宮原 良二

BACKGROUND: Management of small-bowel polyps in Peutz-Jeghers syndrome (PJS) by using fluoroscopic enteroclysis (FE), double-balloon enteroscopy (DBE), and videocapsule enteroscopy (VCE) remains incompletely determined. OBJECTIVE: To evaluate the usefulness of FE, VCE, and DBE and compute the polyp growth rate. DESIGN: Single-center retrospective study. SETTING: Tertiary referral hospital. PATIENTS: Between June 2003 and January 2010, 18 consecutive patients with PJS were enrolled. MAIN OUTCOME MEASUREMENTS: Polyp detection rates among FE, VCE, and DBE, histology of resected polyps, and the polyp growth rate. RESULTS: Total enteroscopy rate was higher at VCE (89%) than at DBE (52%; 27% in patients with ≥2 previous laparotomies and 90% in patients with ≤1 [P = .001]). FE demonstrated fewer polyps than DBE, whereas VCE had detection rates similar to those of DBE. Of 387 DBE-resected and 22 surgically resected polyps, histologic analysis of 110 retrieved polyps showed adenoma or adenocarcinoma in 30.0% of polyps >20 mm and in only 1.3% of polyps ≤20 mm (P < .0001). Multiple linear regression analysis showed that the number of small-bowel polyps >10 mm (X1; P = .0366) and colorectal polyps >5 mm (X2; P = .002) were independent predictors of the growth rate of small-bowel polyps (Y), and a forward stepwise selection model was constructed: Y = 0.136 × X1 + 0.289 × X2 - 0.589 (R(2) = 0.665). LIMITATIONS: Small sample size. CONCLUSIONS: DBE and VCE were useful for the management of small-bowel polyps in PJS. VCE may replace barium examinations for surveillance after polyp resection at intervals depending on the polyp growth rate.

BACKGROUND: Double-balloon endoscopy (DBE) utilizes both oral and anal routes. The proper selection of the initial route is important for more rapid management of obscure gastrointestinal bleeding (OGIB). The aim of this retrospective study was to clarify the accuracy of the transit time of video capsule endoscopy (VCE) to the lesion as a predictive indicator for the decision on the initial DBE route. METHODS: Of 172 patients who underwent both DBE and VCE, 65 who were diagnosed with small-intestinal hemorrhagic lesions by both means were enrolled. The relation between VCE transit time to the lesion and the DBE route by which the lesion was discovered was analyzed, distinguishing between 46 complete and 19 incomplete VCEs. RESULTS: Among the 46 patients with a complete VCE, the transit time and position of the lesion were strongly correlated. The best cutoff values for route selection by the VCE transit time from capsule intake and from the duodenal bulb to the lesion, determined using a receiver operating characteristic (ROC) curve, were 60% and 50%, respectively, of the transit time to the cecum. At that point, the accuracy of route selection was 90% and 94%, respectively. Positions shown by VCE for ileal lesions tended to be more proximal than those shown by surgery. In the 19 patients with incomplete VCEs, the best cutoff for transit time was 180 min from the duodenal bulb. CONCLUSIONS: The VCE transit time was useful for determining the route for DBE in OGIB. This parameter was most accurate when the cutoff value for the selection was half of the small-bowel transit time in the complete VCE examination.

Background/Aims: Colorectal cancer (CRC) was first recognized as a complication of ulcerative colitis (UC) in 1925, and the increased risk has since been confirmed in a multitude of epidemiological studies. To our knowledge, however, all of these studies have been conducted in Western countries. The aim of this study was to identify the clinicopathological features of ulcerative colitis-related CRC in a consecutive series of patients at a single hospital in central Japan. Methodology: 314 (170 males, 144 females, mean age 30) consecutive patients diagnosed with ulcerative colitis were enrolled and investigated for the development of CRC. 240 patients had relapsing-remitting disease, 54 had chronic continuous disease, 16 had experienced one attack only, 2 had the acute fulminating type, and 2 were unknown. With regard to disease extension, 181 cases were of the pan-colitis type, 84 were left-sided colitis, and 42 were proctitis. Two patients (1%) had a family history of colorectal cancer and 45 (14%) were past or current smokers. Results: Colorectal cancer developed in seven patients (male to female ratio of 1:6), which was 2.2% of the total. Average age at the onset of ulcerative colitis was 28 years. Average age at the onset of cancer was 44 years, and average duration of UC at cancer onset was 192 months. Ulcerative colitis was of the pancolitis type in all cases. Three patients (43%) showed the relapse-remitting type and four (57%) the chronic continuing type. Three patients (43%) had a family history of cancer, in particular colorectal cancer in one patient (14%). None of the patients had a history of smoking. The histological type of cancer was well differentiated tubular adenocarcinoma in three patients (43%) and poorly differentiated adenocarcinoma in three patients (43%) each, and endocrine cell carcinoma in one (14%). Conclusions: In this group of Japanese patients, development of colorectal cancer was more likely to occur in patients with ulcerative colitis that was long-standing, and more extensive than left-sided colitis, particularly in those with a family history of colorectal cancer, inflammatory polyps, or dysplasia. CRCs in our patients with UC were often poorly differentiated and had a poor prognosis.

BACKGROUND: Pancreatic endocrine tumors (PETs) develop in relatively few patients, but they are often difficult to diagnose because of their small size and various clinical symptoms. OBJECTIVE: The aim of this study was to investigate the usefulness of EUS combined with contrast enhancement (CE-EUS) in the preoperative localization of PETs and the differentiation between malignant and benign PETs. DESIGN AND SETTING: Single-center retrospective study. PATIENTS: Sixty-two pathologically certified PETs of 41 patients who underwent EUS, multiphasic multidetector computed tomography (MDCT), and transabdominal US at our institute since 2001. INTERVENTIONS: Intravenous injection of US contrast media. MAIN OUTCOME MEASUREMENTS: Comparison of EUS, MDCT, and US in the preoperative identification of PETs, and the characteristic findings of EUS with malignancy. RESULTS: EUS showed high sensitivity (95.1%) in identifying PETs compared with MDCT (80.6%) and US (45.2%). Multivariable logistic regression analysis showed that heterogeneous ultrasonographic texture was the most significant factor for malignancy (OR = 53.33; 95% CI, 10.79-263.58). Most heterogeneous hypoechoic areas and anechoic areas corresponded to hemorrhage or necrosis on pathologic examination. They were identified as filling defects in CE-EUS and were more clearly recognized than in conventional EUS. LIMITATIONS: Retrospective study. CONCLUSION: EUS has higher sensitivity in preoperative localization of PETs compared with MDCT and US. The characteristics of EUS and CE-EUS findings in malignant PETs were clarified, and they will improve the diagnostic accuracy of PETs.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease with relapse and remission. CD patients are admitted to hospital when bowel inflammation flares up severely, which lowers their quality of life. Enteral nutrition (EN) with an elemental diet plays an important role in the treatment for CD patients in Japan, because of its few adverse effects, and it is thought to be effective in maintaining remission. We investigated the effectiveness of EN with an elemental diet with regard to the avoidance of hospitalization. METHODS: A total of 268 patients with CD who visited hospital from 2003-2008 were enrolled. The relationship between the caloric content of an elemental diet and hospitalization as an end-point was examined retrospectively using Cox regression analysis. Cumulative non-hospitalization rates were calculated by the Kaplan-Meier method. RESULTS: Of the 268 patients, 155 received an elemental diet providing 900 kcal/day or more. Among 237 patients with ileal involvement, 135 patients receiving an elemental diet providing 900 kcal/day or more showed a statistically significant improvement in cumulative non-hospitalization rate. Among 31 patients without ileal involvement, in contrast, the cumulative non-hospitalization rate did not differ among those receiving an elemental diet of less or more than 900 kcal/day. CONCLUSION: The use of an elemental diet of 900 kcal/day may be effective in avoiding hospitalization in CD patients with ileal lesions. This diet may be useful in improving the long-term convalescence of these patients.

Restriction-modification (R-M) systems are exclusive to unicellular organisms and ubiquitous in the bacterial world. Bacteria use R-M systems as a defense against invasion by foreign DNA. Analysis of the genome sequences of Helicobacter pylori strains 26 695 and J99 identified an extraordinary number of genes with homology to R-M genes in other bacterial species. All H. pylori strains possess their own unique complement of active R-M systems. All of the methylases that have been studied so far were present in all major human population groupings, suggesting that their horizontal acquisition pre-dated the separation of these populations. The two most strongly conserved methylase genes of H. pylori, hpy IM and hpy IIIM, are both preceded by alternative genes that compete for presence at their loci, and furthermore these genes may be associated with H. pylori pathogenicity. Further study should investigate the roles of H. pylori R-M systems.

BACKGROUND: Analysis of gene expression and gene mutation may add information to be different from ordinary pathological tissue diagnosis. Since samples obtained endoscopically are very small, it is desired that more sensitive technology is developed for gene analysis. We investigated whether gene expression and gene mutation analysis by newly developed ultra-sensitive three-dimensional (3D) microarray is possible using small amount samples from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens and pancreatic juices. METHODS: Small amount samples from 17 EUS-FNA specimens and 16 pancreatic juices were obtained. After nucleic acid extraction, the samples were amplified with labeling and analyzed by the 3D microarray. RESULTS: The analyzable rate with the microarray was 46% (6/13) in EUS-FNA specimens of RNAlater storage, and RNA degradations were observed in all the samples of frozen storage. In pancreatic juices, the analyzable rate was 67% (4/6) in frozen storage samples and 20% (2/10) in RNAlater storage. EUS-FNA specimens were classified into cancer and non-cancer by gene expression analysis and K-ras codon 12 mutations were also detected using the 3D microarray. CONCLUSIONS: Gene analysis from small amount samples obtained endoscopically was possible by newly developed 3D microarray technology. High quality RNA from EUS-FNA samples were obtained and remained in good condition only using RNA stabilizer. In contrast, high quality RNA from pancreatic juice samples were obtained only in frozen storage without RNA stabilizer.

BACKGROUND AND AIM: Relationships between mucin phenotype and malignant potential in gastric cancers have attracted attention. We attempted to assess the possibility of obtaining phenotypic diagnoses by confocal endomicroscopy. METHODS: Confocal images of target lesions were obtained in 29 of 40 patients with gastric cancer. Appearances of the brush border, goblet cells, and gastric foveolar epithelium were investigated with immunohistochemical staining using CD10, MUC2, and human gastric mucin to evaluate phenotypic expression in gastric carcinomas. Confocal images were compared with immunohistochemical findings for goblet cells and brush borders. RESULTS: Both the endoscopists and the pathologist obtained high accuracy rates for differential diagnosis. Sensitivity and specificity for goblet cells were 85.7% and 92.3% (Endoscopist A), and 85.7% and 88.5% (Endoscopist B). The kappa-value for correspondence between two endoscopists for the diagnosis of goblet cells in confocal images was 0.73. Sensitivity and specificity for the brush border were 93.8% and 91.7% (Endoscopist A), and 81.3% and 91.7% (Endoscopist B). The kappa-value for correspondence between two endoscopists for diagnosis of the brush border in confocal images was 0.79. Intestinal phenotypic gastric cancers show a brush border, goblet cells, or both. Sensitivity and specificity for the intestinal phenotype in confocal endomicroscopy were 90.9% and 77.8% (Endoscopist A), and 86.4% and 83.3% (Endoscopist B). CONCLUSION: The confocal endomicroscopic diagnosis of the mucin phenotype in gastric cancers was limited to intestinal and mixed phenotypes, but may be useful for the diagnosis of mucin phenotype and differential diagnosis.

Backgrounds/Aims: At the time of interpretation of Video Capsule Endoscopy (VCE), we sometimes see the characteristic anatomic landmarks like the major papilla of the duodenum. However, the frequency of these images and the factor affecting VCE transit are not well known. The aim of the study is to disclose the characteristics of the advance of VCE through the whole gastrointestinal tract. Methodology: We interpreted retrospectively the details of VCE with 100 patients again and analyzed the transit of VCE, significant factors affecting VCE&apos;s transit, and frequency of the anatomic landmarks observed. Results: The median esophageal transit time was 5.0 seconds; average gastric and small bowel transit times were 48.0 and 291.7 minutes. &apos;In-patient&apos; and &apos;gastric transit time&apos; were detected by statistical analysis as significant factors affecting VCE&apos;s transit to the cecum. The esophageal-cardiac junction, pyloric ring seen from the duodenal bulb, major papilla of the duodenum, ileo-cecal valve seen from the cecum, vermiform appendix, and anal canal were found with the following rates: 17, 33, 18, 20, 3, and 2 %. Conclusions: Present VCE has the limitations. This study may be the preliminary results for VCE investigating the whole gastrointestinal tract in the near future.

BACKGROUND AND AIM: Confocal endomicroscopy is ultra-high-magnification endoscopy with histological observation during ongoing endoscopy. We planned a pilot study of the diagnosis of the depth of esophageal cancer using confocal endomicroscopy for treatment strategies. METHODS: Patients had 14 superficial esophageal cancers and one dysplasia. The depth of neoplasms in 15 lesions was confirmed by endoscopic mucosal resection or surgery. We examined the rate of delineation and compared results of confocal imaging with histological findings. We classified two cellular and three microvascular patterns on confocal endomicroscopic images: CP-N for normal squamous mucosa and CP-Ca for cancerous lesion; VP-type A for normal squamous mucosa; VP-type B for T1a-EP and T1a-LPM cancers; and VP-type C for T1a-MM or a more invasive cancer pattern. We measured diameters of microvessels for the three patterns of confocal endomicroscopic images and histological specimens. RESULTS: The rate of delineation was 73.3% (11/15) for esophageal cancer. The results of confocal imaging coincided well with microvessel distribution on horizontal histology. Two endoscopists blindly diagnosed the two types by cellular pattern and the three types by vascular pattern: their overall accuracies were 96% and 89% for the cellular pattern and 85% and 85% for the vascular pattern, respectively. The k value of the cellular pattern and the vascular pattern diagnosis was 0.84 and 0.75, respectively. CONCLUSION: Scoring and quantification of confocal endomicroscopic images may be useful for the differential diagnosis and diagnosis of superficial invasion by squamous cell carcinoma.

Contrast-enhanced endoscopic ultrasonography (CE-EUS) and EUS-elastography are cutting-edge diagnostic modalities for pancreatic disorders. Each pancreatic disorder has characteristic hemodynamics. CE-EUS uses color Doppler flow imaging to classify pancreatic lesions into a spectrum of solid and cystic patterns. Although there is overlap in the patterns generated by specific types of tumors, some types of tumors tend to produce distinct flow images. EUS-elastography can assess tissue hardness by measuring its elasticity. This parameter appears to correlate with the malignant potential of the lesions. Tissue elasticity studies can provide information on both its pattern and distribution. The former is the conventional method of morphologic diagnosis, but it is restricted to observations made in a region of interest. The latter is an unbiased analysis that can be performed by image analysis software and is theoretically constant, regardless of regions of interest. The evolving modalities of CE-EUS and EUS-elastography might provide clinical utility in the diagnosis of pancreatic disorders.