Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid "cushion" for endoscopic resection of colorectal mucosal neoplasms: A prospective multi-center open-label trial

<p>Abstract</p> <p>Background</p> <p>Sodium hyaluronate (SH) solution has been used for submucosal injection in endoscopic resection to create a long-lasting submucosal fluid "cushion". Recently, we proved the usefulness and safety of 0.4% SH solution in endoscopic resection for gastric mucosal tumors. To evaluate the usefulness of 0.4% SH as a submucosal injection solution for colorectal endoscopic resection, we conducted an open-label clinical trial on six referral hospitals in Japan.</p> <p>Methods</p> <p>A prospective multi-center open-label study was designed. A total of 41 patients with 5–20 mm neoplastic lesions localized in the colorectal mucosa at six referral hospitals in Japan in a single year period from December 2002 to November 2003 were enrolled and underwent endoscopic resection with SH. The usefulness of 0.4% SH was assessed by the <it>en bloc </it>complete resection and the formation and maintenance of mucosal lesion-lifting during endoscopic resection. Safety was evaluated by analyzing adverse events during the study period.</p> <p>Results</p> <p>The usefulness rate was high (82.5%; 33/40). The following secondary outcome measures were noted: 1) steepness of mucosal lesion-lifting, 75.0% (30/40); 2) intraoperative complications, 10.0% (4/40); 3) time required for mucosal resection, 6.7 min; 4) volume of submucosal injection, 6.8 mL and 5) ease of mucosal resection, 87.5% (35/40). Two adverse events of bleeding potentially related to 0.4% SH were reported.</p> <p>Conclusion</p> <p>Using 0.4% SH solution enabled sufficient lifting of a colorectal intramucosal lesion during endoscopic resection, reducing the need for additional injections and the risk of perforation. Therefore, 0.4% SH may contribute to the reduction of complications and serve as a promising submucosal injection solution due to its potentially superior safety in comparison to normal saline solution.</p

Upregulation of HOXA10 in gastric cancer with the intestinal mucin phenotype: reduction during tumor progression and favorable prognosis

Gastric cancer (GC) is one of the most common malignancies worldwide. Better knowledge of the changes in gene expression that occur during gastric carcinogenesis may lead to improvements in diagnosis, treatment and prevention. In this study, we screened for genes upregulated in GC by comparing gene expression profiles from microarray and serial analysis of gene expression and identified the HOXA10 gene. The aim of the present study was to investigate the significance of HOXA10 in GC. Immunohistochemical analysis demonstrated that 221 (30%) of 749 GC cases were positive for HOXA10, whereas HOXA10 was scarcely expressed in non-neoplastic gastric mucosa except in the case of intestinal metaplasia. Next, we analyzed the relationship between HOXA10 expression and clinicopathological characteristics. HOXA10 expression showed a significant inverse correlation with the depth of invasion and was observed more frequently in the differentiated type of GC than in the undifferentiated type of GC. HOXA10 expression was associated with GC with the intestinal mucin phenotype and correlated with CDX2 expression. Furthermore, the prognosis of patients with positive HOXA10 expression was significantly better than in the negative expression cases. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide and wound healing assay revealed that knockdown of HOXA10 in GC cells by short interfering RNA transfection significantly increased viability and motility relative to the negative control, indicating that HOXA10 expression inhibits cell growth and motility. These results suggest that expression of HOXA10 may be a key regulator for GC with the intestinal mucin phenotype

Novel colorectal endoscopic in vivo imaging and resection practice: a short practice guide for interventional endoscopists

Colorectal cancer remains a leading cause of cancer death in the UK. With the advent of screening programmes and developing techniques designed to treat and stage colorectal neoplasia, there is increasing pressure on the colonoscopist to keep up to date with the latest practices in this area. This review looks at the basic principles behind endoscopic mucosal resection and forward to the potential endoscopic tools, including high-magnification chromoscopic colonoscopy, high-frequency miniprobe ultrasound and confocal laser scanning endomicroscopic colonoscopy, that may soon become part of routine colorectal cancer management

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Novel diagnostic and therapeutic techniques for surveillance of dysplasia in patients with inflammatory bowel disease

The risk for developing dysplasia and colorectal cancer in patients with longstanding inflammatory bowel disease (IBD) involving the colon is well documented. Random biopsies during white-light, standard-definition colonoscopy (33 to 50 biopsies) with or without dye spraying chromoendoscopy has been the recommended strategy in North America to detect dysplastic lesions in IBD. However, there are several limitations to this approach including poor physician adherence, poor sensitivity, increased procedure time and considerable cost. The new generation of high-definition endoscopes with electronic filter technology provide an opportunity to visualize colonic mucosal and vascular patterns in minute detail, and to identify subtle flat, multifocal, polypoid and pseudopolypoid neoplastic and non-neoplastic lesions. The application of these new technologies in IBD is slowly being adopted in clinical practice. In addition, the advent of confocal laser endomicroscopy provides an opportunity to explore real-time histology, thus redefining the understanding and characterization of the lesions in IBD. There is emerging evidence that serrated adenomas are also associated with longstanding IBD colitis and may be recognized as another important contributing factor to colorectal cancer development. The circumscribed neoplastic lesions can be treated using endoscopic therapeutic management such as mucosal resection or, especially, endoscopic submucosal dissection. This may replace panproctocolectomy in selected patients. The authors review the potential of these techniques to transform endoscopic diagnosis and therapeutic management of dysplasia in IBD

In situ gelation properties of a collagen&ndash;genipin sol with a potential for the treatment of gastrointestinal ulcers

Takefumi Narita,1 Shunji Yunoki,1 Yoshimi Ohyabu,1 Naohisa Yahagi,2 Toshio Uraoka3 1Biotechnology Group, Tokyo Metropolitan Industrial Technology Research Institute, Koto-ku, 2Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Shinjuku-ku, 3Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Meguro-ku, Tokyo, Japan Abstract: We investigated the potential of collagen&ndash;genipin sols as biomaterials for treating artificial ulcers following endoscopic submucosal dissection. Collagen sol viscosity increased with condensation, allowing retention on tilted ulcers before gelation and resulting in collagen gel deposition on whole ulcers. The 1.44% collagen sols containing genipin as a crosslinker retained sol fluidity at 23&deg;C for &gt;20&nbsp;min, facilitating endoscopic use. Collagen sols formed gel depositions on artificial ulcers in response to body temperature, and high temperature responsiveness of gelation because of increased neutral phosphate buffer concentration allowed for thick gel deposition on tilted ulcers. Finally, histological observations showed infiltration of gels into submucosal layers. Taken together, the present data show that genipin-induced crosslinking significantly improves the mechanical properties of collagen gels even at low genipin concentrations of 0.2&ndash;1&nbsp;mM, warranting the use of in situ gelling collagen&ndash;genipin sols for endoscopic treatments of gastrointestinal ulcers. Keywords: collagen, genipin, in-situ gel, fibril formation, ulcer dressing&nbsp

High-density carrier-accumulated and electrically stable oxide thin-film transistors from ion-gel gate dielectric

The use of indium-gallium-zinc oxide (IGZO) has paved the way for high-resolution uniform displays or integrated circuits with transparent and flexible devices. However, achieving highly reliable devices that use IGZO for low-temperature processes remains a technological challenge. We propose the use of IGZO thin-film transistors (TFTs) with an ionic-liquid gate dielectric in order to achieve high-density carrier-accumulated IGZO TFTs with high reliability, and we discuss a distinctive mechanism for the degradation of this organic-inorganic hybrid device under long-term electrical stress. Our results demonstrated that an ionic liquid or gel gate dielectric provides highly reliable and low-voltage operation with IGZO TFTs. Furthermore, high-density carrier accumulation helps improve the TFT characteristics and reliability, and it is highly relevant to the electronic phase control of oxide materials and the degradation mechanism for organic-inorganic hybrid devices