Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of Helicobacter pylori Eradication and Aspirin

Jiro Watari,Toshihiko Tomita,Katsuyuki Tozawa,Tadayuki Oshima,Hirokazu Fukui,Hiroto Miwa 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.3

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.

Cytapheresis in Patients with Severe Ulcerative Colitis after Failure of Intravenous Corticosteroid: A Long-Term Retrospective Cohort Study

( Ken Fukunaga ),( Kazuko Nagase ),( Takeshi Kusaka ),( Nobuyuki Hida ),( Yoshio Ohda ),( Koji Yoshida ),( Katsuyuki Tozawa ),( Koji Kamikozuru ),( M Iimuro ),( Shiro Nakamura ),( Hiroto Miwa ),( Taka 대한소화기기능성질환·운동학회 2009 Gut and Liver Vol.3 No.1

Background/Aims: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid. Methods: Forty-seven UC patients who had received CAP therapy for the first time within 1 year after UC diagnosis were followed for 36 months. One of the inclusion criteria was a clinical activity index (CAI) of ≥7 points at the end of a 2-week iv course of corticosteroid therapy. CAP therapy consisted of ten sessions over 10 weeks. Results: CAP induced clinical remission (CAI≤4) in 70.2% patients (33/47). The number of submissions for colectomy was higher for severe UC at entry (CAI≥12, n=25) than for moderately severe UC at entry (7≤CAI<12, p=15; p<0.02). The cumulative rates of avoiding surgery and relapse were 54.5% and 24.2%, respectively, at 36 months in patients who responded to CAP therapy. This was similar to that of iv cyclosporine reported recently. Conclusions: This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC. (Gut and Liver 2009;3:41-47)

Prevalence of Irritable Bowel Syndrome-like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease

( Toshihiko Tomita ),( Yu Kato ),( Mayu Takimoto ),( Takahisa Yamasaki ),( Takashi Kondo ),( Tomoaki Kono ),( Katsuyuki Tozawa ),( Yoko Yokoyama ),( Hisatomo Ikehara ),( Yoshio Ohda ),( Tadayuki Oshim 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.4

Background/Aims Few studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD. Methods IBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated. Results IBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn’s disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant. Conclusions The prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients.

Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals

( Takahisa Yamasaki ),( Toshihiko Tomita ),( Mayu Takimoto ),( Takashi Kondo ),( Katsuyuki Tozawa ),( Yoshio Ohda ),( Tadayuki Oshima ),( Hirokazu Fukui ),( Jiro Watari ),( Hiroto Miwa ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.4

Background/Aims When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. Methods Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. Results When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P < 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P < 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P < 0.01) and 60 minutes (20.3 ± 6.7 minutes, P < 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. Conclusion Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity. (J Neurogastroenterol Motil 2017;23:526-532)

Esophagography in Patients With Esophageal Achalasia Diagnosed With High-resolution Esophageal Manometry

( Takahisa Yamasaki ),( Toshihiko Tomita ),( Sumire Mori ),( Mayu Takimoto ),( Akio Tamura ),( Ken Hara ),( Takashi Kondo ),( Tomoaki Kono ),( Katsuyuki Tozawa ),( Yoshio Ohda ),( Tadayuki Oshima ),( 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.3

Background/Aims High-resolution esophageal manometry (HREM) is considered to be the gold standard for the diagnosis of achalasia. However, the Japan Esophageal Society recommends that esophagography is also accurate in either diagnosing or excluding the disorder. Accordingly, we compared the efficacy of esophagography and HREM in diagnosing achalasia patients with upper gastrointestinal symptoms. Methods HREM was performed in 126 patients with dysphagia. The final diagnosis of achalasia was done using HREM. Demographic data, symptoms, quality of life (QOL) were also obtained. We assessed the patients who were not able to be diagnosed by esophagography and compared the diagnostic values for esophagography with HREM-based achalasia diagnosis as the gold standard. Results A total of 48 cases of patients with achalasia, including 21 men and 27 women (mean age, 48.4 ± 19.6 years), were included in the study. Two patients were excluded. Of the remaining 46 patients, 36 (78.3%) patients were diagnosed as having achalasia by esophagography. The diagnostic sensitivity, specificity, and accuracy of esophagography were 78.3%, 88.0%, and 83.0%, respectively. Patients with type III achalasia had significantly lower physical QOL score than those with type I or II achalasia. Although the mental QOL score in patients with type III achalasia tended to decrease compared with that in patients with type I and II achalasia, the difference was not statistically significant. Conclusions Diagnosing esophageal achalasia by using esophagography alone has limited yield. Therefore, HREM should be used in patients with dysphagia and in whom achalasia cannot be diagnosed using EGD or esophagography. (J Neurogastroenterol Motil 2018;24:403-409)

A randomized double-blind placebo-controlled trial on the effect of magnesium oxide in patients with chronic constipation

Sumire Mori,Toshihiko Tomita,Kazuki Fujimura,Haruki Asano,Tomohiro Ogawa,Takahisa Yamasaki,Takashi Kondo,Tomoaki Kono,Katsuyuki Tozawa,Tadayuki Oshima,Hirokazu Fukui,Takeshi Kimura,Jiro Watari,Hiroto 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.4

Background/Aims Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. Methods We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. Results One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo (P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). Conclusion Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms. Background/Aims Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. Methods We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. Results One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo (P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). Conclusion Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms.

Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia

( Haruki Asano ),( Toshihiko Tomita ),( Kumiko Nakamura ),( Takahisa Yamasaki ),( Takuya Okugawa ),( Takashi Kondo ),( Tomoaki Kono ),( Katsuyuki Tozawa ),( Yoshio Ohda ),( Tadayuki Oshima ),( Hirokaz 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.3

Background/Aims Gastric motility abnormalities have been considered to be pathophysiological features of functional dyspepsia (FD) that are closely related to dyspepsia symptoms, especially postprandial distress syndrome (PDS). The aims of this study are to (1) investigate the prevalence of gastric motility disorders and (2) evaluate the association between gastric motility abnormalities and dyspeptic symptoms using gastric scintigraphy in the PDS type of FD. Methods Forty healthy subjects and 94 PDS type FD patients were enrolled in the study. The volunteers and patients ingested a radiolabeled (technetium-99m) solid test meal, and scintigraphic images were recorded. Gastric accommodation and emptying were assessed by scintigraphic imaging. The patients` dyspeptic symptoms were also explored using self-completed symptom questionnaires with 10 variables (4 scales, 0-3 points) at the same time. Results In 94 Japanese FD patients, the prevalence of impaired gastric accommodation and delayed emptying were 14.9% (14/94) and 10.6% (10/94), respectively. Gastric motility abnormalities were seen in 25.5% (24/94) of FD patients. There was no association between gastric motility abnormalities and dyspeptic symptoms. Conclusions Gastric motility abnormalities were seen in 25.5% of Japanese PDS type FD patients. However, there was no association between gastric motility abnormalities and dyspeptic symptoms on gastric scintigraphy. (J Neurogastroenterol Motil 2017;23:392-399)

Prevalence and Self-recognition of Chronic Constipation: Results of an Internet Survey

( Akio Tamura ),( Toshihiko Tomita ),( Tadayuki Oshima ),( Fumihiko Toyoshima ),( Takahisa Yamasaki ),( Takuya Okugawa ),( Takashi Kondo ),( Tomoaki Kono ),( Katsuyuki Tozawa ),( Hisatomo Ikehara ),( 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.4

Background/Aims Although chronic constipation is a common symptom, to date no international consensus has been reached regarding its definition. The aims of this study were (1) to investigate defecation habits and (2) to examine the prevalence of constipation using the Japanese Society of Internal Medicine (JSIM) and the Rome III criteria using an online survey. Methods An online questionnaire composed of items on the frequency, interval, form of defecation, the management, and self-recognition of constipation (reference standard of constipation) was created. A total of 5155 valid responses were received. In addition, constipation symptoms were evaluated through a survey using the JSIM and the Rome III criteria. Results In the internet survey, 28.4% of the respondents considered themselves to be constipated. Stratified by sex, significantly more females (37.5%) than males (19.1%) considered themselves to be constipated (P < 0.001). The prevalence of constipation among the respondents was 28.0% using the Rome III, but only 10.1% using the JSIM. The diagnostic accuracy was 73.2% for the Rome III and 78.1% for the JSIM, while the diagnostic specificity was 81.1% for the Rome III and 97.5% for the JSIM. However, the diagnostic sensitivities for both measures were low, at 52.2% and 29.2% for the Rome III and the JSIM, respectively. Conclusions The online survey developed for this study was able to provide clarification regarding defecation patterns. The results also suggest a discrepancy between the self-recognized prevalence of constipation in Japan and prevalence of constipation based on the JSIM criteria.