The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells.

Intestinal microfold cells (M cells) are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses through the uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood, as the rarity of these cells has hampered analysis. Exogenous administration of the cytokine RANKL can synchronously activate M-cell differentiation in mice. Here we show the Ets transcription factor Spi-B was induced early during M-cell differentiation. Absence of Spi-B silenced the expression of various M-cell markers and prevented the differentiation of M cells in mice. The activation of T cells via an oral route was substantially impaired in the intestine of Spi-B-deficient (Spib(-/-)) mice. Our study demonstrates that commitment to the intestinal M-cell lineage requires Spi-B as a candidate master regulator.

Comparison of a novel predictor of venous thromboembolic complications in inflammatory bowel disease with current predictors.

BACKGROUND AND AIM: Venous thromboembolism (VTE) is a common complication of inflammatory bowel disease (IBD). The aim of the present study was to identify predictors of VTE in hospitalized patients with IBD. METHODS: Patients with IBD who were hospitalized from February 2015 to March 2016 at the Chiba University Hospital were included. VTE was detected using enhanced computed tomography, and VTE onset within 2 months after admission was assessed. Predictors of VTE onset were investigated with clinical factors during hospitalization. Availability of the Caprini risk assessment model and Padua prediction score at the time of admission was also assessed. RESULTS: Seventy-two patients with IBD were hospitalized, and central venous catheters were placed in 43 of the 72 patients. During the observation period, VTE occurred in six patients (8.3%); however, none died as a result of the condition. Cox proportional hazards regression analysis identified D-dimer values on admission as a risk factor that was highly associated with VTE onset (hazard ratio = 1.590; 95% confidence interval, 1.132-2.233; P = 0.007) and significantly predicted the occurrence of VTE using the receiver operating characteristic curve (P = 0.005, area under the curve = 0.893). However, Caprini risk assessment model and Padua prediction scores were not useful tools for predicting VTE onset in patients with IBD. CONCLUSION: In hospitalized patients with IBD, D-dimer values were highly associated with VTE onset. Therefore, measurement of D-dimer values on admission is critical for the management of thromboembolic complications in patients with IBD.

Long-Term Prognosis of Patients with Obscure Gastrointestinal Bleeding: A Retrospective Cohort Study.

AIMS: We evaluated the long-term prognosis of patients with obscure gastrointestinal bleeding (OGIB) who underwent capsule endoscopy (CE). METHODS: In our hospital, 429 patients underwent CE between November 2007 and March 2012. Among them, 259 patients underwent CE as the first examination for OGIB and were then followed at 77 clinics and hospitals. The clinical characteristics were investigated, including age, gender, overt/occult bleeding, the use of antithrombotic drugs and NSAIDs, complications (liver cirrhosis and hemodialysis), and CE. We asked the medical institutions for their survival data as of August 2017 (> 5 years after CE). RESULTS: The prognoses of 240 patients (92.6%) were analyzed. The average follow-up period was 55.7 (1-115) months. During the follow-up period, 57 patients (23.8%) died and the survival rates were 90.5% at 1 year, 81.7% at 3 years, and 74.7% at 5 years. Age 65 years or older and liver cirrhosis were predictive factors for a poor prognosis. Rebleeding occurred in 42 patients (17.9%) and small bowel cancer and gastrointestinal stromal tumor were found at 12 and 21 months after CE, respectively. CONCLUSIONS: Patients with OGIB showed a poor prognosis, especially those who were elderly or who had liver cirrhosis.

Residual adenoma after cold snare polypectomy for small colorectal adenomas: a prospective clinical study.

BACKGROUND: Endoscopic resection of all colonic adenomas prevents the occurrence of colon cancer and death. The European Society of Gastrointestinal Endoscopy Clinical Guideline recommends resection of all polyps predicted to be adenomas and cold snare polypectomy (CSP) for removal of adenomas ≤ 9 mm on the basis of safety; however, it also states that this recommendation lacks adequate evidence of efficacy. The residual adenoma rate after resection is an important indicator of efficacy, but there have been no reports showing this prospectively. Therefore, we aimed to investigate the residual adenoma rate after CSP of small colonic polyps. METHODS: Between March 2015 and April 2017, patients who were endoscopically diagnosed with colorectal adenomas < 9 mm underwent CSP, the site being marked with endoscopic clips. Patients with pathologically confirmed adenomas underwent follow-up colonoscopy 3 weeks after CSP and any post-CSP scars were biopsied. The primary endpoint was the presence of pathological residual adenoma 3 weeks after CSP. RESULTS: Overall, 126 lesions in 39 patients were removed and 125 (99.2 %) were resected en bloc using CSP. Pathologically, 111 lesions (88.1 %) were confirmed as adenomas (4.2 ± 1.5 mm), with 36 of these (32.4 %) determined to be R0 resections. No complications were observed. All 37 patients with pathologically confirmed adenomas underwent follow-up colonoscopy, and 102 of 111 scars were detected in 33 patients. One pathological residual adenoma (0.98 %, 95 % confidence interval 0.02 % - 5.3 %) was identified. CONCLUSIONS: CSP appears to be an effective treatment for diminutive and small colorectal adenomas, with a low residual adenoma rate.

Investigation of novel biomarkers for predicting the clinical course in patients with ulcerative colitis.

BACKGROUND: The clinical course of ulcerative colitis (UC) is characterized by repeated episodes of relapse and remission. We hypothesized that biomarkers that help distinguish refractory UC patients who are in remission using strong anti-immunotherapy could contribute in preventing the overuse of corticosteroids for treatment. Here, we clarified novel autoantibodies for UC patients in remission as clinical indicators to distinguish between refractory and non-refractory UC. METHODS: Antigen proteins recognized by serum antibodies of patients with UC in remission were screened using the protein array method. To validate the results, AlphaLISA was used to analyze the serum antibody titers with candidate protein antigens. Serum samples from 101 healthy controls, 121 patients with UC, and 39 patients with Crohn's disease were analyzed. RESULTS: Of 66 candidate protein antigens screened by ProtoArray™, six were selected for this study. The serum titers of anti-poly ADP-ribose glycohydrolase (PARG), anti-transcription elongation factor A protein-like 1, and anti-proline-rich 13 (PRR13) antibodies were significantly higher in patients with UC than in healthy controls. Anti-PARG and anti-PRR13 antibody titers were significantly higher in patients with refractory UC than in patients with non-refractory UC. There were no significant differences in any antibody titer between the active and remission phases. CONCLUSIONS: The serum titers of anti-PARG, anti-transcription elongation factor A protein-like 1, and anti-PRR13 antibodies were elevated in patients with UC. Anti-PARG and anti-PRR13 antibody titers may be novel clinical indicators for detecting refractory UC in patients in remission.

Long-Term Outcome of Endoscopic Balloon Dilatation for Strictures in Patients with Crohn's Disease.

BACKGROUND/AIMS: Endoscopic balloon dilatation (EBD) is an alternative to surgery for strictures in patients with Crohn's disease (CD). The aim of the present study was to clarify the efficacy and safety of EBD for strictures in patients with CD. METHODS: Twenty-six patients with CD who underwent EBD for strictures from August 2008 to November 2015 were followed up after dilatation. Short-term success was defined as the disappearance of obstructive symptoms after technically adequate dilatation was achieved. The short-term success rate of EBD, safety profile of EBD, and cumulative surgery-free and redilatation-free rates were analyzed. RESULTS: Sixty-five EBDs were performed for CD patients in the follow-up period. The short-term success rate was 100% (26/26), and no complications were encountered during this study. Two (7.7%) patients underwent surgery during the observation period. The cumulative surgery-free rate after the initial EBD was 90.3% at both 2 and 3 years. The cumulative redilatation-free rate after the initial EBD was 52.1% at 2 years and 39.1% at 3 years. CONCLUSION: EBD for strictures secondary to CD provides not only short-term success but also long-term efficacy. Although a high redilatation rate is one of the clinical problems of this procedure, EBD is an effective therapy for avoiding intestinal recession in CD -stricture.

Cold polypectomy for duodenal adenomas: a prospective clinical trial.

Background and study aims Endoscopic resection is effective in treating nonampullary duodenal adenomas but has a high incidence of complications. Cold polypectomy, including cold forceps polypectomy (CFP) and cold snare polypectomy (CSP), is safe and effective in treating colorectal polyps. However, its utility in sporadic nonampullary duodenal adenomas has not been investigated. The purpose of this prospective study was to examine the safety and efficacy of cold polypectomy for sporadic nonampullary duodenal adenomas. Patients and methods Between March 2015 and June 2016, patients who were endoscopically diagnosed with sporadic nonampullary duodenal adenomas up to 6 mm underwent cold polypectomy. Patients with pathologically confirmed adenomas underwent endoscopic biopsy 3 months after resection. The main outcomes of interest were incomplete resection and complications. Results Overall, 39 lesions in 30 patients were removed via cold polypectomy (CFP, 9 lesions in 8 patients; CSP, 30 lesions in 22 patients). Seven of 9 (77.8 %) and 29 of 30 (96.7 %) lesions were removed en bloc via CFP and CSP, respectively. Pathologically, 34 of the 39 lesions (87.2 %) were confirmed as adenomas, and their mean size was 3.9 ±â€Š1.2 mm (range 2 - 6 mm). Of the 34 adenomas, 20 (58.8 %) were R0 resection lesions, of which 3 of 9 (33.3 %) and 17 of 25 (68.0 %) had undergone CFP and CSP, respectively. No delayed bleeding or intraprocedural/delayed perforation was observed. All 30 patients with the 34 pathologically confirmed adenomas underwent upper gastrointestinal endoscopy 3 months after cold polypectomy, and no morphological or pathological recurrence was identified. Conclusions In this small study, cold polypectomy appeared to be safe and effective in treating diminutive and small sporadic nonampullary duodenal adenomas.(Clinical trial registration number: UMIN000016829).

The Effect of Ineffective Esophageal Motility on Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Ineffective esophageal motility (IEM) is the most common gastrointestinal motility disorder. Studies have reported that IEM is related to gastroesophageal reflux disease (GERD). However, the relationship between IEM and GERD remains uncertain. This study aims to clarify this relationship retrospectively. METHODS: We analyzed 195 subjects who underwent high-resolution manometry between January 2011 and September 2016. Of these subjects, 72 had normal esophageal motility (NEM) and 26 had IEM. We investigated differences in the clinical characteristics, severity and duration of GERD symptoms, and comorbid extra-esophageal symptoms of the subjects. Comorbid extra-esophageal symptoms were assessed with the Gastrointestinal Symptom Rating Scale questionnaire. Investigation-defined GERD was diagnosed when erosive esophagitis or abnormal multichannel intraluminal impedance was present. RESULTS: We found no significant difference in the prevalence of IEM between patients with and without GERD (37.5 and 21.1%, respectively; p = 0.174). There were no differences in age, gender, body mass index, presence of hiatal hernia, or duration of GERD between the groups. Compared to patients with NEM, those with IEM were significantly less likely to have comorbid extra-esophageal symptoms (p < 0.05). CONCLUSION: There is no association between IEM and GERD.

Heparin-bridging therapy is associated with a high risk of post-polypectomy bleeding regardless of polyp size.

BACKGROUND AND AIM: Evidence regarding safety and efficacy of heparin-bridging therapy for colonoscopic polypectomy remains scarce. The aim of the present study was to evaluate the risk of post-polypectomy bleeding (PPB) in patients receiving heparin-bridging therapy. METHODS: We retrospectively reviewed the database of patients who underwent colonoscopic polypectomy with prophylactic clip closure between January 2007 and December 2014 at our institution. We evaluated patients receiving heparin-bridging therapy (HB group) compared with those who did not receive antithrombotic therapy (No-HB group). RESULTS: A total of 1421 polypectomies were carried out on 773 patients; 45 patients were in the HB group and 728 patients were in the No-HB group. The incidence of PPB per patient was significantly higher in the HB group (22.2% vs 1.9%, P < 0.0001), and multivariate analysis showed that heparin-bridging therapy was an independent risk factor for PPB (OR 9.80, 95% CI 4.23-22.3, P < 0.0001). In the HB group, the polyp size was not a risk factor for PPB (OR 0.67, 95% CI 0.19-2.26, P = 0.55); the incidence of PPB in lesions of <10 mm and ≥10 mm in size was 14.6% and 10.2% respectively. In contrast, that was a significant risk factor in the No-HB group (OR 4.71, 95% CI 1.41-21.3, P = 0.011). Activated partial thromboplastin time and international normalized ratio were in or under the therapeutic range in the HB group when PPB occurred. CONCLUSIONS: Heparin-bridging therapy is associated with a high risk of PPB regardless of polyp size.

Vonoprazan is superior to proton pump inhibitors in healing artificial ulcers of the stomach post-endoscopic submucosal dissection: A propensity score-matching analysis.

BACKGROUND AND AIM: Proton pump inhibitors (PPI) are effective at healing artificial ulcers after endoscopic submucosal dissection (ESD) for gastric neoplasms; however, the efficacy of vonoprazan is not completely understood. The aim of the present study was to determine the healing effect of vonoprazan on artificial ulcers post-gastric ESD relative to PPI. METHODS: Thirty-five patients who underwent gastric ESD between April and November 2015 were treated with vonoprazan 20 mg/day for 4 weeks and subsequently underwent endoscopy for evaluation of ulcer size (V group). Ulcer contraction rate was determined by the following formula: ([ESD specimen size] - [ulcer size at 4 weeks after ESD])/(ESD specimen size) × 100%. We compared the results with those of a historical control group treated with esomeprazole 20 mg/day for 4 weeks after gastric ESD and subsequently measured their ulcer size (33 patients, E group) by propensity score-matching methods. RESULTS: Sixty-two subjects were enrolled after propensity score-matching. Ulcer contraction rate at 4 weeks after ESD in the V group was significantly higher than that of the E group (97.7 ± 3.2% vs 94.5 ± 6.7%, respectively, P = 0.025). Number of subjects with a scar-stage ulcer (100% contraction rate) tended to be higher in the V group relative to the E group (32% [10 of 31] vs 13% [4 of 31], respectively, P = 0.070, McNemar's chi-squared test). CONCLUSION: Vonoprazan has a faster post-gastric ESD artificial ulcer contraction rate than esomeprazole. Vonoprazan may supersede PPI in treating post-ESD artificial ulcers of the stomach.

Successful sofosbuvir treatment with ribavirin dose reduction for chronic hepatitis C virus genotype 2 infection in a patient with ulcerative colitis: a case report.

BACKGROUND: Ulcerative colitis is a lifelong, immunologically mediated disease. Direct-acting antivirals (DAAs) are now available for the treatment of chronic hepatitis C virus (HCV) infection. An interferon-free regimen appears useful, safe and effective for many patients for whom interferon-based treatment is contraindicated. CASE PRESENTATION: We studied a 56-year-old treatment-naïve Japanese man with chronic HCV genotype 2b infection who had ulcerative colitis. This patient was treated with sofosbuvir and ribavirin for 12 weeks. During treatment, diarrhoea and bloody faeces were frequent. After ribavirin was reduced to 400 mg daily, these symptoms decreased. Finally, the patient achieved a sustained virologic response 12 weeks after the stoppage of the treatment. CONCLUSION: Clinicians should pay careful attention to the ribavirin dose in the treatment of certain HCV patients with inflammatory bowel disease who are receiving sofosbuvir plus ribavirin.

A randomized controlled trial comparing water exchange and air insufflation during colonoscopy without sedation.

OBJECTIVES: Previous studies have shown that water exchange is superior to air insufflation in attenuating insertion pain during colonoscopy. We conducted a randomized controlled trial with head-to-head comparison of these methods to assess their effectiveness in colonoscopy without sedation. METHODS: A total of 447 outpatients were randomized to either water exchange (WE) or the standard air (CO2) insufflation (AI). The primary outcome was the improvement of patient intraprocedural pain (pain score), evaluated using a questionnaire (scores 1 to 5). RESULTS: After exclusion of 44 patients from further analysis, 403 patients were analyzed. There was no difference in clinical background between the WE and AI groups. Patients in the WE group reported less intraprocedural pain than those in the AI group (2.17 ± 1.06 vs. 2.42 ± 1.03; unpaired t test, p = 0.021). We divided the cases into two groups, more or less painful colonoscopy, based on age, body mass index, use of anti-peristaltic drugs or not, and physician's experience. In less painful colonoscopy, the WE method could reduce pain effectively but its effect was limited in the more painful group. CONCLUSION: WE is superior to AI for attenuating insertion pain during colonoscopy without sedation, but its efficacy is limited in more painful endoscopy.

Sporadic nonampullary duodenal adenoma/carcinoma is associated with not only colon adenoma/carcinoma but also gastric cancer: association of location of duodenal lesions with comorbid diseases.

BACKGROUND: It is well known that in patients with sporadic nonampullary duodenal adenoma/carcinoma (SNADA) with no polyposis syndrome, including familial adenomataous polyposis, the rates of colorectal adenoma/carcinoma are high. However, the prevalence rates of other tumor types, for example, gastric cancer, in SNADA patients remain unknown. In this study, we aimed to analyze the prevalence rate of comorbid diseases in SNADA patients. METHODS: We retrospectively analyzed 78 patients with SNADA treated by endoscopic resection between May 2005 and September 2014 at our institution. RESULTS: Overall, 51 of the 78 (65.4%) SNADA patients had comorbid colorectal adenoma/carcinoma. Further, 10 of the 78 (12.8%) SNADA patients had comorbid gastric cancer, and all of them were positive for Helicobacter pylori infection. SNADA lesions were located significantly more frequently at the oral side of the major papilla in patients with H. pylori infection than in those without H. pylori infection (27 of 36 [75.0%] vs. 19 of 42 [45.2%], p = 0.008, chi-square test). In contrast, SNADA lesions were located significantly more frequently at the anal side of the major papilla in patients with colorectal adenoma/carcinoma than in those without colorectal adenoma/carcinoma (27 of 51 [52.9%] vs. 5 of 27 [18.5%], p = 0.003, chi-square test). CONCLUSION: SNADA patients showed comorbidity with not only colorectal adenoma/carcinoma but also gastric cancer. H. pylori infection is known to cause gastric cancer and may influence tumorigenesis of SNADA lesions at the oral side of the major papilla.

Gene expression profiling of laterally spreading tumors.

BACKGROUND: Laterally spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis. In contrast to other forms of tumor, LSTs are generally considered to have a superficial growth pattern and the potential for malignancy. We focused on this morphological character of LSTs, and analyzed the gene expression profile of LSTs. METHODS: The expression of 168 genes in 41 colorectal tumor samples (17 LST-adenoma, 12 LST-carcinoma, 12 Ip [pedunculated type of the Paris classification)-adenoma, all of which were 10 mm or more in diameter] was analyzed by PCR array. Based on the results, we investigated the expression levels of genes up-regulated in LST-adenoma, compared to Ip-adenoma, by hierarchical and K-means clustering. To confirm the results of the array analysis, using an additional 60 samples (38 LST-adenoma, 22 Ip-adenoma), we determined the localization of the gene product by immunohistochemical staining. RESULT: The expression of 129 genes differed in colorectal tumors from normal mucosa by PCR array analysis. As a result of K-means clustering, the expression levels of five genes, AKT1, BCL2L1, ERBB2, MTA2 and TNFRSF25, were found to be significantly up-regulated (p < 0.05) in LST-adenoma, compared to Ip-adenoma. Immunohistochemical analysis showed that the BCL2L1 protein was significantly and meaningfully up-regulated in LST-adenoma compared to Ip-adenoma (p = 0.010). With respect to apoptosis status in LST-Adenoma, it assumes that BCL2L1 is anti-apoptotic protein, the samples such as BCL2L1 positive and TUNEL negative, or BCL2L1 negative and TUNEL positive are consistent with the assumption. 63.2 % LST-adenoma samples were consistent with the assumption. CONCLUSIONS: LSTs have an unusual profile of gene expression compared to other tumors and BCL2L1 might be concerned in the organization of LSTs.

Mosapride citrate increases postprandial glucagon-like peptide-1, insulin, and gene expression of sweet taste receptors.

BACKGROUND AND AIM: Mosapride citrate-a prokinetic agent-improves hemoglobin A1c levels in diabetic patients; however, the underlying mechanism is unclear. We aimed to clarify this mechanism. METHODS: Preprandial and postprandial (90 min after a meal) blood was obtained from 12 healthy men, and serum insulin and plasma active glucagon-like peptide-1 concentrations were measured. Measurements were also taken after the administration of 5 mg of mosapride citrate three times per day after every meal for 14 days. In addition, C57BL/6 mice were permitted free access to water containing 0.04 % domperidone (D group) or 0.02 % mosapride citrate (M group) for 2 weeks (four mice per group). T1r2 (taste receptor, type 1, member 2), T1r3, and Gnat3 (guanine nucleotide-binding protein, alpha transducing 3) mRNA expression levels of the stomach, duodenum, and proximal and mid-jejunum were evaluated. RESULTS: In human subjects, postprandial plasma active glucagon-like peptide-1 and serum insulin concentrations after administration of mosapride citrate were significantly higher than those pre-administration (4.8 ± 2.2 pmol/L, 45.6 ± 41.6 µIU/mL, and 3.7 ± 1.2 pmol/L, 34.1 ± 28.4 µIU/mL, respectively). The mouse expression levels of T1r2 and Gnat3 in the proximal jejunum and mid-jejunum in the M group (4.1 ± 1.8-fold, 3.1 ± 1.6-fold, and 4.6 ± 0.8-fold, 3.1 ± 0.9-fold increases, respectively), were significantly higher than those of the control group. CONCLUSIONS: The administration of mosapride citrate for 2 weeks enhanced postprandial plasma active glucagon-like peptide-1 and serum insulin concentration and increased the expression of sweet taste receptors in the upper intestine.

Irsogladine Maleate Prevents Colitis in Interleukin-10 Gene-Deficient Mice by Reducing Interleukin-12 and -23 Production.

Irsogladine maleate (2,4-diamino-6-[2,5-dichlorophenyl]-s-triazine maleate; IM), an anti-peptic ulcer drug, may have a protective effect on the gastrointestinal mucosa. This study investigated the effects of IM on spontaneous colitis in interleukin-10 gene-deficient (IL-10(-/-)) mice. Five-week-old IL-10(-/-) mice were fed a control diet or one containing 100 ppm of IM for 10 weeks. Colonic tissues were evaluated morphologically and histologically. J774A.1 murine monocyte/macrophage cells were incubated with IM after lipopolysaccharide stimulation. mRNA expression was assessed by quantitative polymerase chain reaction (PCR) and protein concentration by enzyme-linked immunosorbent assay (ELISA). Colonic length, weight, and histological scores clearly demonstrated that spontaneous colitis was prevented in IL-10(-/-) mice fed a diet containing IM compared with those fed control diet. Levels of tumor necrosis factor-alpha (TNF-α) (-2.5-fold), IL-1ß (-5.4), interferon-gamma (IFN-γ) (-4.5), IL-17 (-113.0), IL-12p35 (-21.0), IL-12p40 (-3.4), and IL-23p19 (-4.2) mRNA expression were significantly decreased in the colonic tissues of IM-treated animals, suggesting that oral treatment with IM suppressed the T-helper (Th)1/Th17 immune response in the colonic mucosa. An in vitro study using monocyte/macrophage cells to clarify the pharmacological action of IM indicated that IL-12p40 and IL-23p19 mRNA expression levels were dose-dependently decreased by IM treatment. ELISA showed that IL-12p40 and IL-23 protein secretion were significantly decreased by IM in a dose-dependent manner. Oral treatment with IM prevented spontaneous colitis in IL-10(-/-) mice by suppressing the colonic mucosal Th1/Th17 immune response through inhibition of IL-12 and -23 production in monocyte/macrophage cells.

[A case of Kaposi's sarcoma of the rectum presenting with hematochezia and rectal pain].

A man in his 20s was referred to our hospital with hematochezia and rectal pain. Total colonoscopy revealed a reddish, protruding, ulcerated lesion occupying approximately half of the luminal circumference of the rectum. Examination of biopsy specimens showed proliferating spindle cells infiltrating the lamina propria, a finding consistent with Kaposi's sarcoma. The patient was also found to be anti-human immunodeficiency virus (HIV) antibody positive;therefore, we diagnosed acquired immunodeficiency syndrome (AIDS). The lesions of Kaposi's sarcoma were also seen in the skin, lung, and lymph nodes, but there were no lesions elsewhere in the gastrointestinal tract other than the rectum. We started anti-HIV therapy and chemotherapy against these lesions, and the lesions subsequently reduced in size. We present a rare case of a man with Kaposi's sarcoma presenting with a rectal lesion.

Risk factors for early and delayed post-operative bleeding after endoscopic submucosal dissection of gastric neoplasms, including patients with continued use of antithrombotic agents.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become widely accepted as a standard treatment for gastric epithelial neoplasms. Antithrombotic agents are widely used to prevent thromboembolic disease. However, the feasibility of endoscopic procedures for patients using such agents has been rarely investigated. The aim of this study was to identify risk factors for post-operative bleeding after gastric ESD and to evaluate the relationship between the use of antithrombotic agents and post-operative bleeding. METHODS: From June 2005 to March 2014, 413 patients with 425 gastric neoplasms were treated by ESD. The demographic and clinical parameters associated with post-operative bleeding were investigated. 83 patients receiving antithrombotic agents were separately assessed using various methods of administration during the ESD procedure. Post-operative bleeding that occurred within 5 days of ESD was defined as early post-operative bleeding, whereas subsequent bleeding was defined as delayed bleeding. RESULTS: The overall post-operative bleeding rate was 4.7%. In patients with continued low-dose aspirin (LDA), heparin replacement (HR), or continued LDA along with HR, post-operative bleeding rates were 9.5%, 23.8%, and 25.0%, respectively. On multivariate analysis, a specimen size of ≥40 mm was a risk factor for early post-operative bleeding [odds ratio (OR) 6.08, 95% CI: 1.74-21.27], and HR and chronic kidney disease (CKD) requiring hemodialysis were risk factors for delayed bleeding (OR 12.23, 95% CI: 2.63-56.77 and OR 28.35, 95% CI: 4.67-172.11, respectively). Continued LDA was not a risk factor for post-operative bleeding. CONCLUSIONS: Large specimen size is a risk factor for early post-operative bleeding, and HR and CKD requiring hemodialysis are risk factors for delayed bleeding. Patients with risk factors should be carefully watched, allowing for the timing of post-operative bleeding after ESD.

Expression level of sonic hedgehog correlated with the speed of gastric mucosa regeneration in artificial gastric ulcers.

BACKGROUND AND AIM: Gastric ulcer healing is a complex process involving cell proliferation and tissue remodeling. Sonic hedgehog (Shh) activates the Shh signaling pathway, which plays a key role in processes such as tissue repair. Shh and interleukin 1ß (IL1ß) have been reported to influence the proliferation of gastric mucosa. We evaluated the relationships between the speed of gastric ulcer healing and the levels of expression of Shh and IL1ß. METHODS: The study included 45 patients (mean age 71.9 ± 9.0 years; M/F, 30/15) who underwent endoscopic submucosal dissection (ESD) for gastric cancer, followed by standard dose of oral proton-pump inhibitor for 4 weeks. Subsequently, the size of ESD-induced artificial ulcers were measured to determine the speed of gastric ulcer healing, and regenerating mucosa around the ulcers and appropriately matched controls were collected from patients by endoscopic biopsy. Polymerase chain reaction (PCR) array analysis of genes in the Shh signaling pathway was performed, and quantitative reverse transcription (RT)-PCR was used to measure IL1ß mRNA. RESULTS: The levels of Shh and IL1ß mRNA were 3.0 ± 2.7-fold and 2.5 ± 2.5-fold higher, respectively, in regenerating mucosa of artificial ulcers than in appropriately matched controls, with the two being positively correlated (r = 0.9, P < 0.001). Shh (r = 0.8, P < 0.001) and IL1ß (r = 0.7, P < 0.005) expression was each positively correlated with the speed of gastric ulcer healing, but multivariate analysis showed that Shh expression was the only significant parameter (P = 0.045). CONCLUSIONS: Expression of Shh was correlated with the speed of gastric ulcer healing, promoting the regeneration of gastric mucosa.

Fibrocytes are involved in inflammation as well as fibrosis in the pathogenesis of Crohn's disease.

BACKGROUND: We previously showed that fibrocytes, a hematopoietic stem cell source of fibroblasts/myofibroblasts, infiltrated the colonic mucosa of a murine colitis model. AIM: We investigated whether fibrocytes were involved in the pathogenesis of Crohn's disease. METHODS: Human surgical intestinal specimens were stained with anti-leukocyte-specific protein 1 and anti-collagen type-I (ColI) antibodies. Circulating fibrocytes in the human peripheral blood were quantified by fluorescence-activated cell sorting with anti-CD45 and anti-ColI antibodies. Cultured human fibrocytes were prepared by culturing peripheral CD14(+) monocytes. RESULTS: In the specimens of patients with Crohn's disease, the fibrocyte/total leukocyte percentage was significantly increased in inflammatory lesions (22.2 %, p < 0.01) compared with that in non-affected areas of the intestine (2.5 %). Interestingly, the percentage in fibrotic lesions was similar (2.2 %, p = 0.87) to that in non-affected areas. The percentages of circulating fibrocytes/total leukocytes were significantly higher in patients with Crohn's disease than in healthy controls. Both CXC-chemokine receptor 4(+) and intercellular adhesion molecule 1(+) fibrocyte numbers were significantly increased in Crohn's disease, suggesting that circulating fibrocytes have a higher ability to infiltrate injured sites and traffic leukocytes. In cultured fibrocytes, lipopolysaccharide treatment remarkably upregulated tumor necrosis factor (TNF)-α mRNA (17.0 ± 5.7-fold) and ColI mRNA expression (12.8 ± 5.7-fold), indicating that fibrocytes stimulated by bacterial components directly augmented inflammation as well as fibrosis. CONCLUSIONS: Fibrocytes are recruited early in the inflammatory phase and likely differentiate into fibroblasts/myofibroblasts until the fibrosis phase. They may enhance inflammation by producing TNF-α and can directly augment fibrosis by producing ColI.