Pilot study on clinical effectiveness of autofluorescence imaging for early gastric cancer diagnosis by less experienced endoscopists.

This study aimed to assess and compare effectiveness of Autofluorescence imaging (AFI) in diagnosis of early gastric cancer (EGC) between experienced and less experienced endoscopists. Fifty selected images (20 neoplastic lesions and 30 benign lesions/areas) of both white light endoscopy (WLE) and AFI were blindly reviewed by two groups; first consisted of five experienced endoscopists and second included five less experienced endoscopists. Sensitivity, specificity, and accuracy were 70%, 78%, and 75%, respectively, for AFI and 81%, 76%, and 78%, respectively, for WLE in the experienced group. In the less experienced group, sensitivity, specificity and accuracy were 80%, 81% and 80%, respectively, for AFI and 65%, 77%, and 72%, respectively, for WLE. Interobserver variability for the less experienced group was better with AFI than WLE. AFI improved sensitivity of endoscopic diagnosis of neoplastic lesions by less experienced endoscopists, and its use could beneficially enhance the clinical effectiveness of EGC screening.

A case of lobulated and pedunculated duodenal hyperplastic polyp treated with snare polypectomy.

We report herein the case of a lobulated and pedunculated hyperplastic polyp in the third portion of the duodenum causing anemia and occult blood in stools, which was detected by capsule endoscopy (CE) and treated with snare polypectomy. A 71-year-old man was referred to our hospital because of anemia and occult blood in stools. Three months earlier, he had been admitted to another hospital because of hemorrhage from gastric antral vascular ectasia (GAVE). Despite being treated for GAVE, hemoglobin decreased gradually. Esophagogastroduodenoscopy (EGD) and colonoscopy revealed no source of bleeding. However, CE revealed a polyp at the distal duodenum. Barium meal and EGD revealed a lobulated and pedunculated polyp in the third portion of the duodenum. The polyp was treated with snare polypectomy. Histopathological examination of the polyp revealed hyperplasia. After treatment of the polyp, the anemia improved gradually. To our knowledge, there are only 6 reported cases of a duodenal hyperplastic polyp, including our case. The polyp was pedunculated in only 2 cases and lobulated only in our case. Moreover, our case was diagnosed by CE. When a patient presents with anemia or obscure gastrointestinal bleeding undiagnosed by EGD and colonoscopy, CE is useful for detecting the bleeding lesion.

Pseudomembranous colitis complicating ulcerative colitis.

Clostridium difficile toxin (CD toxin) causes antibiotic-associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71-year-old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3-week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing.

Efficacy of an endo-knife with a water-jet function (Flushknife) for endoscopic submucosal dissection of superficial colorectal neoplasms.

OBJECTIVES: Endoscopic submucosal dissection (ESD) is currently not a common treatment for colorectal neoplasms because it is time consuming and technically difficult. Flushknife--an electrosurgical endo-knife with a water-jet function--is expected to reduce the difficulty of colorectal ESD. The objective of this study was to investigate the efficacy of a water-jet function for colorectal ESD. METHODS: This study was a prospective randomized controlled trial, which was conducted at a cancer referral center. A total of 49 patients, with a total of 51 superficial colorectal neoplasms (median tumor size of 30 mm), were enrolled and randomly assigned to undergo ESD using either the Flexknife (electrosurgical endo-knife without a water-jet function) or the Flushknife. Tumors were resected by ESD using each endo-knife. The procedures were conducted by two endoscopists. Operation time was defined as the main outcome measure. RESULTS: En bloc resection was achieved in 23 out of 26 (88%) lesions in the Flexknife group and in 24 out of 24 (100%) lesions in the Flushknife group. The mean operation time (95% confidence interval) was 87.3 (71.3-103.4) min in the Flexknife group and 61.0 (49.3-72.7) min in the Flushknife group (P=0.02). The Flushknife reduced the number of endoscopic device changes (P=0.001), the number of submucosal injections (P=0.001), and the mean amount of injected hyaluronate sodium (P=0.001) compared with the Flexknife. No severe adverse events were observed in either group. CONCLUSIONS: Without increasing adverse events, the endo-knife with a water-jet function efficiently reduced the operation time of colorectal ESD in patients with large superficial colorectal neoplasms. (University hospital Medical Information Network Clinical Trials Registry number UMIN000001302).

Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated Type I (slow twitch/red muscle) fiber genes, and impaired glycemic control.

FOXO1, a member of the FOXO forkhead type transcription factors, is markedly up-regulated in skeletal muscle in energy-deprived states such as fasting and severe diabetes, but its functions in skeletal muscle have remained poorly understood. In this study, we created transgenic mice specifically overexpressing FOXO1 in skeletal muscle. These mice weighed less than the wild-type control mice, had a reduced skeletal muscle mass, and the muscle was paler in color. Microarray analysis revealed that the expression of many genes related to the structural proteins of type I muscles (slow twitch, red muscle) was decreased. Histological analyses showed a marked decrease in size of both type I and type II fibers and a significant decrease in the number of type I fibers in the skeletal muscle of FOXO1 mice. Enhanced gene expression of a lysosomal proteinase, cathepsin L, which is known to be up-regulated during skeletal muscle atrophy, suggested increased protein degradation in the skeletal muscle of FOXO1 mice. Running wheel activity (spontaneous locomotive activity) was significantly reduced in FOXO1 mice compared with control mice. Moreover, the FOXO1 mice showed impaired glycemic control after oral glucose and intraperitoneal insulin administration. These results suggest that FOXO1 negatively regulates skeletal muscle mass and type I fiber gene expression and leads to impaired skeletal muscle function. Activation of FOXO1 may be involved in the pathogenesis of sarcopenia, the age-related decline in muscle mass in humans, which leads to obesity and diabetes.

A forkhead transcription factor FKHR up-regulates lipoprotein lipase expression in skeletal muscle.

Lipoprotein lipase (LPL) plays a role in lipid usage in skeletal muscle by hydrolyzing plasma triglycerides into fatty acids, which are further utilized for beta-oxidation. Lipid usage is stimulated during fasting, diabetes mellitus and exercise, concomitant with enhanced LPL expression in skeletal muscle. Here we show that the forkhead type transcription factor FKHR is strongly induced in skeletal muscle in fasting mice, in mice with streptozotocin-induced diabetes and in mice after treadmill running. Ectopic expression of FKHR enhanced LPL gene expression in C2C12 muscle cells in culture. These results implicate FKHR as an important modulator of lipid metabolism in skeletal muscle.

Identification of a novel human eicosanoid receptor coupled to G(i/o).

We have conducted an in silico data base search for and cloned a novel G-protein-coupled receptor (GPCR) named TG1019. Dot and Northern blotting analyses showed that transcripts of the novel GPCR were expressed in various tissues except brain, and the expression was more intense in liver, kidney, peripheral leukocyte, lung, and spleen than in other tissues. By GTP gamma S binding assay using the TG1019-G alpha(i1)-protein fusion expressed in insect cells, eicosanoids, and polyunsaturated fatty acids such as 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE), 5(S)-hydroperoxy-6E,8Z, 11Z,14Z-eicosatetraenoic acid, and arachidonic acid were identified to exhibit agonistic activities against TG1019. 5-oxo-ETE was the most potent to enhance the specific binding by 6-fold at a maximum effect dose of submicromolar to micromolar order with an ED(50) value of 5.7 nM. Conversely, polyunsaturated fatty acids such as docosahexaenoic acid and eicosapentaenoic acid showed antagonistic activities against TG1019. In Chinese hamster ovary cells transiently expressing TG1019, the forskolin-stimulated production of cAMP was inhibited up to approximately 70% by 5-oxo-ETE, with an IC(50) value of 33 nM. This inhibition was sensitive to pretreatment of the cells with pertussis toxin.