Search

Background and Aims: Magnifying endoscopy (ME) with narrow-band imaging (NBI) revealed a white opaque substance (WOS) within the superficial part of the gastric neoplasia; however, its nature has remained obscure. A WOS noted within the duodenum was reported to comprise lipid droplets (LD) absorbed by the duodenal epithelium. We attempted to ascertain whether the WOS within gastric neoplasia could also comprise LD and whether the presence of this WOS could be correlated with a specific phenotype. Methods: Forty-three patients with early gastric epithelial neoplasia underwent ME with NBI. The presence or absence of WOS in the neoplasias was recorded based on the findings of ME with NBI. One biopsy specimen was taken from each of the neoplasias. Cryostat sections underwent oil red O staining for LD. Serial sections were immunostained using the first antibody of CD10, MUC2, CDX2, human gastric mucin, MUC5AC and MUC6. The tissue phenotype was classified as intestinal (I), gastric (G) and gastrointestinal (GI) type based on the results of immunostaining. In total, 49 gastric neoplasias from 43 patients were investigated. Results: Prevalence of LD in WOS-positive versus WOS-negative lesions was 96.2% (25/26) and 4.3% (1/23), respectively ( P < 0.001, Fisher's exact test). WOS was present in GI- and I-type lesions, but not in G-type lesions. Conclusions: WOS may be LD that have been accumulated in the superficial part of the gastric neoplasia of a certain intestinal phenotype. [ABSTRACT FROM AUTHOR]

Abstract: Recent evidence indicates that adenosine A2A receptor antagonists hold therapeutic potential for the treatment of Parkinson''s disease (PD). A study on the novel adenosine A1 and A2A receptor dual antagonist 5-[5-amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854) showed it to be effective in various rodents models of PD and cognition. In the present study, we further investigated the potential of ASP5854 as an anti-PD drug using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets, which is a highly predictive model of clinical efficacy in PD, and compared its effect with those of existing anti-PD drugs. ASP5854 significantly and dose-dependently improved the total motor disability score for 7h at doses higher than 1mg/kg, and significantly increased total locomotor activity at doses higher than 0.1mg/kg without adverse effects. l-3,4-Dihydroxyphenylalanine+benserazide and bromocriptine also significantly improved the motor disability score and the hypolocomotion caused by MPTP treatment in a dose-dependent fashion. This amelioration was significant at 32+8 and 10–32mg/kg, respectively, although bromocriptine induced severe emesis. Trihexiphenidyl also significantly improved the total motor disability score at doses of 10–32mg/kg; however, while a significant increase in the total locomotor activity was observed at 10mg/kg, the drug induced ataxia-like behavior at 32mg/kg. On the other hand, neither selegiline nor amantadine improved the total motor disability and hypolocomotion. These data substantiate the evidence that the novel adenosine antagonist ASP5854 exerts comparable anti-PD activity with existing anti-PD drugs, which indicates that ASP5854 might have potential to ameliorate motor deficits in PD. [Copyright &y& Elsevier]

Abstract: Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2. SBDD analysis via a combination of X-ray structural study and homology modeling suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2. [Copyright &y& Elsevier]

We have developed a magnified endoscopic technique for observing the microvascular architecture within the gastric mucosa in units as small as capillary and we have reported the characteristic findings of the microvascular architecture in both normal gastric mucosa and early gastric cancer. The findings in the normal stomach were different depending on the section of the stomach. The body mucosa demonatrated a regular honeycomb-like subepithelial capillary network pattern with a collecting venule, while the antral mucosa demonstrated a regular coil-shaped subepithelial capillary network pattern. The magnified endoscopic findings of early gastric carcinoma were different depending on the types of histological differentiation. The characteristic findings of differentiated carcinoma were (1) the presence of a demarcation line; (2) the disappearance of the regular subepithelial capillary network pattern; and (3) the presence of an irregular microvascular pattern. The findings of undifferentiated carcinoma showed only a reduction in or else the complete disappearance of the regular subepithelial capillary network pattern. In clinical practice, the magnified endoscopic findings of differentiated carcinoma are useful both for determining the margin of early gastric cancer and for making a differential diagnosis between gastritis and gastric cancer in the case of flat reddened lesions. The microvascular architecture as visualized by magnified endoscopy could be a new diagnostic system for the endoscopic diagnosis of early gastric cancer. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with incomplete gastric intestinal metaplasia (GIM) have a higher risk of gastric cancer (GC) than those with complete GIM. We aimed to clarify whether micromucosal patterns of GIM in magnifying endoscopy with narrow‐band imaging (M‐NBI) were useful for diagnosis of incomplete GIM. Methods: We enrolled patients with a history of endoscopic resection of GC or detailed inspection for suspicious or definite GC. The antrum greater curvature and corpus lesser curvature were regions of interest. Areas with endoscopic findings of light blue crest and/or white opaque substance (WOS) were defined as endoscopic GIM, and subsequent M‐NBI was applied. Micromucosal patterns were classified into Foveola and Groove types, and targeted biopsies were performed on GIM with each pattern. GIM was classified into complete and incomplete types using mucin (MUC)2, MUC5AC, MUC6, and CD10 immunohistochemical staining. The primary endpoint was the association between micromucosal pattern and histological subtype. The secondary endpoint was endoscopic findings associated with incomplete GIM. Results: We analyzed 98 patients with 156 GIMs. Univariate analysis (odds ratio [OR] 3.4, P = 0.004), but not multivariate analysis (OR 0.87, P = 0.822), demonstrated a significant association between micromucosal pattern and subtype. The antrum (OR 3.7, P = 0.006) and WOS (OR 43, P = 0.002) were independent predictors for incomplete GIM. The WOS had 69% sensitivity and 93% specificity. Conclusions: The M‐NBI micromucosal pattern is not useful for diagnosis of GIM subtype. WOS is a promising endoscopic indicator for diagnosis of incomplete GIM. (UMIN‐CTR000041119). [ABSTRACT FROM AUTHOR]

Background and aims: With the improvement in endoscopic equipment functions, narrow-band imaging (NBI) for endoscopic observation of the stomach, which is an organ with a large lumen, is now feasible. Studies evaluating the NBI utility without magnifying endoscopy to diagnose the invasion extent for the demarcation line identification in early gastric cancer have not been reported. This study aimed to investigate the demarcation line diagnostic performance of NBI in early gastric cancer compared to that of white-light imaging (WLI) using prospectively collected consecutive specimens from early gastric cancer patients. Methods: Thirty consecutive lesions were collected from patients who underwent endoscopic submucosal dissection for early gastric cancer. Next, 30 NBI and 30 WLI images, each with the same degree of gastric wall extension, angle, and layout for one lesion, were selected, and a total of 60 images were prepared for testing. The early gastric cancer invasion ranges in the endoscopic images was plotted using the web-developed software, and 264 independent endoscopists, unaware of the diagnosis, performed the web tests, with the concordance rates between the ranges of responses. After estimating the actual early gastric cancer invasion ranges, the NBI and WLI results were compared. Results: The concordance rates for NBI and WLI images were 43.1% (95% confidence interval [CI] 42.5–43.7%) and 37.2% (95% CI 36.6–37.7%), respectively, showing that the concordance rate for NBI was significantly higher than that for WLI. Conclusion: This study suggested that NBI was more useful for identifying demarcation lines than WLI. [ABSTRACT FROM AUTHOR]

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn's disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials. [ABSTRACT FROM AUTHOR]

Aims: To investigate the clinicopathological characteristics of 20 primary gastric T-cell lymphoma (GTCL) cases without human T-lymphotropic virus type I infection in Japan, a non-endemic area for coeliac disease. Methods and results: Fifteen cases had no history of persistent diarrhoea or severe hypoproteinaemia. Histologically, 13 cases (65%) consisted of large cell lymphoma and seven (35%) were of medium-sized cells. Intraepithelial lymphoma cell invasion was found in three cases (15%). Two of 10 surgical cases (20%) showed intramucosal tumour cell spreading with enteropathy-like features. Helicobacter pylori CagA gene was detected in three of 10 cases (30%). The lymphoma cells of all 20 cases were positive for CD3 and/or TCRβF1 and negative for CD56. CD4− and CD8− lymphoma was found in 11 cases (55%), CD4+ lymphoma in seven (35%) and CD8+ lymphoma in two (10%). CD30+, CD5+ and CD25+ lymphomas were detected in nine (45%), 10 (50%) and 11 (55%) cases, respectively. Five-year survival of the 16 available cases was 54%. Early clinical stage and medium-sized cell lymphoma were significantly ( P < 0.05) better prognostic factors. Conclusions: Patients with GTCL exhibit distinct clinicopathological findings and prognoses from those with enteropathy-associated T-cell lymphomas. GTCL may be mainly derived from lamina propria and parafollicular T cells. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial membrane potential plays an important role in cell survival. Transitions in mitochondrial permeability, which indicate the imminent destruction of the organelles, have been observed in damaged neuronal cells both in vitro and in vivo. In this study, C57/BL6n mouse thymocytes were put under stress using thapsigargin, a Ca2+ ATP-ase inhibitor, after which the change in mitochondrial membrane potential was monitored with a JC-1 dual-emission probe. This was done in an attempt to identify a novel compound that can suppress mitochondrial membrane potential reduction and cell death. In this assay system, the novel compound SCH-20148 [2,3-dihydroxypropyl-5-bromo-N-(2-methyl-3-trifluoromethylphenyl)anthranilate] was found to protect mouse thymocytes against thapsigargin (3 nM)-induced mitochondrial membrane potential reduction (IC50 =42 nM). SCH-20148 also prevented A23187- or ionomycin-induced shifts in mitochondrial membrane potential but it did not have any effect on the changes induced by tunicamycin, staurosporine, or dexamethasone. The potent immunosuppressants tacrolimus and cyclosporine A prevented the effect of thapsigargin, but did not prevent the A23187- or ionomycin-induced changes. Calcium-modulating agents, an anti-oxidant, a protein kinase C inhibitor, and anti-inflammatory agents were not effective against thapsigargin-induced mitochondrial permeability transition which implies that SCH-20148 exerts a protective effect via its specific mechanism. In addition, SH-20148 demonstrated a neuroprotective effect against thapsigargin-induced neuronal cell death in neuroblastoma SH-SY5Y cells. Taken together, these results suggest the potential of SCH-20148 as novel neuroprotective drug. [Copyright &y& Elsevier]

A retrospective endoscopic follow-up study was conducted to elucidate the development of minute or superficial-type cancers. The development of eight colorectal cancers that were followed up by endoscopy was evaluated. (i) Cancer with high-grade atypia frequently developed from lesions diagnosed histologically by biopsy as adenoma; (ii) two polypoid adenomas developed into invasive cancers with non-polypoid configuration; (iii) a superficial elevated-type cancer with high-grade atypia remained a mucosal cancer for more than 1 year; (iv) a superficial depressed (SD)-type cancer that had a concomitant adenomatous component grew slowly, maintaining the same configuration for more than 2 years. Another SD-type cancer grew rapidly to an advanced cancer; and (v) a superficial elevated adenoma developed into a IIa + IIc-type submucosally invasive cancer while maintaining the size of the initial tumor. From the analysis of the literature, 35 lesions were collected, but it was impossible to speculate which specific type of tumor grew rapidly. From the endoscopic observations of the present study and the review of the literature, developments of superficial type cancers were diverse, sessile-type cancers with marked configurational change, and early cancers developed slowly, although the speed of their growth accelerated according to the downward invasion of the cancer. [ABSTRACT FROM AUTHOR]

Background and study aims: Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) was reported as a subtype of gastric adenocarcinoma. This study aimed to investigate the endoscopic findings of GA-FGM and to evaluate the differences between GA-FGM and GA-FG. Patients and methods: This was a single-center retrospective study. Participants were selected from patients with gastric cancer treated at Fukuoka University Chikushi Hospital, between September 2007 and May 2020. Patients histologically diagnosed with GA-FGM or GA-FG were enrolled, and endoscopic findings were analyzed in detail. Results: A total of 12 GA-FGM lesions (12 patients) and 14 GA-FG lesions (13 patients) were analyzed. The two lesion types showed similar features: most lesions were of elevated type, located in the upper stomach, and developed in the stomach without Helicobacter pylori infection. On conventional endoscopy using the dye-spraying method, well-demarcated fine granular areas were observed in 7 GA-FGM lesions (58%) but not in any GA-FG lesions, with a significant difference between the two groups (P = 0.001). Magnifying endoscopy with narrow-band imaging (NBI) showed that 11 GA-FGM lesions (92%) met the diagnostic criteria for cancer according to the vessel plus surface classification system, whereas none of the GA-FG lesions met the same criteria (0%, 0/14) (P = 0.001). Conclusion: Our results suggest that magnifying endoscopy with NBI is a potentially useful method for the diagnosis of GA-FGM. [ABSTRACT FROM AUTHOR]

Endoscopic findings of the depressed type of poorly differentiated adenocarcinoma at an early stage have rarely been described. Herein is reported the endoscopic appearance of a typical case of depressed-type carcinoma with poor differentiation in the transverse colon. The depressed-type carcinoma, which had penetrated to the submucosa, was detected as a shallow depressed rough mucosa with interruption of the mucosal vascular pattern. The color of the lesion was almost the same as that of the surrounding non-cancerous mucosa. Using the surface-dyeing method, the lesion was demonstrated as a slightly depressed lesion with a well-defined and irregular margin. With magnification, the surface of the lesion proved to have no pit structure. These endoscopic characteristics might be useful in detecting and evaluating the depressed type of poorly differentiated adenocarcinoma at an early stage. [ABSTRACT FROM AUTHOR]

Cases of inflammatory type cancer have a relatively good prognosis among diffusely infiltrating colorectal cancers.1 We experienced an extremely rare case of submucosal invasive cancer showing a similar morphology to inflammatory type cancer.2-4 A man in his 50s was referred to us because of a positive fecal occult blood test. Colonoscopy showed unilateral stenosis in the sigmoid colon. The lesion showed Crohn's disease-like inflammation; there was inflammatory cell infiltration into all layers and numerous epithelioid cell granulomas were observed (Figs. The lesion showed Crohn's disease-like inflammation; there was inflammatory cell infiltration into all layers and lymphocyte aggregation, and numerous epithelioid cell granulomas were observed in the tissue surrounding of the tumor. [Extracted from the article]

This study aims to investigate the clinicopathological features of in situ follicular neoplasm (ISFN) in Japan. ISFN is a rare condition formerly considered as an early precursor of follicular lymphoma (FL). This is a first original report of ISFN from Asian country. We reviewed 19 biopsy samples of ISFN. ISFNs were categorized into two groups: (1) ISFN, consisting of ISFN with strong positivity for BCL-2 immunohistochemical staining (IHC), and obvious translocation of BCL-2; and (2) ISFN-like FL, featuring cases without obvious translocation but having morphological features and characteristic IHC findings of ISFN. As control, we adopted obvious FL. For some cases showing coexisting ISFN and FL lesions in the same lymph node, we could conduct further clonality analysis for each lesion. Nine of the 19 cases of ISFN coexisted with FL or had a history of overt B- or T-cell lymphoma including FL. Statistical comparison among ISFN-like FL and FL showed no significant differences in pathological features. Molecular analysis suggested that ISFN lesion and FL lesion in the same lymph node each have a different clonality. ISFN coexists or associates with other overt lymphomas frequently. [ABSTRACT FROM AUTHOR]

Background: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center.Methods: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000.Results: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis.Conclusion: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs. [ABSTRACT FROM AUTHOR]

Background and aim: The ability to differentiate between mucosal (M) or microinvasive submucosal (SM1: depth of less than 500 µm) and invasive submucosal (SM2: depth of 500 µm or more) cancer is paramount when choosing the method of treatment for early gastric cancer (EGC). The 'non-extension sign' relates to a localized increase in thickness and rigidity due to massive submucosal invasion by a cancer. The present study sought to assess the ability of conventional endoscopy (CE) to correctly identify SM2 cancer using only the non-extension sign. Methods: This is a retrospective study based on a prospectively collected database. EGCs had been diagnosed according to invasion depth as M-SM1 or SM2. In terms of the endoscopic diagnostic criterion, lesions positive for the non-extension sign were classified as SM2 cancers, while those negative for the non-extension sign were classified as M-SM1 cancers. Histopathological findings were used as the gold standard. Results: We examined a total of 863 lesions from 704 patients, comprising 104 true-positive, 733 true-negative, 9 false-positive, and 17 false-negative lesions. This yielded a sensitivity of 92.0 % (95 % confidence interval (CI), 87.0-97.0 %), a specificity of 97.7 % (95 % CI, 96.7-98.8 %), a positive predictive value of 85.9 % (95 % CI, 79.7-92.1 %), a negative predictive value of 98.8 % (95 % CI, 98.0-99.6 %), and a diagnostic accuracy of 96.9 % (95 % CI, 95.8-98.1 %). Conclusion: The non-extension sign may be useful for accurately determining the suitability of minimally invasive endoscopic treatment. Nevertheless, considering the limitations of retrospective analysis, a further prospective study is warranted to confirm the diagnostic reliability of the non-extension sign. [ABSTRACT FROM AUTHOR]

Background and Aim: White opaque substance (WOS) is a novel endoscopic finding in gastric neoplasms, indicating the intracellular accumulation of lipid droplets (LDs). However, gastric lipid metabolism has not been extensively investigated, even in normal mucosa. We investigated the expression profiles of lipid-metabolism-associated genes in gastric neoplasms. Methods: Thirty-four patients with early gastric cancer or adenoma were enrolled in this study. Paired biopsy samples from tumor and adjacent non-tumor areas were obtained and analyzed by real-time polymerase chain reaction. Endoscopically resected specimens were evaluated histopathologically. Results: Genes associated with β-oxidation (peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1A, and hydroxyacyl-CoA dehydrogenase), lipoprotein excretion (apolipoprotein B, microsomal triglyceride transfer protein, and acyl-CoA:cholesterol acyltransferase 2), fatty acid transport (fatty acid-binding protein), construction of triglycerides in the endoplasmic reticulum (acyl-CoA:diacylglycerol acyltransferase 1), and LD degradation/lipolysis (comparative gene identification-58, adipose triglyceride lipase) were significantly downregulated in neoplasms compared with non-tumor areas. Pyruvate dehydrogenase lipoamide kinase isozyme 4 (negative regulator of glycolysis) and adipophilin (LD surface component) were also repressed. Conversely, expression levels of genes associated with de novo lipogenesis (sterol regulatory element-binding protein 1c, acyl-CoA:diacylglycerol acyltransferase 2) were significantly enhanced in neoplasms. There was no significant difference in gene expression levels between carcinomas and adenomas, or between WOS-positive and WOS-negative neoplasms. Conclusion: Gene expression profiles in neoplasms suggest a predominance of lipid storage (lipogenesis/LD formation) over consumption ( β-oxidation/excretion/lipolysis). Lipid accumulation and WOS in gastric epithelial neoplasms may be caused by impaired mitochondrial oxidation, lipoprotein excretion, and LD degradation. [ABSTRACT FROM AUTHOR]

Background: Magnifying endoscopy (ME) with narrow-band imaging (NBI) can visualize a white opaque substance (WOS) in gastric epithelial neoplasms, gastric intestinal metaplasias, and colorectal epithelial neoplasms. Histological examination showed the WOS to be lipid droplets accumulated in the epithelium. The white appearance of colorectal hyperplastic polyps suggests that they may contain WOS, but this has not been investigated as yet. Aims: The purpose of this study was to determine whether WOS is present in colorectal hyperplastic polyps. Methods: We retrospectively evaluated endoscopic images of 26 consecutive lesions investigated by ME with NBI and subsequently endoscopically resected and confirmed to be hyperplastic polyps. Results: WOS was present in 21 of the 26 colorectal hyperplastic polyps (80.8%) based on the findings of ME with NBI. Adipophilin was present in 24 of the 26 colorectal hyperplastic polyps (92.3%). Conclusions: This study is the first to demonstrate that WOS (i.e. lipid droplets) accumulates in the epithelium of colorectal hyperplastic polyps. [ABSTRACT FROM AUTHOR]

The second sentence in the second paragraph under the heading "SMRs" on page 46 should be "SMRs were especially high for small intestinal cancer at 200 (95% CI 34.6-806.7), CRC at 29.7 (95% CI 16.5-53.7), and brain tumor at 12.5 (95% CI 1.8-88.7)". The fourth sentence in the second paragraph under the "SMRs" on page 46-47 should be "However, high SMRs were not observed for many conditions, such as respiratory disease (1.4; 95% CI 0.4-5.7), cardiovascular disease (1.3; 95% CI 0.4-3.9), suicide (1.2; 95% CI 0.4-3.6), and traffic injuries (0.7; 95% CI 0.1-5.1)". [Extracted from the article]

Background: Chromoendoscopy (CE) is relatively ineffective at identifying the cancer-specific morphological characteristics of minute gastric cancers less than or equal to 5 mm in diameter, and on its own is insufficient to make an accurate diagnosis. The aim of this study is to assess the diagnostic performance of magnifying endoscopy with narrow band imaging (M-NBI) for minute gastric cancers. Methods: The minute cancer group comprised consecutive endoscopic submucosal dissection-resected minute gastric cancers histologically measured as no larger than 5 mm in diameter. The non-cancer group comprised consecutive non-cancer lesions no larger than 5 mm in diameter. The two groups were subject to retrospective analysis to evaluate the diagnostic ability (sensitivity, specificity, and diagnostic accuracy) and reproducibility of CE and M-NBI. Results: The results for CE versus M-NBI were as follows: sensitivity 43.7 % (95 % CI, 26.5-61.0 %) versus 78.0 % (95 % CI, 64.0-92.0 %); specificity 81.6 % (95 % CI, 72.6-90.6 %) versus 92.9 % (95 % CI, 87.0-98.9 %); and diagnostic accuracy 69.9 % (95 % CI, 61.0-78.6 %) versus 88.3 % (95 % CI, 82.0-94.5 %). The sensitivity and diagnostic accuracy were, therefore, significantly higher for M-NBI than for CE. The inter-observer variability was κ = 0.08 for CE and κ = 0.56 for M-NBI, while the intra-observer variability was κ = 0.38 and κ = 0.65, respectively. Conclusions: M-NBI has greater sensitivity and reproducibility than CE for the diagnosis of minute gastric cancers. [ABSTRACT FROM AUTHOR]

Background: The presence of a white opaque substance (WOS) on magnifying endoscopy (ME) with narrow-band imaging (NBI) has been reported for gastric epithelial neoplasms, but the presence of WOS in colorectal epithelial neoplasms has not been investigated. Aims: The purpose of this study was to determine whether WOS is present in colorectal epithelial neoplasms and to clarify its clinical significance. Methods: A total of 590 colorectal epithelial neoplasms from 368 consecutive patients were retrospectively analyzed using prospectively collected data. Presence or absence of WOS in colorectal epithelial neoplasms was recorded based on the findings of ME with NBI. Results: White opaque substance was present in 236 of the 590 (40 %) colorectal epithelial neoplasms. Compared with WOS-negative patients, WOS-positive patients showed significantly larger tumors ( p < 0.0001) and significantly more tumors in the proximal colon ( p = 0.0003). WOS was more frequently present in carcinomas (66.0 %) than in adenomas (31.8 %; p < 0.0001). WOS was also more frequent in submucosal carcinomas (75.9 %) than in intramucosal carcinomas (59.0 %; p = 0.0380). Conclusions: This study confirmed the presence of WOS in colorectal epithelial neoplasms, and prevalence increased with the progression of cancer, from adenoma to carcinoma and from intramucosal carcinoma to submucosal carcinoma. [ABSTRACT FROM AUTHOR]

Background and aims: Pathological studies indicate papillary adenocarcinomas are more aggressive than tubular adenocarcinomas, but a definitive diagnosis is difficult using conventional endoscopy alone. The vessels within an epithelial circle (VEC) pattern, visualized using magnifying endoscopy with narrow-band imaging (ME-NBI), may be a feature of papillary adenocarcinoma. The aims of our study were to investigate whether the VEC pattern is useful in the preoperative diagnosis of papillary adenocarcinoma and to determine whether VEC-positive adenocarcinomas are more malignant than VEC-negative lesions. Patients and materials: From 395 consecutive early gastric cancers resected using the endoscopic submucosal dissection method, we analyzed 35 VEC-positive lesions and 70 VEC-negative control lesions matched for size and macroscopic type. We evaluated (1) the correlation between the incidence of VEC-positive cancers and the histological papillary structure and (2) differences in the incidence of coexisting undifferentiated carcinoma in VEC-positive and VEC-negative cancers and the incidence of submucosal and vascular invasion. Results: Histological papillary structure was seen in 94 % (33/35) of VEC-positive and 9 % (6/70) of VEC-negative cancers, a significant difference ( P < 0.001). The incidence of coexisting undifferentiated carcinoma was 23 % (8/35) in VEC-positive and 3 % (2/70) in VEC-negative cancers ( P = 0.002). The incidence of submucosal invasion by the carcinoma was 26 % (9/35) in VEC-positive cancers and 10 % (7/70) in VEC-negative cancers ( P = 0.045). Conclusions: The VEC pattern as visualized using ME-NBI is a promising preoperative diagnostic marker of papillary adenocarcinoma. Coexisting undifferentiated carcinoma and submucosal invasion were each seen in approximately one fourth of VEC-positive cancers. [ABSTRACT FROM AUTHOR]

Background: Fujifilm has developed a novel endoscope system with two kinds of lasers that enables us to allow narrow-band light observation with blue laser imaging (BLI). The aim of this study was to evaluate BLI magnification in comparison with narrow-band imaging (NBI) magnification for the diagnosis of colorectal neoplasms. Methods: This was a multicenter open study. A total of 104 colorectal neoplasms were examined with BLI and NBI magnifications in Kyoto Prefectural University of Medicine and Fukuoka University Chikushi Hospital. Vascular and surface patterns of tumors under BLI magnification were compared with those under NBI magnification, using a published NBI classification. The main outcome was the correlation between the NBI classification diagnosed by BLI or NBI magnification and the histopathological analyses. Results: Sixty-two cases of adenoma, 34 cases of intramucosal cancer and shallowly invaded submucosal cancer, and eight cases of deeply invaded submucosal cancer were diagnosed. The diagnostic accuracy of BLI magnification in the NBI classification was 74.0 % (77/104), similar to that of NBI magnification (77.8 %). The consistency rate between BLI and NBI magnification in the NBI classification was 74.0 %. Concerning image evaluation, the interobserver variability of two expert endoscopists (N.Y. and T.H.) in BLI magnification was κ = 0.863. On the other hand, the intraobserver variability of the two endoscopists was κ = 0.893 (N.Y.) and 0.851 (T.H.). Conclusions: BLI magnification by laser source could predict histopathological diagnosis and invasion depth of colorectal neoplasms. The diagnostic effectiveness of this method was similar to that of NBI magnification. [ABSTRACT FROM AUTHOR]

The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme 'Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, 'Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by 'Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: In Japan, aphthous-type Crohn's disease (type A CD) is thought to represent an early phase of Crohn's disease (CD), and diagnosis of type A CD is possible in the diagnostic criteria for CD in Japan. However, the details of type A CD are not well understood. Methods: Subjects comprised 649 CD patients diagnosed between 1985 and 2011. The incidence of type A CD over time was clarified in two periods (1985-2004 and 2005-2011). The course of type A CD was also investigated, and cases that did and did not progress to typical CD were compared. Results: No significant difference was seen in the incidence of type A CD between the two periods (5.2 vs. 8.5%, p = 0.125). Type A CD patients followed at our hospital progressed to typical CD at a rate of 59.3%. In comparing progressive and nonprogressive cases, the frequency of large, densely distributed aphthous lesions in the small intestine was higher among progressive cases (p = 0.018). Conclusion: Type A CD is an early phase of CD, and CD diagnostic criteria including early cases are valid in Japan. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The usefulness of magnifying gastroscopy has been reported in differentiating between benign and malignant gastric mucosal lesions. However, there have been no studies of the usefulness of magnifying endoscopy with narrow-band imaging (M-NBI) in the diagnosis of superficial (non-polypoid) elevated lesions of the stomach. In this study, we investigated the ability of M-NBI to differentiate between cancer and adenoma in superficial elevated lesions of the stomach. Methods: We examined 93 consecutive superficial elevated lesions of the stomach. We defined the endoscopic criteria for early cancer as red coloring using conventional white light imaging (C-WLI), and an irregular microvascular pattern with a demarcation line, or irregular microsurface pattern with a demarcation line, using M-NBI. We determined the sensitivity, specificity and accuracy of C-WLI and M-NBI in the diagnosis of these 93 lesions. Results: The sensitivity, specificity, and accuracy (95 % confidence interval) of C-WLI versus M-NBI were 64 % (52-76 %) versus 95 % (90-100 %), 94 % (86-100 %) versus 88 % (77-99 %), and 74 % (66-83 %) versus 92 % (86-98 %), respectively. Sensitivity and accuracy were significantly higher for M-NBI than C-WLI. Conclusions: M-NBI appears to be useful in differentiating between cancerous and adenomatous superficial elevated lesions of the stomach. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is an outstanding endoscopic technique in which a colonic lesion can be resected en-bloc. However, the procedure requires a high level of skill and the procedure has yet to be standardized. At the present time, colorectal ESD is only permitted in Japanese institutions that have been certified for advanced medical treatments. Methods: We examined 200 cases of colorectal ESD that were performed in our hospital. Results: Over time, it was found that there was a continuous improvement in the treatment outcomes along with advances in both the procedures and the peripheral equipment utilized. Conclusion: Current results suggest that the colorectal ESD procedure is relatively stable. To ensure colorectal ESD continues to be safe, indications for its use need to be more fully investigated and medical personnel must be trained to carefully perform the procedure. [ABSTRACT FROM AUTHOR]

Background: Although rare, duodenal lesions have been reported in association with ulcerative colitis (UC); however, there have been very few reports on small bowel lesions, and many aspects of their pathology and frequency remain unknown. This study determined whether small bowel lesions are present in UC by using wireless capsule endoscopy (WCE). Patients and Methods: WCE was performed on 20 patients with active UC and 10 who had undergone proctocolectomy. Results: Small bowel lesions (e.g. edema or ulcers) were observed in 11 of the 30 patients (36.6%): in eight (40%) of the 20 patients with active UC and in three (33.3%) of the 10 post-proctocolectomy patients. Ulcers that extended over a long segment or whole tertile of the small bowel were observed in five patients, and the disease type was extensive colitis in three of these and pouchitis in the other two. Age at onset was significantly lower in the 20 active UC patients that had small bowel lesions. Conclusion: WCE revealed the presence of ulcers that extended over a long segment or a whole tertile in the small bowel in active extensive colitis and pouchitis. In future, it will be necessary to assess the clinical significance of small bowel lesions in UC in detail. [ABSTRACT FROM AUTHOR]

Recent reports have focused on the development of secondary amyloidosis (AMY) as a complication of Crohn's disease (CD). The present study was carried out to investigate the frequency of AMY secondary to CD, its clinical and endoscopic features, and the importance of duodenal biopsy in detecting this disease. This study involved 408 patients diagnosed with CD who were endoscopically and histologically examined at our hospital. At follow up, we analyzed the incidence of AMY complications, the clinical features of AMY and the methods to diagnose AMY. The incidence of AMY was 2.5% (10/408). The disease type at the time of CD diagnosis was small and large bowel type (SL) in eight patients, small bowel type in one and large bowel type in one. The incidence of AMY was significantly higher in patients with SL than in patients with other disease types. The length of time from onset of CD to diagnosis of AMY was 14.1 ± 8.0 years. The cumulative incidence of AMY was 1.0% at 10 years and 5.7% at 20 years after onset. In terms of the method used to diagnose AMY, the positive rate of AMY diagnosis was 100% with endoscopic duodenal biopsy. The incidence of AMY as a complication of CD was low (2.5%). However, because this complication adversely affects patients' prognoses, it is important to check for the presence of AMY, particularly in the duodenum, in patients for whom more than 10 years have elapsed since the development of CD. [ABSTRACT FROM AUTHOR]

Takeshita M, Nakamura S, Kikuma K, Nakayama Y, Nimura S, Yao T, Urabe S, Ogawara S, Yonemasu H, Matsushita Y, Karube K & Iwashita A (2011) Histopathology, 395-407 To elucidate the clinicopathological findings of primary intestinal enteropathy-associated T cell lymphoma (EATL) in Japan, a non-endemic area for coeliac disease. Of the 24 cases, four (17%) had large-cell lymphoma (type I), and the remaining 20 (83%) had medium-sized lymphoma (type II). Lymphoma cells of the three type I cases were CD56-positive. Only one (4%) case showed typical CD56- and CD8-negative and CD30-positive type I EATL. In type II EATL, lymphoma cells of the 16 (80%) and 11 (55%) cases were positive for CD56 and CD8, respectively. Intramucosal tumour spreading and adjacent enteropathy-like lesions were detected in 15 (71%) and 16 (76%) of 21 cases, with a severe increase of intraepithelial lymphocytes (IELs) in 12 (57%). IELs of enteropathy-like lesions in five (24%) cases expressed T-bet, with no cases of CD30-positive IELs. Characteristic findings from comparative genomic hybridization of 15 cases indicated gains of 8q2 (47%), Xp (53%) and Xq (73%), but no gain of 9q3. Regarding, human leucocyte antigen (HLA) status, six cases examined did not express the DQB1*02 allele. Japanese EATL exhibited different histology, cytogenetic findings and HLA status from those of typical type I EATL. The rare incidence of coeliac disease may influence the tumour cell characteristics of EATL and IELs. [ABSTRACT FROM AUTHOR]

Background and Aim: Ulcerative colitis (UC) is not only characterized by pathological lesions localized to colonic mucosa, but also to various complications involving other organs, including postoperative pouchitis. Among these complications, diffuse gastroduodenitis with lesions resembling colonic lesions has been reported, albeit rarely. The aim of the present study was to attempt to characterize the lesions of the upper gastrointestinal tract occurring as a complication of UC, and to assess the frequency and clinical course of these lesions. Methods: A total of 322 UC patients who had undergone upper gastrointestinal endoscopy were retrospectively analyzed. We assessed the frequency of endoscopic findings, including diffuse gastroduodenal lesions resembling colonic lesions. Ulcerative gastroduodenal lesion (UGDL) associated with UC was diagnosed if lesions satisfied the following criteria: (i) improvement of the lesions with treatment of UC; and/or (ii) resemblance to UC in pathological findings. Results: UGDL satisfying the aforementioned criteria was found in 15 (4.7%) of 322 patients. All the 15 patients had UGDL accompanied by pancolitis or after proctocolectomy. Frequency in 146 patients with pancolitis was 6.2% (nine patients) and that in 81 patients who had undergone proctocolectomy was 7.4% (six patients). Four patients with diffuse ulcerative upper-gastrointestinal mucosal inflammation (DUMI) had pouchitis. In all patients except one, the lesions resolved easily with medical treatment. Conclusions: In more than half of the post-proctocolectomy patients, UGDL was related to the occurrence of pouchitis. The existence of characteristic UGDL must be taken into account in the diagnosis and treatment of UC, and UGDL is possibly related to the occurrence of pouchitis. [ABSTRACT FROM AUTHOR]

Most previous studies of the natural history of small colorectal adenomas showed no increase in size, no changes that would have necessitated treatment within a couple of years and that malignant transformation is rare. Using endoscopic follow up for a mean period of 43.1 months we assessed the development and progression of 408 protuberant adenomas that were under 10 mm in diameter. Of the 408 lesions, 22 (5.4%) underwent morphological changes. There were 12 lesions (2.9%) whose final tumor diameter had reached 10 mm or more. There were three lesions (0.7%) that developed and progressed into intramucosal cancer. We concluded from the literature and from our own results that small colorectal protuberant adenomas do not grow to advanced adenomas within 5 years. [ABSTRACT FROM AUTHOR]

Background and Aim: No reports on the relative risk of development of colorectal cancer (CRC) in Japanese patients with Crohn's disease (CD) have been published. The present study aimed to investigate the relative risk and the clinical features of CRC complicating CD among patients managed at Fukuoka University Chikushi Hospital, Fukuoka, Japan (a tertiary referral center for inflammatory bowel diseases). Methods: The clinical backgrounds were analyzed of 512 patients with CD who have been treated by our department during the last 20-year period (1985–2005) (total 6212.6 person years at risk). The standardized incidence ratio (SIR) refers to the relative risk of CRC in the subjects as compared with that in a sex- and age-matched healthy population. Results: There were six cases with CRC. The SIR was significantly higher (3.2-fold higher; 95% confidence interval, 1.2–6.9 P < 0.05) in the CD group than in the healthy population. The significant risk factors identified were female sex, mixed small and large bowel type, observation period over 20 years, onset of CD at less than 25 years of age, presence of anal disease, and positive history of surgery. The prognosis for the six cases with CRC was very poor (five cases died within 1.5 years). Conclusion: The risk of CRC in longstanding CD in Japan was similar to that in Western countries. The necessity of surveillance in the management of CD would also need to be discussed in the near future, especially in CD patients with anal lesions or fistulae, and are particularly important in patients with a 20-year or more history of CD. [ABSTRACT FROM AUTHOR]

Abstract: A successful design of conformationally restricted novel quinazolinone derivatives linked via a cyclopentene moiety as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been developed. One selected member of the new series, 8-chloro-2-[(3S)-3-(4-phenylpiperidin-1-yl)cyclopent-1-en-1-yl]quinazolin-4(3H)-one (S-16d), was found to be highly potent with IC50 =8.7nM and good brain penetration. [Copyright &y& Elsevier]

Two modern endoscopic techniques are presented with a view to determining the horizontal extent of gastric cancer. They are based on differences in the microvascular structure and density of early gastric cancer compared with those of the non-cancerous background mucosa. One technique requires magnifying endoscopy which can identify microvascular architecture that shows the characteristic findings of carcinoma. The other technique is an image-processing technique which enhances the differences in microvascular structure and density between carcinomatous mucosa and non-carcinomatous mucosa. We demonstrate an example of these techniques applied to an intramucosal carcinoma of a differentiated type, the margin of which could not be determined simply by traditional endoscopy with dye spreading. Magnified observation could detect a demarcation line between the carcinoma and non-carcinomatous mucosa. In addition, the image-processing technique enhanced the contrast of redness between cancerous area and non-cancerous mucosa. Both of these techniques are useful for detecting the precise extent of a carcinoma. The combined application of these techniques should be helpful in determining the precise horizontal extent of early gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2 inhibitors. We have recently discovered several novel classes of quinazolinones, quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may represent attractive therapeutic candidates. In PARP enzyme assays using recombinant PARP-1 and PARP-2, the quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2, and the quinazolidinone derivatives did not have selectivity for PARP-1/2. Structure-based drug design analysis via a combination of X-ray structural study utilizing the complexes of inhibitors and human PARP-1 catalytic domain, and homology modeling using murine PARP-2 suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2. [Copyright &y& Elsevier]

Abstract: We have shown that a 4-phenyl-1,2,3,6-tetrahydropyridine fragment plays an important role in improving inhibitory potency against poly(ADP-ribose) polymerase-1 (PARP-1). Various benzamide analogues linked with this fragment via alkyl spacers have been prepared and evaluated. As a result, some of them have been found to be highly potent PARP-1 inhibitors. [Copyright &y& Elsevier]

Since 1997 we have experienced three cases of low-grade colonic mucosal-associated lymphoid tissue (MALT) lymphomas. The depth of tumor invasion was evaluated by endoscopic ultrasonography (EUS) and the mass lesions were all diagnosed as having extended beyond the deep region of the submucosal layer. Although all of these patients tested negative for gastric Helicobacter pylori, their tumor lesions regressed after antibiotic treatment in accordance with H. pylori eradication therapy. In general, consensus has been reached regarding antibiotic therapy for gastric MALT lymphomas. However, as a prerequisite for antibiotic therapy, the therapy has been deemed effective against these gastric tumors if the extent of infiltration, as evaluated by EUS, is limited to the mucosal layer or the superficial region of the submucosal layer. Based on the therapeutic outcomes seen in the three patients studied here, it is suggested that antibiotic therapy might be useful in treating MALT lymphomas of the colon, even in patients with advanced invasive tumors, in contrast to the extent of the lesions in the stomach suitable for antibiotic treatment. The success of the antibiotic treatment also suggests that MALT lymphomas may be caused by unknown luminal microorganisms, other than H. pylori. [ABSTRACT FROM AUTHOR]

Abstract: The origin of a ring chromosome in a monophasic synovial sarcoma of the diaphragmatic pleura of an 18-year-old man was investigated using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis revealed the following clonal karyotypic abnormalities: 47,Y,t(X;18)(p11.2;q11.2),t(11;19)(q12;q13.4),+12,−13,+r[6]. The SYT-SSX1 fusion transcript was detected with reverse transcriptase-polymerase chain reaction analysis. SKY analysis suggested that the ring chromosome was composed of material from chromosome 8. Subsequent FISH analysis with a whole-chromosome 8 paint probe confirmed the SKY results. This study demonstrates the usefulness of SKY as an adjunct for determining the chromosomal composition of ring chromosomes. [Copyright &y& Elsevier]

Background. Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC. Methods. SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt’s classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined. Results. For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 µm if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 µm. Conclusions. These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC. [ABSTRACT FROM AUTHOR]

The crystal structure of human recombinant poly(ADP-ribose) polymerase (PARP) complexed with a potent inhibitor, FR257517, was solved at 3.0 A˚ resolution. The fluorophenyl part of the inhibitor induces an amazing conformational change in the active site of PARP by motion of the side chain of the amino acid, Arg878, which forms the bottom of the active site. Consequently, a corn-shaped hydrophobic subsite, which consists of the side chains of Leu769, Ile879, Pro881, and the methylene chain of Arg878, newly emerges from the well-known active site. [Copyright &y& Elsevier]

Discusses the clinical features and pattern of indeterminate colitis. Difficulty of differentiating between inflammatory bowel disease and ulcerative colitis (UC) and Crohn's disease (CD); UC changing to CD; CD changing to UC; Overlapping CD-like and UC-like presentations.

Background. The diagnostic accuracy of the determination of anti-Saccharomyces cerevisiae antibodies (ASCA) and its clinical significance in Crohn's disease (CD) have been reported in Western countries, but scarcely reported in Japan, where the dietary habits of people differ markedly from those of Western countries. Th present study was undertaken to examine the diagnostic accuracy and clinical significance of ASCA determination in Japanese patients with CD or ulcerative colitis (UC). Methods. Seventy-five serum samples obtained from 68 patients with CD, 34 serum samples obtained from 30 patients with UC, 35 serum samples from 35 patients with liver cirrhosis, and 31 serum samples from 31 healthy controls were examined. The optical density of each sample was measured by an enzyme-linked immunosorbent assay (ELISA) method to quantify ASCA IgA and IgG. Results. The cutoff level, as determined by discriminant analysis of the data, was 0.1502 for ASCA IgA and 0.156 for ASCA IgG. Of the 68 patients with CD, 31 (45.6%) were ASCA-positive, and of the 30 patients with UC, 4 (13.3%) were ASCA-positive according to these cutoff levels. The sensitivity and specificity of ASCA determination for the differential diagnosis of CD from UC were 45.6% and 86.7%, respectively. When the relationship between ASCA and the clinical features of CD was analyzed, ASCA positivity was found to be correlated with duration of illness. Conclusions. The specificity of ASCA was high; however, the sensitivity was not. ASCA titers were generally low in the Japanese population examined. It would be desirable to determine cutoff levels for ASCA tailored to the Japanese people for the diagnosis of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Histopathological differentiation between dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) is often difficult, because both neoplasms share some clinical features and the presence of a storiform pattern. In the present study, we investigated the usefulness of comparative genomic hybridization (CGH) in the diagnosis of these entities by examining 12 DFSP and 12 DF cases. The most frequent DNA sequence copy number changes detected in 10 (83%) of 12 DFSP cases (mean, 1.9 aberrations/tumor; range, 0–3) consisted of gains of 17q22∼qter (10 tumors), 22q13 (nine tumors), and 8q24.1∼qter (three tumors). High-level amplification, which was detected in three tumors, was seen only in chromosome 17, with 17q23∼q25 as the minimal common region. Loss of DNA sequences was not found in DFSP cases. In contrast, two (17%) of the 12 DF cases (mean, 0.5 aberrations/tumor; range, 0–4) showed DNA sequence copy number changes, although recurrent gains and losses and high-level amplifications were not observed. Gains were more common than losses in DF. Overrepresentation of 17q and 22q sequences was a common finding in DFSP but not in DF. Thus, CGH seems to be useful for distinguishing DFSP from DF in most cases. [Copyright &y& Elsevier]

Background: The prevalence of Helicobacter pylori infection in Crohn's disease (CD) patients was investigated to determine whether the presence and severity of gastroduodenal lesions were related to H. pylori infection.Methods: Infection rates were compared between CD group (n = 90) and the control group (n = 525). Correlations between endoscopically detected lesions and H. pylori positive rates were investigated. The relationship between drug therapy and the prevalence of H. pylori infection was also analyzed.Results: H. pylori-positive rate of the 90 CD patients attending our clinic was 16.7%, significantly lower than the rate in healthy controls (40.2%) (P = 0.0001). The involvement of H. pylori infection in the gastroduodenal lesions of CD patients was also examined. The prevalence of gastroduodenal lesions in all CD patients was high, 92.2%. The lesions observed included ulcers, erosion, and "bamboo joint-like lesions" of the stomach, and ulcers, erosion, stenosis, and elevated lesions of the duodenum. None of these lesions were found to be related to H. pylori infection. However, H. pylori infection was found to exacerbate gastric ulcers (P = 0.036). The analysis of a possible relationship between a history of drug therapy and the low prevalence of H. pylori infection in CD patients showed that the prevalence of H. pylori infection was significantly lower in patients who had received antibiotics for 2 weeks or more (P = 0.002).Conclusions: The results suggest that H. pylori infection is essentially unrelated to the gastroduodenal lesions observed in CD. It seems likely, however, that H. pylori infection may exacerbate gastric ulcers and that H. pylori can be eradicated by prolonged use of antibiotics. [ABSTRACT FROM AUTHOR]

Background: Early detection of ulcerative colitis-associated neoplasia (UCAN) is often difficult. The aim of this study was to clarify the morphology of initial UCAN. Methods: White-light colonoscopy images obtained within the 2 years before UCAN diagnosis were retrospectively reviewed. The primary endpoint was the frequency of visible or invisible neoplasia on the endoscopic images before UCAN diagnosis. The secondary endpoints were comparisons of (1) visible or invisible neoplasia on initial endoscopic images of early-stage and advanced cancers, (2) the clinical backgrounds of patients in whom neoplasia was visible or invisible on initial endoscopic images, and (3) the clinical backgrounds of patients with distinct and indistinct UCAN borders. Results: Of the 27 UCAN lesions (11 early-stage; 16 advanced-stage), 25.9% (n = 7) were initially visible and 74.1% (n = 20) were invisible. The mean interval between the last surveillance colonoscopy and UCAN diagnosis was 14.5 ± 6.7 months. Of early-stage cancers, 18.2% (n = 2) were visible and 81.8% (n = 9) were invisible. Of advanced-stage cancers, 31.3% (n = 5) were visible and 68.8% (n = 11) were invisible. Invisible lesions were significantly more common in the rectum (p = 0.011) and tended to be more common in patients with inflammation and left-sided colitis (p = 0.084, p = 0.068, respectively). Patients with indistinct UCAN borders were significantly more likely to present with inflammation than those with distinct UCAN borders (p = 0.021). Conclusion: More careful surveillance is needed because rectum lesions and inflammation are difficult to identify as neoplasia even within the 2 years before a UCAN diagnosis. [ABSTRACT FROM AUTHOR]

Villous tumors are rare and their histological diagnosis from biopsy specimens is often difficult. To ascertain its tumor progression, including the genetic events, would be useful for clinical treatment. Clinicopathological features and the expression of p53 and bcl-2 proteins were investigated in 50 villous tumors from 49 patients. The patients’ ages ranged widely from 32 to 84 years (average, 61 years). Females were more frequently affected than males (male: female ratio, 20: 29). Thirty-six (72%) of the villous tumors were present within the sigmoid colon and rectum. Histologically, 17 (34%) of these contained carcinomas in villous adenomas (CIVA), while 24 (73%) of 33 villous adenomas (VA) contained high-grade dysplasia. Most of the CIVA revealed well-differentiated adenocarcinoma, often with focal or diffuse mucin pools. Three lesions of invasive carcinomas were composed of extremely well-differentiated components. The average size of the CIVA (79 mm) was significantly larger than that of the VA (51 mm). Overexpression of p53 protein was recognized in 12% of VA, in 24% of mucosal components of CIVA and in 18% of invasive components of CIVA. Overexpression of bcl-2 was recognized in 57% of VA, 33% of mucosal components of CIVA, and 7% of invasive components of CIVA. Several characteristic features were recognized in villous tumors, which comprised: (i) a high frequency of coexistence of carcinoma; (ii) multiple foci of carcinomas arising in adenomatous tumors; (iii) a lower histological grade of carcinomas, often with mucin pools; (iv) the existence of extremely well-differentiated adenocarcinomas; and (v) less frequent expression of p53 protein in the carcinomatous components. According to these findings, the pathway of tumor progression in the villous tumors is possibly different from that of sporadic colorectal carcinomas. Because of the peculiarity of villous tumors, careful clinical management is required. [ABSTRACT FROM AUTHOR]