Efficacy of a Traction Device for Endoscopic Submucosal Dissection Using a Scissor-Type Knife: A Randomized Controlled Trial.

INTRODUCTION: Although safe, colorectal endoscopic submucosal dissection (ESD) using a scissor-type knife has a slow resection speed. We aimed to evaluate the efficacy of a traction device to hasten the resection speed. METHODS: This multicenter randomized controlled trial was conducted at 3 Japanese institutions. Patients with a 20-50-mm superficial colorectal tumor were enrolled and randomly assigned to a conventional-ESD (C-ESD) group or a traction-assisted ESD (T-ESD) group. The primary outcome was the resection speed. RESULTS: The C-ESD and T-ESD groups comprised 49 and 48 patients, respectively. Although the mean resection speed was not significantly different in the entire cohort between the groups (23.7 vs 25.6 mm 2 /min, respectively; P = 0.43), it was significantly faster with T-ESD than with C-ESD at the cecum (32.4 vs 16.7 mm 2 /min, respectively; P = 0.02). The mean resection speed of tumors ≥30 mm tended to be faster by T-ESD than by C-ESD (34.6 vs 27.8 mm 2 /min, respectively; P = 0.054). The mean procedure time of T-ESD was significantly shorter than that of C-ESD (47.3 vs 62.3 minutes, respectively; P = 0.03). The en bloc (100% vs 100%), complete (98.0% vs 97.9%), and curative resection (93.9% vs 91.7%) rates were similar between the 2 groups. Perforation and delayed hemorrhage occurred in only 1 patient each in the T-ESD group. DISCUSSION: Although the resection rates were sufficiently high and adverse event rates were extremely low in both the groups, the use of a traction device for ESD in the proximal colon and for large lesions may increase the resection speed.

Contrast-enhanced CT for Colonic Diverticular Bleeding before Colonoscopy: A Prospective Multicenter Study.

Purpose To demonstrate the usefulness of precolonoscopy intravenous contrast material-enhanced CT for colonic diverticular bleeding (CDB). Materials and Methods A prospective, multicenter, observational study was performed. Patients with acute-onset hematochezia who were admitted to hospital were included, and those without CDB were excluded. CT was performed before colonoscopy. A Mann-Whitney U test, χ2 test, and multivariable logistic regression analysis were performed to determine the accuracy of CT before colonoscopy. Results A total of 442 patients (mean age, 71.2 years; 302 male patients; 68.3% men) were included between January 2014 and December 2015, and 202 patients were diagnosed as having CDB. The positive extravasation rate during CT was 50 of 202 (24.7%) among all patients and five of nine (55.6%) among patients who underwent CT within 1 hour of the last hematochezia. At multivariable analysis, the interval from the last hematochezia until CT was a predictor of extravasation (beta coefficient, -.0038 ± 0.0014 [standard deviation]). Extravasation at CT had a sensitivity of 38 of 66 (57.6%; 95% confidence interval: 44.8%, 69.7%) and a specificity of 124 of 136 (91.2%; 95% confidence interval: 85.1%, 95.4%) for the prediction of stigmata of recent hemorrhage of diverticula during colonoscopy. The sensitivity was higher in patients who underwent CT examination within 4 hours of hematochezia, compared with those examined after 4 hours (64.7% [33 of 51] vs 33.3% [five of 15]; P < .01). Conclusion Extravasation findings for CT with intravenous contrast material had high specificity for the prediction of stigmata of recent hemorrhage of diverticula during colonoscopy, regardless of the timing of the CT examination. Although the sensitivity was relatively low, it was higher when the CT examination was performed within 4 hours after the last hematochezia. Therefore, urgent precolonoscopy CT may contribute to decision making regarding whether an urgent colonoscopy should be performed.

Assessment of colonic contents in patients with chronic constipation using MRI.

Although chronic constipation is common, colonic functional evaluating tests are uncommon. This study examines whether chronic constipation and gastrointestinal symptoms are correlated with the lateral diameter of the colon measured from MRI images. We included chronic constipation patients in a prospective, cross-sectional study using MRI at three centers. We divided 3D MRI colorectal images into 6 segments using with specified sequences and selected the maximum luminal diameter from each segment. We used the GSRS questionnaire to evaluate gastrointestinal symptoms. We evaluated the correlation between luminal diameters and GSRS scores. We found the following positive correlations: descending colon and unsatisfactory defecation symptoms; sigmoid colon and diarrhea; and rectum and constipation. The sum and ratio of the ascending and sigmoid colon diameters correlated with nausea and diarrhea. The sum of the transvers to the sigmoid colon diameter also correlated with nausea and diarrhea. The sum of all segment diameters correlated with nausea and constipation. In conclusion, we showed cross-sectional study of colonic MRI correlate with gastrointestinal symptoms. MRI might be useful for colonic motility evaluations to determine appropriate constipation treatments (Clinical trial registry number UMIN 000021274).

[Successful endoscopic ultrasound-guided cyst drainage (EUS-CD) of pancreatic pseudocyst in the abdominal cavity to the cervical region accompanied by spontaneous rupture into the portal vein:a case study].

A 53-year-old man was admitted to our hospital with the complaint of neck pain and dyspnea. His blood examination revealed increased C-reactive protein and amylase levels. Enhanced computed tomography (CT) images demonstrated a retropharyngeal and a mediastinal low-density area extending to the portal area. He was diagnosed with pancreatic pseudocyst from the abdominal cavity to the cervical region accompanied by spontaneous rupture into the portal vein. Endoscopic ultrasound-guided cyst drainage (EUS-CD) of the most inferior cavity around the superior mesenteric artery was performed through the gastric wall. No adverse events were recorded during the procedure, and a near-complete resolution of his symptoms and the pseudocyst was achieved.

Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial.

BACKGROUND: The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence. METHODS: This trial was a multicentre, double-blind, placebo-controlled, randomised phase 3 trial. Non-diabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were enrolled into the study from five hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive oral metformin (250 mg daily) or identical placebo tablets by a stratified computer-based randomisation method, with stratification by institute, age, sex, and body-mass index. All patients, endoscopists, doctors, and investigators were masked to drug allocation until the end of the trial. After 1 year of administration of metformin or placebo, colonoscopies were done to assess the co-primary endpoints: the number and prevalence of adenomas or polyps. Our analysis included all participants who underwent random allocation, according to the intention-to-treat principle. This trial is registered with University Hospital Medical Information Network (UMIN), number UMIN000006254. FINDINGS: Between Sept 1, 2011, and Dec 30, 2014, 498 patients who had had single or multiple colorectal adenomas resected by endoscopy were enrolled into the study. After exclusions for ineligibility, 151 patients underwent randomisation: 79 were assigned to the metformin group and 72 to the placebo group. 71 patients in the metformin group and 62 in the placebo group underwent 1-year follow-up colonoscopy. The prevalence of total polyps (hyperplastic polyps plus adenomas) and of adenomas in the metformin group was significantly lower than that in the placebo group (total polyps: metformin group 27 [38·0%; 95% CI 26·7-49·3] of 71 patients, placebo group 35 [56·5%; 95% CI 44·1-68·8] of 62; p=0·034, risk ratio [RR] 0·67 [95% CI 0·47-0·97]; adenomas: metformin group 22 [30·6%; 95% CI 19·9-41·2] of 71 patients, placebo group 32 [51·6%; 95% CI 39·2-64·1] of 62; p=0·016, RR 0·60 [95% CI 0·39-0·92]). The median number of polyps was zero (IQR 0-1) in the metformin group and one (0-1) in the placebo group (p=0·041). The median number of adenomas was zero (0-1) in the metformin group and zero (0-1) in the placebo group (p=0·037). 15 (11%) of patients had adverse events, all of which were grade 1. We recorded no serious adverse events during the 1-year trial. INTERPRETATION: The administration of low-dose metformin for 1 year to patients without diabetes was safe. Low-dose metformin reduced the prevalence and number of metachronous adenomas or polyps after polypectomy. Metformin has a potential role in the chemoprevention of colorectal cancer. However, further large, long-term trials are needed to provide definitive conclusions. FUNDING: Ministry of Health, Labour and Welfare, Japan.

Clinical value of capsule endoscopy for detecting small bowel lesions in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: To evaluate the clinical value of capsule endoscopy (CE) in patients with intestinal Behçet's disease (BD). METHODS: The present study was a case-control pilot study conducted in intestinal BD patients and healthy volunteers. A total of 19 patients with intestinal BD (intestinal BD group) and 19 healthy volunteers (control group) matched for age and sex were enrolled. Frequency, number of small bowel lesions per subject, and Lewis score were comparatively evaluated between the two groups. RESULTS: Of the 19 patients with intestinal BD, 18 (94.7%) had reddened lesions, 15 (78.9%) had erosions, and nine (47.4%) had ulcers. There were significant differences in the frequency of reddened lesions (P < 0.0001), erosions (P < 0.0001) and ulcers (P = 0.0011) between the two groups. The difference in the number of small bowel lesions between the two groups was also statistically significant. The median Lewis score in the intestinal BD group was significantly higher than that in the control group (intestinal BD group 237 (0-768) vs. control group 8 (0-135); P < 0.0001). Analysis according to the location in the small bowel revealed that the frequency of ulcers tended to increase towards the distal intestine. CONCLUSION: This is the first CE study conducted to examine small bowel involvement in intestinal BD patients. Our results suggest that CE evaluation is necessary, in addition to colonoscopy, in all intestinal BD patients.

Conditional knockout of the leptin receptor in the colonic epithelium revealed the local effects of leptin receptor signaling in the progression of colonic tumors in mice.

Leptin, secreted by the adipose tissue and known to be related to obesity, is considered to be involved in the onset and progression of colorectal cancer. However, the exact role of leptin in colorectal carcinogenesis is still unclear, as several controversial reports have been published on the various systemic effects of leptin. The aim of this study was to clarify the local and precise roles of leptin receptor (LEPR)-mediated signaling in colonic carcinogenesis using intestinal epithelium-specific LEPRb conditional knockout (cKO) mice. We produced and used colonic epithelium-specific LEPRb cKO mice to investigate the carcinogen-induced formation of aberrant crypt foci (ACF) and tumors in the colon, using their littermates as control. There were no differences in the body weight or systemic condition between the control and cKO mice. The tumor sizes and number of large-sized tumors were significantly lower in the cKO mice as compared with those in the control mice. On the other hand, there was no significant difference in the proliferative activity of the normal colonic epithelial cells or ACF formation between the control and cKO mice. In the control mice, marked increase of the LEPRb expression level was observed in the colonic tumors as compared with that in the normal epithelium; furthermore, signal transducer and activator of transcription (STAT3) was activated in the tumor cells. These findings suggest that STAT3 is one of the important molecules downstream of LEPRb, and LEPRb/STAT3 signaling controls tumor cell proliferation. We demonstrated the importance of local/regional LEPR-mediated signaling in colorectal carcinogenesis.

Metabolic factors accelerate colorectal adenoma recurrence.

BACKGROUND: Metabolic factors have been reported to increase the prevalence of colorectal adenomas, however, whether metabolic factors might also accelerate the recurrence after removal of adenomas has not yet been discussed. In this retrospective multicenter study, we clarified the risk factors for adenoma recurrence focusing on metabolic factors. METHODS: We analyzed the medical records of 43,195 patients who had undergone colonoscopy between January 2005 and December 2011 at 5 hospitals in Japan. Of these, the data of 1111 patients who had undergone removal of adenomas at the first screening colonoscopy, and then been followed up by colonoscopy 1 year and 2 years later were analyzed. RESULTS: The following 8 factors were demonstrated with a multivariate analysis as being associated with colorectal adenomas recurrence: for adenoma-related factors, 5 factors (villous features, grade of dysplasia, location and size of the largest removed adenoma, and number of the removed adenomas) were identified; for metabolic factors and other factors, 3 factors (age, body mass index (BMI), and fasting blood glucose (FBG)) were identified. A risk score (0-10 points) was developed based on these 8 factors. The risk of adenoma recurrence increased as the risk score increased. When the risk score was ≥3 (3-10) points, the odds ratio relative to <3 (0-2) points was 7.07 (95% CIs 5.30-9.43). CONCLUSIONS: In addition to adenoma-related factors (villous features, grade of dysplasia, location, size and number), 3 factors (age, BMI and FBG) were demonstrated to influence the recurrence rate of colorectal adenoma. When the risk score was ≥3, the risk of recurrence was significantly elevated.

Correlation between gastric transit time measured by video capsule endoscopy and gastric emptying determined by the continuous real-time 13C breath test (BreathID system).

BACKGROUND/AIMS: The aim of this study was to determine the possible existence of a correlation between the gastric transit time (GTT) measured by video capsule endoscopy (VCE) and the parameters of gastric emptying determined using 13C breath test (BreathID system). METHODS: Eight healthy male volunteers participated in this randomized, two-way crossover study. The subjects were randomly assigned to undergo VCE using the PillCam SB capsule endoscopy system or the 13C breath test for 4 hours after a test meal (400 kcal per 400 mL) containing 100 mg of 13C acetic acid administered after overnight fasting. The VCE images were analyzed and the GTT was determined using the proprietary RAPID software. The parameters, namely T lag, T 1/2 and GEC were calculated using the Oridion Research Software (ß version). The GTT measured by VCE and the parameters of gastric emptying were compared statistically. RESULTS: No significant correlation was observed between the GTT and T lag (p = 0.5263), T 1/2 (p = 0.4100) or GEC (p = 0.2410), as determined by calculation of the Spearman's rank correlation coefficient. CONCLUSIONS: GTT measured by VCE cannot serve as asubstitute for the gastric emptying time measured bythe 13C breath test.

Eicosapentaenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a double-blind randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly occurring neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Eicosapentaenoic acid (EPA), the omega-3 polyunsaturated fatty acid that is widely used in the treatment of hyperlipidemia and prevention of cardiovascular disease, has recently been suggested to have a suppressive effect on tumorigenesis and cancer cell growth. In CRC chemoprevention trials, in general, the incidence of polyps or of the cancer itself is set as the study endpoint. Although the incidence rate of CRC would be the most reliable endpoint, use of this endpoint would be unsuitable for chemoprevention trials, because of the relatively low occurrence rate of CRC in the general population and the long-term observation period that it would necessitate. Moreover, there is an ethical problem in conducting long-term trials to determine whether a test drug might be effective or harmful. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are considered as a reliable surrogate biomarker of CRC. Thus, we devised a prospective randomized controlled trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of EPA against colorectal ACF formation and the safety of this drug, in patients scheduled for polypectomy. METHODS: This study is a multicenter, double-blind, placebo-controlled, randomized controlled trial to be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients shall be recruited for the study and the number of ACF in the rectum counted at the baseline colonoscopy. Then, the participants shall be allocated randomly to either one of two groups, the EPA group and the placebo group. Patients in the EPA group shall receive oral 900-mg EPA capsules thrice daily (total daily dose, 2.7 g per day), and those in the placebo group shall receive oral placebo capsules thrice daily. After one month's treatment with EPA/placebo, colonoscopic examination and polypectomy will be performed to evaluate the formation of ACF, and the cell-proliferative activity and cell-apoptotic activity in normal colorectal mucosa and colorectal polyps. DISCUSSION: This is the first study proposed to explore the effect of EPA against colorectal ACF formation in humans.This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000008172.

Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial.

BACKGROUND: Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients. METHODS/DESIGN: This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation. DISCUSSION: This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with type 2 diabetes taking under treatment with metformin have been reported to be at a lower risk of cancer development than those not taking under treatment with metformin. We showed in a previous study that metformin suppressed the formation of human colorectal ACF. We therefore decided to conduct a study to determine whether metformin might suppress the formation of human colorectal polyps. TRIAL REGISTRATION: This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000006254.

Risk factors for colonic diverticular hemorrhage: Japanese multicenter study.

BACKGROUND AND AIM: Diverticular hemorrhage is the common cause of lower gastrointestinal bleeding, and its incidence has been increasing in Japan. However, the exact cause of diverticular hemorrhage is not well understood. We investigated the risk factors for diverticular hemorrhage. METHODS: We selected 103 patients with diverticular hemorrhage as cases and patients with colonic diverticulosis without a history of bleeding were selected as control subjects, exactly matched for age and gender. We collected the data from the medical records of each of the patients, such as those related to the comorbidities, medications and findings of colonoscopy, and conducted a matched case-control study to analyze the risk factors for diverticular hemorrhage. RESULTS: Both groups were composed of 75 men and 28 women. The median age of the patients in both groups was 72.0 years (47.0-87.0). The body weight (p = 0.0065), body mass index (p = 0.006), prevalence of hypertension (p = 0.0242), prevalence of ischemic heart disease (p = 0.0015), and frequency of use of low-dose aspirin (p = 0.042) were significantly different between the two groups. The percentage of patients with bilateral diverticula, that is, diverticula on both the right and left hemicolon, was significantly higher in the diverticular hemorrhage group (p = 0.0011). Multiple regression analysis identified only the diverticular location as being significantly associated with the risk of diverticular hemorrhage (p = 0.0021). CONCLUSIONS: Only the diverticular location (bilateral) was found to be an independent risk factor for diverticular hemorrhage.

[A case of endocrine cell carcinoma of the esophagus successfully treated by chemoradiotherapy].

The patient was a 74-year-old man who suffered from epigastric abdominal pain. He visited our hospital in April 2008. An esophageal endocrine cell carcinoma was pointed out by gastrointestinal endoscopy, and he was diagnosed as esophageal endoscopic cell carcinoma with mediastinum lymph node by CT scan(Stage IVa: cT3N4M0). Concurrent chemoradiotherapy using CDDP+EP was started. After two courses, the primary tumor was markedly reduced, and endoscopy showed only a scar. We diagnosed the patient as being in complete remission. However, CT showed a liver metastasis relapse in June 2009, and we started AMR as second-line chemotherapy. His general condition went into a decline, however, He died on October 2, 2009.

Capsule-endoscopic findings of ulcerative colitis patients.

BACKGROUND/AIMS: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by diffuse mucosal inflammation, traditionally regarded as being limited to the colorectum. Although several gastroduodenal lesions have also been reported recently in cases of UC, in general, small-bowel lesions in UC are believed to be extremely rare. The aim of this study was to examine the small bowel by capsule endoscopy in patients with UC. METHODS: The study was conducted in 23 well-documented UC patients and 23 control volunteers. The frequency of small-bowel lesions, the number of small-bowel lesions per patient and the capsule endoscopy score were comparatively evaluated between the two groups. RESULTS: Of the 23 UC patients, 13 (57%) showed small-bowel lesions, and 8 (35%) had erosions. There were significant differences in the frequency of the small-bowel lesions (p < 0.001) and erosions (p = 0.009) between the two groups. The capsule endoscopy score was correlated with the UC disease activity index (r = 0.718, p < 0.001). CONCLUSIONS: This is the first capsule-endoscopic study conducted to examine the small-bowel involvement in UC patients as compared with the healthy volunteers. It was concluded that UC, a chronic inflammatory bowel disease, can also involve the small bowel.

Temperature-dependent changes in the molecular orientation and visible color of phthalocyanine films.

A simple phthalocyanine zinc complex exhibits a visible color change in response to weak external stimuli, i.e., changes in solvent and temperature. Its chromism was attributed to its controlled aggregation via weak interactions between the central metal and peripheral oxygen atoms. In solution, intense absorption and fluorescence bands appeared in both the longer-wavelength and NIR region in non-coordinating solvents, while a simple sharp Q band was observed in coordinating solvents. Variable-temperature absorption spectra and fluorescence lifetime measurements were used to characterize the aggregation-induced absorption and emission in non-coordinating solvents. A selective aggregation-disaggregation process was also observed in thin films of this phthalocyanine zinc complex, and the optical properties of the film depend on the annealing temperature. The changes in the NIR region lead to a sizable visible color change that is recognizable by the naked human eye. The temperature-dependent control of the aggregation process in the thin film was confirmed using operando spectroscopy techniques.

END-phenomenon negative bovine viral diarrhea virus that induces the host's innate immune response supports propagation of BVDVs with different immunological properties.

Our previous study reported that persistently infected (PI) cattle of bovine viral diarrhea virus (BVDV) have co-infected with BVDV/END- and /END+ that promote and inhibit host's type-I interferon (IFN) production, respectively. However, the relationship between co-infection of immunologically distinct BVDVs and persistent infection as well as the biological significance of END- viruses remains unknown. Experiments using cultured cells revealed that END+ virus, which is unable to propagate in situations where the host's immune response is induced by IFN-α addition, is able to propagate under those conditions when co-infecting with END- virus. These results indicate that BVDV/END- can coexist with BVDV/END+ and that co-infection with END- viruses supports the propagation of END+ viruses. Our in vitro experiments strongly suggest that co-infection with END- virus is involved in the maintenance of persistent infection of BVDV.

Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers.

BACKGROUND AND AIMS: The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called "leaky gut syndrome." As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. METHODS: Healthy male volunteers were treated with lubiprostone (24 µg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. RESULTS: The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. CONCLUSIONS: This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal trial is needed to confirm our finding.

Evaluation of endoscopic findings for discriminating between early carcinomas and low-grade adenomas in superficial elevated gastric lesions.

BACKGROUND/AIMS: This study aimed to determine the useful endoscopic findings in a differential diagnosis between early carcinomas (EC) and low-grade adenomas (LGA) in superficial elevated gastric epithelial neoplasia during conventional endoscopy with white-light imaging (C-WLI). MATERIALS AND METHODS: We investigated 270 consecutive cases of superficial elevated gastric epithelial neoplasias, which were removed by endoscopic submucosal dissection. The pathological diagnostic criteria were based on the revised Vienna classification: category 4 (mucosal high-grade neoplasia) or 5 (submucosal invasion by carcinoma) lesions were diagnosed as EC, while category 3 (mucosal low-grade neoplasia) lesions were diagnosed as LGA. The association between the postoperative pathological diagnoses (EC or LGA) and the following endoscopic findings: localized site, lesion size, color (reddish or whitish), shape (smooth, petal, or irregular), and presences of depression, erosion, ulceration, or nodularity on the surface, were evaluated. RESULTS: Of 270 epithelial neoplasias, 222 (58 LGA and 164 EC) were retrospectively evaluated. Multiple logistic regression analysis revealed that the lesion size [odds ratio (OR), 1.216; p<0.001) and reddish color (OR, 5.274; p<0.001) were independent findings for EC. CONCLUSION: The lesion size and reddish color were useful optical findings for discriminating between EC and LGA.

Can magnifying endoscopy with narrow-band imaging discriminate between carcinomas and low grade adenomas in gastric superficial elevated lesions?

Background and study aims: The aim of this study was to investigate the capability of magnifying endoscopy with narrow-band imaging (ME-NBI) to discriminate between early carcinomas (EC) and low grade adenomas (LGA) in gastric superficial elevated epithelial neoplasias. Patients and methods: We investigated 100 consecutive cases of gastric superficial elevated epithelial neoplasias that were removed using endoscopic submucosal dissection. The pathological diagnostic criteria were based on the revised Vienna classification; category 4 (mucosal high grade neoplasia) and category 5 (submucosal invasion by carcinoma) lesions were diagnosed as EC, whereas category 3 (mucosal low grade neoplasia) lesions were diagnosed as LGA. The associations between the postoperative pathological diagnoses and the ME-NBI findings were analyzed, and included the shape, specification, and area of irregularity in the microvascular architecture (MV) and the microsurface structure (MS). Results: Seventy-nine EC and 21 LGA cases diagnosed postoperatively were evaluated retrospectively. The lesion size (median; range (mm)) was significantly larger in the EC group (14; 2 - 95) compared to the LGA group (5; 2 - 16) (P < 0.001). Wavy forms in the MV shapes (P = 0.031), extension in the MV specifications (P = 0.035), and area with MV irregularity (P = 0.001) were found to be statistically significant predictive findings for EC. Villous forms in the MS shapes (P = 0.026), enlargement in the MS specifications (P = 0.044), and area with MS irregularity (P = 0.021) were also found to be statistically significant predictive findings for EC. The rates of preoperative sensitivity, specificity, and diagnostic accuracy of ME-NBI for discriminating EC were 86.1 %, 38.9 %, and 75 %, respectively. Conclusions: The present study suggests that ME-NBI is useful for the differential diagnosis of EC and LGA in gastric superficial elevated epithelial neoplasias. STUDY REGISTRATION: UMIN000012925.