Increasing trend of Helicobacter pylori-uninfected gastric cancer without gastric atrophy.

The prevalence of Helicobacter pylori (H. pylori) has decreased during several decades due to improvements in the sanitary environment in Japan. Consequently, a relative increase in the incidence of H. pylori-uninfected gastric cancer is expected. We analyzed the trends in H. pylori-uninfected gastric cancer. Two hundred fifty-eight patients with gastric cancer were retrospectively analyzed. The study was divided into four periods: 2008-2011 (first period), 2012-2014 (second period), 2015-2017 (third period), and 2018-2021 (fourth period). The status of H. pylori infection was divided into four categories: uninfected, successful eradication, spontaneous eradication, and persistent infection. Gastric mucosal atrophy was divided into six grades according to the Kimura-Takemoto classification. The proportion of H. pylori infections significantly changed over the study period (p = 0.007). In particular, the rate of H. pylori-uninfected gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 13.4% in the first, second, third, and fourth periods, respectively; p = 0.0013). The rate of no atrophy (C-0) in gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 11.0% in the first, second, third, and fourth periods, respectively; p = 0.0046). In conclusion, the rate of H. pylori-uninfected gastric cancer without gastric atrophy tended to increase over time.

Brown slits for colorectal adenoma crypts on conventional magnifying endoscopy with narrow band imaging using the X1 system.

BACKGROUND: Accurate diagnosis of colorectal premalignant polyps, including adenomas, is vital in clinical practice. AIM: To investigate the diagnostic yields of novel findings of brown slits for adenomas. METHODS: Patients who underwent colonoscopy at the Toyoshima Endoscopy Clinic were enrolled. Polyps sized ≥ 5 mm suspected of adenomas or clinically significant serrated polyps were included in the study. We defined the surface structures of colorectal polyps, which were brown curves inside and along the tubular glands identified using a combination of a new X1 system (Olympus Corporation) and a conventional magnifying colonoscope with non-staining narrow band imaging (NBI), as brown slits. The brown slits corresponded to slit-like lumens on endocytoscopy and histological crypt openings of an adenoma. We evaluated the diagnostic performance of brown slits for adenoma. RESULTS: A total of 108 Lesions from 62 patients were eligible. The average age was 60.4 years and 41.9% were male. The mean polyp size was 7.45 ± 2.83 mm. Fifty-seven lesions were positive for brown slits. Histopathological diagnosis comprised 59 low-grade tubular adenomas, 16 sessile serrated lesions, and 33 hyperplastic polyps. Among 59 adenomas, 56 (94.9%) were positive for brown slits. Among 16 sessile serrated lesions, 0 (0%) was positive for brown slits. Among 33 hyperplastic polyps, 1 (3.0%) was positive for brown slits. The sensitivity, specificity, and accuracy of brown slits for adenoma were 94.9%, 98.0%, and 96.3%, respectively. The positive predictive value and negative predictive value of brown slits for adenoma were also excellent for 98.2%, and 94.1%, respectively. CONCLUSION: Brown slits on conventional magnifying endoscopy with non-staining NBI using the X1 system were useful for diagnosing colorectal adenoma. The new endoscopy system could be examined using new standards.

Consistency between the endoscopic Kyoto classification and pathological updated Sydney system for gastritis: A cross-sectional study.

BACKGROUND: Two methods are used to evaluate gastritis: the updated Sydney system (USS) with pathology and Kyoto classification, a new endoscopy-based diagnostic criterion for which evidence is accumulating. However, the consistency of their results is unclear. This study investigated the consistency of their results. METHODS: Patients who underwent esophagogastroduodenoscopy and were evaluated for Helicobacter pylori infection for the first time were eligible. The association between corpus and antral USS scores (neutrophil activity, chronic inflammation, atrophy, and intestinal metaplasia) and Kyoto classification scores (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) was assessed. RESULTS: Seven-hundred-seventeen patients (mean age, 49.2 years; female sex, 57.9%; 450 H. pylori-positive and 267 H. pylori-negative patients) were enrolled. All endoscopic gastritis cases in the Kyoto classification were associated with high corpus and antral USS scores for neutrophil activity and chronic inflammation. A subanalysis was performed for H. pylori-positive patients. Regarding atrophy and intestinal metaplasia, endoscopic findings were associated with USS scores. Enlarged folds, nodularity, and diffuse redness were associated with high corpus USS scores for neutrophil activity and chronic inflammation, but with low antral USS scores for atrophy and intestinal metaplasia. The Kyoto classification scores were also associated with the pathological topographic distribution of neutrophil activity and intestinal metaplasia. CONCLUSIONS: Among H. pylori-positive individuals, endoscopic and pathological diagnoses were consistent with atrophy and intestinal metaplasia. Enlarged folds, nodularity, and diffuse redness were associated with pathological inflammation (neutrophil activity and chronic inflammation) of the corpus; however, they were inversely associated with pathological atrophy and intestinal metaplasia. The endoscopy-based Kyoto classification of gastritis partially reflects pathology.

Enlarged folds on endoscopic gastritis as a predictor for submucosal invasion of gastric cancers.

BACKGROUND: Accurate diagnosis of the depth of gastric cancer invasion is crucial in clinical practice. The diagnosis of gastric cancer depth is often made using endoscopic characteristics of the tumor and its margins; however, evaluating invasion depth based on endoscopic background gastritis remains unclear. AIM: To investigate predicting submucosal invasion using the endoscopy-based Kyoto classification of gastritis. METHODS: Patients with gastric cancer detected on esophagogastroduodenoscopy at Toyoshima Endoscopy Clinic were enrolled. We analyzed the effects of patient and tumor characteristics, including age, sex, body mass index, surveillance endoscopy within 2 years, current Helicobacter pylori infection, the Kyoto classification, and Lauren's tumor type, on submucosal tumor invasion and curative endoscopic resection. The Kyoto classification included atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. Atrophy was characterized by non-reddish and low mucosa. Intestinal metaplasia was detected as patchy whitish or grayish-white flat elevations, forming an irregular uneven surface. An enlarged fold referred to a fold width ≥ 5 mm in the greater curvature of the corpus. Nodularity was characterized by goosebump-like multiple nodules in the antrum. Diffuse redness was characterized by uniform reddish non-atrophic mucosa in the greater curvature of the corpus. RESULTS: A total of 266 gastric cancer patients (mean age, 66.7 years; male sex, 58.6%; mean body mass index, 22.8 kg/m2) were enrolled. Ninety-three patients underwent esophagogastroduodenoscopy for surveillance within 2 years, and 140 had current Helicobacter pylori infection. The mean Kyoto score was 4.54. Fifty-eight cancers were diffuse-type, and 87 cancers had invaded the submucosa. Multivariate analysis revealed that low body mass index (odds ratio 0.88, P = 0.02), no surveillance esophagogastroduodenoscopy within 2 years (odds ratio 0.15, P < 0.001), endoscopic enlarged folds of gastritis (odds ratio 3.39, P = 0.001), and Lauren's diffuse-type (odds ratio 5.09, P < 0.001) were independently associated with submucosal invasion. Similar results were obtained with curative endoscopic resection. Among cancer patients with enlarged folds, severely enlarged folds (width ≥ 10 mm) were more related to submucosal invasion than mildly enlarged folds (width 5-9 mm, P < 0.001). CONCLUSION: Enlarged folds of gastritis were associated with submucosal invasion. Endoscopic observation of background gastritis as well as the lesion itself may help diagnose the depth of cancer invasion.

Comparison of endoscopic gastritis based on Kyoto classification between diffuse and intestinal gastric cancer.

BACKGROUND: Gastric cancers can be categorized into diffuse- and intestinal-type cancers based on the Lauren histopathological classification. These two subtypes show distinct differences in metastasis frequency, treatment application, and prognosis. Therefore, accurately assessing the Lauren classification before treatment is crucial. However, studies on the gastritis endoscopy-based Kyoto classification have recently shown that endoscopic diagnosis has improved. AIM: To investigate patient characteristics including endoscopic gastritis associated with diffuse- and intestinal-type gastric cancers in Helicobacter pylori (H. pylori)-infected patients. METHODS: Patients who underwent esophagogastroduodenoscopy at the Toyoshima Endoscopy Clinic were enrolled. The Kyoto classification included atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. The effects of age, sex, and Kyoto classification score on gastric cancer according to the Lauren classification were analyzed. We developed the Lauren predictive background score based on the coefficients of a logistic regression model using variables independently associated with the Lauren classification. Area under the receiver operative characteristic curve and diagnostic accuracy of this score were examined. RESULTS: A total of 499 H. pylori-infected patients (49.6% males; average age: 54.9 years) were enrolled; 132 patients with gastric cancer (39 diffuse- and 93 intestinal-type cancers) and 367 cancer-free controls were eligible. Gastric cancer was independently associated with age ≥ 65 years, high atrophy score, high intestinal metaplasia score, and low nodularity score when compared to the control. Factors independently associated with intestinal-type cancer were age ≥ 65 years (coefficient: 1.98), male sex (coefficient: 1.02), high intestinal metaplasia score (coefficient: 0.68), and low enlarged folds score (coefficient: -1.31) when compared to diffuse-type cancer. The Lauren predictive background score was defined as the sum of +2 (age ≥ 65 years), +1 (male sex), +1 (endoscopic intestinal metaplasia), and -1 (endoscopic enlarged folds) points. Area under the receiver operative characteristic curve of the Lauren predictive background score was 0.828 for predicting intestinal-type cancer. With a cut-off value of +2, the sensitivity, specificity, and accuracy of the Lauren predictive background score were 81.7%, 71.8%, and 78.8%, respectively. CONCLUSION: Patient backgrounds, such as age, sex, endoscopic intestinal metaplasia, and endoscopic enlarged folds are useful for predicting the Lauren type of gastric cancer.

Helicobacter pylori eradication improved the Kyoto classification score on endoscopy.

BACKGROUND AND AIM: Endoscopy-based Kyoto classification predicts the risk of Helicobacter pylori infection and gastric cancer; however, the change in score following H. pylori eradication remains unknown. We retrospectively compared the Kyoto score before and after H. pylori eradication. METHODS: H. pylori-positive patients who underwent baseline esophagogastroduodenoscopy (EGD), successful H. pylori eradication, and surveillance EGD were enrolled. The Kyoto score is a sum of scores for atrophy (Kimura-Takemoto atrophic-border classification none or C1: 0, C-II or C-III: 1, O-I to O-III: 2), intestinal metaplasia (none: 0, antrum: 1, corpus and antrum: 2), enlarged folds (absence: 0, presence: 1), nodularity (absence: 0, presence: 1), and diffuse redness (none: 0, mild: 1, severe: 2) and ranges from 0 to 8. RESULTS: Eighty-three patients (mean age: 54.9 years; 65.1% women) were enrolled. The mean duration from successful eradication to surveillance EGD was 256 days. The Kyoto score significantly decreased from 3.90 to 2.78 following H. pylori eradication (P < 0.001). Scores for endoscopic atrophy (from 1.43 to 1.46, P = 0.638) and endoscopic intestinal metaplasia (from 0.53 to 0.47, P = 0.543) did not change; however, there was significant improvement in the scores for enlarged folds (from 0.14 to 0.00, P = 0.002), nodularity (from 0.18 to 0.04, P = 0.002), and diffuse redness (from 1.61 to 0.82, P < 0.001). CONCLUSION: The Kyoto classification score decreased following H. pylori eradication. A decrease in the scores for enlarged folds, nodularity, and diffuse redness contributed to the decrease in Kyoto score.

Clinical features of cardiac nodularity-like appearance induced by Helicobacter pylori infection.

BACKGROUND: We have previously reported that Helicobacter pylori (H. pylori)-associated nodular gastritis could occur in both the antrum and the cardia. Cardiac nodularity-like appearance (hereafter, called as cardiac nodularity) had a high predictive accuracy for the diagnosis of H. pylori infection. In the previous study, we included only the patients who were evaluated for H. pylori infection for the first time, and excluded patients with a history of eradication. Therefore, the prevalence and clinical features of cardiac nodularity remains unknown. AIM: To perform this cross-sectional study to explore the characteristics of cardiac nodularity. METHODS: Consecutive patients who underwent esophagogastroduodenoscopy between May, 2017 and August, 2019 in the Toyoshima Endoscopy Clinic were enrolled in this study. We included H. pylori-negative, H. pylori-positive, and H. pylori-eradicated patients, and excluded patients with unclear H. pylori status and eradication failure. H. pylori infection was diagnosed according to serum anti-H. pylori antibody and the urea breath test or histology. Cardiac nodularity was defined as a miliary nodular appearance or the presence of scattered whitish circular small colorations within 2 cm of the esophagogastric junction. Nodularity was visualized as whitish in the narrow-band imaging mode. We collected data on the patients' baseline characteristics. RESULTS: A total of 1078 patients were finally included. Among H. pylori-negative patients, cardiac nodularity and antral nodularity were recognized in 0.14% each. Among H. pylori-positive patients, cardiac nodularity and antral nodularity were recognized in 54.5% and 29.5%, respectively. Among H. pylori-eradicated patients, cardiac nodularity and antral nodularity were recognized in 4.5% and 0.6%, respectively. The frequency of cardiac nodularity was significantly higher than that of antral nodularity in H. pylori-positive and -eradicated patients. The frequencies of cardiac nodularity and antral nodularity in H. pylori-eradicated patients were significantly lower than those in H. pylori-positive patients (P < 0.001). The patients with cardiac nodularity were significantly younger than those without cardiac nodularity (P = 0.0013). Intestinal metaplasia score of the patients with cardiac nodularity were significantly lower than those without cardiac nodularity (P = 0.0216). Among H. pylori-eradicated patients, the patients with cardiac nodularity underwent eradication significantly more recently compared with those without cardiac nodularity (P < 0.0001). CONCLUSION: This report outlines the prevalence and clinical features of cardiac nodularity, and confirm its close association with active H. pylori infection.

Kyoto classification in patients who developed multiple gastric carcinomas after Helicobacter pylori eradication.

BACKGROUND: Endoscopic Kyoto classification predicts gastric cancer risk; however, the score in the patients with primary gastric cancer after Helicobacter pylori (H. pylori) eradication therapy is unknown. AIM: To elucidate the Kyoto classification score in patients with both single gastric cancer and multiple gastric cancers developed after H. pylori eradication. METHODS: The endoscopist recorded the Kyoto classification at the endoscope and the Kyoto classification score at the time of the first diagnosis of gastric cancer after H. pylori eradication. The score was compared between single gastric cancer group and multiple gastric cancers group. RESULTS: The Kyoto score at the time of diagnosis of 45 cases of gastric cancer after H. pylori eradication was 4.0 points in average. The score was 3.8 points in the single gastric cancer group, and 5.1 points in the multiple gastric cancers group. The multiple group had a significantly higher score than the single group (P = 0.016). In the multiple gastric cancers group, all the patients (7/7) had 5 or higher Kyoto score, while in single gastric cancer group, the proportion of patients with a score of 5 or higher was less than half, or 44.7% (17/38). CONCLUSION: Patients diagnosed with gastric cancer after H. pylori eradication tended to have advanced gastritis. In particular, in cases of multiple gastric cancers developed after H. pylori eradication, the endoscopic Kyoto classification score tended to be 5 or higher in patients with an open type atrophic gastritis and the intestinal metaplasia extended to the corpus.

Colonoscopy using back brace support belt: A randomized, prospective trial.

BACKGROUND AND AIM: Looping is a major problem in colonoscopy, and it prolongs procedure time. We evaluated the efficacy and safety of an external abdominal compression device (back brace support belt; Maxbelt) with respect to cecal insertion time and other outcomes. METHODS: We performed a prospective study on outpatients undergoing elective colonoscopy in Toyoshima Endoscopy Clinic. Subjects were randomly assigned to groups and were subjected to either Maxbelt (n = 39) or no device (control, n = 38) during colonoscopy. The colonoscopist was blinded to the study. The primary outcome that was observed was insertion time. RESULTS: The intubation time of the Maxbelt group was shorter than that of the no device group, but the difference was not significant (3.29 vs 4.49 min, P = 0.069). After stratifying by age, the use of Maxbelt significantly decreased cecal intubation time in elderly participants (age ≥ 45) compared to no device group (3.27 vs 5.00 min, P = 0.032). The use of the Maxbelt significantly decreased insertion difficulty encountered by the colonoscopist (P = 0.01). There was no difference in adenoma detection rate, manual pressure, position change, and adverse event. CONCLUSIONS: The use of a back brace support belt could be a viable approach for colonoscopy in elderly patients. (University Hospital Medical Information Network: UMIN000029361).

Nodularity-like appearance in the cardia: novel endoscopic findings for Helicobacter pylori infection.

Background and study aims Helicobacter pylori -associated nodular gastritis, which is associated with follicular lymphoid hyperplasia, is mainly recognized in the antrum. However, we have also observed nodularity-like appearance in the cardia. This study aimed to investigate the clinical significance of cardiac nodularity-like appearance in H. pylori -associated gastritis. Patients and methods Patients who underwent esophagogastroduodenoscopy and were evaluated for H. pylori infection for the first time were enrolled. A nodularity-like appearance in the cardia was defined as a miliary nodular appearance or scattered appearances of small circular whitish coloration. H. pylori infection was diagnosed according to serum anti- H. pylori antibody and the urea breath test or histology. Accuracy of the H. pylori infection diagnoses based on nodularity-like appearance were assessed. Results Among 265 patients, 42 patients (15.8 %) were diagnosed as positive for H. pylori . Cardiac nodularity-like appearance and antral nodularity were recognized in 25 and 15 patients, respectively. In accuracy of predicting H. pylori by cardiac nodularity-like appearance, specificity was 0.996, sensitivity was 0.571, positive predictive value was 0.960, negative predictive value was 0.925, and accuracy was 0.928. The sensitivity of cardiac nodularity-like appearance was significantly higher than that of antral nodularity ( P  = 0.0284). Conclusions Cardiac nodularity-like appearance had a high accuracy rate for H. pylori infection diagnosis. Cardiac nodularity-like appearance was found more frequently than antral nodularity.

Adverse events associated with bidirectional endoscopy with midazolam and pethidine.

Same-day bidirectional endoscopy has been reported to reduce recovery time, and procedure-related cost. The safety of bidirectional endoscopy vs colonoscopy only, while using midazolam and pethidine, has never been evaluated. We reviewed 1,202 consecutive patients who underwent bidirectional endoscopy or colonoscopy only with administration of midazolam and pethidine in Toyoshima Ensdoscopy Clinic. We compared the clinical characteristics and adverse events associated with method of endoscopy (colonoscopy only vs bidirectional endoscopy). Furthermore, multivariate logistic regression analyses were conducted to study the role of age, sex, use of sedative, polypectomy, and bidirectional endoscopy in adverse events. In the bidirectional endoscopy group, the doses of pethidine and midazolam, and the incidence rates of hypoxia and posto-endoscopic nausea were significantly higher. On multivariate analysis, age (odds ratio = 1.061, p<0.001), use of pethidine (odds ratio = 4.311, p = 0.003), and bidirectional endoscopy (odds ratio = 3.658, p<0.001) were independently associated with hypoxia. On multivariate analysis, female sex (odds ratio = 10.25, p = 0.027) and bidirectional endoscopy (odds ratio = 6.051, p = 0.022) were independently associated with post-endoscopic nausea. In conclusion, bidirectional endoscopy could increase hypoxia in elderly patients using pethidine and post-endoscopic nausea in female patients.

Small-caliber endoscopes are more fragile than conventional endoscopes.

Background and study aims The repair costs of gastrointestinal endoscopes account for a significant proportion of the total budget of an endoscopy unit. This study evaluated the repair costs of small-caliber endoscopes and conventional endoscopes used in esophagogastroduodenoscopy (EGD). Patients and methods A retrospective analysis of upper gastrointestinal endoscope damage and repair costs between April 2012 and May 2019 was performed at the Toyoshima Endoscopy Clinic. Conventional endoscopes (GIF-H260, GIF-HQ290, and GIF-H290Z) were used for transoral EGD while small-caliber endoscopes (GIF-XP260N and GIF-XP290N) were used for transnasal or transoral EGD. Results Three small-caliber endoscopes and five conventional endoscopes were used for 1,031 procedures and 31,192 procedures, respectively. The number of procedures/damage incidence for small-caliber endoscope and conventional endoscopes was 344 and 1950, respectively. Damage incidence for small-caliber endoscopes was significantly higher than for conventional endoscopes ( P  = 0.014). Repair costs/procedure were $ 5.95 ±â€Š$132 for small-caliber endoscopes and $2.41 ±â€Š$115 for conventional endoscopes. Repair costs/procedure for small-caliber endoscopes were more than twice those for conventional endoscopes. Conclusions Small-caliber endoscopes are more fragile than conventional endoscopes.

CF290 for pancolonic chromoendoscopy improved sessile serrated polyp detection and procedure time: a propensity score-matching study.

Background and study aims The benefits of the new-generation CF290 (Olympus, Tokyo, Japan) for pancolonic chromoendoscopy (PCC) for colorectal polyp detection and its procedure time remain questionable. We compared the CF290 with the previous CF260 for PCC. Methods We performed a propensity score-matching study using baseline characteristics such as age, sex, indications, endoscopist, and bowel preparation. We compared the detection of adenomas and sessile serrated polyps (SSPs) and procedure times of two expert endoscopists who performed PCC using the CF290 series (high-quality system with flushing pump) and the CF260 series (high-definition system). Results We matched 374 patients who underwent PCC using the CF290 and 187 patients who underwent PCC using the CF260. The adenoma detection rate of the 290 series was higher than that of the 260 series, but not significantly. The SSP detection rate for the 290 series was higher than that for the 260 series ( P  = 0.01). Insertion time required for the 290 series was shorter than that required for the 260 series ( P  < 0.0001). Withdrawal time of the 290 series was shorter than that of the 260 series ( P  < 0.0001). Conclusion Advanced technology can provide accuracy and help save time, and therefore, should be applied whenever possible.

A combination of serum anti-Helicobacter pylori antibody titer and Kyoto classification score could provide a more accurate diagnosis of H pylori.

Background: We previously showed that the endoscopic Kyoto classification for gastritis could predict Helicobacter pylori infection in individuals with a high negative titer of serum anti-H pylori antibodies. This study evaluated H pylori infection and the Kyoto classification score in patients with a low negative titer (<3 U/ml), high negative titer (3-9.9 U/ml), low positive titer (10-49.9 U/ml), and high positive titer (≥50 U/ml). Methods: Serum antibody levels, Kyoto classification score and histology were investigated in 870 individuals with no history of H pylori-eradication therapy. Urea breath tests (UBTs) were additionally conducted for patients with a low negative titer and a Kyoto score ≥1 or an antibody titer ≥10 U/ml and a Kyoto score of 0 or 1. UBTs and/or histological studies were conducted for participants with a high negative titer. Results: False diagnoses based on anti-H pylori antibody titers were observed in 0.3% of the low-negative-titer group, 11.7% of the high-negative-titer group, 18.9% of the low-positive-titer group and 2.2% of the high-positive-titer group. Surprisingly, false diagnoses based on antibody titers were noted in 63.2% of patients with a low positive titer and a Kyoto score of 0 and in 62.5% of patients with a high negative titer and a Kyoto score ≥2, respectively. Conclusions: Endoscopic findings could predict false diagnoses determined using serum antibody titers.

Serum anti-Helicobacter pylori antibody titer and its association with gastric nodularity, atrophy, and age: A cross-sectional study.

AIM: To clarify the role of serum anti-Helicobacter pylori (H. pylori) antibody titers in gastric cancer. METHODS: In this cross-sectional study, the effect of patients' baseline characteristics and endoscopic findings on their serum antibody titers were assessed. We evaluated consecutive patients who underwent esophagogastroduodenoscopy and their first evaluation for H. pylori infection using a serum antibody test. We excluded patients with a history of eradication therapy. The participants were divided into four groups according to their E-plate serum antibody titer. Patients with serum antibody titers < 3, 3-9.9, 10-49.9, and ≥ 50 U/mL were classified into groups A, B, C, and D, respectively. RESULTS: In total, 874 participants were analyzed with 70%, 16%, 8.7%, and 5.1% of them in the groups A, B, C, and D, respectively. Patients in group C were older than patients in groups A and B. Gastric open-type atrophy, intestinal metaplasia, enlarged folds, diffuse redness, and duodenal ulcers were associated with a high titer. Regular arrangements of collecting venules, fundic gland polyps, superficial gastritis, and gastroesophageal reflux disease were related to a low titer. Multivariate analysis revealed that nodularity (P = 0.0094), atrophy (P = 0.0076), and age 40-59 years (vs age ≥ 60 years, P = 0.0090) were correlated with a high serum antibody titer in H. pylori-infected patients. Intestinal metaplasia and atrophy were related to age ≥ 60 years in group C and D. CONCLUSION: Serum antibody titer changes with age, reflects gastric mucosal inflammation, and is useful in predicting the risk of gastric cancer.

Early detection of gastric cancer after Helicobacter pylori eradication due to endoscopic surveillance.

BACKGROUND: Helicobacter pylori eradication therapy is commonly performed to reduce the incidence of gastric cancer. However, gastric cancer is occasionally discovered even after successful eradication therapy. Therefore, we examined the prognosis of gastric cancer patients, diagnosed after successful H. pylori eradication therapy. MATERIALS AND METHODS: All-cause death rates and gastric cancer-specific death rates in gastric cancer patients who received successful H. pylori eradication treatment was tracked and compared to rates in patients who did not receive successful eradication therapy. RESULTS: In total, 160 gastric cancer patients were followed-up for up to 11.7 years (mean 3.5 years). Among them, 53 gastric cancer patients received successful H. pylori eradication therapy prior to gastric cancer diagnosis. During the follow-up period, 11 all-cause deaths occurred. In the successful eradication group, the proportion of patients with cancer stage I was higher. The proportions of patients who received curative endoscopic therapy and endoscopic examination in the 2 years prior to gastric cancer diagnosis were also higher in the successful eradication group. Kaplan-Meier analysis of all-cause death and gastric cancer-specific death revealed a lower death rate in patients in the successful eradication group (P = .0139, and P = .0396, respectively, log-rank test). The multivariate analysis showed that endoscopy within 2 years before cancer diagnosis is associated with stage I cancer. CONCLUSIONS: Possible early discovery of gastric cancer after H. pylori eradication due to regular endoscopic surveillance may contribute to better prognosis of patients with gastric cancer.

Adhesive Interactions between Mononuclear Phagocytes and Intestinal Epithelium Perturb Normal Epithelial Differentiation and Serve as a Therapeutic Target in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Disturbance of intestinal homeostasis is associated with the development of inflammatory bowel disease [IBD], and TGF-ß signalling impairment in mononuclear phagocytes [MPs] causes murine colitis with goblet cell depletion. Here, we examined an organoid-MP co-culture system to study the role of MPs in intestinal epithelial differentiation and homeostasis. METHODS: Intestinal organoids were co-cultured with lamina propria leukocytes and bone marrow-derived dendritic cells [BMDCs] from CD11c-cre Tgfbr2fl/fl mice. Organoid-MP adhesive interactions were evaluated by microscopy, RT-PCR, and flow cytometry. Murine colitis models (dextran sodium sulphate [DSS], CD11c-cre Tgfbr2fl/fl, T-cell-transfer) were used for histological and immunohistochemical analysis. Anti-E-cadherin antibody treatment or CD11c+-cell-specific CDH1 gene deletion were performed for E-cadherin neutralization or knockout. Colonic biopsies from patients with ulcerative colitis were analysed by flow cytometry. RESULTS: Intestinal organoids co-cultured with CD11c+ lamina propria leukocytes or BMDCs from CD11c-cre Tgfbr2fl/fl mice showed morphological changes and goblet cell depletion with Notch signal activation, analogous to CD11c-cre Tgfbr2fl/fl colitis. E-cadherin was upregulated in CD11c+ MPs, especially CX3CR1+CCR2+ monocytes, of CD11c-cre Tgfbr2fl/fl mice. E-cadherin-mediated BMDC adhesion promoted Notch activation and cystic changes in organoids. Anti-E-cadherin antibody treatment attenuated colitis in CD11c-cre Tgfbr2fl/fl and T-cell-transferred mice. In addition, E-cadherin deletion in CD11c+ cells attenuated colitis in both CD11c-cre Tgfbr2fl/fl and DSS-treated mice. In patients with ulcerative colitis, E-cadherin expressed by intestinal CD11c+ leukocytes was enhanced compared with that in healthy controls. CONCLUSIONS: E-cadherin-mediated MP-epithelium adhesion is associated with the development of colitis, and blocking these adhesions may have therapeutic potential for IBD.

Helicobacter pylori infection in subjects negative for high titer serum antibody.

AIM: To investigate the clinicopathological features of the patients testing negative for high titer serum anti-Helicobacter pylori (H. pylori) antibody. METHODS: The antibody titers were measured using antigens derived from Japanese individuals. 13C-urea breath test-positive individuals were defined as having H. pylori infection. We investigated the demographic characteristics, laboratory data, endoscopic findings including Kyoto classification of gastritis, and histology in negative-high titer patients without H. pylori eradication therapy. Kyoto classification consisted of scores for gastric atrophy, intestinal metaplasia, enlarged folds, nodularity, and redness. RESULTS: Of the 136 subjects enrolled, 23 (17%) had H. pylori infection. Kyoto classification had an excellent area under the receiver operating characteristics curve (0.886, 95% confidence interval: 0.803-0.968, P = 3.7 × 10-20) for predicting H. pylori infection with a cut-off value of 2. Further, Kyoto classification, H. pylori density, and neutrophil activity had high accuracies (89.7%, 96.3%, and 94.1%, respectively). Kyoto classification was independent of the demographic and laboratory parameters in multivariate analysis. CONCLUSION: Endoscopic Kyoto classification of gastritis is a useful predictor of H. pylori infection in negative-high titer antibody patients.

Overexpression of HER2 in the pancreas promotes development of intraductal papillary mucinous neoplasms in mice.

Pancreatic ductal adenocarcinoma (PDA) has a 5-year survival rate of less than 5% and is the sixth leading cause of cancer death. Although KRAS mutations are one of the major driver mutations in PDA, KRAS mutation alone is not sufficient to induce invasive pancreatic cancer in mice model. HER2, also known as ERBB2, is a receptor tyrosine kinase, and overexpression of HER2 is associated with poor clinical outcomes in pancreatic cancer. However, no report has shown whether HER2 and its downstream signaling contributes to the pancreatic cancer development. By immunohistochemical analysis in human cases, HER2 protein expression was detected in 40% of PDAs and 29% of intraductal papillary mucinous carcinomas, another type of pancreatic cancer. In a mouse model, we showed overexpression of activated HER2 (HER2 NT ) in the pancreas, in which cystic neoplastic lesions resembling intraductal papillary mucinous neoplasm-like lesions in humans had developed. We also found that HER2 NT cooperated with oncogenic Kras to accelerate the development of pancreatic intraepithelial neoplasms. In addition, using pancreatic organoids in 3D cultures, we found that organoids cultured from HER2 NT /Kras double transgenic mice showed proliferative potential and tumorigenic ability cooperatively. HER2-signaling inhibition was suggested to be an new therapeutic target in some types of PDAs.

Decline in perception of acid regurgitation symptoms from gastroesophageal reflux disease in diabetes mellitus patients.

OBJECTIVES: To determine if a discrepancy exists between subjective symptoms and the grade of endoscopic gastroesophageal reflux disease (GERD) in diabetes mellitus (DM) patients. METHODS: All 2,884 patients who underwent esophagogastroduodenoscopy completed the modified Gastrointestinal Symptom Rating Scale (GSRS), an interview-based rating scale consisting of 16 items including a question on acid regurgitation. Patients were divided into DM and non-DM groups (1,135 and 1,749 patients, respectively). GERD was diagnosed endoscopically and graded according to the Los Angeles classification. Grade B or more severe GERD was defined as severe endoscopic GERD. The intergroup GSRS score was compared statistically. RESULTS: In severe endoscopic GERD patients, the prevalence of patients with a positive GSRS score in the acid regurgitation question was statistically lower in DM patients than non-DM patients. Of the 60 non-DM patients with severe endoscopic GERD, 40 patients (67%) had a positive GSRS score for acid regurgitation; however, of the 51 DM patients with severe endoscopic GERD, 23 patients (45%) had a positive GSRS score. Multivariate analysis showed that severe endoscopic GERD (OR: 2.01; 95% CI: 1.21-3.33; p = 0.0066), non-DM (OR: 0.74; 95% CI: 0.54-0.94; p = 0.0157), younger age (OR: 0.98; 95% CI: 0.97-0.99; p = 0.0125), and hiatal hernia (OR: 1.46; 95% CI: 1.12-1.90; p = 0.0042) were associated with acid regurgitation symptoms. CONCLUSIONS: There is a discrepancy between subjective symptoms and endoscopic GERD grade in DM patients. The ability of DM patients to feel acid regurgitation may be decreased.