Risk Factors for Developing Metachronous Superficial Gastric Epithelial Neoplasms after Endoscopic Submucosal Dissection.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.

Natural History of Small Gastric Subepithelial Lesions Less than 20 mm: A Multicenter Retrospective Observational Study (NUTSHELL20 Study).

BACKGROUND AND AIM: Small gastric subepithelial lesions (SELs) are sometimes encountered in daily esophagogastroduodenoscopy (EGD) practice, but whether once-annual or twice-annual endoscopy can provide sufficient follow-up remains unclear. Because follow-up based on small-SEL characteristics is important, this study clarified the natural history of gastric SELs less than 20 mm. METHODS: This retrospective multicenter observation study conducted at 24 Japanese hospitals during April 2000 to March 2020 examined small gastric SELs of ≤20 mm diameter. The primary outcome was the rate of size increase of those SELs detected using EGD, with growth times assessed irrespective of SEL pathological diagnoses. RESULTS: We examined 824 cases with tumors of 1-5 mm diameter in 298 (36.2%) cases, 6-10 mm in 344 (41.7%) cases, 11-15 mm in 112 (13.6%) cases, and 16-20 mm in 70 (8.50%) cases. An increase of small gastric SELs was observed in 70/824 patients (8.5%). The SELs larger than 6 mm increased, even after 10 years. No-change and increasing groups had no significantly different malignant findings at diagnosis. In cases of gastrointestinal stromal tumors (GISTs), internal cystic change in endoscopic ultrasound (EUS) is a risk factor for an increased tumor size. The predictive tumor growth cutoff size at initial diagnosis was 13.5 mm. CONCLUSIONS: Small gastric SELs less than 20 mm have an approximately 8.5% chance of increase. Predictive markers for GIST growth are tumor size ≥13.5 mm and internal cystic change in EUS.

Size reduction of gastric fundic gland polyposis by de-escalation of acid-suppressive therapy.

The patient, a 73-year-old woman, had been taking acid-suppressive therapy for refractory reflux esophagitis for 10 years. A potassium-competitive acid blocker was administered to strengthen acid-suppressive therapy for worsening symptoms of gastroesophageal reflux disease. Esophagogastroduodenoscopy showed an increase in the number and size of fundic gland polyposis (FGPs). When acid-suppressive therapy was changed from potassium-competitive acid blocker to proton pump inhibitor, the FGPs showed reduced size 1 year later. Furthermore, when acid-suppressive therapy was changed from proton pump inhibitor to histamine-2 receptor antagonist, FGPs were even smaller after 1 and 2 years. The patient, who had no flare-up of gastroesophageal reflux disease symptoms, continues to be treated medically with histamine-2 receptor antagonist. This case report describes changes in endoscopic findings of a patient with FGPs caused by acid-suppressive therapy for refractory gastroesophageal reflux disease.

Proton Pump Inhibitor to Treat an Eosinophilic Duodenal Ulcer with Esophageal Involvement: A Pediatric Case.

Eosinophilic gastrointestinal disorders are diseases that cause inflammation and dysfunction due to infiltration of eosinophils into various regions of the gastrointestinal tract. Symptoms and treatment vary depending on lesion severity. We describe the first pediatric case of an eosinophilic duodenal ulcer with esophageal involvement that was effectively treated using proton pump inhibitor monotherapy. A 12-year-old boy with no relevant family or medical history presented with a one-month history of epigastric pain. Laboratory test results were as follows: white blood cell count, 4,700/µL; eosinophil count, 150/µL (3.2%); and total IgE, 151.6 IU/L; and IgG antibodies for Helicobacter pylori were absent. Esophagogastroduodenoscopy revealed longitudinal linear furrows in the esophagus, indicating eosinophilic esophagitis with an A1 ulcer from the duodenal bulb to the descending duodenum. The patient was diagnosed with an eosinophilic duodenal ulcer with esophageal involvement based on pathological findings. Esomeprazole, a common proton pump inhibitor, was orally administered, after which the symptoms promptly improved. After two months, the esophagogastroduodenoscopy and pathological examination results showed improvement in both the esophagus and duodenum. There have been no previous reports of an eosinophilic duodenal ulcer with esophageal involvement without post-duodenal involvement at the time of diagnosis. The possibility of eosinophilic gastrointestinal disorders should be investigated in patients with duodenal ulcers by means of active biopsy, and patients should be investigated for other types of gastrointestinal lesions. Proton pump inhibitor monotherapy may be considered a first-line treatment for eosinophilic duodenal ulcers with esophageal involvement, depending on lesion severity.

Guidelines for standardizing cleansing and disinfection of gastrointestinal endoscopes.

As part of the activities toward standardizing endoscopy procedures, the Japan Gastroenterological Endoscopy Society has prepared guidelines for cleansing and disinfection of gastrointestinal endoscopes. The environment of gastrointestinal endoscopy differs between Japan and advanced Western countries. In advanced Western countries, gastrointestinal endoscopy is performed almost exclusively at specialized facilities, where strict provisions are observed for cleansing and disinfecting endoscopes. In Japan, however, gastrointestinal endoscopy is performed even in small clinics, and the annual number of gastrointestinal endoscopy cases is enormous. In addition, the method for cleansing and disinfecting endoscopes differs among hospitals. Although there is a distinct lack of evidence for how gastrointestinal endoscopes are cleaned and disinfected, it is necessary to standardize the method for doing so to advance the field of endoscopic medicine.

Efficacy and safety of twice-daily rabeprazole maintenance therapy for patients with reflux esophagitis refractory to standard once-daily proton pump inhibitor: the Japan-based EXTEND study.

BACKGROUND: Rabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to be highly effective in the treatment of proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) that is refractory to the standard once-daily PPI regimen. We evaluated the efficacy and safety of rabeprazole maintenance therapy at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks. METHODS: Patients with RE refractory to standard PPI regimens for at least 8 weeks were enrolled. They were treated with rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive rabeprazole 10 mg q.d. (control) or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52. RESULTS: In total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%; p < 0.001, χ2 test) than in the q.d. group (44.8%). In particular, the b.i.d. regimen was more effective in all subgroups with Los Angeles Classification Grade B to D at treatment entry. CONCLUSIONS: In the maintenance treatment of PPI-resistant RE, rabeprazole at 10 mg b.i.d. exerted a stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No particular safety issues were noted during long-term administration. ClinicalTrials.gov number: NCT02135107.

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.

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.

Evaluation of a novel high-resolution magnifying videoendoscope that is capable of photodynamic diagnosis and therapy for gastric cancer.

OBJECTIVE: To evaluate the usefulness of a novel high-resolution magnifying videoendoscope called the XG-0001 (Fujifilm, Tokyo, Japan) that is capable of PDD and PDT in experimental and clinical situations. MATERIALS AND METHODS: The fluorescences of three photosensitizers (i.e., porfimer sodium (Photofrin), protoporphyrin IX and talaporfin sodium (Laserphyrin)) were studied experimentally via excitation with a purple diode laser (VDL, wavelength 405nm). Five consecutive patients with superficial early gastric cancer not indicated for surgery or other curative endoscopic treatment due to complicated serious diseases were enrolled in this study. After close endoscopic examinations, 2mg/kg of Photofrin were intravenously injected into the patients for PDT, and 5-aminolevulinic acid (ALA; 15-20mg/kg) was orally taken for PDD. PDD using VDL and PDT using an excimer-dye laser (630nm, 4mJ, 60Hz) were performed with the XG-0001. RESULTS: Photofrin and Laserphyrin had experimentally the lowest and highest fluorescence intensities, respectively. The five patients comprised four men and one woman with a mean age 75.2 year and an age range of 56-83 years. Two additional cancerous lesions were newly detected by magnifying pharmacoendoscopy. In each patient, PDD was successfully performed. PDT could also safely performed and CR was obtained in 71.4% (5/7) of the cancerous lesions in five patients, and no serious complications were encountered. CONCLUSION: The XG-0001, which is based on a simultaneous videoendoscopy method that uses an RGB color chip CCD, proved extremely useful in routine use and also in PDD and PDT for gastric cancer.

A second-look endoscopy may not reduce the bleeding after endoscopic submucosal dissection for gastric epithelial neoplasm.

BACKGROUND: Gastric endoscopic submucosal dissection (ESD) has gradually come to be recommended as the optimal treatment for early gastric cancer; however, one of the primary issues is postoperative bleeding. Although second-look endoscopy is conventionally performed to reduce the risk of postoperative bleeding, its benefit has not yet been clearly elucidated. The objective of this study was to elucidate the benefit of second-look endoscopy. METHODS: A total of 459 lesions in patients were underwent gastric ESD from May 2004 to April 2013 at our hospital were included in the analysis. The patients were divided into those who had bleeding within 24 hours after ESD (immediate bleeding) and those in whom bleeding occurred 24 hours or more after the procedure (delayed bleeding); the underlying disease, age, lesion site, diameter of the resected specimen, and lesion diameter were analyzed to identify the risk factors for postoperative bleeding after ESD. RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459 cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%) excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases (53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the 210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant difference between the two groups. Overall, the following factors were identified as the risk factors for postoperative bleeding: young age (P = 0.005), lesions in the L segment (P = 0.042), and large size of the resected specimen (P = 0.005). The risk factors identified in the immediate bleeding group were lesions in the L segment (P = 0.032), large size of the resected specimen (P < 0.001), and large tumor size (P = 0.011), and those in the delayed bleeding group were young age (P = 0.013) and concomitant renal disease (P = 0.011). CONCLUSIONS: The results of this study suggest that second-look endoscopy after gastric ESD may not be useful for preventing postoperative bleeding.

Evaluation of microvessels in colorectal tumors by narrow band imaging magnification: including comparison with magnifying chromoendoscopy.

BACKGROUND/AIMS: Narrow band imaging (NBI) magnification analysis has entered use in clinical settings to diagnose colorectal tumors. Pit pattern analysis with magnifying endoscopy is already widely used to assess colorectal lesions and invasion depth. Our study compared diagnoses by vascular pattern analysis and pit pattern analysis with NBI magnification. METHODS: We examined 296 colorectal lesions-15 hyperplastic polyps (HP), 213 low-grade adenomas (L-Ad), 26 high-grade adenomas (H-Ad), 31 with intramucosal to scanty submucosal invasion (M-Sm-s), and 11 with massive submucosal invasion (Sm-m)-applying the system of Kudo et al. to analyze pit patterns, and the system of Tanaka et al. to analyze and classify vascular patterns by NBI into three categories: type A (hyperplasia pattern), type B (adenomatous pattern), and type C (carcinomatous pattern). Type C cases were subdivided into subtypes C1, C2, and C3. We used this system to examine histology type and invasion depth. RESULTS: Diagnostic sensitivity, specificity, and accuracy were 100% for both type II pit pattern HP and type A HP. Diagnostic sensitivity, specificity, and accuracy were 85.4, 94.5, and 93.2% for Vi and Vn pit pattern cancer and 95.2, 91.7, and 92.2% for type C cancer (no significant differences in sensitivity, specificity, or accuracy). Diagnostic sensitivity, specificity, and accuracy were comparable for Vi high-grade irregularity and Vn pit pattern Sm-m (90.9, 96.8, and 96.7%) and type C2/C3 Sm-m (90.1, 98.2, and 98.0%), with no significant differences in sensitivity, specificity, or accuracy. CONCLUSIONS: Vascular pattern analysis by NBI magnification proved comparable to pit pattern analysis.

Endoscopic submucosal dissection in 100 lesions with early gastric carcinoma.

BACKGROUND/AIMS: ESD is a new diagnostic and treatment technique for early gastric cancer. This study aimed to evaluate the therapeutic effects observed at our department. METHODOLOGY: The subject group included 95 patients with 100 early-stage gastric cancers. According to the Gastric Cancer Treatment Guidelines published by the Japanease Gastric Cancer Association (JGCA) in 2001. Sixty-seven lesions presented a tumor measuring less than 20 mm and were concave (if not flat) without ulceration (specified indication of the guidelines of the Japanese Gastric Cancer Association), and 33 lesions were expanded indications. We then compared one-piece resection rates, en-bloc resection rates (one-piece resection that is lateral- and vertical-stump negative), curative en-bloc resection rates (en-bloc resection that fulfills the following three criteria: 1. differentiated adenocarcinoma; 2. no lymphtic or venous invasion, 3a. intramucosal cancer regardless of tumor size without ulceration, 3b. intramucosal cancer 30 mm in size with ulceration, 3c. minute submucosal cancer 30 mm in size). RESULTS: Among the specified indications and expanded indications, one-piece resection rates accounted for 97.0% and 75.8%, en-bloc resection rates for 83.6% and 60.6%, and curative en-bloc resection rates for 83.6% and 57.6%. The numbers of accident cases were three (postoperative hemorrhage; n = 1 perforation; n = 2) and four (postoperative hemorrhage; n = 1, perforation; n = 3), respectively. CONCLUSIONS: These studies indicated higher one-piece resection rates, en-bloc resection rates and curative en-bloc resection rates for lesions based on the guidelines than those based on the expanded guidelines.

Magnifying pharmacoendoscopy: response of microvessels to epinephrine stimulation in differentiated early gastric cancers.

BACKGROUND: Magnifying endoscopy is a promising modality for fine observation of minute surface structures and microvessel architecture in gastric lesions. OBJECTIVE: To observe the response of microvessels to epinephrine stimulation in early gastric cancer tissues and to assess the usefulness of magnifying pharmacoendoscopy for histologic diagnosis. DESIGN: This was a prospective pilot study. SETTING: This study was conducted at an academic hospital. PATIENTS: Twenty-nine patients with differentiated early gastric cancer were enrolled. INTERVENTIONS: Microvessels in both the cancerous lesion and its adjacent non-neoplastic gastric mucosa were observed by magnifying endoscopy before and after focal spray with epinephrine solution (0.05 mg/mL). MAIN OUTCOME MEASUREMENTS AND RESULTS: After epinephrine stimulation, noncancerous gastric mucosa surrounding the cancerous lesion showed a change in color from red to white; no microvessels were evident. On the other hand, all the cancerous lesions examined clearly showed enhancement of tumor microvessels. The rate of detection of tumor microvessels by magnifying pharmacoendoscopy (100%) was significantly higher than that by magnifying endoscopy alone (41.3%). LIMITATIONS: This was small pilot study. CONCLUSIONS: Magnifying pharmacoendoscopy with epinephrine is a powerful tool for assessing tumor vascularity and may contribute to the histologic diagnosis of differentiated early gastric cancers before endoscopic treatment.

[Recent view of gastro-esophageal reflux disease according to the guideline for gastric ulcer treatment].

The guideline for gastric ulcer treatment in Japan recommends eradication of Helicobacter pylori (H. pylori) for the first choice. Recently, it is well known that some patients develop gastro-esophageal reflux disease (GERD) after successful eradication. H. pylori infection may play a protective role against GERD by impairing gastric acid secretion. Acid secretion is influenced by the distribution of gastritis in the stomach. Antrum-predominant gastritis is associated with gastric hypersecretion. Patients with corpus-predominant gastritis have decreased acid secretion. The latter is common in Japan and at high risk of GERD after eradication. To arise GERD, both acid secretion and reflux of acid caused by hiatus hernia or gastro-esophageal dysmotility are needed. Although most of GERD developed after eradication are mild, severe GERD are also experienced at times. Recent view of GERD and H. pylori infection is described.