Yosuke Tsuji

Background Factors of Reflux Esophagitis and Non-Erosive Reflux Disease: A Cross-Sectional Study of 10,837 Subjects in Japan

Background Despite the high prevalence of gastroesophageal reflux disease (GERD), its risk factors are still a subject of controversy. This is probably due to inadequate distinction between reflux esophagitis (RE) and non-erosive reflux disease (NERD), and is also due to inadequate evaluation of adjacent stomach. Our aim is therefore to define background factors of RE and NERD independently, based on the evaluation of Helicobacter pylori infection and gastric atrophy. Methods We analyzed 10,837 healthy Japanese subjects (6,332 men and 4,505 women, aged 20–87 years) who underwent upper gastrointestinal endoscopy. RE was diagnosed as the presence of mucosal break, and NERD was diagnosed as the presence of heartburn and/or acid regurgitation in RE-free subjects. Using GERD-free subjects as control, background factors for RE and NERD were separately analyzed using logistic regression to evaluate standardized coefficients (SC), odds ratio (OR), and p-value. Results Of the 10,837 study subjects, we diagnosed 733 (6.8%) as RE and 1,722 (15.9%) as NERD. For RE, male gender (SC = 0.557, OR = 1.75), HP non-infection (SC = 0.552, OR = 1.74), higher pepsinogen I/II ratio (SC = 0.496, OR = 1.64), higher BMI (SC = 0.464, OR = 1.60), alcohol drinking (SC = 0.161, OR = 1.17), older age (SC = 0.148, OR = 1.16), and smoking (SC = 0.129, OR = 1.14) are positively correlated factors. For NERD, HP infection (SC = 0.106, OR = 1.11), female gender (SC = 0.099, OR = 1.10), younger age (SC = 0.099, OR = 1.10), higher pepsinogen I/II ratio (SC = 0.099, OR = 1.10), smoking (SC = 0.080, OR = 1.08), higher BMI (SC = 0.078, OR = 1.08), and alcohol drinking (SC = 0.076, OR = 1.08) are positively correlated factors. Prevalence of RE in subjects with chronic HP infection and successful HP eradication denotes significant difference (2.3% and 8.8%; p<0.0001), whereas that of NERD shows no difference (18.2% and 20.8%; p = 0.064). Conclusions Significantly associated factors of NERD are considerably different from those of RE, indicating that these two disorders are pathophysiologically distinct. Eradication of Helicobacter pylori may have disadvantageous effects on RE but not on NERD.

Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue to cover wounds after colorectal endoscopic submucosal dissection (with video).

BACKGROUND Colorectal endoscopic submucosal dissection (ESD) has made it possible to resect large specimens in an en bloc fashion. However, this can lead to postoperative adverse events, such as perforation and bleeding. Prevention of adverse events after colorectal ESD is therefore an important goal. OBJECTIVE To evaluate the utility of a shielding method using polyglycolic acid (PGA) sheets and fibrin glue to manage ulcers after colorectal ESD. DESIGN Prospective, single-arm, pilot study. SETTING Single tertiary care center for colorectal ESD in Japan. PATIENTS Ten patients with 10 colorectal tumors scheduled for ESD were enrolled between September and November 2012. INTERVENTIONS Just after ESD, we placed PGA sheets on the mucosal defect with biopsy forceps. After the whole defect was covered, we sprayed fibrin glue through a special double-lumen spraying tube. We sprayed fibrinogen through 1 lumen and then thrombin through the other lumen. MAIN OUTCOME MEASUREMENTS Success rate, mean procedure time, and adverse events associated with the covering technique and the persistence of PGA sheets at follow-up colonoscopy. RESULTS All 10 tumors were successfully resected. Mean tumor size was 39.7 ± 15.2 mm. All mucosal defects were successfully covered with PGA sheets. Mean procedure time was 18.7 ± 15.9 minutes. No procedure-related adverse events occurred. Upon colonoscopy 9 to 12 days after ESD, the PGA sheets were still fixed on the whole defect in 8 patients. LIMITATIONS Small sample size. CONCLUSIONS Our technique, which uses PGA sheets and fibrin glue, appears to shield mucosal defects, and it may be effective in reducing postoperative adverse events.

Polyglycolic acid sheets with fibrin glue can prevent esophageal stricture after endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS Suitable techniques for the prevention of stricture formation after esophageal endoscopic submucosal dissection (ESD) are still lacking. We investigated the efficacy of polyglycolic acid (PGA) sheets with fibrin glue to prevent post-ESD stricture. PATIENTS AND METHODS We conducted a pilot study on a total of eight consecutive patients who underwent esophageal ESD that left a mucosal defect of more than three-quarters of the esophageal circumference. PGA sheets were attached to the defect with fibrin glue immediately after the completion of ESD. The primary endpoint was the incidence of post-ESD stricture. The secondary endpoints were the number of sessions of endoscopic balloon dilation (EBD) required to resolve any stricture and the rate of complications. RESULTS There were no adverse events related to the use of PGA sheets and fibrin glue. Post-ESD stricture occurred in 37.5 % of the subjects and 0.8 ± 1.2 sessions of EBD were required. CONCLUSION The use of PGA sheets and fibrin glue after esophageal ESD is a novel method that radically decreases the incidence of esophageal stricture and the number of EBD sessions subsequently required. University Hospital Medical Network Clinical Trial Registry (UMIN000011058).

Effective training system in colorectal endoscopic submucosal dissection.

Although colorectal endoscopic submucosal dissection (ESD) is superior to endoscopic mucosal resection (EMR) in en bloc resection rate, it is technically quite difficult because of the anatomical and histological characteristics of the colorectal wall. This difficulty prevents wide spread of the technique. Establishment of the training system for colorectal ESD is necessary to standardize training and to achieve wider acceptance of this technique. Herein, we describe our training system for colorectal ESD, and assess the validity of the training system for colorectal ESD, based on the clinical outcomes and learning curve of trainees. Our training system for colorectal ESD would help the spread of this procedure.

An effective training system for endoscopic submucosal dissection of gastric neoplasm.

BACKGROUND AND STUDY AIMS A standard training system for endoscopic submucosal dissection (ESD) remains to be established. In this study, we evaluated the validity of our training program for gastric ESD. PATIENTS AND METHODS Four trainees performed gastric ESD for a total of 117 lesions in 107 patients (27 to 30 consecutive lesions per trainee) at a tertiary referral center during 2 years in the training program. Trainees, who already had the fundamental skills and knowledge needed for ESD, each assisted at 40 gastric ESD procedures, then in 20 cases applied post-ESD coagulation (PEC) to gastric mucosal defects; they then began to perform ESD, starting with gastric antral lesions. Treatment outcomes, including mean procedure time, and rates of en bloc resection, en bloc plus R0 resections, complications, and self-completion, were evaluated, for the initial 15 and subsequent 12 to 15 cases. RESULTS Overall rates of en bloc resection and en bloc plus R0 resection were as high as 100 % and 96.6 %, respectively. Regarding complications, seven cases of delayed hemorrhage (6.0 %) and three cases of perforation (2.6 %) occurred; all complications were solved endoscopically. The most frequent reason for operator change was lack of submucosal dissection skill. The self-completion rate was more than 80 % even in the early period, and did not increase for later cases. CONCLUSIONS Our training system enabled novice operators to perform gastric ESD without a decline in clinical outcomes. Key features of this training are prior intensive learning and actual ESD during the learning period under expert supervision.

Complications Related to Gastric Endoscopic Submucosal Dissection and Their Managements

Endoscopic submucosal dissection (ESD) for early gastric cancer is a well-established procedure with the advantage of resection in an en bloc fashion, regardless of the size, shape, coexisting ulcer, and location of the lesion. However, gastric ESD is a more difficult and meticulous technique, and also requires a longer procedure time, than conventional endoscopic mucosal resection. These factors naturally increase the risk of various complications. The two most common complications accompanying gastric ESD are bleeding and perforation. These complications are known to occur both intraoperatively and postoperatively. However, there are other rare but serious complications related to gastric ESD, including aspiration pneumonia, stenosis, venous thromboembolism, and air embolism. Endoscopists should have sufficient knowledge about such complications and be prepared to deal with them appropriately, as successful management of complications is necessary for the successful completion of the entire ESD procedure.

Prospective controlled study on the effects of polyethylene glycol in capsule endoscopy.

AIM To prospectively confirm whether a small amount of polyethylene glycol (PEG) ingested after swallowing endoscopy capsule improves image quality and completion rate. METHODS Forty-four consecutive patients referred to us for capsule endoscopy (CE) were randomized to two groups. All patients were restricted to clear fluids for 12 h before the examination. Patients in group A (22 cases) received no additional preparation, while those in group B (20 cases) ingested 500 mL of PEG within a 2 h period starting 30 min after swallowing the capsule. Clear fluids and meals were allowed 2 h and 4 h after capsule ingestion, respectively. Image quality was assessed as the percentage of visualized bowel surface area as follows: 1: < 25%; 2: 25%-49%; 3: 50%-74%; 4: 75%-89%; 5: > 90%. The small bowel record was divided into five segments by time, and the score for each segment was evaluated. All CE examinations were performed with the Pillcam SB capsule endoscopy system (Given Imaging Co. Ltd., Yoqnem). RESULTS This study ended in December 2009, because sample size was considered large enough. A total of 44 patients were enrolled. Two patients in group B were excluded from the analysis because small bowel images could not be obtained from these patients; one had a full stomach, while the other presented with a massive gastric bleed. Thus, 22 patients from group A and 20 patients from group B completed the study. There was no significant difference in age (P = 0.22), sex (P = 0.31), and indication for CE. No significant adverse events occurred in any of the study patients. In group A, image quality deteriorated as the capsule progressed distally. However, in group B, image quality was maintained to the distal small bowel. In each of the five segments, the visibility score was significantly higher in group B than in group A (segment 1: 4.3 ± 0.7 vs 4.7 ± 0.5, P = 0.03; segment 2: 4.2 ± 0.9 vs 4.8 ± 0.4, P = 0.01; segment 3: 4.0 ± 1.0 vs 4.6 ± 0.7, P = 0.04; segment 4: 3.6 ± 1.1 vs 4.5 ± 0.6, P = 0.003; segment 5: 2.7 ± 1.0 vs 4.4 ± 0.8, P = 0.00004). Thus, the use of PEG during CE examination significantly improved image quality in all time segments, and this effect was more pronounced in the distal ileum. The completion rate to the cecum was not significantly different between groups A and B (81.8% vs 85.0%, P = 0.89). There was no difference in the gastric transit time between groups (36.2 ± 35.0 min vs 54.0 ± 56.6 min, P = 0.23), but the small bowel transit time was significantly longer in group A than in group B (246.0 ± 107.0 min vs 171.0 ± 104.0 min, P = 0.04). CONCLUSION The ingestion of a small amount of PEG after the swallowing of an endoscopy capsule significantly improved CE image quality, but did not enhance the completion rate to the cecum.

Associated Factors of Atrophic Gastritis Diagnosed by Double-Contrast Upper Gastrointestinal Barium X-Ray Radiography: A Cross-Sectional Study Analyzing 6,901 Healthy Subjects in Japan

Background Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. Methods We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Results Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects. Conclusions The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.

Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV

Early detection of esophageal squamous cell carcinoma (ESCC) is an important prognosticator, but is difficult to achieve by conventional endoscopy. Conventional lugol chromoendoscopy and equipment-based image-enhanced endoscopy, such as narrow-band imaging (NBI), have various practical limitations. Since fluorescence-based visualization is considered a promising approach, we aimed to develop an activatable fluorescence probe to visualize ESCCs. First, based on the fact that various aminopeptidase activities are elevated in cancer, we screened freshly resected specimens from patients with a series of aminopeptidase-activatable fluorescence probes. The results indicated that dipeptidylpeptidase IV (DPP-IV) is specifically activated in ESCCs, and would be a suitable molecular target for detection of esophageal cancer. Therefore, we designed, synthesized and characterized a series of DPP-IV-activatable fluorescence probes. When the selected probe was topically sprayed onto endoscopic submucosal dissection (ESD) or surgical specimens, tumors were visualized within 5 min, and when the probe was sprayed on biopsy samples, the sensitivity, specificity and accuracy reached 96.9%, 85.7% and 90.5%. We believe that DPP-IV-targeted activatable fluorescence probes are practically translatable as convenient tools for clinical application to enable rapid and accurate diagnosis of early esophageal cancer during endoscopic or surgical procedures.

Trend and Risk Factors of Diverticulosis in Japan: Age, Gender, and Lifestyle/Metabolic-Related Factors May Cooperatively Affect on the Colorectal Diverticula Formation

Background Despite the marked increase of diverticulosis, its risk factors have not been adequately elucidated. We therefore aim to identify significantly associated factors with diverticulosis. We also aim to investigate the present state of diverticulosis in Japan. Methods We reviewed the medical records from 1990 to 2010 that included the data of consecutive 62,503 asymptomatic colonoscopy examinees from the general population in Japan. Most recent 3,327 examinees were analyzed with 16 background factors. Results Among the 62,503 subjects (47,325 men and 15,178 women; 52.1 ± 9.2 years old), diverticulosis was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0% (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than the former in all age groups and for both genders. Considering the anatomical locations of colorectal diverticula, left-sided ones have markedly increased with age but not significantly changed with times. Univariate analyses of the 3,327 subjects showed significant association of diverticulosis with four basic factors (age, sex, body mass index, blood pressure), three life style-related factor (smoking, drinking, severe weight increase in adulthood), and two blood test values (triglyceride, HbA1c). The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that age (β = 0.217-0.674, OR = 1.24-1.96), male gender (β = 0.185, OR = 1.20), smoking (β = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (β = 0.153, OR = 1.17), HbA1c (β = 0.136, OR = 1.15), drinking (β = 0.109, OR = 1.11), and serum triglyceride (β = 0.098, OR = 1.10) showed significantly positive association with diverticulosis whereas body mass index and blood pressure did not. Conclusions The large-scale data of asymptomatic colonoscopy examinees from the general population from 1990 to 2010 indicated that the prevalence of diverticulosis is still increasing in Japan. Age, male gender, smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum triglyceride showed significant positive association with diverticulosis.