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.

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.

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.

Predictive factor of re-bleeding after negative capsule endoscopy for obscure gastrointestinal bleeding: over 1-year follow-up study.

BACKGROUND AND AIM: Capsule endoscopy (CE) is now widely accepted as a first-line diagnostic modality for obscure gastrointestinal bleeding (OGIB), with a high diagnostic yield compared to other modalities. However, even after negative CE examination, re-bleeding is often known to occur. The aim of the present study was to identify predictive factors of re-bleeding after negative CE, and to clarify the clinical utility of double-balloon enteroscopy (DBE) after negative CE for OGIB. METHODS: Two hundred and sixty patients who underwent CE for OGIB between October 2007 and September 2012 were included, and followed up for at least 1 year after CE examination. Demographic and clinical parameters associated with re-bleeding after negative CE were investigated. RESULTS: A total of 154 patients (59.2%) had negative findings. Thirteen of those patients (8.4%) had one or more re-bleeding episodes during the follow-up period. In comparing patients with and without re-bleeding, Cox hazard regression analysis revealed that advanced age was a predictive factor for re-bleeding after negative CE (hazard ratio 1.05 [1.01-1.10], P = 0.03). Subsequent DBE for reasons other than re-bleeding was carried out in 51 patients (33.1%). Mucosal lesions (ulcer or multiple erosions) were subsequently detected in seven patients (13.7%), and endoscopic therapies were carried out in two patients (3.9%). CONCLUSIONS: In patients of advanced age, more extensive follow up is needed, even if the CE result is negative. In addition, DBE subsequent to negative CE may be useful to detect lesions that were overlooked on CE.

Evaluation of periesophageal nerve injury after pulmonary vein isolation using the (13)C-acetate breath test.

BACKGROUND: Pulmonary vein isolation (PVI) has become an important option for treating patients with atrial fibrillation (AF). Periesophageal nerve (PEN) injury after PVI causes pyloric spasms and gastric hypomotility. This study aimed to clarify the impact of PVI on gastric motility and assess the prevalence of gastric hypomotility after PVI. METHODS: Thirty consecutive patients with AF underwent PVI under luminal esophageal temperature (LET) monitoring. The (13)C-acetate breath test was conducted before and after the procedure for all patients (PVI group). Gastric emptying was evaluated using the time to peak concentration of (13)CO2 (T max). This test was also conducted in another 20 patients who underwent catheter ablation procedures other than PVI (control group). RESULTS: The number of patients with abnormal T max (≥75 min) increased from seven (23%) to 13 (43%) and from three (15%) to five (25%) after the procedure in the PVI group and control group, respectively. The mean T max was longer after PVI than before PVI (64±14 min vs. 57±15 min, p=0.006), whereas there was no significant difference before and after the procedure in the control group. However, no significant difference in ΔT max was observed between the two groups (p=0.27). No patients suffered from symptomatic gastric hypomotility. CONCLUSIONS: Asymptomatic gastric hypomotility occurred more often after PVI. However, the average impact of PVI on gastric motility was minimal.

Two-week treatment with proton pump inhibitor is sufficient for healing post endoscopic submucosal dissection ulcers.

AIM: To investigate the optimum period of treatment for post endoscopic submucosal dissection (ESD) ulcers. METHODS: Patients who underwent ESD for gastric cancer were randomized to two groups and treated with esomeprazole 20 mg per day for 4 wk (4W group) or 2 wk (2W group). At 4 wk after ESD, we measured the size of the artificial ulcers by endoscopy and determined the ulcer healing rate, compared with the size of the ESD specimens. This randomized controlled trial study was approved by our ethics committee and registered in the UMIN Clinical Trial Registry. RESULTS: A total of 60 consecutive patients were included in the study. All patients received rebamipide 300 mg per day for 4 wk. One patient in 2W group who showed bleeding within two weeks and received endoscopic treatment was excluded from further analysis. The numbers of patients with ulcers in the healing/scar stage in the 2W and 4W groups at 4 wk after ESD were 20/6 and 28/5, respectively, with no significant difference. The ulcer healing rate in the 2W and 4W groups were 96.1% [95% confidence interval (CI): 94.6%-97.55] vs 94.8% (95%CI: 92.6%-97.1%), respectively, with no statistical difference (UMIN000006951). CONCLUSION: Two-wk treatment with a proton pump inhibitor is as effective as four-week treatment for healing post ESD ulcers.

Severe diffuse duodenitis successfully treated with intravenous tacrolimus after colectomy for ulcerative colitis.

We encountered a rare case of severe diffuse duodenitis associated with ulcerative colitis (UC). A 23-year-old man underwent total proctocolectomy with ileal J-pouch anal anastomosis for UC. He suffered from severe abdominal pain, fever and bloody diarrhea for six months after the surgery. Upper double-balloon enteroscopy disclosed severe diffuse duodenitis, of which the findings were endoscopically and histologically similar to those of colonic lesions of UC. Although the administration of prednisolone was ineffective, treatment with intravenous tacrolimus markedly improved the clinical findings. This is the first report of the successful treatment of severe UC-associated diffuse duodenitis with intravenous tacrolimus.

A primary arterio enteric fistula with Takayasu arteritis.

Arterio enteric fistulas (AEFs) are rare. We herein report a case of a primary arterio enteric fistula of the rectum associated with Takayasu arteritis. A 77-year-old woman presented with acute massive hematochezia and was taken to our hospital. Colonoscopy revealed pulsatile extrinsic rectal wall compression with an exposed blood vessel. Transvaginal ultrasonography and Doppler ultrasound revealed a localized vascular growth laying on the dorsal surface of the uterus that showed an arterial blood-flow signal. We diagnosed the patient to have a pelvic aneurism that had formed a fistula within the rectal wall. We eliminated the aneurysm by ligating the drainage and feeder arteries. Following surgery, the patient did not experience any relapses of hematochezia.