/high power field) was diagnosed in 21%. Esophagography showed abnormal findings in 9% of the patients. For the initial therapy, 47 patients received medical treatment followed by peroral endoscopic myotomy (21 patients) and laparoscopic myotomy (two patients). Thirteen patients did not receive any treatment and 10 of those (77%) reported spontaneous resolution of symptoms. Patients who required invasive treatment experienced severe disability in their quality of life and greater maximal distal contractile integral than those who did not. CONCLUSIONS: HRM showed that the prevalence of JE was very low (2%). Esophagogastroduodenoscopy revealed some characteristic features of JE in patients. Some patients showed improvement of symptoms without invasive treatments. Follow-up with/without medical treatment should be considered before performing invasive treatment in patients whose distal contractile integral is relatively low and the quality of life is not impaired.

Development of a program to prevent sexual violence among teens in Japan: education using DVD video teaching materials and web-based learning.

BACKGROUND: This study aimed to develop an education system using DVD video-based teaching materials or web-based learning to reduce sexual violence among teens in Japan. METHODS: During the first stage, June 2018 to March 2019, an education program using DVD video teaching materials was carried out at three high schools and four universities with research consent from the director of the facility. From 1337 high school students and first- and second-year university students, subjects in their teen years were targeted for analysis. A survey was conducted at baseline and after the DVD video teaching. During the second stage, November 2019 to March 2020, web-based learning using improved video teaching materials was developed and carried out. From the adolescents who participated in the web-based learning, subjects in their teen years were targeted for analysis. A survey was conducted at baseline and after the web-based learning. RESULTS: In the first stage, 876 students consented to and participated in the education using DVD video teaching materials and baseline and after surveys (collection rate 65.5%). Among these, the number of respondents in their teens both baseline and after education was 705 persons (valid response rate 80.4%). In the second stage, the number of respondents in their teens both baseline and after education was 250 respondents in their teens who received web-based learning using the improved video teaching materials (valid response rate 87.1%). The improvement effect of the two programs was observed in attitudes that lead to physical violence, attitudes that lead to mental violence, attitudes that promote healthy conflict resolution, and dangerous attitudes that lead to sexual violence from persons in the community or through the Internet. The web-based learning program achieved an improvement of preventive attitudes toward sexual violence. CONCLUSIONS: The education program using DVD video teaching materials or web-based learning may help prevent sexual violence among teens in Japan.

Sex differences in associations among metabolic syndrome, obesity, related biomarkers, and colorectal adenomatous polyp risk in a Japanese population.

To investigate sex differences in the associations among metabolic syndrome, obesity, adipose tissue-related biomarkers, and colorectal adenomatous polyps, a cross-sectional, multicenter study was conducted on 489 consecutive individuals who underwent their first colonoscopy at 3 hospitals. Plasma concentrations of adiponectin and leptin, as well as homeostatic model assessment of insulin resistance were also evaluated. The presence and number of adenomatous polyps, including advanced adenoma, were higher in men than in women. Metabolic syndrome was a risk factor for adenomatous polyps in both sexes. Large waist circumference was an independent risk factor for adenomatous polyps in men, and high BMI and large waist circumference were risk factors for adenomatous polyps in women. Interestingly, low BMI was associated with large adenomatous polyps (≥10 mm) and advanced adenoma, and waist-hip ratio was involved in proximal adenomatous polyp development only in women. In contrast, the highest quartile of leptin concentration had a 3.67-fold increased adenomatous polyp risk compared with the lowest quartile only in men. These results indicate that regarding colorectal pathogenesis, sex differences were identified in obesity but not in metabolic syndrome. Visceral obesity and a high serum leptin level may be risk factors for colorectal adenomatous polyp development in Japanese men.

Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility.

The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract.NEW & NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work.

Expression of Reg family genes in the gastrointestinal tract of mice treated with indomethacin.

Regenerating gene (Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.

FGF9 from cancer-associated fibroblasts is a possible mediator of invasion and anti-apoptosis of gastric cancer cells.

BACKGROUND: Cancer-associated fibroblasts (CAFs), which reside around tumor cells, are suggested to play a pivotal role in tumor progression. Here we performed microarray analyses to compare gene expression profiles between CAFs and non-cancerous gastric fibroblasts (NGFs) from a patient with gastric cancer and found that fibroblast growth factor 9 (FGF9) was a novel growth factor overexpressed in CAFs. We then examined the biological effects of FGF9 during progression of gastric cancer. METHODS: Expression of FGF9 in CAFs and NGFs, and their secreted products, were examined by Western blotting. The effects of FGF9 on AGS and MKN28 gastric cancer cells in terms of proliferation, invasion and anti-apoptosis were assessed by WST-1 assay, invasion chamber assay and FACS, respectively. Furthermore, the intracellular signaling by which FGF9 exerts its biological roles was examined in vitro. RESULTS: FGF9 was strongly expressed in CAFs in comparison with NGFs, being compatible with microarray data indicating that FGF9 was a novel growth factor overexpressed in CAFs. Treatment with FGF9 promoted invasion and anti-apoptosis through activation of the ERK and Akt signaling pathways in AGS and MKN28 cells, whereas these effects were attenuated by treatment with anti-FGF9 neutralizing antibody. In addition, FGF9 treatment significantly enhanced the expression of matrix metalloproteinase 7 (MMP7) in both cell lines. CONCLUSIONS: FGF9 is a possible mediator secreted by CAFs that promotes the anti-apoptosis and invasive capability of gastric cancer cells.

Collagenous sprue diagnosed by double balloon endoscopy.

Double balloon endoscopy (DBE) is useful for diagnosing many intestinal diseases and for endoscopic procedures. We report a case of chronic diarrhea in a 58-year-old Japanese man. He was initially suspected to have malabsorption syndrome. DBE showed reduction of folds, scalloping, mucosal nodularity and granularity. Pathological examinations of biopsies from the jejunum showed severe villous atrophy with subepithelial collagen bands. These findings led to the final diagnosis of collagenous sprue (CS). With1 month of total parenteral nutrition followed by a low-gluten diet, his symptoms gradually improved. CS has never been reported before in Japan. DBE is useful for making a diagnosis of CS, and may be considered for patients who are suffering from diarrhea of unknown cause.

[A case of malignant peritoneal mesothelioma with the epithelioid histological type, successfully treated with pemetrexed plus cisplatin].

A 45-year-old man presented with severe abdominal distention with massive ascites due to a diffusely disseminated peritoneal tumor. A core needle biopsy specimen was obtained from the peritoneal lesion. Histological diagnosis was epithelioid type mesothelioma. He did not choose to receive chemotherapy. For 2.5 years, he went without medical intervention, and his disease gradually progressed, leading to a worsening of his symptoms. The patient then chose to be treated with combination chemotherapy of cisplatin and pemetrexed, followed by pemetrexed alone. There was remarkable tumor shrinkage and his symptoms improved. These effects have been sustained for two years after the initial chemotherapy. Chemotherapy appears to have contributed to survival prolongation for this patient. This case exemplifies the fact that malignant peritoneal mesothelioma may progress slowly when fits with some good prognostic factors, and it is important to consider the prognostic factors.

Management of colorectal high-grade dysplasia or cancer resected by cold snare polypectomy: a multicenter exploratory study.

BACKGROUND: The clinical course and surveillance strategy for patients who undergo cold snare polypectomy (CSP) for high-grade dysplasia (HGD) or cancer is unclear. We investigated the management of colorectal HGDs and cancers following CSP. METHODS: This Japanese nationwide multicenter exploratory study was retrospectively conducted on patients who had undergone CSP for colorectal HGDs or cancers and follow-up colonoscopy at least once from 2014 to 2020. We investigated the detection rate of CSP scars, local recurrence rate (LRR), risk factors for local recurrence, and follow-up strategy. This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000043670). RESULTS: We included 155 patients with 156 lesions. CSP scars were identified in 22 (31.4%), 41 (54.7%), and 10 (90.9%) patients with curative, borderline, and non-curative resection, respectively. Among them, residual tumors were observed in one (4.5%), six (14.6%), and three (30.0%) cases, respectively. The total LRR was 13.7% (95% confidence interval: 6.8-23.8). R1 resection cases (either horizontal or vertical margins positive for tumors) were associated with local recurrence (p = 0.031). Salvage endoscopic and surgical resections were performed on 21 and 10 patients, respectively. Among them, the proportion of endoscopically suspected residual tumors was significantly higher (p < 0.001) in the residual tumor-positive group (100%) than in the residual tumor-negative group (28.6%). CONCLUSIONS: LRR after CSP for HGDs or cancers was 13.7% based on scar-identified cases. Salvage endoscopic or surgical resection should be performed according to the curability of the lesion and endoscopic findings during colonoscopic surveillance.

Gastric Xanthoma Is Related to the Rapid Growth of Gastric Cancer.

Early detection of gastric cancer is important. However, rapid growth of gastric cancers that cannot be resected endoscopically occurs even with periodic check-ups. Accordingly, we assessed factors associated with the speed of gastric cancer growth by examining historical endoscopic images. A total of 1996 gastric cancer cases were screened, and characteristics of lesions with slow and rapid growth were assessed. A total of 114 lesions from 114 patients were included in the assessment. Sixty slow-growing and fifty-four rapidly growing gastric cancers were compared. Female sex and incidence of lesions in the lower part of the stomach were significantly less frequent in the rapid-growth group than in the slow-growth group. History of endoscopic treatment tended to be more frequent in the rapid-growth group. Age, body mass index, histology, Helicobacter pylori status, and medications did not differ significantly between groups. Xanthoma was significantly related to rapid growth of gastric cancer, and map-like redness tended to be more frequent in the rapid-growth group in univariate analysis. Xanthoma was significantly related to rapid growth of gastric cancer on multivariate analysis. Further studies are warranted to clarify the pathophysiological mechanisms involved in the speed of gastric cancer growth.

Gastric Xanthelasma, Microsatellite Instability and Methylation of Tumor Suppressor Genes in the Gastric Mucosa: Correlation and Comparison as a Predictive Marker for the Development of Synchronous/Metachronous Gastric Cancer.

A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12-122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134-9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC.

Effect of Instruction on Preventing Delayed Bleeding after Colorectal Polypectomy and Endoscopic Mucosal Resection.

BACKGROUND: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6-2.8%. With the increasing performance of polypectomy under continuous use of antithrombotic agents, care is required regarding delayed post-polypectomy bleeding (DPPB). Better instruction to educate endoscopists is therefore needed. We aimed to evaluate the effect of instruction and factors associated with delayed bleeding after endoscopic colorectal polyp resection. METHODS: This single-center, retrospective study was performed to assess instruction in checking complete hemostasis and risk factors for onset of DPPB. The incidence of delayed bleeding, comorbidities, and medications were evaluated from medical records. Characteristics of historical control patients and patients after instruction were compared. RESULTS: A total of 3318 polyps in 1002 patients were evaluated. The control group comprised 1479 polyps in 458 patients and the after-instruction group comprised 1839 polyps in 544 patients. DPPB occurred in 1.1% of polyps in control, and 0.4% in after-instruction. Instruction significantly decreased delayed bleeding, particularly in cases with antithrombotic agents. Hot polypectomy, clip placement, and use of antithrombotic agents were significant independent risk factors for DPPB even after instruction. CONCLUSION: The rate of delayed bleeding significantly decreased after instruction to check for complete hemostasis. Even after instruction, delayed bleeding can still occur in cases with antithrombotic agents or hot polypectomy.

Patients with dyspepsia have impaired mucosal integrity both in the duodenum and jejunum: in vivo assessment of small bowel mucosal integrity using baseline impedance.

BACKGROUND: Recent studies reported that impaired proximal duodenal mucosa, assessed by duodenal biopsy, could play an important role in the development of dyspeptic symptoms. The aims of this study were (a) to develop a method to measure "in vivo" duodenal and jejunal baseline impedance (BI) and (b) to assess small bowel mucosal integrity in patients with functional dyspepsia (FD) and healthy controls (HC). METHODS: We recruited 16 patients with FD and 15 HC. All subjects underwent ambulatory duodeno-jejunal manometry combined with impedance (HRM/Z), BI were determined by measuring impedance immediately after the passage of nocturnal migrating motor complex (MMC) phase IIIs. RESULTS: The number of MMC phase IIIs in FD was significantly lower than that in HC (2.6 ± 1.4 vs 4.8 ± 1.7, p < 0.001). The BI in patients was significantly lower than that in HC in D1(164.2 ± 59.8 Ω in FD and 243.1 ± 40.5 Ω in HC, p = 0.0061), D2 (191.2 ± 34.1 and 256.5 ± 91.4 Ω, p = 0.01), D3 (214.0 ± 76.9 and 278.1 ± 45.3 Ω, p = 0.009), D4 (270.8 ± 54.2 and 351.8 ± 50.2 Ω, p < 0.001), and J1 (312.2 ± 55.4 and 379.3 ± 38.3 Ω, p = 0.001). CONCLUSIONS: This is the first study reporting the duodenal and jejunal BI in vivo. The results have shown significantly lowered BI in the proximal small intestine in patients with FD compared to HC. Furthermore it suggests that measurements of small bowel BI could be used as a biomarker for diagnosis and follow up of patients with FD.

Purification and characterization of gelatinase-like proteinases from the dark muscle of common carp (Cyprinus carpio).

Gelatinolytic proteinases from common carp dark muscle were purified by 30-60% ammonium sulfate fractionation and a combination of chromatographic steps including ion exchange on DEAE-Sephacel, gel filtration on Sephacryl S-200, ion exchange on High-Q, and affinity on gelatin-Sepharose. The molecular masses of these proteinases as estimated by SDS-PAGE were 75, 67, and 64 kDa under nonreducing conditions. The enzymes revealed high activity at a slightly alkaline pH range, and their activities were investigated using gelatin as substrate. Metalloproteinase inhibitors, EDTA, EGTA, and 1,10-phenanthroline, almost completely suppressed the gelatinolytic activity, whereas other proteinase inhibitors did not show any inhibitory effect. Divalent metal ion Ca (2+) is essential for the gelatinolytic activity. Furthermore, these gelatinolytic proteinases hydrolyze native type I collagen effectively even at 4 degrees C, strongly suggesting their involvement in the texture softening of fish muscle during the post-mortem stage.

[A case of sigmoid colon cancer with multiple liver metastases responding to S-1].

A 74-year-old woman was referred to our hospital with complaints of constipation and abdominal distention caused by a sigmoid colon tumor. After examination, she was diagnosed as sigmoid colon cancer with multiple liver metastases. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative days 15, S-1 was started, and she was discharged on postoperative day 26. Each course consisted of daily oral administration S-1 for 4 weeks followed by 2 drug-free weeks. However, because of grade 2 anorexia in the 1st course, the treatment plan was changed to administration for 2 weeks and withdrawal for 1 week. After 7 courses of treatment, computed tomography revealed that the liver metastases were remarkably reduced. Although she experienced an adverse event involving a cutaneous symptom of grade 2, the treatment was continued under ambulatory management. After eight courses, elevation of tumor marker and metastasis at the right femur were found, and she died of the cancer 12 months after the operation. S-1 is expected to be an effective agent for the treatment of advanced colorectal cancer.

Esophagography in Patients With Esophageal Achalasia Diagnosed With High-resolution Esophageal Manometry.

BACKGROUND/AIMS: High-resolution esophageal manometry (HREM) is considered to be the gold standard for the diagnosis of achalasia. However, the Japan Esophageal Society recommends that esophagography is also accurate in either diagnosing or excluding the disorder. Accordingly, we compared the efficacy of esophagography and HREM in diagnosing achalasia patients with upper gastrointestinal symptoms. METHODS: HREM was performed in 126 patients with dysphagia. The final diagnosis of achalasia was done using HREM. Demographic data, symptoms, quality of life (QOL) were also obtained. We assessed the patients who were not able to be diagnosed by esophagography and compared the diagnostic values for esophagography with HREM-based achalasia diagnosis as the gold standard. RESULTS: A total of 48 cases of patients with achalasia, including 21 men and 27 women (mean age, 48.4 ± 19.6 years), were included in the study. Two patients were excluded. Of the remaining 46 patients, 36 (78.3%) patients were diagnosed as having achalasia by esophagography. The diagnostic sensitivity, specificity, and accuracy of esophagography were 78.3%, 88.0%, and 83.0%, respectively. Patients with type III achalasia had significantly lower physical QOL score than those with type I or II achalasia. Although the mental QOL score in patients with type III achalasia tended to decrease compared with that in patients with type I and II achalasia, the difference was not statistically significant. CONCLUSIONS: Diagnosing esophageal achalasia by using esophagography alone has limited yield. Therefore, HREM should be used in patients with dysphagia and in whom achalasia cannot be diagnosed using EGD or esophagography.

Effect of Helicobacter pylori infection on the link between GLP-1 expression and motility of the gastrointestinal tract.

BACKGROUND: Although Helicobacter pylori (H. pylori) infection is closely associated with the development of peptic ulcer, its involvement in pathophysiology in the lower intestinal tract and gastrointestinal (GI) motility remains unclear. Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the lower intestinal tract and involved in GI motility. Here, we investigated the effect of H. pylori infection on the link between GLP-1 expression and motility of the GI tract. METHODS: C57BL/6 mice were inoculated with a H. pylori strain. Twelve weeks later, the H. pylori-infected mice underwent H. pylori eradication treatment. GI tissues were obtained from the mice at various time intervals, and evaluated for the severity of gastric inflammatory cell infiltration and immunohistochemical expression of GLP-1 and PAX6 in the colonic mucosa. Gastrointestinal transit time (GITT) was measured by administration of carmine-red solution. RESULTS: GLP-1 was expressed in the endocrine cells of the colonic mucosa, and PAX6 immunoreactivity was co-localized in such cells. The numbers of GLP-1- and PAX6-positive cells in the colon were significantly increased at 12 weeks after H. pylori infection and showed a positive correlation with each other. The GITT was significantly longer in H. pylori-infected mice than in non-infected controls and showed a positive correlation with GLP-1 expression. When H. pylori-infected mice underwent H. pylori eradication, GITT and PAX6/GLP-1 expression did not differ significantly from those in untreated H. pylori-infected mice. CONCLUSIONS: H. pylori infection may impair GI motility by enhancing the colonic GLP-1/PAX6 expression.

Involvement of gut microbiota in the association between gastrointestinal motility and 5­HT expression/M2 macrophage abundance in the gastrointestinal tract.

Serotonin (5­hydroxytryptamine; 5­HT) may be a key player in gastrointestinal (GI) motility and the GI immune system. In the present study, the effect of gut microbiota on the association between GI motility, and 5­HT expression and macrophage abundance in the GI tract was examined. Germ­free (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogen­free mice and their GI tissues were evaluated 4 weeks later. The expression of 5­HT and mannose receptor (MR) was examined by immunohistochemistry, and GI transit time (GITT) was measured by administration of carmine red solution. The numbers of 5­HT­positive endocrine cells and muscularis MR­positive macrophages were significantly increased in the upper GI and colon of GF mice subjected to fecal transplantation (FT) compared with control GF mice without FT. GITT was significantly decreased in GF mice subjected to FT compared with GF mice without FT, and negatively correlated with the numbers of 5­HT­positive cells in the upper GI and muscularis MR­positive macrophages throughout the GI tract. The numbers of 5­HT­positive endocrine cells and muscularis MR­positive macrophages were significantly correlated throughout the GI tract. The present results suggest that the gut microbiota is involved in the association between accelerated GI motility and induction of the 5­HT/muscularis MR­positive macrophage axis in the GI tract.

Genetic instability, CpG island methylator phenotype, and proliferative activity are distinct differences between diminutive and small tubular adenoma of the colorectum.

It is recommended that small (6-10 mm) lesions be treated with endoscopic resection (ER), whereas diminutive (≤5 mm) lesions are not currently an indication for ER according to the Japanese guidelines. The aim of this study was to evaluate the molecular alterations, and therefore treatment indications, in diminutive versus small tubular adenoma (TA). We prospectively analyzed genetic instability, including microsatellite instability and loss of heterozygosity, methylation status, KRAS/BRAF mutations, and Ki-67 staining in 96 TAs without a villous component. Although no microsatellite instability was identified in either diminutive or small TAs, genetic instability was seen in small TAs (9.1%) but not diminutive TAs (P = .04). In addition, the low-level CpG island methylator phenotype (CIMP-L) was more frequently observed in small TAs (31.8%) than in diminutive TAs (P = .01). Thus, genetic instability and CIMP-L were associated with small TAs, and only CIMP-L was an independent predictive marker for small TAs (odds ratio, 3.29; P = .03). Intriguingly, the Ki-67 proliferative index tended to be higher in small TAs than in diminutive TAs (P = .06) and higher in TAs with CIMP-L than in those without CIMP (P = .08). KRAS mutations were seen in codon 12 in 5.2% of TAs, but no BRAF gene mutations were found. As the molecular events and proliferative activity for the progression may increase from diminutive to small TAs, small TAs should be treated with ER, whereas a "predict, resect, and discard" strategy may be acceptable in most diminutive lesions except flat and depressed-type lesions, in keeping with the current strategy in the West.