[Usefulness and safety of observing anorectal lesions by colon capsule endoscopy].

We investigated the findings of rectoanal lesions in 190 patients who underwent colon capsule endoscopy (CCE) at our hospital. Internal hemorrhoids were observed in 70 (36.8%) patients and rectal polyps in 19 (10%) patients. When conventional endoscopy (colonoscopy and double balloon endoscopy) was considered the gold standard, the sensitivity and specificity of rectal polyps were 75% and 93.4%, respectively, and those of internal hemorrhoids were 88.9% and 92.7%, respectively. The prevalence of constipation was significantly higher in the false-negative group for internal hemorrhoids, and the colonic transit time was significantly shorter in the false-negative and false-positive groups for rectal polyps. No adverse events occurred in any of the patients. CCE might be a useful and safe examination method for rectoanal lesions.

[A case of melena and perforation during chemotherapy for peripheral T-cell lymphoma, not otherwise specified of the small intestine].

A 71-year-old male presented with gastrointestinal bleeding. Double-balloon endoscopy revealed diffuse thickening of the wall and a shallow ulcer measuring approximately 10cm in the mid jejunum. Biopsy revealed diffuse proliferation of large lymphoid cells that were immunohistochemically positive for CD3, CD5, and bcl-2 but negative for CK, CD10, CD20, and bcl-6. The cyclin D1 labeling index was 3% and the MIB-1 labeling index was 61%. On the basis of these findings, he was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) of the small intestine. Following four courses of THP-COP chemotherapy, he developed intestinal perforation and underwent partial resection of the small intestine. He is currently undergoing further chemotherapy.

Follow-up outcomes in patients with negative initial colon capsule endoscopy findings.

BACKGROUND: Colon capsule endoscopy (CCE), which became clinically applicable in 2006, is a simple and noninvasive procedure to evaluate colonic diseases; the accuracy of second-generation CCE, introduced in 2009, has dramatically improved. Currently, CCE is used as an alternative method for colorectal cancer screening, as well as for evaluating the mucosal lesions of inflammatory bowel disease, in cases where performing colonoscopy (CS) is difficult. However, the outcomes of CCE are uncertain. AIM: To investigate the outcomes of Japanese patients with negative findings (no polyps or colorectal cancer) on initial CCE. METHODS: This retrospective, single-center study was conducted at the Endoscopic Center at Aishinkai Nakae Hospital. This study included patients who underwent continuous CCE between November 2013 and August 2019, that exhibited no evidence of polyps or colorectal cancer at the initial CCE, and could be followed up using either the fecal immunochemical test (FIT), CS, or CCE. The observational period, follow-up method, presence or absence of polyps and colorectal cancer, pathological diagnosis, and number of colorectal cancer deaths were evaluated. RESULTS: Thirty-one patients (mean age, 60.4 ± 15.6 years; range, 28-84 years; 14 men and 17 women) were enrolled in this study. The reasons for performing the first CCE were screening in 12, a positive FIT in six, lower abdominal pain in nine, diarrhea in two, and anemia in two patients. The mean total water volume at the time of examination was 3460 ± 602 mL (2250-4800 mL), and a total CS was performed in 28 patients (90%). The degree of cleanliness was excellent in 15 patients and good in 16, and no poor cases were observed. No adverse events, such as retention or capsule aspiration, were observed in any of the patients. The mean follow-up period was 3.1 ± 1.5 years (range, 0.3-5.5 years). Follow-up included FIT in nine, CS in 20, and CCE in four patients (including duplicate patients). The FIT was positive in two patients, while CS revealed five polyp lesions (three in the ascending colon, one in the transverse colon, and one in the descending colon), with sizes ranging between 2 mm and 8 mm. Histopathological findings revealed a hyperplastic polyp in one patient, and adenoma with low grade dysplasia in four patients; colorectal cancers were not recognized. In the follow-up example by CCE, polyps and colorectal cancer could not be recognized. During the follow-up period, there were no deaths due to colorectal cancer in any of the patients. CONCLUSION: We determined the outcomes in patients with negative initial CCE findings.

Nodular gastritis in Japanese young adults: endoscopic and histological observations.

BACKGROUND: Endoscopic findings of nodular gastritis (NG) are characterized by the presence of Helicobacter pylori infection and follicular gastritis. A possible association with diffuse-type gastric cancer has recently been suggested from observations in Japanese. Our aim was to analyze antral nodularity and histological scores in young adults. METHODS: Subjects (55 men and 45 women; age range, 18-25 years) with upper gastrointestinal (GI) symptoms or positive H. pylori antibodies underwent endoscopy. One specimen each was obtained from the greater and lesser curvatures (curves) of the corpus and from those of the antrum. Endoscopic appearance was assessed using 0.2% indigo carmine, and histopathological grading was evaluated by the updated Sydney System. RESULTS: Antral nodularity was identified in none of 17 H. pylori-negative subjects and in 55 of 83 (66.3%) H. pylori-positive subjects. By the distribution of nodular or granular elevated lesions in the antrum, NG was divided into diffuse (n = 27) or nondiffuse (n = 28) types. The diffuse-type NG predominantly affected women (odds ratio, 3.9; 95% confidence interval, 1.5-10). The atrophy scores in the lesser curve of the antrum were significantly higher in the nondiffuse than in the diffuse group. However, the scores for activity, inflammation, and H. pylori density were not significantly different among the three groups. CONCLUSIONS: Diffuse-type NG depended on sex, and antral nodularity seemed to change from the diffuse to the nondiffuse type in association with atrophy.

Histological risk markers for non-cardia early gastric cancer. Pattern of mucin expression and gastric cancer.

There are limited data regarding the prognostic value of the pattern of mucin expression in IM. To examine the role of the type of IM and pattern of mucin expression in IM as histological risk markers of gastric cancer, 80 patients with a history of endoscopic mucosal resection (EMR) for early gastric cancer and 80 sex and age-matched controls were studied. Serum levels of pepsinogen (PG) were measured by RIA, and MUC2, MUC5AC and MUC6 were evaluated immunohistochemically. There is a significant association between types of IM and atrophic scores or PG levels. The most incomplete IM (type II and III) preserving gastric mucin is the gastric and intestinal mixed (GI) type, whereas the complete type is the intestinal (I) type especially in the corpus lesser curve. Gastric cancer was most significantly associated with incomplete IM in the corpus lesser curve (OR=6.4; 95% CI, 2.0-21, p=0.002). Asynchronous multiple lesions were associated with incomplete IM in the corpus greater curve (OR=4.8; 95% CI, 1.4-16, p=0.01). Classification of IM obtained using fixed-point biopsy samples may enhance the ability of surveillance programs to detect patients at increased risk of gastric cancer.

Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation in paramalignant lesions.

BACKGROUND: Gastric cancer is typically an end result of Helicobacter pylori-associated chronic gastritis. The pathogenesis is thought to involve effects on gastric mucosal epithelial cell turnover. In this study, we aimed to compare apoptosis and proliferation in the noncancer-containing mucosa of H. pylori-positive patients with early gastric cancer with these phenomena in H. pylori-positive controls. METHODS: Two specimens each were obtained from the greater and lesser curvatures of the corpus and from the greater curvature of the antrum. The histopathological grading used was the updated Sydney System. Apoptotic epithelial cells were detected using the terminal deoxy nucleotidyl transferase-mediated deoxy-uridine triphosphate (dUTP) biotin nick-end labeling (TUNEL) method. The expression of Ki 67 was evaluated by immunostaining. RESULTS: Forty-five H. pylori-positive patients with endoscopic mucosal resection for early gastric cancer and 52 H. pylori-positive controls were studied. Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (IM; odds ratio [OR], 19.1; 95% confidence interval [CI], 6.9-53.2; P < 0.001). The apoptotic index (AI) in the greater curvature of the corpus and the proliferation index (PI) in each part were significantly higher in cancer patients than in the control group. The median PI in the antrum was significantly higher in the incomplete IM group than that in the complete IM group (17.6 vs 12.6; P = 0.009). The PI and the AI in the greater curvature of the corpus correlated with the activity score, and the PI correlated with the IM score. CONCLUSIONS: In the cancer patients, H. pylori-induced gastritis was associated with increased cell proliferation and apoptosis compared with mucosal findings in the controls. IM seems to be one of the most important factors affecting cell proliferation and may be one of the components of carcinogenesis that results in proliferation-dominant cell kinetics.

Effects in the control of edema of the papilla of Vater by epinephrine saline irrigation after endoscopic retrograde cholangiopancreatography in an endoscopy center in Japan, 2003 to 2007: exploratory retrospective analysis to evaluate the characteristics of eligible patients with a focus on serum amylase levels.

OBJECTIVE: To evaluate the effects of localized irrigation with epinephrine saline after endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: One hundred and fourteen patients who underwent ERCP in our institute were treated with or without irrigation using epinephrine diluted in saline after ERCP to prevent post-ERCP pancreatitis. The serum amylase levels, white blood cell counts, and urine amylase levels were measured at 24 and 48 hours after ERCP. RESULTS: The treatment resulted in improvements in all items. A univariate analysis of the explanatory variables between the treatment and untreated groups revealed the treatment to be effective, but not statistically significant. Gender and cannulation of the pancreatic duct were the only variables with significant partial regression coefficients in the multiple regression model with all explanatory variables (p=0.045). When a stratified analysis was conducted using gender as a moderator variable, the treatment became a significant preventive factor (p=0.038), and cannulation of the pancreatic duct was a significant risk factor (p=0.027) in female patients. CONCLUSION: We suggest that irrigating with epinephrine saline into the papilla may be effective for preventing pancreatitis in female patients who received ERCP with cannulation of their pancreatic duct.

Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia.

Loss of Sonic Hedgehog (Shh) and aberrant CDX2 expression are early changes correlating with the presence of intestinal metaplasia that occur in the gastric mucosa prior to neoplastic transformation. The aim of this study was to compare the improvement in corpus gastritis with Shh and CDX2 expression after H. pylori eradication between subjects at high risk for gastric cancer and controls. The usefulness of serum pepsinogen levels as a predictor of resolved corpus gastritis was also examined. Seventy patients with endoscopic resection for early gastric cancer and 30 controls were studied. Expression of Shh and CDX2 were evaluated by immunostaining. Serum levels of pepsinogen I before eradication in the patients scored as having improvement of corpus atrophy were significantly higher than in the patients without improvement (<0.01). Residual inflammation at the corpus lesser curve was more frequently detected in the cancer group than in the controls (OR 4.6 95% C.I. 1.6-13.5) and in the mucosa with incomplete intestinal metaplasia rather than in those without incomplete intestinal metaplasia (OR 7.6 95% C.I. 2.4-24.3). Atrophy, expression of Shh and CDX2 at the corpus lesser curve significantly improved in mucosa without incomplete intestinal metaplasia (p < 0.01), but not in mucosa with incomplete intestinal metaplasia. In conclusion, H. pylori eradication prior to development of incomplete intestinal metaplasia improves corpus gastritis and may prevent gastric cancer. Pepsinogen I may be a useful marker in patients with a residual higher risk of gastric cancer after H. pylori eradication.

Histologic and serum risk markers for noncardia early gastric cancer.

Corpus dominant gastritis and intestinal metaplasia (IM) are considered markers of increased risk of gastric carcinoma. The aim of our study was to determine serum and histologic risk markers of gastric cancer. Antral and corpus histology, pepsinogen and gastrin 17 levels were compared among patients with history of endoscopic mucosal resection (EMR) for early gastric cancer and controls. Serum pepsinogen (PG) and gastrin 17 levels were measured by RIA. There were 53 gastric cancer patients and 75 controls. The scores for IM in each region and atrophy at the lesser curvature of the corpus were significantly higher in the cancer group than in the H. pylori-positive control group. IM at the greater curvature of the corpus and atrophy at the lesser curvature of the corpus were associated with multiple malignant lesions. Although corpus gastritis was associated with an increased risk of gastric cancer (odds ratio [OR] = 3.4; 95% confidence interval [CI] 1.6-7.0) (p = 0.001), the most important marker was the presence of IM at the lesser curvature of the corpus (OR = 15.1; 95% CI 4.3-52.6) (p < 0.001)). The best cut-off points of serum markers for gastric cancer were a PG I concentration of 45 ng/mL or less and a gastrin 17 >60 pg/mL (sensitivity = 83%; specificity = 68%). IM at the lesser curvature of the corpus and the combination of serum gastrin 17 and PG I identified a group at high risk for development of gastric cancer. Annual endoscopic follow-up is warranted for patients with IM found at the greater curvature of the corpus.

Evidence that loss of sonic hedgehog is an indicator of Helicobater pylori-induced atrophic gastritis progressing to gastric cancer.

BACKGROUND: The absence of sonic hedgehog (Shh) correlates with the development of intestinal metaplasia (IM) suggesting the possibility of an association between Shh expression and neoplastic transformation. AIM: To examine Shh expression in the noncancerous mucosa of patients with gastric cancer and compare it to Shh expression in Helicobater pylori-infected and uninfected controls. We also assessed the relationship between the type of IM and Shh expression. METHODS: Fifty-three patients with endoscopic mucosal resection (EMR) for early gastric cancer and 48 sex- and age-matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. The histopathological grading used was the updated Sydney System. IM was categorized by staining with Alcian blue/high iron diamine. Expression of Shh was evaluated by immunostaining. RESULTS: The Shh immunostaining in the corpus lesser curve significantly correlated with the scores of atrophy and IM. Shh staining in the antrum was significantly higher in H. pylori-negative controls than those in H. pylori-positive controls as well as in patients without IM compared to those with IM (p < 0.001). The Shh staining in the corpus lesser curve decreased in H. pylori-negative controls, -positive controls and the cancer group respectively (p= 0.003), and was significantly higher (p= 0.006) in the complete IM group compared to those in the incomplete IM group. CONCLUSIONS: Loss of Shh is an early change that occurs in the mucosa prior to neoplastic transformation. Its loss correlates with the type of IM and may play a role in carcinogenesis.