Learning Effect of Diagnosing Depth of Invasion Using Non-Extension Sign in Early Gastric Cancer.

BACKGROUND: Determining the depth of invasion is important when considering therapeutic strategies for early gastric cancer (EGC). We determined the effects of learning the non-extension sign, that is, an index of T1b2 in EGC, on identifying its depth of invasion. METHODS: Endoscopic images of 40 EGC cases (20 showing positive non-extension sign on endoscopy as T1b2 and 20 showing negative non-extension sign on endoscopy as T1a-T1b1) were randomly displayed on PowerPoint. Participants read endoscopy findings (pretest) and attended a 60-min lecture on how to read the non-extension sign. Then, they read the same images using the non-extension sign as the marker (posttest). The primary endpoint was a change in accuracy rate for determining the depth of invasion before and after attending the lecture, for nonexperts (< 80%). RESULTS: Among 35 endoscopists, 12 were nonexperts; their test results were used for analyses. Accuracy rates for pretest and posttest among nonexperts were 75.2 and 82.5%, respectively, showing a significant increase in the accuracy rate after learning to read the non-extension sign (p = 0.003). CONCLUSION: Nonexperts' diagnostic ability to determine the depth of invasion of EGC improved by learning to read the non-extension sign. Thus, the non-extension sign is considered a simple and useful diagnostic marker.

Factors associated with the clinical impact of capsule endoscopy in patients with overt obscure gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) does not necessarily identify positive findings in patients with overt obscure gastrointestinal bleeding (OGIB). We aimed to identify factors predictive of positive CE findings and those of re-bleeding after negative CE in overt OGIB. PATIENTS AND METHODS: We retrospectively analyzed 68 patients who underwent CE for overt OGIB. CE findings, therapeutic interventions, and clinical course after CE were reviewed. Clinical variables associated with positive CE findings and those associated with re-bleeding after negative CE findings were investigated. RESULTS: Positive CE finding was found in 36 (53%) patients. Marked decrease in hemoglobin value [OR; 18.8, 95% CI; 3.4-152.0] and earlier CE examination within a week after the last episode of bleeding [OR; 8.0, 95% CI; 2.2-35.9] were factors associated with positive CE findings. Nine (28%) of 32 patients with negative CE findings re-bled. Marked decrease in hemoglobin value was more frequent in patients with re-bleeding than those without (P = 0.07). CONCLUSION: Patients with massive and overt OGIB are the best candidates for CE. Earlier CE, virtually within a week, contributes to the better diagnostic yield of the procedure. Careful follow-up seems necessary for patients with massive bleeding even in cases of negative CE findings.

Double-balloon endoscopy depicts diminutive small bowel lesions in gastrointestinal lymphoma.

The aim was to determine the prevalence of small bowel involvement in patients with gastrointestinal (GI) lymphoma by double-balloon endoscopy (DBE). We examined 29 patients with primary GI lymphoma by oral and anal DBEs. Clinicopathologic features related to the prevalence of diminutive small bowel involvement and the clinical outcome were retrospectively investigated. Diminutive small bowel lesions were found in 14 patients. The prevalence of the lesions was not different between patients with primary small bowel lymphoma and those with primary extra-small bowel lymphoma (50% versus 47%, P = 0.6). However, clinical stage was more advanced in patients with the lesions than in those without (P < 0.05). The lesions were more frequently found in T-cell lymphoma (100%) and follicular lymphoma (77%) than in the other types of lymphoma (15%) (P < 0.05). Diminutive small intestinal lesions occur in patients with GI lymphoma, especially in those with follicular lymphoma and T-cell lymphoma. GI lymphomas of these histologic types are candidates for scrutiny by DBE.

Small-intestinal involvement in familial adenomatous polyposis: evaluation by double-balloon endoscopy and intraoperative enteroscopy.

BACKGROUND: Small-intestinal adenoma occurs in patients with familial adenomatous polyposis (FAP). OBJECTIVES: The aim was to analyze the diagnostic yield of a double-balloon endoscopy (DBE) and an intraoperative enteroscopy (IOE) for small-intestinal involvement in FAP. PATIENTS: Forty-one patients with FAP. INTERVENTIONS: We examined 12 patients with FAP by using oral DBE before a colectomy and 29 patients with FAP by using IOE. The incidence and the endoscopic findings of adenoma were compared between the 2 procedures. Phenotypes of FAP and genotypes of adenomatous polyposis coli (APC) were then compared between patients with small-intestinal adenomas and those without. The genotype was classified into a 5' mutation (exons 1-14), a 3' mutation (exon 15), and a negative mutation of APC. MAIN OUTCOME MEASUREMENT: The prevalence of adenoma. RESULTS: A DBE detected small-intestinal adenomas in 9 of 12 patients (75%), as did an IOE in 15 of 29 patients (52%, P > .05). The adenomas occurred predominantly in the jejunum, with a configuration of diminutive polyps in 22 patients. In addition, a DBE detected nonpolypoid adenoma in a patient, and nodular, broad-based protrusion (advanced lesions) in 3 patients, whereas an IOE detected advanced lesions in a patient. Patients with small-intestinal adenoma had more severe duodenal adenomatosis than those patients without small-intestinal adenoma (P < .001). In cases in which APC was analyzed, the prevalence of small-intestinal adenoma was higher in patients with a 3' mutation (100%) than in those with a 5' mutation (44%) and with a negative mutation (42%, P < .02). LIMITATION: Not a prospective randomized study. CONCLUSIONS: A DBE is equal to an IOE for scrutiny of small-intestinal adenomas in FAP. There seems to be a genotype-jejunal phenotype correlation in FAP.

Linear mucosal defect may be characteristic of lansoprazole-associated collagenous colitis.

BACKGROUND: Although some cases of collagenous colitis have been induced by lansoprazole (LPZ), the clinicopathologic features of LPZ-associated collagenous colitis have not been elucidated. OBJECTIVE: To elucidate the clinical, endoscopic, and histopathologic features of LPZ-associated collagenous colitis. DESIGN: Retrospective case study. PATIENTS: The subjects were 13 patients with collagenous colitis diagnosed during a period from 2002 to 2007. MAIN OUTCOME MEASUREMENTS: The colonoscopic and histopathologic findings were compared retrospectively between 9 cases of LPZ use (LPZ group) and 4 cases without the use of LPZ (non-LPZ group). RESULTS: A colonoscopy revealed a linear mucosal defect more frequently in the LPZ group (7 of 9 cases [78%]) than in the non-LPZ group (0 of 4 cases [0%], P = .02). Friable mucosa was also noted in 4 patients (44%) in the LPZ group but none in the non-LPZ group. The colonoscopic finding in the non-LPZ group was either normal mucosa or nonspecific minimal abnormalities, whereas patients in the LPZ group had either a linear mucosal defect, mucosal bleeding, or both (P = .001). On histologic examination, the subepithelial collagen band was thicker in patients in the LPZ group than in those in the non-LPZ group (median 45 vs 26.3 mum). All patients in the LPZ group recovered from diarrhea after discontinuance of LPZ. LIMITATION: A small number of patients. CONCLUSIONS: Linear mucosal defects and friable mucosa may be characteristic colonoscopic findings in cases of LPZ-associated collagenous colitis.

Is small-bowel radiography necessary before double-balloon endoscopy?

OBJECTIVE: Small-bowel radiography may be replaced by enteroscopy in the diagnosis of small-intestine lesions. We retrospectively elucidated the diagnostic yield of small-bowel radiography performed before double-balloon endoscopy. MATERIALS AND METHODS: One hundred twenty-four patients who underwent double-balloon endoscopy during the period 2004-2006 were classified into those with abnormal radiographic findings (n = 45), normal radiographic findings (n = 31), and no small-bowl radiographs (n = 48). The classification was based on the use of small-bowel radiography and the diagnosis before double-balloon endoscopy. The indications for, approaches to, and diagnostic yields of double-balloon endoscopy were compared for the three groups. The diagnostic yield of small-bowel radiography was considered positive when any sign of pathologic change in the small bowel was identified. The diagnostic yield of double-balloon endoscopy was considered positive when endoscopic or biopsy findings explained the clinical manifestations. RESULTS: The group with abnormal findings on small-bowel radiography was younger (15-86 years) and less frequently had obscure bleeding (8.9%) than the group with normal findings on small-bowel radiography (age, 17-84 years; frequency of obscure bleeding, 45.2%) (p = 0.01) or the group without small-bowel radiographs (age, 15-91 years; frequency of obscure bleeding, 64.6%) (p < 0.0001). The positive diagnostic yield of double-balloon endoscopy was highest in the group with abnormal findings on small-bowel radiography (71.1%), followed by the group with no small-bowel radiographs (45.8%) and the group with normal findings on small-bowel radiography (35.5%) (p = 0.0002). Among patients who did undergo small-bowl radiography, the accuracy of the technique was 68.4%, the positive predictive value was 71.1%, and the negative predictive value was 64.5%. The positive diagnostic yields of small-bowel radiography and double-balloon endoscopy were not statistically different (59.2% for small-bowel radiography, 56.6% for double-balloon endoscopy; p > 0.1). CONCLUSION: The diagnostic accuracy of double-balloon endoscopy seems to improve if the procedure is preceded by small-bowel radiography.

Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis.

OBJECTIVE: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a potentially effective therapy for Crohn's disease. The purpose of this study was to test the rhG-CSF in murine dextran sulfate sodium-induced colitis (DSS colitis). MATERIAL AND METHODS: Murine colitis was induced by feeding with water containing 3% DSS for 9 days. Six to 7-week-old female BALB/c mice were given rhG-CSF (100 microg/kg) or phosphate-buffered saline (PBS) subcutaneously once a day from day 0 to day 8, and the mice were sacrificed at days 3, 5, 7 and 9. Tissue specimens from the transverse colon, descending colon and rectum were obtained and stained with hematoxylin and eosin. Inflammation was scored for severity, extent, epithelial damage and crypt loss. TUNEL staining was performed to assess epithelial cell apoptosis. RESULTS: Treatment with rhG-CSF significantly attenuated body-weight loss, stool score and shortening of the colon length in comparison with treatment with PBS (p<0.01,<0.05,<0.01, respectively). Histological scores for inflammation, epithelial cell damage and crypt loss of the rectum were less severe at day 9 in the rhG-CSF group than in the PBS group (p<0.01, 0.05, 0.01, respectively). The number of TUNEL-positive cells in the rectum was smaller in the rhG-CSF group than in the PBS group (p<0.001). CONCLUSIONS: Treatment with rhG-CSF ameliorates murine DSS colitis by suppressing mucosal inflammation and epithelial damage in the rectum. The prevention of epithelial cell apoptosis seems to precede the anti-inflammatory action of rhG-CSF.

Colonic obstruction due to giant inflammatory polyposis in a patient with ulcerative colitis.

A 32-year-old Japanese woman with a 14-month history of ulcerative colitis (UC), pancolitis type, was referred to our institution, because of abdominal distention. Plain abdominal X-ray and computed tomography (CT) showed marked dilatation of the right side of the colon. The patient was treated by immediate total colectomy, with the diagnosis of toxic megacolon. Macroscopically, there was a constricting lesion with giant polyposis in the middle part of the transverse colon. Histologically, there was transmural inflammation with a thickened proper muscular layer overlaid by inflammatory polyposis. This case suggests that giant polyposis in UC patients may result in severe stenosis and that such a condition should not be misinterpreted as toxic megacolon or as colitic cancer.

Significance of telemedicine for video image transmission of endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography procedures.

BACKGROUND: With the rapid and marked progress in gastrointestinal endoscopy, the education of doctors in many new diagnostic and therapeutic procedures is of increasing importance. Telecommunications (telemedicine) is very useful and cost-effective for doctors' continuing exposure to advanced skills, including those needed for hepato-pancreato-biliary diseases. Nevertheless, telemedicine in endoscopy has not yet gained much popularity. We have successfully established a new system which solves the problems of conventional ones, namely poor streaming images and the need for special expensive teleconferencing equipment. METHODS: The digital video transport system, free software that transforms digital video signals directly into Internet Protocol without any analog conversion, was installed on a personal computer using a network with as much as 30 Mbps per channel, thereby providing more than 200 times greater information volume than the conventional system. Kyushu University Hospital in Japan was linked internationally to worldwide academic networks, using security software to protect patients' privacy. RESULTS: Of the 188 telecommunications link-ups involving 108 institutions in 23 countries performed between February 2003 and August 2009, 55 events were endoscopy-related, 19 were live demonstrations, and 36 were gastrointestinal teleconferences with interactive discussions. The frame rate of the transmitted pictures was 30/s, thus preserving smooth high-quality streaming. CONCLUSIONS: This paper documents the first time that an advanced tele-endoscopy system has been established over such a wide area using academic high-volume networks, funded by the various governments, and which is now available all over the world. The benefits of a network dedicated to research and education have barely been recognized in the medical community. We believe our cutting-edge system will be a milestone in endoscopy and will improve the quality of gastrointestinal education, especially with respect to endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) procedures.

Differential expression of leukocyte functions associated antigen-1 (LFA-1) on peripheral blood mononuclear cells in patients with Crohn's disease.

BACKGROUND: The leukocyte function associated antigen-1 (LFA-1) intracellular adhesion molecule-1 pathway is presumed to play a pivotal role in the perpetuation of inflammatory bowel disease. We aimed to elucidate the effect of 2 different therapies on LFA-1 expression in patients with Crohn's disease (CD) and correlate LFA-1 expression with disease activity. METHODS: In all, 30 patients with active CD were recruited for the present investigation. Eleven patients were treated with infliximab and 19 patients with total parenteral nutrition. The clinical activity and the expression of LFA-1 in peripheral blood mononuclear cells were assessed prior to and 4 weeks after treatment. Clinical activity was determined by measuring the Crohn's Disease Activity Index and LFA-1 expression was measured by mean fluorescence intensity (MFI) under fluorescence-activated cell sorter analysis. RESULTS: In each treatment group the clinical disease activity index decreased significantly 4 weeks after treatment. In patients treated with infliximab, LFA-1 expression decreased significantly (mean MFI decreased from 1983 to 1487, P < 0.05). However, LFA-1 expression remained unchanged in the total parenteral nutrition group (mean MFI elevated from 1684 to 1902, P > 0.05). CONCLUSIONS: The mechanism of therapeutic action on CD is different between infliximab and total parenteral nutrition.

A case of Crohn's disease associated with Takayasu's arteritis and Henoch-Schönlein purpura.

A 14-year-old Japanese man was diagnosed with Crohn's disease in October 2001. Four years later, the patient was referred to our institution because of neck pain, fever and asymmetrical blood pressure. Magnetic resonance angiography, computed tomography and ultrasonography revealed findings compatible with Takayasu's arteritis. In March 2006, the patient developed purpura over bilateral hands and lower extremities, arthralgia, lower abdominal pain and microhematuria. The patient was diagnosed with Henoch-Schönlein purpura. This is the first reported case of Crohn's disease associated with two types of vascular complications.

Effective monotherapy with amrubicin for a refractory extrapulmonary small-cell carcinoma of the liver.

Small-cell carcinoma of the liver is a rare neoplasm, and no standard treatment for it has yet been established. A 72-year-old man with an extensive disease stage of small-cell carcinoma of the liver was treated with systemic chemotherapy consisting of cisplatin and etoposide (PE) followed by irinotecan. Although the masses were markedly decreased once after the sixth course of PE, amrubicin monotherapy as third-line chemotherapy was started because the hepatic masses had increased again. The administration of amrubicin was repeated in 8 courses with regression of the disease, resulting in a 26-month survival since the first-line chemotherapy was started. This is the first case report of a refractory EPSCC successfully treated with amrubicin.

Factors affecting recurrence in patients with Crohn's disease under nutritional therapy.

PURPOSE: This retrospective study was designed to determine risk factors for recurrence of Crohn's disease under enteral nutrition. METHODS: The clinical course of 145 patients with Crohn's disease, who were primarily induced into remission by total parenteral nutrition, was reviewed. The patients were classified into two groups: enteral nutrition group (n = 98; >/=1,200 kcal/day of enteral nutrition), or nonenteral nutrition group (n = 47;<1,200 kcal/day of enteral nutrition) according to the amount of their daily elemental or polymeric diet. Contributions of enteral nutrition and other clinical variables to the recurrence were analyzed retrospectively. A Crohn's disease activity index of >150 plus an increase in Crohn's disease activity index of >70 from the baseline value was defined as recurrence. RESULTS: Forty-two patients in the enteral nutrition group and 29 patients in the nonenteral nutrition group recurred during periods ranging from 3 to 159 months. The cumulative rate of recurrence was significantly higher in the nonenteral nutrition group than in the enteral nutrition group (P = 0.047). Among the Crohn's disease patients in the enteral nutrition group, penetrating type (relative risk, 3.89; 95 percent confidence interval, 1.58-9.62), colonic involvement (relative risk, 3.10; 95 percent confidence interval, 1.39-6.9), and previous history of surgery (relative risk, 2.48; 95 percent confidence interval, 1.16-5.33) were factors that significantly affected recurrence. In contrast, penetrating type was the only possible factor associated with recurrence in the nonenteral nutrition group (relative risk, 2.75; 95 percent confidence interval, 0.96-7.81). CONCLUSIONS: Among patients with Crohn's disease under maintenance enteral nutrition, the risk of recurrence differs according to the disease type and the site of involvement. The maintenance treatment by enteral nutrition alone seems insufficient for patients with penetrating type or with colonic involvement.

Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphoma.

BACKGROUND: Although caspase recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) and CARD9 play important roles in lymphocyte activation, the significance of CARMA1 and CARD9 in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma remains to be elucidated. METHODS: By using reverse transcription-polymerase chain reaction analysis, the expression levels of mRNA of CARMA1, CARD9, Bcl10, and the apoptosis inhibitor 2 (API2)-MALT1 chimeric transcript were determined in tissue specimens from 65 patients with primary gastric B-cell lymphoma (43 patients with low-grade MALT lymphoma, 16 patients with MALT lymphoma plus diffuse large B-cell lymphoma [DLBL], and 6 patients with DLBL without MALT lymphoma) and in tissue specimens from 18 patients with chronic gastritis. The expression levels of CARMA1 and BCL10 were examined immunohistochemically in 30 patients with lymphoma. RESULTS: CARMA1 mRNA was detected in 55% of lymphoma patients but in only 17% of chronic gastritis patients. The positive rates for CARD9, Bcl10, and API2-MALT1 chimeric transcript in the lymphoma patients were 48%, 98%, and 8%, respectively, whereas the 3 molecules were not detected in any specimens from patients with chronic gastritis. The expression of CARMA1 and CARD9 was frequent in the Helicobacter pylori-negative patients (100% and 86%, respectively), in the API2-MALT1 chimeric transcript-positive patients (100% and 100%, respectively), and in the specimens from patients who did not respond to H. pylori eradication (76% and 71%, respectively). In addition, CARMA1 expression was positive more frequently in patients of DLBL without MALT lymphoma (100%) than in patients of MALT lymphoma (51%). CARMA1 protein expression was correlated significantly with the expression of CARMA1 mRNA and also with the expression of nuclear BCL10. CONCLUSIONS: The overexpression of CARMA1 and CARD9 presumably is associated with the development or progression of gastric B-cell lymphoma, especially among patients who have disease in which the pathogenesis is not related to H. pylori.

Role of CXCR3 in the immune response to murine gammaherpesvirus 68.

The chemokine IP-10 (CXCL10) and its cellular receptor CXCR3 are upregulated in the lung during murine gammaherpesvirus 68 (MHV-68) infection. In order to determine the role of the CXCR3 chemokine receptor in the immune response to MHV-68, CXCR3-/- mice were infected with the virus. CXCR3-/- mice showed delayed clearance of replicating MHV-68 from the lungs. This correlated with delayed T-cell recruitment to the lungs and reduced cytolytic activity prior to viral clearance. Splenomegaly and the numbers of latently infected cells per spleen were transiently increased. However, CXCR3-/- mice showed normal virus-specific antibody titers and effective long-term control of MHV-68 infection.

The role of p53 and Fas in a model of acute murine graft-versus-host disease.

Graft-vs-host disease (GVHD) is a devastating, frequently fatal, pathological condition associated with lesions in specific target organs, including the intestine, liver, lung, and skin, as well as pancytopenia and alopecia. Bone marrow (BM) atrophy is observed in acutely diseased animals, but the underlying mechanisms of hemopoietic stem cell depletion remained to be established. We used an experimental mouse model of acute GVHD in which parental cells were injected into F(1) hosts preconditioned by sublethal irradiation. The resulting graft-vs-host response was kinetically consistent, resulting in lethality within 3 wk. We observed disease pathology in the liver and small intestine, and consistent with previous observations, we found BM atrophy to be a factor in the onset of acute disease. The product of the protooncogene, p53, is known to be a key player in many physiological examples of apoptosis. We investigated the role of p53 in the apoptosis of BM cells (BMC) during the development of acute disease and found that at least one copy of the p53 gene is necessary for depletion of BM and subsequent lethality in host animals. BM depletion was preceded by induction of the death receptor, Fas, on the surface of host stem cells, and induction of Fas was coincidental with the sensitization of BMC to Fas-mediated apoptosis. Our data indicate that BM depletion in acute GVHD is mediated by p53-dependent up-regulation of Fas on BMC, which leads to Fas-dependent depletion and subsequent disease.

Histological and immunological features of appendix in patients with ulcerative colitis.

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

Radiation-induced crypt intestinal epithelial cell apoptosis in vivo involves both caspase-3-dependent and -independent pathways.

Caspases play a major role in virtually all forms of apoptosis. Radiation is well known to induce apoptosis of crypt intestinal epithelial cells (IEC). Here, we examined the role of caspase-3 in radiation-induced IEC apoptosis. We demonstrate that while caspase-3 is present in IEC and activated upon irradiation, IEC in caspase-3-deficient mice partially underwent radiation-induced apoptosis. Typical morphological changes of IEC undergoing radiation-induced apoptosis (ie, blebbing, shrinkage, and nuclear condensation) can occur independently of caspase-3; however DNA fragmentation, as analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, is mostly, but not entirely, caspase-3-dependent. Overall, these results demonstrate that radiation-induced crypt IEC apoptosis has both caspase-3-independent and -dependent components.