Kazuhiro Kashiwagi

High copy amplification of the aurora-A gene is associated with chromosomal instability phenotype in human colorectal cancers

Chromosomal instability (CIN) is a common but not universal feature of colorectal cancer (CRC); however, the molecular basis for CIN is controversial and poorly understood. Among the many plausible mechanisms proposed for CIN include disruption of G1/S and G2/M checkpoint regulation, and alterations in the spindle checkpoint genes. However, mutations in individual growth regulatory genes are not commonly observed in CRC. Therefore, a more comprehensive analysis of the genes involved in each cell cycle checkpoint regulatory pathway might be required to evaluate a possible role for involvement in CIN. We investigated the presence of high copy amplification of the cyclin E, Aurora-A, Skp2 genes, mutation of ubiquitin ligase CDC4 and promoter methylation of Mad2L1, as well as the expression of the gene products in a panel of 11 human CRC cell lines as well as 48 human CRC specimens. In the cell lines with CIN, we found amplification of the Aurora-A, cyclin E and Skp2 genes, and a mutation in the CDC4 gene, all of which resulted in altered expression of the cognate proteins. In the human CRC tissues, amplification of Aurora-A was frequent (29%), while alterations were rarely observed in cyclin E, Skp2 or CDC4. Aurora-A amplification was strongly associated with a high fractional allelic loss score (p=0.0001), but not with microsatellite instability, nor with the promoter methylation phenotype in these tumors. Our data confirm involvement in the CDC4-cyclin E pathway in the development of the CIN phenotype in human CRC, and find that amplification of the Aurora-A is a common target for disruption of this pathway.

Clinical significance of microsatellite instability in the inflamed mucosa for the prediction of colonic neoplasms in patients with ulcerative colitis

Background and Aim:  Although molecular mechanisms underlying ulcerative colitis (UC)‐associated neoplasms have been studied for years, understanding of these mechanisms remains incomplete and no good predictable marker for development of colonic neoplasms in patients with UC has been established. The aim of this study was to assess if microsatellite instability (MSI) contributes to the development of colonic neoplasms in patients with UC.

Applicability of second-generation colon capsule endoscope to ulcerative colitis: a clinical feasibility study.

Colon capsule endoscopy has already been used for colon visualization and detection of polyps but its applicability to inflammatory bowel disease is still unconfirmed. The aim of this study was to assess the feasibility of evaluating the severity of mucosal inflammation in patients with ulcerative colitis (UC) using a second‐generation colon capsule endoscope (CCE‐2).

Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-α for Crohn's disease in Japan: Evaluation by rapid turnover proteins, and radiologic and endoscopic findings

Background: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)‐α (Infliximab) is extremely valuable in the treatment of Crohns disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohns disease.

NOVEL TECHNIQUE OF ENDOSCOPIC SUBMUCOSAL DISSECTION USING AN EXTERNAL GRASPING FORCEPS FOR SUPERFICIAL GASTRIC NEOPLASIA

Endoscopic submucosal dissection (ESD) for early stage gastric cancer (EGC) has improved the success rate of en bloc resection but results in perforation more often than does endoscopic mucosal resection. We report a novel technique of ESD using an external grasping forceps. A total of 265 lesions with EGC or gastric adenoma were enrolled in this study. Sixteen lesions were located in the upper third portion of the stomach, 114 in the middle third portion, and 135 in the lower third portion. After submucosal injection followed by circumcision of the lesions with a flex knife, the external grasping forceps was introduced with the help of a second grasping forceps and anchored at the margin of the lesion. Oral traction applied with this forceps could elevate the lesion and make the submucosal layer wider and more visible, thereby facilitating dissection of the submucosal layer under direct vision. The mean lesion size was 15.0 mm (range: 5–50 mm). All but 11 lesions (95.8%) could be resected en bloc with free margins. Mean procedure time was 45 min (range: 20–180 min). It was difficult to carry out this procedure when the lesions were located in the cardia, lesser curvature, or posterior wall of the upper third of the gastric body. Bleeding after ESD occurred in 10 patients (3.8%) and perforation occurred in one patient (0.4%). The endoscopic submucosal dissection using an external grasping forceps for superficial gastric neoplasia is efficacious and safe.

Advanced endoscopic submucosal dissection with traction

Endoscopic submucosal dissection (ESD) has been established as a standard treatment for early stage gastric cancer (EGC) in Japan and has spread worldwide. ESD has been used not only for EGC but also for early esophageal and colonic cancers. However, ESD is associated with several adverse events, such as bleeding and perforation, which requires more skill. Adequate tissue tension and clear visibility of the tissue to be dissected are important for effective and safe dissection. Many ESD methods using traction have been developed, such as clip-with-line method, percutaneous traction method, sinker-assisted method, magnetic anchor method, external forceps method, internal-traction method, double-channel-scope method, outerroute method, double-scope method, endoscopic-surgical-platform, and robot-assisted method. Each method has both advantages and disadvantages. Robotic endoscopy, enabling ESD with a traction method, will become more common due to advances in technology. In the near future, simple, noninvasive, and effective ESD using traction is expected to be developed and become established as a worldwide standard treatment for superficial gastrointestinal neoplasias.

A case of Behçet’s disease accompanied by colitis with longitudinal ulcers and granuloma

A 37‐year‐old female presenting with oral and genital ulcers and erythema nodosum on both arms was diagnosed as having Behçet’s disease. The symptoms resolved spontaneously. However, she was admitted to our hospital (Keio University Hospital) several months later because of fever, aphthous ulcers of the oral cavity, lower abdominal pain and frequent diarrhea. A colonoscopic examination revealed multiple ulcers including longitudinal ulcers in the ascending and transverse colon, and histological examination of biopsied specimens demonstrated non‐caseating epithelioid granuloma. Treatment with prednisolone and 5‐aminosalicylic acid was started, and the patient responded well clinically. One month later, a repeated colonoscopy confirmed that the lesions including longitudinal ulcers had disappeared. In this report, we describe our experience of this rare case of Behçet’s disease concomitant with colonic longitudinal ulcers and epithelioid granuloma, and discuss the difficulties in making a differential diagnosis, primarily with regard to Crohn’s disease.

Novel technique of endoscopic submucosal dissection by using external forceps for early rectal cancer (with videos)

BACKGROUND Endoscopic submucosal dissection (ESD) is more difficult for rectal cancer than for gastric cancer. OBJECTIVE To evaluate the feasibility and safety of an ESD procedure by using external forceps for early rectal cancer. DESIGN A case series. SETTING A tertiary medical center. PATIENTS Thirteen patients with early-stage rectal cancer were enrolled. Twelve of the 13 lesions were granular-type laterally spreading tumors and 1 was a protruding tumor. INTERVENTIONS After circumferential incision around the lesion with a dual-knife or a flex-knife, bendable external forceps were introduced with the help of grasping forceps inserted through the accessory channel and anchored at the anal margin of the lesion. After the forceps were bent, they were locked. With gentle anal traction and bending applied with the forceps, the lesion was elevated, the submucosal layer was opened, and the submucosal layer was dissected from the grasped side, facilitating dissection of the submucosal layer under direct vision. MAIN OUTCOME MEASUREMENTS Technical success, complication rates. RESULTS The mean lesion size was 33.0 mm (range 20-80 mm), and the mean operating time was 60 minutes (range 20-150 minutes). All lesions could be resected en bloc with tumor-free margins. Major bleeding after ESD occurred in only 1 patient (7.7%), who did not require blood transfusion. Perforation did not occur in any patient. LIMITATIONS Single-center experience, small number of patients. CONCLUSION This ESD procedure using external forceps for early-stage rectal cancers is feasible and safe.

Modified bowel preparation regimen for use in second-generation colon capsule endoscopy in patients with ulcerative colitis

We have reported that second‐generation colon capsule endoscopy (CCE‐2) might be feasible for assessing the severity of mucosal inflammation in ulcerative colitis (UC). However, because of the low rate (69%) of complete evaluation of the colon and owing to inadequate cleansing. We believe that the method of bowel preparation could be improved by reducing volume. In the present study, we attempted to improve the colon‐cleansing regimen in order to optimize the usefulness of CCE‐2 in the management of UC patients.

Autofluorescence videoendoscopy system using the SAFE-3000 for assessing superficial gastric neoplasia.

Background:  Autofluorescence (AF) videoendoscopy has an advantage over ordinary videoendoscopy in the diagnosis of gastric neoplasias, and the aim of the present study was to evaluate the effectiveness of using the SAFE‐3000 videoendoscopy system to diagnose superficial gastric neoplasias.