Naoto Yoshitake

Matched case‐control study comparing endoscopic submucosal dissection and endoscopic mucosal resection for colorectal tumors

Background and Aim:  For large colorectal tumors, the en bloc resection rate achieved by endoscopic mucosal resection (EMR) is insufficient, and this leads to a high rate of local recurrence. As endoscopic submucosal dissection (ESD) has been reported to achieve a higher rate of en bloc resection and a lower rate of local recurrence in the short‐term, it is expected to overcome the limitations of EMR. We conducted a matched case‐control study between ESD and EMR to clarify the effectiveness of ESD for colorectal tumors.

Colonic expression of heme oxygenase-1 is associated with a better long-term survival in patients with colorectal cancer

Objective. Heme oxygenase-1 (HO-1) has emerged as a crucial mediator of mucosal defense in the gastrointestinal tract. Its metabolic pathway products, biliverdin/bilirubin and carbon monoxide, can reduce oxidative stress and inflammation, and promote resistance to apoptosis. The role of HO-1 in gastrointestinal malignancies, however, remains to be elucidated. The purpose of this study was to analyze HO-1 expression in human colon adenoma and cancer samples. Material and methods. Fifty-five paraffin-embedded surgical specimens of colorectal cancer and 19 colonic adenoma samples were stained immunhistochemically for HO-1 expression using an anti-HO-1 monoclonal antibody. HO-1 expression was evaluated independently by two different investigators and subsequently correlated to clinical data and patients’ life expectancy. Results. Focal HO-1 expression could be documented in 41.8% (23/55) of patients with colorectal cancer. HO-1 expression in colonic adenoma was detectable in 36.8% (7/19) of cases. The rate of lymphatic tumor invasion was significantly lower in colorectal cancer samples expressing HO-1 (p=0.048). Additionally, fewer lymph node metastases were found in colorectal cancer samples with HO-1 expression, but these differences did not reach statistical significance. Mean observation period was 65.87±3.96 months. Kaplan-Meier analysis showed a significantly better survival for colorectal cancer patients with colonic HO-1 expression (p=0.018). Conclusions. This study demonstrates that colonic HO-1 may be a prognostic marker of colorectal-cancer outcome.

Relationship between the Degree of Endoscopic Atrophy of the Gastric Mucosa and Carcinogenic Risk

Background: The relationship between Helicobacter pylori infection and gastric cancer has been demonstrated, and the risk of gastric cancer occurrence is known to increase with the progression of atrophic changes associated with chronic gastritis. Endoscopic evaluation of the degree and extent of atrophy of the gastric mucosa is a simple and very important means of identifying a group at high risk for gastric cancer. This study aimed to clarify the carcinogenic risk in relation to the degree of atrophy. Methods: A total of 27,777 patients (272 with early gastric cancer and 135 with advanced gastric cancer) were included in this study. Endoscopically evaluated atrophy of the gastric mucosa was classified as C-0 to O-3 according to the Kimura and Takemoto classification system. Results: The cancer detection rate in relation to the degree of gastric mucosal atrophy was 0.04% (2/4,183 patients) for C-0, 0% (0/4,506) for C-1, 0.25% (9/3,660) for C-2, 0.71% (21/2,960) for C-3, 1.32% (75/5,684) for O-1, 3.70% (140/3,780) for O-2 and 5.33% (160/3,004) for O-3. As to the proportions of differentiated and undifferentiated cancers, the latter were relatively frequent in the C-0 to C-2 groups, but differentiated cancers became predominant as atrophy progressed. On the other hand, the number of both differentiated and undifferentiated cancers detected increased as gastric mucosal atrophy progressed. In addition, open-type atrophy was found in 29 (96.7%) of 30 patients with synchronous multiple gastric cancers and in all 20 patients with metachronous multiple gastric cancers. Conclusion: Endoscopic evaluation of gastric mucosal atrophy can provide a simple and reliable predictive index for both current and future carcinogenic risk.

Role of Necl-5 in the pathophysiology of colorectal lesions induced by dimethylhydrazine and/or dextran sodium sulphate.

Necl‐5 is an immunoglobulin‐like molecule that was originally identified as a poliovirus receptor. Although Necl‐5 expression is often up‐regulated in cancer cells, its pathophysiological significance in the development of cancer remains unclear. We investigated the roles of Necl‐5 in the development of colitis‐associated neoplasia. Necl‐5‐deficient mice were generated and treated with dimethylhydrazine (DMH) and/or dextran sodium sulphate (DSS) to induce colitis and its associated neoplasias. Colon tissues were examined for histology, Ki‐67 expression by immunohistochemistry and K‐ras gene mutation. Colon tumours occurred significantly less frequently in heterozygous (Necl‐5+/−) or homozygous Necl‐5‐deficient (Necl‐5−/−) mice than in wild‐type (WT) mice with DMH/DSS treatment. Total ulcer index and inflammatory cell infiltration were significantly lower in Necl‐5−/− mice than in WT mice with DSS alone or DMH/DSS treatment. Colon tumours in both WT and Necl‐5−/− mice showed high cell proliferation ability but lacked K‐ras mutation. The total Ki‐67 labelling index in non‐neoplastic colon epithelium was significantly higher in WT (45.9 ± 0.94) than in Necl‐5+/− (34.3 ± 1.40) or Necl‐5−/− (27.7 ± 1.15) mice with DMH/DSS treatment (p < 0.001). Necl‐5 plays a role in the development of colitis‐associated cancer by up‐regulating colonic mucosal cell proliferation. Copyright

Clinical importance of colonoscopy in patients with gastric neoplasm undergoing endoscopic submucosal dissection

AIM To evaluate the usefulness of total colonoscopy (TCS) for patients undergoing gastric endoscopic submucosal dissection (ESD) and to assess risk factors for colorectal neoplasms. METHODS Of the 263 patients who underwent ESD at our department between May 2010 and December 2013, 172 patients undergoing TCS during a one-year period before and after ESD were targeted. After excluding patients with a history of surgery or endoscopic therapy for colorectal neoplasms, 158 patients were analyzed. Of the 868 asymptomatic patients who underwent TCS during the same period because of positive fecal immunochemical test (FIT) results, 158 patients with no history of either surgery or endoscopic therapy for colorectal neoplasms who were matched for age and sex served as the control group for comparison. RESULTS TCS revealed adenoma less than 10 mm in 53 patients (33.6%), advanced adenoma in 17 (10.8%), early colorectal cancer in 5 (3.2%), and advanced colorectal cancer in 4 (2.5%). When the presence or absence of adenoma less than 10 mm, advanced adenoma, and colorectal cancer and the number of adenomas were compared between patients undergoing ESD and FIT-positive patients, there were no statistically significant differences in any of the parameters assessed. The patients undergoing ESD appeared to have the same risk of colorectal neoplasms as the FIT-positive patients. Colorectal neoplasms were clearly more common in men than in women (P = 0.031). Advanced adenoma and cancer were significantly more frequent in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus (P = 0.019). CONCLUSION In patients undergoing gastric ESD, TCS appears to be important for detecting synchronous double neoplasms. Advanced adenoma and cancer were more common in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus. Caution is therefore especially warranted in patients with these risk factors.