Rintarou Narisawa

Nuclear translocation of beta-catenin in colorectal cancer

Post-translational stabilization of beta-catenin through mutation of the adenomatous polyposis coli (APC) gene has been proposed as an early step in colorectal carcinogenesis. Beta-catenin may translocate from the cytoplasm to the nucleus, where it might serve as a transcriptional factor to stimulate tumour formation. We investigated intracellular localization of beta-catenin in sporadic colorectal adenomas and cancers as well as familial adenomatous polyposis (FAP). Nuclear over-expression of beta-catenin was observed in 35% (7/20) of intramucosal cancers and 42% (23/55) of invasive cancers but was not seen in any adenomas from sporadic or FAP cases. Cytoplasmic beta-catenin in adenomas was significantly higher than that of normal mucosa in both sporadic and FAP cases. The cytoplasmic intensity index of cancers was significantly higher than that of sporadic adenomas, but the index was not correlated with nuclear expression in cancers. These findings suggest that nuclear translocation of beta-catenin is involved in development of intramucosal cancer rather than adenoma, independent of APC mutations. Cytoplasmic accumulation of beta-catenin may occur in adenomas, but it remains to be determined whether this is a cause or a consequence of colorectal cancer.

Impact of endoscopic screening on mortality reduction from gastric cancer

AIM To investigate mortality reduction from gastric cancer based on the results of endoscopic screening. METHODS The study population consisted of participants of gastric cancer screening by endoscopy, regular radiography, and photofluorography at Niigata city in 2005. The observed numbers of cumulative deaths from gastric cancers and other cancers were accumulated by linkage with the Niigata Prefectural Cancer Registry. The standardized mortality ratio (SMR) of gastric cancer and other cancer deaths in each screening group was calculated by applying the mortality rate of the reference population. RESULTS Based on the results calculated from the mortality rate of the population of Niigata city, the SMRs of gastric cancer death were 0.43 (95%CI: 0.30-0.57) for the endoscopic screening group, 0.68 (95%CI: 0.55-0.79) for the regular radiographic screening group, and 0.85 (95%CI: 0.71-0.94) for the photofluorography screening group. The mortality reduction from gastric cancer was higher in the endoscopic screening group than in the regular radiographic screening group despite the nearly equal mortality rates of all cancers except gastric cancer. CONCLUSION The 57% mortality reduction from gastric cancer might indicate the effectiveness of endoscopic screening for gastric cancer. Further studies and prudent interpretation of results are needed.

Size-dependent expression of cyclooxygenase-2 in sporadic colorectal adenomas relative to adenomas in patients with familial adenomatous polyposis.

Several studies have indicated that administration of non‐steroidal anti‐inflammatory drugs (NSAID) to patients with familial adenomatous polyposis (FAP) results in a regression of colorectal adenomas through inhibition of cyclooxygenase‐2 (COX‐2). It is thought that sporadic colorectal adenomas might also be useful targets for the chemoprevention of colorectal cancer, but a marked effect of NSAID on the regression of sporadic adenomas has not been observed. We investigated the immunohistochemical expression of COX‐2 in sporadic tubular adenomas (n = 100) from 63 patients and in tubular adenomas (n = 121) from 12 patients with FAP, in order to determine if chemoprevention might be more successful in sporadic adenomas once they have reached a certain size. COX‐2 scores were significantly lower (P < 0.0001) in small (< 5 mm in diameter) adenomas than in large (≥ 5 mm) adenomas. This was observed in both sporadic cases and in cases involving patients with FAP. With regard to small (< 5 mm) adenomas, significantly higher (P = 0.02) COX‐2 scores were obtained in adenomas resulting from FAP than sporadic adenomas. The variation in COX‐2 expression observed among sporadic adenomas of different sizes should be taken into account when making decisions regarding attempts at chemoprevention using NSAID. Sporadic adenomas 5 mm or larger with upregulated COX‐2 expression are potentially useful targets for the antiproliferative effects of NSAID.

Comparison of cyclo-oxygenase 2 expression in colorectal serrated adenomas to expression in tubular adenomas and hyperplastic polyps

Background and aims: Serrated adenoma (SA) is a newly defined category of colorectal neoplasia that contains features of both adenoma and hyperplastic polyp, and has two patterns, hyperplastic and cerebriform patterns. Since cyclo-oxygenase 2 (COX-2) has been found upregulated in colorectal cancers and adenomas, we examined whether either the hyperplastic or cerebriform pattern of SA has the potential for tumor progression and should be a target for clinical treatment. Patients and methods: An immunohistochemical scoring system was used to compare COX-2 expression in colorectal SAs (n=79), tubular adenomas (n=66), and hyperplastic polyps (n=21). Results: COX-2 scores were significantly higher in SA of the cerebriform pattern (n=44) than in SA of the hyperplastic pattern (n=35). There was no difference in COX-2 scores between SA of the cerebriform pattern and tubular adenoma. In SA accompanied by hyperplastic polyp (n=26) the hyperplastic components expressed little COX-2, the same as traditional hyperplastic polyps. COX-2 expression in the SA component was similar to that in pure SA. Conclusion: SA of the cerebriform pattern should be treated similarly as traditional tubular adenomas. COX-2 induction may additionally be involved in progression from hyperplastic polyp to SA.

Comparison of the Effectiveness of Geranylgeranylacetone with Cimetidine in Gastritis Patients with Dyspeptic Symptoms and Gastric Lesions: A Randomized, Double-Blind Trial in Japan

Background and Aim: Controversy remains regarding the treatment of choice for chronic gastritis patients with dyspeptic symptoms when Helicobacter pylori eradication is not indicated or fails for their gastric lesions. A multicenter, randomized, double-blind trial was performed to compare the effectiveness of geranylgeranylacetone (GGA), a mucoprotective drug, against cimetidine (CIT), an H2-receptor antagonist, on the treatment of erosions and petechial hemorrhage in H. pylori-infected patients with dyspeptic symptoms. Methods: 128 H. pylori-positive gastritis patients with mucosal erosions and/or petechial hemorrhage were randomized to receive 150 mg GGA t.i.d. or 400 mg CIT b.i.d. for 2 weeks. Improvement and cure rates on endoscopic findings, symptom disappearance rates, and changes in mucosal neutrophil infiltration were compared. Results: Endoscopic improvement rates were significantly higher in the GGA group (n = 50) than in the CIT group (n = 54; 86.0 vs. 64.8%, p = 0.014). Endoscopic cure rates were also significantly higher for GGA than for CIT (80.0 vs. 55.6%, p = 0.012). Symptom disappearance rates were 52.0% for GGA and 42.6% for CIT, but the difference was not significant. There was also no significant difference in mucosal neutrophil infiltration between the groups. Conclusion: GGA treatment appears to be more effective than CIT for chronic gastritis-associated erosion and petechial hemorrhage.

Morphological Study of Pancreas Divisum in Niigata Using ERCP

Abstract: The morphological characteristics and incidence of pancreas divisum (PD) in Niigata were investigated by studying 16,646 cases diagnosed by ERCP. These cases had been patients in 16 hospitals located in Niigata prefecture.

4487 A novel approach to detecting colorectal cancers: direct identification of histology by magnifying endoscopy.

Background: By magnifying endoscopic examination with dye spraying method, the openings of colonic glands, “pits” of various shapes and sizes, are found on the surface of colonic mucosa. In our data, pits of roundish, asteroid, tubular, and branching shape are seen on the surface of benign lesions. On the other hand, pits of irregular and complicated shapes can be seen on the surface of early cancers. Accordingly, it is important to clarify whether surface structure of colorectal cancer really reflects its histological findings. Aims: To examine whether complexity of pits revealed by magnifying endoscopic findings is correlated with that of histological findings, finding of the glandular structure and cellular atypia. Methods: 36 submucosal invasive cancers, 27 mucosal cancers, 40 adenomas and 10 specimens of normal mucosa were investigated. Pits of all lesions were examined by means of the magnifying video endoscope (Olympus, 240-Z) as well as the stereomicroscope after endoscopic or surgical removal. Histological sections were prepared from the area where pits of irregular shapes were located. Complexity of shapes of pits and histological glandular structures were evaluated by fractal dimension (FD) with the boxcounting method. In the present study irregular pits were morphologically classified into three types: irregularly roundish (IR), irregularly polygonal (IP) and irregularly branching (IB) pits. Results: 1) Fractal dimensions of pits were significantly correlated with those of glandular structures as revealed by the analysis of variance in regression (p

6977 Colonoscopic and pit pattern diagnosis in serrated adenomas of the colon.

Background and aims: The histological features of serrated adenomas (SAs) have been proposed (Fenoglio, 1990), and discussed in several reports. However, the characteristic features of these polyps observed by endoscopy are still debatable.We compared the endoscopic features and pit patterns of SAs and hyperplastic polyps (HPs), and attempted to correlate them with histological features. Materials and methods: Endoscopic findings in 74 SAs and 90 HPs were investigated with respect to location and configuration. All of them were endoscopically resected. After fixation and crystal violet staining, the surface pit patterns of these polyps (SAs 52 lesions) were analyzed by dissecting microscopy.We attempted to correlate macroscopic with histologic features, and calculated the incidence of highgrade dysplasia (according to the WHO criteria). Results: SAs were divided into two types according to their endoscopic features; 50 were of the polypoid type (P-type) with a cerebriform or granular surface, and 24 were of the flat type (F-type) with a smooth surface, sometimes showing a granular surface when larger than 10 mm.Thirty-eight (76.0%) of the P-type lesions were reddish and 18 (75.0%) of the F-type were whitish. F-type SAs were similar to HPs in both color and configuration. Although P-type lesions were located predominantly in the proctosigmoid (C, A 12% vs S, R 60%), F-type lesions were distributed almost evenly (C, A 33.3% vs S, R 45.8%). The mean size of P-type lesions was 10.0±5.7 mm and that of Ftype lesions was 8.9±4.5mm, both being significantly larger than HPs (5.4±2.9mm) (P