Naoki Ohmiya

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.

[Purpose] Recently, video capsule endoscopy (VCE) and double-balloon endoscopy (DBE) have been introduced into clinical practice for obscure gastrointestinal bleeding (OGIB). Both are said to be very useful. This study assessed the VCE images and effectiveness of VCE. [Methods] 116 patients who had both VCE and DBE for OGIB were enrolled in the study. The diagnosis or findings obtained by VCE were compared to the final diagnosis, and the results and the efficacy of VCE were assessed. [Results] The VCE positive finding rate was 62.9%, but a definitive diagnosis was made in only 13 patients (11.2%) using VCE. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 76.7% , 74.2 %, 87.5% , 57.5% , and 76.0% , respectively. The accuracy of VCE diagnosis was around 76%. [Conclusion] It is difficult to make a definitive diagnosis based on VCE findings. However, VCE findings play a "guide role" to the definitive diagnosis.

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.

BACKGROUND: Double-balloon endoscopy (DBE) and videocapsule endoscopy (VCE) have been useful in managing obscure GI bleeding (OGIB). OBJECTIVE: This study compared diagnostic yields of OGIB between DBE and VCE, and evaluated the outcome after DBE. DESIGN: A single-center retrospective study. SETTING: A tertiary-referral hospital. PATIENTS: Between June 2003 and February 2007, 162 consecutive patients with OGIB were enrolled and treated. The diagnostic yield between VCE and DBE was compared in 74 patients. MAIN OUTCOME MEASUREMENTS: Comparison of diagnostic yields between DBE and VCE, and the prognosis after DBE. RESULTS: Of 162 patients, 95 (59%) were diagnosed with small-bowel diseases. They were treated by medical, enteroscopic, and surgical therapies (n = 35, 30, and 30, respectively). A comparison of the overall diagnostic yield between DBE (64%) and VCE (54%) was not significantly different. The 4 VCE-positive DBE-negative cases were because of inaccessibility of DBE. The 11 VCE-negative DBE-positive cases were because of a failure to detect lesions in the proximal small bowel and the Roux-en-Y loop, and because of diverticula. At a median follow-up of 555 days after DBE, 11 patients with small-bowel diseases developed rebleeding; all were treated by enteroscopic or medical therapies. Vascular diseases, comorbidities, especially portal hypertensive disease and chronic renal failure that required hemodialysis, and severe anemia (Hb </=7.0 g/dL) were associated with rebleeding. LIMITATIONS: A retrospective comparative study, and participation bias. CONCLUSIONS: A complementary combination between DBE and VCE was useful for the management of OGIB. In particular, patients with vascular disease, comorbidities, and severe anemia should be intensively treated.

OBJECTIVES: Dendritic cell (DC) therapy frequently induces a measurable immune response. However clinical responses are seen in a minority of patients, presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes (CTLs) capable of eradicating tumor cells. To increase therapeutic efficacy of DC-based vaccination, we have undertaken the first clinical trial involving a combination therapy of gemcitabine (GEM) with immunotherapy for patients with inoperable locally advanced pancreatic cancer. METHODS: Patients (n = 5) received the treatment course, which consisted of intravenous GEM administration at 1000 mg/m (day 1) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody (CD3-LAKs) (day 4), at 2-week intervals. RESULTS: No serious treatment-related adverse events were observed during the study period. Three of the 5 patients demonstrated effective responses to this clinical trial; 1 had partial remission and 2 had long stable disease more than 6 months. In the patient with partial remission, it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs. CONCLUSION: This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs.

BACKGROUND AND AIM: Intraductal papillary mucinous neoplasms (IPMNs)have a wide pathologic spectrum and it is difficult to differentiate malignant from benign tumors. The aim of this study was to identify predictors of malignancy using contrast-enhanced endoscopic ultrasound (CE-EUS). SUBJECTS AND METHODS: In our institute, main duct type and mixed type IPMNs, branch duct type IPMNs with mural nodules, and IPMNs with coexistent invasive ductal cancer were indications for surgery. Eighty-seven IPMNs (14 main duct, 25 mixed, and 48 branch duct type) were resected and CE-EUS findings were compared with pathologic findings. Twelve clinicopathological variables and CE-EUS morphologic findings were assessed.Mural nodules defined as blood flow supplied protrusions were classified into 4 types: type I: low papillary nodule, type II: polypoid nodule, type III:papillary nodule, and type IV: invasive nodule. RESULTS: Forty-two, 26, 16, and 3 were pathologically diagnosed as adenoma,noninvasive carcinoma, invasive IPMNs, and coexistent invasive ductal cancer, respectively. Multivariable logistic regression analysis showed that types III/IV mural nodule (odds ratio = 10.8; 95% confidential intervals = 2.75-56.1) and symptomatic IPMNs (odds ratio = 4.31; 95% confidential intervals = 1.37-14.7) were significant for malignancy. For mural nodule diameter, invasive IPMNs were significantly larger, but types III and IV mural nodules were more frequently associated with malignancy, particularly invasive cancer, at 88.9% and 91.7%, respectively. The diagnosis of IPMNs with types III or IV mural nodule as malignant resulted in a sensitivity of 60%, specificity of 92.9%, and accuracy of 75.9%. CONCLUSIONS: In conclusion, new morphologic criteria were useful to identify the malignant potentials of IPMNs.

OBJECTIVES: Pancreatic cystic (PC) lesions are not necessarily rare, and it is important to diagnose whether PC lesions are neoplastic such as intraductal papillary mucinous neoplasm (IPMN) because of its malignant potential. Reports on PC lesions in hemodialysis (HD) patients are remarkably limited. The aim of this study was to clarify the prevalence and characteristics of PC lesions in HD patients. METHODS: We reviewed 1012 consecutive HD patients and 11,100 patients (controls) without renal disease who underwent transabdominal ultrasonography between January 2003 and December 2005. Patients' sex ratio (female-to-male) was less, and the age was older in HD patients. Clinical findings of these patients were examined. RESULTS: The prevalence both of PC lesions and IPMNs was significantly higher in HD patients than in controls (9.3% vs 1.3% and 2.8% vs 0.2%, P < 0.0001). The incidence of IPMNs in HD patients with PC lesions was higher than that in controls with PC lesions (29.8% vs 17.0%, P = 0.021). Multivariate logistic regression analysis revealed that the odds ratios of PC lesions and IPMNs were 6.38 (95% confidence interval, 4.82-8.45) and 9.39 (95% confidence interval, 5.36-16.49) in HD patients compared with controls. CONCLUSION: The prevalence of PC lesions in HD patients is higher, and HD patients with PC lesions have high prevalence of IPMNs.

OBJECTIVES: We investigated the feasibility of using real-time tissue elastography (EG) with transcutaneous ultrasonography (EG-US) for pancreatic diseases. METHODS: A preliminary study (phase I) and a prospective (phase II) study were conducted. Phase I: subjects were 10 volunteers, 5 with cancer, 2 with endocrine tumor, 5 with chronic pancreatitis, 14 with intraductal papillary-mucinous neoplasm. To determine the characteristic EG images (diagnostic criteria for phase II), B-mode images were compared with EG images and histopathologic findings. Phase II: 53 consecutive patients were enrolled. The visualization rate by EG-US in lesions visualized by B mode was assessed, and the correct diagnosis rate by B mode alone (B diagnosis) or in combination with EG-US was evaluated. RESULTS: Phase I: normal parenchyma was a homogeneous color. In cancer, EG-US showed a markedly hard area with soft spots inside. Endocrine tumor was uniform and soft comparable to parenchyma. Chronic pancreatitis showed a mixture of various colors. Phase II: we identified 77.4% (41/53) of the lesions and observed 60.0% (15/25) of the cancers, 100% (3/3) of the endocrine tumor, 92.0% (23/25) of the cases of chronic pancreatitis cases on EG-US. The B-diagnosis rates ranged from about 70% to 80%. The diagnosis rates of the combination were more than 90% of lesions of each type. CONCLUSIONS: The EG-US is feasible in the diagnosis of pancreatic diseases.

BACKGROUND: Small-bowel obstruction (SBO) sometimes remains undiagnosed and untreatable without surgery. OBJECTIVE: To evaluate the diagnostic yields of SBO between double-balloon endoscopy (DBE) and fluoroscopic enteroclysis (FE), and the outcome of enteroscopic treatment. DESIGN: Single-center, retrospective, and prospective study. SETTING: Tertiary-referral hospital. PATIENTS: Between June 2003 and July 2007, 66 consecutive patients with SBO were enrolled, investigated, and treated. MAIN OUTCOME MEASUREMENTS: A comparison of diagnostic yields between DBE and FE, and the prognosis after enteroscopic balloon dilation. RESULTS: The diagnostic yield of DBE for SBO (95%) was higher than that of FE (71%) in 59 patients who underwent both examinations (P= .004). The first treatment included 27 surgical, 25 enteroscopic, and 14 conservative therapies. Of 47 enteroscopic balloon dilation procedures in 22 patients, 45 (96%) were successful. Of 16 patients with Crohn's disease, 11 (69%) remained asymptomatic over the postdilation follow-up period but 5 relapsed: 2 recovered by repeated dilations, but 3 required surgery. Of 6 patients who had diseases other than Crohn's disease, 4 (67%) remained asymptomatic but 2 relapsed: one with remission of metastasis recovered by repeated dilations, and one with ischemic enteritis required surgery. Anastomotic stricture was an independent marker of the symptom-free outcome (hazard ratio 0.037-0.084, P= .037). Two acute pancreatitis, one perforation, and one exacerbation of SBO complications occurred. LIMITATIONS: Small sample size and participation bias. CONCLUSIONS: DBE was useful for the diagnosis of SBO. Balloon dilation is considered an alternative to surgery in patients with fibrotic strictures both related and unrelated to Crohn's disease.

BACKGROUND/AIMS: Matrix metalloproteinases (MMPs) are endopeptidases which perform important functions in extracellular matrix remodeling, cell proliferation, and inflammatory processes. Here, we compared MMP-3 levels with those of tissue inhibitor of metalloproteinases (TIMP)-1 and several inflammatory cytokines in gastric ulcer (GU) patients. METHODS: This study enrolled 50 patients with GU and 6 with functional dyspepsia (FD). Samples of gastric mucosa from the antrum and the ulcer site were harvested from GU patients and of antral mucosa alone from FD patients during upper gastrointestinal endoscopy. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-3, TIMP-1, IL-1beta, IL-6, and IL-8. RESULTS: All GU patients were positive for Helicobacter pylori, while all FD patients were negative. Antral levels of TIMP-1, IL-1beta, IL-6, and IL-8 were significantly higher in GU than FD patients. Further, MMP-3 levels were significantly higher in GU patients at the ulcer site than in the antrum, and had a significantly positive correlation with TIMP-1, IL-1beta, IL-6, and IL-8. CONCLUSION: MMP-3 levels were significantly higher at the ulcer site than in the antrum, suggesting that MMP-3 may perform an important function in gastric ulcer healing.

AIM: The aim of the present study was to use video capsule endoscopy (VCE) to objectively evaluate bowel movements in patients with irritable bowel syndrome (IBS) compared with healthy volunteers. METHODS: Subjects were nine healthy volunteers (group A) and five IBS patients (group B) whose VCE reached the cecum within the examination time. As the darkest component in an image of VCE is the lumen, we regarded real movements of the intestine observed in the images as the changes of luminal movement, and analyzed them. We trimmed the luminal edge, counted pixels in the lumen and the low brightness area (LBA), of all VCE images and compared them between the groups. RESULTS: There was no difference in the frequency observed in the LBA corresponding to the luminal area between the groups. As for the average volume of the LBA found in an image, it was 1702 pixels in healthy persons versus 305 in IBS patients (P = 0.21) and in healthy persons it tends to be larger. We drew a graph of LBA by time-course. A periodic change in the volume of LBA was found in eight of nine (88.9%) healthy persons over time, but in only two of five (40.0%) IBS patients (P = 0.62). Using endoscopy, a difference in the bowel movement between groups A and B could be evaluated objectively. CONCLUSION: The present study presents the possibility of a new technique to evaluate functional bowel disorders objectively using an endoscopic procedure.

BACKGROUND AND AIMS: Little information is available regarding the prevention and treatment of small intestinal mucosal injuries caused by non-steroidal anti-inflammatory drugs (NSAIDs). We planned a pilot study to investigate the protective effects of geranylgeranylacetone (GGA) against NSAID-induced small intestinal injuries using video capsule endoscopy (VCE). SUBJECTS AND METHODS: Ten healthy male volunteers took oral GGA 300 mg/day (regimen A) or placebo (regimen B) in addition to diclofenac 75 mg/day + rabeprazole 20 mg/day for 7 days. We conducted a cross-over trial of regimens A and B with a 2-week washout period. All subjects underwent VCE before and after each administration period, and were evaluated for NSAID-induced gastric and small intestinal mucosal lesions. RESULTS: The number of mucosal lesions (erosions, ulcers and a red spot with possible bleeding) detected in both stomach and small bowel changed between prior to and immediately after administration period, with significantly fewer lesions for regimen A after administration period (mean +/- SD A:B = 2.6 +/- 3.2:9.5 +/- 8.5; p = 0.027). CONCLUSIONS: Combination therapy with GGA and rabeprazole reduced the incidence of gastroenteropathy induced by 1-week administration of diclofenac. Our findings suggest this therapy as a candidate for protecting patients on long-term NSAID therapy.

BACKGROUND: Helicobacter pylori infection induces a biased T helper type 1 (Th1) response that produces IFN-gamma and Fas ligand (FasL). Th1 cytokines are associated with apoptosis in the gastric epithelial cells. AIM: We aimed to define the role of the recently cloned IL-18, a IFN-gamma inducing factor, in gastric mucosal injury induced by H. pylori infection. METHODS: Twenty-seven gastric ulcer (GU) patients and 20 functional dyspepsia (FD) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used for histological examination, H. pylori culture and in-situ stimulation for 48 h in the presence of 10 microg/ml phytohemagglutinin-P. IL-18, IFN-gamma, and soluble FasL (sFasL) levels in culture supernatants were assayed by the enzyme-linked immunosorbent assay method. IL-18, IL-1beta-converting enzyme (ICE) and caspase-3 were evaluated by western blotting in gastric cancer cell lines (MKN45) cocultured with H. pylori. RESULTS: All 27 GU patients and ten out of 20 FD patients were found to be H. pylori-positive, whereas ten FD patients were H. pylori-negative. Antral mucosal tissues from H. pylori-positive FD patients contained (P<0.01) higher levels of IL-18, IFN-gamma, and sFasL than those from uninfected FD patients. IL-18, IFN-gamma, and sFasL levels at the ulcer site were significantly (P<0.01) higher than those at distant sites in the antrum. A significant relationship was seen between IL-18 and IFN-gamma levels at the ulcer site (r=0.7, P<0.01). H. pylori eradication led to a significant decrease in the levels of IL-18, IFN-gamma, and sFasL at the ulcer site. Western blotting showed that IL-18, ICE, and caspase-3 were activated in gastric cancer cell lines cocultured with H. pylori. CONCLUSION: This study suggests that H. pylori infection enhanced mucosal injury by stimulating a Th1 response, which was mediated by IL-18 upregulation as well as activation of ICE and caspase-3.

BACKGROUND: The chronic inflammatory process in patients with Crohn's disease (CD) may affect any part of the gastrointestinal (GI) tract. The pathogenesis of CD involves immunological abnormalities, including deficient or excessive expression of cytokines. We examined Helicobacter pylori infection status, endoscopic and histopathological findings, and cytokine production in the duodenum of CD patients in comparison with controls. METHODS: Thirty-eight CD patients underwent diagnostic upper GI endoscopy. Twelve age- and sex-matched health checkup examinees were used as controls. H. pylori infection status was assessed by the (13)C-urea breath test. At the time of endoscopy, two biopsy specimens each were obtained from the second portion of the duodenum, one for hematoxylin-eosin staining and immunohistochemical analysis with anti-CD68 antibody, and one for in vitro organ culture. Interleukin (IL)-6 and -8 levels were measured in organ culture supernatant by enzyme-linked immunosorbent assay. RESULTS: H. pylori infection was significantly (P<0.05) more frequent in controls (42%) than in CD patients (8%). In the duodenum, erosions or ulcers were more frequent in CD patients (53%) than in controls (8%). Mononuclear cell infiltration in the duodenum was more severe in CD patients than in controls and IL-6 production was higher, whereas IL-8 production showed no significant difference. CD68+ cells in the duodenum were more prominent in CD patients than in controls. CONCLUSIONS: H. pylori infection is unlikely in CD patients, but they show immunological abnormalities in the duodenum, possibly from innate immune responses.

BACKGROUND: Confocal endomicroscopy is a new technology that provides microscopic images of cellular morphology in the gastrointestinal tract in vivo. In particular, confocal microendoscopy allows histological diagnosis during the endoscopic examination. We examined patients with ulcerative colitis (UC) using confocal endoscopy and investigated the features of confocal endomicroscopic images of inflamed and non-inflamed rectal mucosa. METHODS: Seventeen patients with UC, 12 in the active phase and 5 in the non-active phase, and 14 non-UC control patients who had colon polyps or colon cancer underwent colonoscopy, during which fluorescence images of the rectal mucosa were obtained with confocal endomicroscopy. Histological findings of rectal biopsy specimens were compared with the microendoscopic images. RESULTS: Confocal microendoscopy allowed observation of cellular and subcellular structures. The crypts of normal colonic mucosa were small, round and regularly arranged, and the crypt lumens of the colonic glands were small and round. The crypts of colonic mucosa in non-active UC were small, round and slightly irregular in arrangement and the crypt lumens of the colonic glands were small and round. Inflammatory cells and capillaries were visible in the lamina propria. The crypts of colonic mucosa in active UC were large, variously shaped and irregular in arrangement. The crypt lumens of the colonic glands were large and the crypt structure could not be recognized in some areas. Numerous inflammatory cells and capillaries were visible in the lamina propria. CONCLUSIONS: Images taken with the confocal microendoscope provided information that was equivalent to conventional histology, and improve our understanding of the differences in rectal tissues (crypts, capillaries and inflammatory cells) between normal controls and active and non-active UC patients during ongoing endoscopy.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct low-grade lymphoma that often regresses upon Helicobacter pylori eradication. It was reported that the chemokine receptor CXCR3 is expressed not only on activated T cells, but also on MALT lymphoma cells, and that CXCR3-positive B lymphocytes migrate or home to the MALT of MALT lymphoma. In the present study, we aimed to elucidate the correlation between CXCR3 expression and the clinicopathological features of gastric MALT lymphoma, and to determine whether CXCR3 expression was predictive of responsiveness to H. pylori eradication. Sixty-seven patients with gastric MALT lymphoma in a single-center study were treated with H. pylori eradication therapy. We evaluated the correlation of CXCR3 expression with response to H. pylori eradication therapy by logistic regression stratified according to potential confounders. Immunohistochemical analysis revealed that 28 of 67 cases (42%) were positive for CXCR3 expression. CXCR3 expression was significantly more prevalent in those without H. pylori infection, advanced-stage disease, and in those with API2-MALT1 fusion. In overall analysis, those with CXCR3 expression showed a significantly increased risk of non-responsiveness to H. pylori eradication therapy (odds ratio = 28.6; 95% confidence interval 5.70-143.4) compared to those without CXCR3 expression. This higher risk was observed consistently regardless of sex, API2-MALT1 fusion, H. pylori infection, or clinical stage. We showed that CXCR3 expression was an independent predictive factor for non-responsiveness to H. pylori eradication therapy in patients with gastric MALT lymphoma.

In 2001, the new endoscopic procedures for small bowel, video capsule endoscopy (VCE) and double balloon enteroscopy (DBE), were introduced in clinical routine. Those devices were the breakthrough for the imaging examination of small bowel. And each device has many different characteristics as the approach into the target organ. But the characteristic common to both is the ability having a total observation of small bowel with the high rate. The understanding of the small bowel disease is being deeper by diagnosis in collaboration with VCE and DBE recently. VCE is superior as the first examination for small bowel and DBE is useful for detailed examination and endoscopic therapy.

Meckel's diverticulum and duplication of the alimentary tract are very important as the congenital anomalies of ileum. As these two diseases have the common clinical characteristics such as sex, age, symptoms and complications, it is often difficult to diagnose before surgery. This report describes and compared the clinical aspects of Meckel's diverticulum and duplication of the alimentary tract, which were experienced at Nagoya University Hospital and Kariya Toyota General Hospital.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. Some UC patients remain refractory to conventional medical treatment while, in others, the effectiveness of drugs is limited by side-effects. Recently, cyclosporine and leukocyte removal therapy have been used for refractory UC patients. To predict the efficacy of these therapies is important for appropriate selection of treatment options and for preparation for colectomy. Endoscopy is the cornerstone for diagnosis and evaluation of UC. Endoscopic parameters in patients with severe or refractory UC may predict a clinical response to therapies, such as cyclosporine or leukocyte removal therapy. As for the patients with quiescent UC, relapse of UC is difficult to predict by routine colonoscopy. Even when routine colonoscopy suggests remission and a normal mucosal appearance, microscopic abnormalities may persist and relapse may occur later. To more accurately identify disease activity and to predict exacerbations in UC patients with clinically inactive disease is important for deciding whether medical treatment should be maintained. Magnifying colonoscopy is useful for the evaluation of disease activity and for predicting relapse in patients with UC.

Until recently, the diagnosis of small bowel disease by the endoscopic procedure was difficult due to the organ characteristics. Video capsule endoscopy (VCE), which enables the whole small bowel observation safely and noninvasively, was introduced in 2000 and these problems are now being resolved. The best adaptation of VCE is the diagnosis of obscure gastrointestinal bleeding (OGIB) and its diagnostic value is superior to other imagings. For OGIB, the algorithm of the diagnosis has been established. In addition, it is useful for the inspection of small bowel tumor, and the diagnostic rate was 84.1% in our study. But VCE sometimes misses small bowel tumors, and we should recognize that. Besides, the quantitative diagnosis of the tumor is often difficult, and our diagnostic rate was 45.5%. Now, VCE has a limitation in terms of detailed diagnosis and the improvement of the mechanical systems. The complications of VCE are aspiration and retention of VCE. The aspiration is rare, but retention occurs in 1-2% of the cases. Preventive care is important. VCE will be a reliable procedure in future for small bowel disorders together with double balloon endoscopy, detailed diagnosis and therapeutic procedure introduced in 2001.

BACKGROUND: Although obscure gastrointestinal bleeding cannot be detected by colonoscopy or upper endoscopy, wireless video capsule endoscopy (VCE) is capable of imaging it. Few data are available on medical therapy for patients with nonsteroidal anti-inflammatory drug (NSAID)-induced small-intestinal mucosal injuries. The aim of this study was to compare prevention by rebamipide and placebo of NSAID-induced smallintestinal injury in healthy subjects. METHODS: Ten healthy subjects who provided written informed consent were enrolled. Rebamipide or placebo plus diclofenac was administered with omeprazole for 7 days, and for an additional 7-day period with treatments reversed in the same subjects, with a 4-week washout period between treatments. VCE of the small intestine was performed four times, before and after each of the two study periods. RESULTS: The number of subjects with small-intestinal mucosal injuries was higher in the placebo group (8/10) than in the rebamipide group (2/10) (P = 0.023). Two cases of ulcer and one of bleeding were observed in the placebo group, while no ulcer or bleeding was observed in the rebamipide group. CONCLUSIONS: Rebamipide had significantly higher efficacy than placebo in preventing NSAID-induced small-intestinal mucosal injury.

BACKGROUND/AIMS: Ulcerative colitis (UC) mainly affects the colon and rectum, whereas the chronic inflammatory process in Crohn's disease (CD) can affect any part of the gastrointestinal tract. Recently, however, upper gastrointestinal lesions have been reported in UC patients. In this study, we investigated the immunological status of the stomach in UC or CD patients. METHODS: 26 patients each with UC, CD or functional dyspepsia (FD) underwent diagnostic upper gastrointestinal endoscopy, and biopsy specimens were obtained from the gastric antrum. The contents of interleukin (IL)-6 and IL-8 in the organ culture supernatants of antral mucosal tissues were measured with enzyme-linked immunosorbent assay. RESULTS: Endoscopically abnormal findings in the stomach were more frequent in CD than in UC or FD patients. Mononuclear cell infiltration and IL-6 production in the gastric antrum did not significantly differ between UC and FD patients, but were higher in those with CD. There was no significant difference in neutrophil infiltration or IL-8 production between UC, CD, and FD patients. CONCLUSIONS: UC patients did not show the immunological abnormalities in the stomach seen in CD patients.

A 65-year-old man was referred for a gallbladder elevated lesion. Abdominal US showed a hypoechoic tumor with wide base at the gallbladder body. The maximum velocity of the gallbladder wall blood flow was 20 cm/s. The outermost hyperechoic layer was irregular, but not disrupted on EUS images. We diagnosed the lesion as gallbladder carcinoma with the depth of subserosa. Cholecystectomy was performed and the tumor was diagnosed as tubular adenoma of the gallbladder. The p53 immumostaining was negative. A gallbladder adenoma with wide base is rare, here we report this case with the several considerations.

Ginger has been used throughout the world as spice, food and traditional herb. We found that 6-gingerol, a phenolic alkanone isolated from ginger, enhanced the TRAIL-induced viability reduction of gastric cancer cells while 6-gingerol alone affected viability only slightly. 6-Gingerol facilitated TRAIL-induced apoptosis by increasing TRAIL-induced caspase-3/7 activation. 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL-induced NF-kappaB activation. As 6-shogaol has a chemical structure similar to 6-gingerol, we also assessed the effect of 6-shogaol on the viability of gastric cancer cells. Unlike 6-gingerol, 6-shogaol alone reduced the viability of gastric cancer cells. 6-Shogaol was shown to damage microtubules and induce mitotic arrest. These findings indicate for the first time that in gastric cancer cells, 6-gingerol enhances TRAIL-induced viability reduction by inhibiting TRAIL-induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules.

BACKGROUND AND AIM: In Japan, screening examination with photofluorography is widely performed to reduce the mortality due to gastric cancer. The possibility of a future decline in gastric cancer cases and changes in its characteristics is suggested. The aim of this study was to examine the usefulness of direct radiology as a general health screening technique and the historical changes of gastric cancer in Japan. METHODS: This study involved 936 patients with gastric cancer whose carcinomas were detected by direct radiology as part of a general health screening at the Aichi Prefectural Center for Health Care from 1970 to 2000. We studied the prevalence of gastric carcinoma, its prognosis, differences between the two histological types of carcinoma and historical changes. RESULTS: The age-adjusted cancer detection rate slightly decreased. Comparing two histological types, diffuse-type carcinoma cases relatively increased. Intestinal-type carcinomas increased in the lower portion of the stomach, whereas diffuse-type increased in the upper portion. The 5-year survival rate was 92.7% for intestinal-type carcinoma and 84.8% for diffuse-type. Diffuse-type carcinomas were further progressed than intestinal-type when detected by direct radiology; however, detection of diffuse-type improved, so the percentage of early gastric cancer of diffuse type significantly increased, and the survival rate significantly improved, from 70.4% to 90.5%. CONCLUSION: The prevalence of gastric cancer has been decreasing, but the proportion of diffuse-type carcinoma localized in the upper portion of the stomach has been increasing in Japan.

BACKGROUND: Double balloon endoscopy (DBE) and videocapsule endoscopy (VCE) have been useful in managing obscure GI bleeding (OGIB). OBJECTIVE: This study evaluated the usefulness of DBE for diagnosis, treatment, and prognosis of OGIB and compared diagnostic yield between DBE and VCE in Japan. METHODS: Detection rates of abnormalities and diagnostic yields between VCE and DBE were compared in 74 patients at 5 centers. Of 244 patients who underwent DBE at Nagoya University Hospital, 130 (53%) with OGIB were enrolled for investigation of therapeutic procedures. SETTING: Seven Japanese medical centers. PATIENTS: Of 1034 patients who underwent DBE between September 2000 and December 2005 at 7 medical centers, 479 (46%) with OGIB were enrolled. RESULTS: Overall diagnostic yield of DBE for OGIB was 277 of 479 (58%). In patients with overt-ongoing bleeding, overt-previous bleeding of sporadic type, overt-previous bleeding of first attack only, occult bleeding with continuous positive fecal occult blood test (FOBT), or occult bleeding with 1 positive FOBT with iron deficiency anemia, diagnostic yield was 24 of 31 (77%), 179 of 310 (58%), 34 of 72 (47%), 24 of 35 (71%), and 56 of 93 (60%), respectively. Regarding positive findings in 277 patients, ulcers or erosions (53%) were the most frequent, followed by angiodysplasia (23%), tumors or polyps (22%), and diverticula (4%). Diagnoses in these patients were as follows: chronic inflammatory diseases (24%), vascular diseases (24%), tumor or polyps (21%), drug or radiation injury (7%), other small-bowel diseases (7%), upper GI diseases (9%), colorectal diseases (9%), and biliary disease (0.4%). Small-bowel diseases were confirmed in 226 patients (47%). Comparison of overall detection rate of abnormalities in the small bowel between VCE (65%) and DBE (53%) was not significantly different, nor was that of overall diagnostic yield between VCE (50%) and DBE (53%). Eight acute pancreatitis and 4 perforation episodes occurred with no mortalities at DBE. Of 130 patients at Nagoya University Hospital, 78 (60%) were diagnosed with small-bowel diseases and underwent treatments as follows: medication or observation only (n = 30), enteroscopic therapies (electrocoagulation in 21, clipping in 4, and polypectomy in 3), and surgery (n = 22). Small-bowel vascular diseases were more prone to rebleeding than small-bowel nonvascular diseases in patients without surgical treatment at a median follow-up of 423 days. CONCLUSIONS: DBE was relatively safe and useful for diagnosis and treatment of OGIB. A spectrum of small-bowel diseases presenting with OGIB in Japan may be distinct from that in the Western world.

Acetate is a principal short chain fatty acid produced by bacterial fermentation in the colon and a major end product of alcohol metabolism. In the present study, we assessed the effects of acetate on T cell activation and found that acetate inhibited NFAT activation but not NF-kappaB activation. Moreover, acetate impaired the nuclear translocation of NFAT but not that of NF-kappaB. Unlike cyclosporin A (CsA), acetate did not affect the dephosphorylation of NFAT and calcineurin activity. Acetate impaired the binding of NFAT to importin beta1, which is involved in NFAT nuclear translocation. NFAT is a critical transcription factor in cytokine and early response gene expression in activated T cells. Agents targeting NFAT such as CsA are used to suppress harmful immune responses in inflammatory diseases. Therefore, we also evaluated the efficacy of acetate in murine models of inflammatory diseases, and found that acetate administration (as well as administration of dexamethasone) attenuated trinitrobenzenesulfonic acid-induced colitis and dinitrofluorobenzene-induced dermatitis. These findings indicate for the first time that acetate inhibits NFAT activation by interfering with the interaction between NFAT and importin beta1 in T cells and that acetate can potentially act as an anti-inflammatory agent.

OBJECTIVES: Infection with Helicobacter pylori has been linked to chronic gastritis with atrophy or hyperrugosity. The development of noncardia gastric carcinoma, especially the intestinal type in Lauren's classification, has been associated with severe atrophic gastritis and p53 mutations. The objective of this study was to determine the association between hyperrugosity and gastric carcinogenesis, including p53 mutations. PARTICIPANTS AND METHODS: Barium meal roentgenograms were performed in 395 control participants and 132 gastric carcinoma patients. The fold width was measured at the greater curvature of the middle portion of the gastric body. Serum pepsinogens I and II were determined along with gastrin levels. Complete coding sequences and splice junctions for exons 5-8 of p53 gene were screened for mutations by polymerase chain reaction-based single-strand conformational polymorphism analysis. RESULTS: Rugal hyperplastic gastritis (gastric body fold width>or=5 mm) increased the risk of gastric carcinoma [odds ratio, 2.60; 95% confidence interval, 1.69-4.01] as compared with the control group, especially diffuse-type gastric carcinoma (odds ratio, 4.13; 95% confidence interval, 2.36-7.24). The p53 mutational rate was significantly lower in gastric carcinoma patients with rugal hyperplastic gastritis. In intestinal-type gastric carcinoma with hyperrugosity, the incidence of p53 gene mutations decreased, but no association was found in diffuse-type gastric carcinoma between p53 mutations and rugal hyperplastic gastritis. CONCLUSIONS: Rugal hyperplastic gastritis was associated with an elevated risk of gastric carcinoma, especially diffuse-type, and a lower frequency of p53 mutations.

Small bowel tuberculosis is sometimes encountered in oriental countries, and because its symptoms are vague and present a nonspecific pattern, confirmative diagnosis is difficult to achieve. In 2001, two new innovative endoscopic techniques for the small bowel, video capsule endoscopy and double balloon enteroscopy, were introduced, thus advancing the diagnostic technology for small bowel disorders. Our asymptomatic patient with small bowel tuberculosis was diagnosed definitively using the combination of video capsule endoscopy and double balloon enteroscopy. The number of such cases will increase when those procedures become more widely used. At present, the endoscopic view of small bowel tuberculosis is difficult to differentiate from Crohn's disease and drug-induced enteropathy, but from now on it will be possible to distinguish them utilizing endoscopic and fluoroscopic images. On the basis of the characteristics of small bowel tuberculosis with its endoscopic images, referring to our case report and previous literature, we report a topical diagnostic procedure, the combination of video capsule endoscopy and double balloon enteroscopy.

OBJECTIVE: The usefulness of 18F-fluoro-2-deoxyglucose positron emission tomography (18FDG-PET), whose high rate of FDG accumulation indicates high metabolism and malignant potential, has already been reported. The aims of this study were to evaluate the malignancy of primary gastrointestinal stromal tumour (GIST) in the stomach by 18FDG-PET and to correlate the FDG uptake values with known risk factors as determined by histology after EUS-guided fine needle aspiration (EUS-FNA) or endoscopic biopsy. MATERIAL AND METHODS: Of 29 patients with histologically proven GI-mesenchymal tumours, 21 with gastric GISTs underwent 18FDG-PET. Tumour size, mitotic index, Ki-67 labelling index (LI) and cellularity of the tumour tissue were compared with the standardized uptake value (SUV) of FDG. RESULTS: Strong correlations were found between the SUV of FDG and EUS size, and mitotic index of EUS-FNA specimens (tumour size versus SUV, p=0.004, r=0.542; number of mitotic cells versus SUV, p=0.0078; n=21). Moreover, we examined the association between SUV and risk categories based on EUS-FNA findings using ROC curves. The cut-off values of FDG SUV were 2.2, 4.2 and 6.5 for the very low-, low-, intermediate- and high-risk groups, respectively. CONCLUSIONS: 18FDG-PET may be used to assess malignancy of GISTs. This image modality helps us determine the management strategy for these patients and complements the information on the biological behaviour and cellular proliferation of the tumours.

AIM: To investigate active cytomegalovirus (CMV) infection following the cyclosporine A (CyA) treatment of steroid-refractory ulcerative colitis (UC). METHODS: Twenty-three patients with severe UC not responding to steroid therapy (male 14, and female 9) enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA (average 4 mg/kg per day) for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology (IgM antibody by ELISA), quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin (HE)-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS: No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV (IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%). There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection (83.3%) required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION: Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immuno-suppressive therapy.

Recently, decellularized tissue has been reported to have the potential to regenerate a variety of tissues. However, the optimal protocol for a decellularized esophagus has not been studied. Here, we investigated the effect of different decellularization protocols on the histology and biocompatibility of decellularized esophagi in view of future applications to tissue engineering. The esophageal mucosal epithelium (EP) from 4-week-old Wistar rats was enzymatically dissociated and cultured with growth-arrested feeder cells. Two methods for decellularization using deoxycholic acid (DEOX) or Triton X-100 (TRITON) were compared on esophagi from adult Wistar rats. Those treated with DEOX showed superior mechanical properties, maintenance of extracellular matrix, and lower DNA content than those treated with TRITON. To evaluate the biocompatibility of the scaffold, cultured (passage 3) esophageal epithelial cells were seeded inside the decellularized esophagus and cultured for 7 days. The cells seeded onto the decellularized esophagus were examined histologically and immunocytochemically. Esophageal epithelial cells were stratified into three to four cellular layers in vitro inside the decellularized esophagus, to show polarity. The results from immunocytochemistry indicated that the seeded epithelial cells expressed characteristic marker proteins for native esophageal EP. Decellularized esophagus showed suitable compatibility as a scaffold material for esophageal tissue engineering.

DNA hypermethylation is one of major epigenetic changes. Hypermethylation of many genes has been reported to be related with carcinogenesis and tumor progression of colorectal cancer. Some genes including estrogen receptor is associated with ageing, and changes related with ageing may be accelerated in inflammatory bowel disease. Furthermore, fecal DNA methylation will be able to be used as a marker of colorectal cancer and inflammatory bowel disease. Evaluation of hypermethylation potentially contributes diagnosis of colorectal diseases. © Birkhäuser Verlag, 2006.

Paeonol, a major phenolic component of Moutan Cortex, is known to have anti-inflammatory activity. However, the effect of Paeonol on colitis has not been evaluated and the molecular mechanism of its anti-inflammatory action remains unknown. The aim of this study was to determine if Paeonol enema attenuates trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. We also investigated the effects of Paeonol in colon cancer-derived CW-2 cells and T cell leukemia-derived Jurkat cells treated with tumor necrosis factor alpha (TNFalpha) and/or interferon gamma (IFNgamma), which play critical roles in TNBS-induced colitis. Paeonol enema attenuated TNBS-induced colitis judging by body weigh reduction, colon length and histological score. Myeloperoxidase activity and inducible nitric oxide synthase (iNOS) production in the colon were also reduced with Paeonol enema. In CW-2 cells, Paeonol inhibited iNOS protein and mRNA expression induced by costimulation of TNFalpha and IFNgamma. Furthermore, Paeonol reduced TNFalpha-induced NF-kappaB transactivation and IFNgamma-induced STAT1 transactivation in CW-2 cells and also in Jurkat cells. These findings suggest that Paeonol enema may be useful for the treatment of colitis.

PURPOSE: Recently, a single-nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to lower the age of onset of tumors and increase the occurrence of multiple primary tumors in Li-Fraumeni syndrome, and accelerate the development of sporadic adult soft tissue sarcoma. The aim of this study was to determine whether SNP309 is associated with susceptibility to gastric carcinoma and its prognosis. PATIENTS AND METHODS: In a case-control study including 438 controls and 410 patients with sporadic gastric carcinoma, MDM2 SNP309 was genotyped. Serum pepsinogens (PGs) I and II were measured in 438 control subjects and 253 cases selected from 410 patients. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using polymerase chain reaction-based single strand conformational polymorphism analysis and direct sequencing. RESULTS: The risk of overall gastric carcinoma for SNP309 (G/G) was significantly increased when compared with T carriers (P = .039), especially carcinomas with extragastric tumors (P = .005), carcinoma with severe atrophic gastritis positive for PG assay (PG I level < 70 ng/mL and PG I/II < 3.0; P = .005), antral carcinoma (P = .020), intestinal-type carcinoma (P = .023), p53-immunopositive carcinoma (P = .007), and carcinoma with p53 mutations (P = .007). No significant difference in age at diagnosis was observed among genotypes. SNP309 (G/G) was an independent marker of poor overall survival in advanced carcinoma (hazard ratio, 3.16; 95% CI, 1.22 to 8.20; P = .018). CONCLUSION: This study provides evidence supporting the association of SNP309 with gastric carcinogenesis via p53 tumor suppressor pathway, extragastric tumorigenesis, and poor prognosis.

BACKGROUND AND AIM: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. METHODS: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B-511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. RESULTS: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. CONCLUSIONS: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking.

BACKGROUND AND AIMS: Infection with Helicobacter pylori (Hp) has been linked to atrophic gastritis, an inflammatory precursor of non-cardia gastric carcinoma. Mutations in the p53 gene are one of the most frequent genetic alterations in gastric carcinoma. In a subgroup of atrophic gastritis, antiparietal cell antibody (APCA) has been detected. This study was aimed to clarify the role of APCA in the progression of atrophic gastritis and gastric carcinogenesis, and to determine the relationship of the severity of atrophic gastritis to gastric carcinoma and to p53 mutations. METHODS: In 494 control subjects and 284 gastric carcinoma patients, serum APCA was evaluated and all subjects and patients were classified into four groups using serologic markers (anti-Hp IgG antibody and pepsinogen (PG) test: positive; PG I < 70 microg/L and PG I/II ratio < 3.0) as follows: A, HP- PG-; B, HP+ PG-; C, HP+ PG+ and D, HP- PG+. p53 mutations were analyzed in 174 of 284 patients. RESULTS: Antiparietal cell antibody seropositivity increased from group B to D, however, no difference in its positivity was found between controls and patients. The incidence of gastric carcinoma increased from A to D, especially the intestinal subtype. The frequency of p53 gene mutations was higher in PG+ than in PG- gastric carcinoma. CONCLUSIONS: Antiparietal cell antibody seropositivity is involved in the progression of a subgroup of atrophic gastritis, but not associated with gastric carcinogenesis. Severe atrophic gastritis is associated with susceptibility to gastric carcinoma, especially the intestinal subtype, and p53 mutations.

BACKGROUND/AIMS: Endoscopic ultrasonography (EUS) is considered the most useful diagnostic modality for regional staging; however, it is still difficult to diagnose lymph node metastasis by EUS images only. In this study, we report the usefulness of contrast-enhanced EUS (CE-EUS) in the evaluation of benign lymph nodes (BLN) or malignant lymph nodes (MLN) based on blood flow patterns. SUBJECTS AND METHODS: In the retrospective study, CE-EUS was performed in 46 patients in whom EUS revealed lymph node in the mediastinum or abdominal cavity. The subjects consisted of 22 patients with BLN and 24 patients with MLN. The lesions were examined by EUS, and the maximal and minimal diameters of lymph nodes were measured. Thereafter, the shape and internal echoes were investigated, and the findings were morphologically classified based on Catalano's report. Enhancement effects and the diagnostic capability of CE-EUS were evaluated. In the prospective study, BLNs were differentiated from MLN using the enhancement patterns on CE-EUS based on the results of the retrospective study, and the diagnostic capability was evaluated. RESULTS: In the retrospective study, there were no significant differences in the maximal diameter and maximal/minimal diameter ratio between MLN and BLN. The morphology was classified into four types. Based on the morphological classification, the sensitivity, specificity, and accuracy rate were 88.2%, 77.3%, and 82.1%, respectively. On CE-EUS, the enhancement pattern was classified into three types. The BLN lesions showed uniform enhancement (19/22). In all patients with MLN, a defect of enhancement was observed (24/24). The sensitivity, specificity, and accuracy rate of CE-EUS were 100%, 86.4%, and 92.3%, respectively. In the prospective study, the sensitivity, specificity, and accuracy rate of CE-EUS were 100%, 81.8%, and 92.0%, respectively. CONCLUSIONS: CE-EUS is useful for differentiating BLN from MLN.

In recent years, ultrasound technology has made remarkable strides, and the application of these latest advances to endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS) is crucially important. EUS equipped with electronic scanners (both radial and convex types) has been developed, and now EUS with the function of tissue harmonic imaging (THI) and color/power Doppler is applicable clinically. THI facilitates the acquisition of ultrasound images clearer than those of fundamental imaging, and color/power Doppler sonography demonstrates the precise hemodynamics with the use of a contrast agent. In addition, the progress of image processing technology has realized three-dimensional (3D) images in EUS and IDUS. Reconstruction of 3D images enables us to diagnose more objectively. Here we describe the roles of these new ultrasound technologies in the diagnosis of biliary malignancies.