Shouko Ono

Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in Japan

Objective A multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after Helicobacter pylori eradication. Methods 420 patients with gastric low-grade MALT lymphoma who had undergone successful H pylori eradication and been followed up for at least 3 years were registered from 21 participating institutes. Responders to treatment were defined as patients whose post-treatment biopsies showed complete histological response (ChR) or probable minimal residual disease (pMRD). Treatment failure was defined as the status of progressive disease or lymphoma relapse after ChR/pMRD. Results 323 patients (77%) responded to H pylori eradication. A logistic regression analysis showed that absence of H pylori, submucosal invasion determined by endoscopic ultrasonography and t(11;18)/API2-MALT1 were independent predictors of resistance to H pylori eradication. During the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04 years), the disease relapsed in 10 of 323 responders (3.1%) while progressive disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients (8.8%) were regarded as treatment failures. Of these 37 patients, transformation into diffuse large B cell lymphoma occurred in nine patients. Among the non-responders and relapsed patients, 17 patients were subjected to a ‘watch and wait’ strategy while 90 patients underwent second-line treatments including radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6), chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1) or endoscopic resection (n=1). Probabilities of freedom from treatment failure, overall survival and event-free survival after 10 years were 90%, 95% and 86%, respectively. Cox multivariate analysis revealed endoscopic non-superficial type to be an independent prognostic factor for adverse freedom from treatment failure, overall survival and event-free survival. Conclusions The excellent long-term outcome of gastric MALT lymphoma after H pylori eradication was confirmed by this large-scale follow-up study.

Frequency of Helicobacter pylori-Negative Gastric Cancer and Gastric Mucosal Atrophy in a Japanese Endoscopic Submucosal Dissection Series Including Histological, Endoscopic and Serological Atrophy

Background: The definition of Helicobacter pylori-negative gastric cancer depends on the accuracy of diagnosis of H. pylori infection. The aim of this study was to determine the frequency of H. pylori-negative gastric cancer and to clarify relationships with histological atrophy, endoscopic atrophy, and serological atrophy. Methods: A total of 240 early gastric cancers were included in this study. The status of H. pylori infection was determined from the rapid urease test, 13C-urea breath test, H. pylori culture, histopathological examination and examination of IgG antibodies. In H. pylori-negative gastric cancer, histological atrophy and intestinal metaplasia, endoscopic atrophy and serological atrophy were assessed by pepsinogen. Results: The rate of H. pylori infection was 77.9% and 19 patients (7.9%) had a history of eradication. 34 patients (14.2%) were diagnosed with H. pylori-negative gastric cancer using diagnostic tools of H. pylori. However, most of the patients with H. pylori-negative gastric cancer had histological atrophy and intestinal metaplasia. Only 1 gastric cancer (0.42%) occurred in the mucosa without histological atrophy, endoscopic atrophy or serological atrophy. Conclusion: Early gastric cancers in the Japanese endoscopic submucosal dissection series were strongly related to current or past infection with H. pylori and to gastric mucosal atrophy.

Eradication of Helicobacter pylori for primary gastric cancer and secondary gastric cancer after endoscopic mucosal resection

Because most gastric cancers develop from a background of Helicobacter pylori-infected gastric mucosa, H. pylori plays an important role in gastric carcinogenesis. Therefore, eradication of H. pylori may inhibit the incidence of gastric cancers. In experimental studies, H. pylori eradication has proved to act as a prophylaxis against gastric cancer. However, the results of recent randomized controlled studies are absolutely contradictory. In Japan, mucosal gastric cancer is usually resected by endoscopic treatment. As only a small part of the gastric mucosa is resected, secondary gastric cancer after endoscopic resection of the primary gastric cancer often develops at another site in the stomach. A nonrandomized Japanese study involving 132 early gastric cancer patients reported that eradication of H. pylori after endoscopic resection tended to reduce the development of secondary gastric cancer. Also, a retrospective multicenter survey indicated that the incidence rate of secondary gastric cancer in H. pylori-eradicated patients was about one-third that among patients in the noneradication group. We conducted a large-scale multicenter randomized trial to confirm the effect of H. pylori eradication on secondary and residual gastric cancer after endoscopic resection. This study was begun in 2003 and is ongoing at present. Diagnosis of a new carcinoma at another site of the stomach is defined as the primary end point, and recurrence of tumors at the resection site as a secondary end point. A total of 542 subjects have been enrolled in the study. This study will have the statistical power to demonstrate whether H. pylori eradication decreases the incidence and recurrence of gastric cancer.

Endoscopic resection (endoscopic mucosal resection/ endoscopic submucosal dissection) for superficial esophageal squamous cell carcinoma: current status of various techniques.

Endoscopic resection (ER) has been widely accepted as an effective and minimally invasive treatment for patients with superficial esophageal squamous cell carcinoma (SCC). Techniques of conventional endoscopic mucosal resection (EMR) were first developed for ER. There are three representative methods of conventional EMR: endoscopic esophageal mucosal resection (EEMR)‐tube method, EMR using a cap‐fitted endoscope (EMRC) method and two‐channel EMR method. In the past decade, techniques of endoscopic submucosal dissection (ESD) have become established as standard methods of ER. ESD allows en bloc resection of a lesion, irrespective of the size and shape of the lesion. Recently, results of retrospective cohort studies confirming that ESD is superior to EMR as a curative treatment for superficial esophageal SCC have been reported. Representative knives that are now frequently used in esophageal ESD include Hook knife, Triangle tip knife, IT knife nano, Flush knife‐BT, Dual knife, SB knife, and so on. Although there are various knives developed for ESD, the basic techniques for safe and effective ESD are the same.

Characteristics of magnified endoscopic images of gastric extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue, including changes after treatment

BACKGROUND The utility of magnifying endoscopy for diagnosis of epithelial tumors has been reported, but there are few reports for nonepithelial tumors. OBJECTIVE To determine the characteristics of magnified images of gastric extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) before and after treatment. DESIGN This was a retrospective study. SETTING Endoscopy Unit, Hokkaido University Hospital. PATIENTS Eleven patients diagnosed with MALT lymphoma were enrolled. INTERVENTIONS The microstructural pattern, collecting venules, and abnormal vessels in gastric MALT lymphoma were assessed before treatment and at 4 to 7 months after treatment by using magnifying endoscopy. MAIN OUTCOME MEASUREMENT AND RESULTS: The characteristics of magnified endoscopic images before treatment were the disappearance of gastric pits and the appearance of abnormal vessels. Ten cases of Helicobacter pylori-infected MALT lymphoma were treated by H. pylori eradication, and 1 H. pylori-negative case was treated by radiation therapy after eradication therapy. Ten patients achieved complete disease remission. After the treatment, recovery of gastric pits and subepithelial capillary network, and the disappearance of abnormal vessels were revealed by magnifying endoscopy. LIMITATION This was a small pilot study. CONCLUSIONS Magnified findings of gastric MALT lymphoma before and after therapy seem to correlate with complete response and no response.

Effects of preoperative administration of omeprazole on bleeding after endoscopic submucosal dissection: a prospective randomized controlled trial.

BACKGROUND AND AIMS The effectiveness of preoperative administration of proton pump inhibitors (PPIs) for the prevention of bleeding after endoscopic submucosal dissection (ESD) is unclear. Our aim was to evaluate the benefit of starting PPI treatment 1 day before ESD to prevent bleeding after the procedure. PATIENTS AND METHODS This was a prospective randomized controlled trial. Data for 155 patients who underwent ESD (preoperative administration group: N = 81; postoperative administration group: N = 74) were analyzed. All patients received standard ESD using an insulation-tipped knife. Patients in the preoperative group were administered omeprazole from the day before ESD, and patients in the postoperative group received omeprazole after ESD. Follow-up endoscopy was performed on day 1, day 7, and day 28. Intragastric pH was measured from samples of gastric juice. The primary endpoint of this study was major bleeding related to ESD, and the secondary endpoint was minor bleeding. RESULTS Major bleeding occurred in one patient from the postoperative group who had hematemesis. Minor bleeding occurred on day 1 in six patients from the preoperative group and five patients from the postoperative group (7.7 % vs. 7.4 %). There was no significant difference between major and minor bleeding ratios in the two groups. Intragastric pH at ESD in the postoperative group was lower than that in the preoperative group ( P < 0.05). CONCLUSIONS Preoperative administration of omeprazole offers no additional benefit over postoperative administration alone in the prevention of bleeding after ESD among elderly Japanese people.

Preliminary Trial of Rebamipide for Prevention of Low-Dose Aspirin-Induced Gastric Injury in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study

Although low-dose aspirin is widely used, since it is a cheap and effective means of prevention of cardiovascular events, it can cause hemorrhagic gastrointestinal complications. The aim of this study was to evaluate the efficacy of rebamipide in preventing low-dose aspirin-induced gastric injury. A randomized, double-blind, placebo-controlled, crossover trial was performed in twenty healthy volunteers. Aspirin 81 mg was administered with placebo or rebamipide 300 mg three times daily for 7 consecutive days. The rebamipide group exhibited significant prevention of erythema in the antrum compared with the placebo group (p = 0.0393, respectively). Results for the body and fornix did not differ significantly between the placebo and rebamipide groups. In conclusion, short-term administration of low-dose aspirin induced slight gastric mucosal injury in the antrum, but not in the body or fornix. Rebamipide may be useful for preventing low-dose aspirin-induced gastric mucosal injury, especially which confined to the antrum.

Target biopsy using magnifying endoscopy in clinical management of gastric mucosa‐associated lymphoid tissue lymphoma

Background and Aim:  We have reported the characteristics of magnified endoscopic images of gastric mucosa‐associated lymphoid tissue (MALT) lymphoma before and after treatment. In this study, we investigated the diagnostic efficacy of magnified endoscopic images for target biopsy and evaluation of clinical remission.

Long‐term treatment of localized gastric marginal zone B‐cell mucosa associated lymphoid tissue lymphoma including incidence of metachronous gastric cancer

Background and Aim:  According to a few recent reports on the long‐term clinical outcome of gastric marginal zone B‐cell mucosa associated lymphoid tissue lymphoma (MALT lymphoma); localized gastric MALT lymphoma generally has a favorable prognosis. However, the risk of metachronous gastric cancer has not been evaluated. In this study, we analyzed long‐term outcomes of localized gastric MALT lymphoma including the incidence of metachronous gastric cancer.

Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study

BackgroundDetecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples.MethodsgGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured.ResultsAll four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application.ConclusionsFluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.