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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 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 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]

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]

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]

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: 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]

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]

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]

Since superficial tumors have been found, their peculiar pathologic features have evoked questions concerning their biologic behavior, their natural history. The aim of the present study was to elucidate the natural history of colorectal cancers (CRCs) including superficial cancers, using a retrospective radiologic method. Forty nine cancers that had had initial configurations of early cancer seen by previous radiography and that were examined pathologically were the subject of the present study. Growth speeds [doubling time (DT) calculation] and configurational changes at the various stages (invasion depth) were compared between polypoid growth (PG) and nonpolypoid growth (NPG). Growth speeds of mucosal cancer and submucosal cancer were also compared. The results showed that early CRC grows slowly (DT 31.2 months) when the cancer is limited to the mucosa. However, as tumors grow down to the submucosa, their growth speed accelerates (DT 25.8 months). The DT of these early cancers were longer than that of advanced cancers. The pathologic growth pattern (NPG or PG) of the CRCs did not affect the tumor growth speed. In respect to tumor configuration, when the tumor is limited to the submucosa the antecedent growth pattern may be easily deduced. It seems difficult, however, to know the initial growth patterns in advanced cancers because cancers with polyloid growth frequently change to a nonpolypoid growth pattern when in advanced stages. Among 32 advanced cancers, only 6 (19%) derived from IIc/IIc+IIa cancer. The most common (more than 70%) origin of advanced cancer seems to be IIa, Is, and Isp lesions. These results suggest that NPG cancers or superficial depressed cancers are not the main origins of advanced cancers, and that these cancer do not show extraordinarily rapid growth. [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]

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]

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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]

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]

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]