Keiko Niimi

Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms.

BACKGROUND The long-term outcomes of endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell neoplasms (ESCNs) have not been evaluated to date. OBJECTIVE Assess the long-term outcomes of ESD for ESCNs from our consecutive cases. DESIGN AND SETTING Retrospective study from a single institution. PATIENTS AND INTERVENTION From January 2002 to July 2008, 107 superficial ESCNs in 84 patients were treated by ESD. The enrolled patients were divided into 2 groups based on the lesion with the deepest invasion in each patient: group A, intraepithelial neoplasm or invasive carcinoma limited to the lamina propria mucosa and group B, invasive carcinoma deeper than the lamina propria mucosa. MAIN OUTCOME MEASUREMENTS Rates of en bloc resection, complete resection, and complication were evaluated as short-term outcomes. Overall survival, cause-specific survival, and postoperative stricture rates were evaluated as long-term outcomes. RESULTS The rates of en bloc resection and complete resection were 100% and 88%, respectively. Perforation accompanied by mediastinal emphysema was observed in 4 (4%) patients. No patient experienced massive bleeding. During the median observation of 632 days (range 8-2358), 15 (18%) patients experienced benign esophageal stricture with dysphagia, which was successfully managed by balloon dilation for a median of 2 sessions (range 1-20). One patient had local recurrence 6 months after ESD. In 2 patients with intramucosal invasive carcinomas in the muscularis mucosa, distant metastases were observed 9 and 18 months after ESD. During the observation period, 3 patients died of esophageal carcinoma. The 5-year cause-specific survival rates of groups A and B were 100% and 85%, respectively. LIMITATIONS This was a retrospective study with a relatively short follow-up and a small number of patients from a single institution. CONCLUSION This long-term follow-up study revealed that ESD is a potentially curative treatment for superficial ESCNs. There were substantial risks of perforation and stricture that were successfully managed endoscopically.

Predictors of postoperative stricture after esophageal endoscopic submucosal dissection for superficial squamous cell neoplasms

BACKGROUND AND STUDY AIMS Although endoscopic submucosal dissection (ESD) is becoming accepted as an established treatment for superficial esophageal squamous cell neoplasms, the risks for developing postoperative stricture have not been elucidated. PATIENTS AND METHODS This was a retrospective study at a single institution. From January 2002 to October 2008, 65 patients with high-grade intraepithelial neoplasms (HGINs) or m2 carcinomas treated by ESD were enrolled. Predictors of postoperative stricture were investigated by comparing results from 11 patients who developed strictures with those from 54 patients who did not. RESULTS Significant differences between the two groups were observed in longitudinal diameter (45.0 +/- 15.9 mm vs. 31.5 +/- 13.6 mm) and circumferential diameter (37.2 +/- 8.6 mm vs. 26.8 +/- 9.7 mm) of the resected specimens, and the proportion of extension to the whole circumference of the lumen (< 1 / 2/ > 1 / 2/ > 3 / 4 : 2 / 4 / 5 vs. 40 / 13 / 1), histologic depth (HGIN/m2 : 2 / 9 vs. 41 / 13), and procedure time (85.6 +/- 42.8 minutes vs. 53.3 +/- 30.1 minutes). Multivariate analysis revealed that circumferential extension of > 3 / 4 (odds ration [OR]: 44.2; 95 % confidence interval [CI]: 4.4 - 443.6) and histologic depth to m2 (OR: 14.2; 95 %CI: 2.7 - 74.2) are reliable risk factors. Subanalysis for each category by combinations of these risk factors revealed that patients with lesions in > 3 / 4 of the circumferential area were associated with a high rate of postoperative stricture. By contrast, patients with HGIN lesions in < 3 / 4 extension have no probability of postoperative strictures. Additionally, subanalysis of patients with m2 lesions in < 3 / 4 circumferential extension revealed that circumferential diameter can be a reliable predictor for postoperative stricture. CONCLUSIONS Circumferential extension and histologic depth are the reliable risk factors for postoperative strictures. In combination with circumferential diameter, we can perform effective and appropriate preventive balloon dilatations after esophageal ESD.

Long-term outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms

BACKGROUND AND AIMS Endoscopic submucosal dissection (ESD) provides a high en bloc resection rate with less invasiveness than surgical resection for large or scarring gastrointestinal neoplasms. However, detailed outcomes in colorectal ESD are still lacking. The aim of our study was to elucidate short- and long-term outcomes of colorectal ESD. PATIENTS AND METHODS 310 consecutive colorectal epithelial neoplasms (146 adenomas, 164 carcinomas), in 290 patients, which fulfilled our indication criteria and were treated with ESD between July 2000 and December 2008 were studied. ESD was done by three skilled endoscopists. As short-term outcomes, rates of en bloc resection, en bloc plus R0 resection, and major complications were analyzed. As long-term outcomes, disease-free and overall survival were assessed in 224 patients. RESULTS Rates of en bloc resection and en bloc plus R0 resection were 90.3 % and 74.5 %, respectively. Eight patients underwent additional colectomy due to histopathologically proven possible node-positive cancer. Intraoperative perforations occurred with 14 lesions (4.5 %), which were treated successfully only by endoscopic clipping. Emergent surgery was needed for one case of postoperative perforation. Blood transfusion due to intraoperative massive bleeding was required in 1 case (0.3 %). Postoperative bleeding occurred with four lesions (1.3 %), and was endoscopically managed without blood transfusion. Local recurrence was detected in 4 lesions (4/202 patients, 2.0 %); resection had been piecemeal in all 4. During a median follow-up of 38.7 months (range 12.8 - 104.2), the 3- and 5-year overall/disease-specific survivals were 97.1/100 % and 95.3/100 %, respectively. CONCLUSIONS Colorectal ESD showed favorable long-term outcomes. It may largely replace colectomy for node-negative colorectal epithelial neoplasia.

A second-look endoscopy after endoscopic submucosal dissection for gastric epithelial neoplasm may be unnecessary: a retrospective analysis of postendoscopic submucosal dissection bleeding

BACKGROUND Endoscopic submucosal dissection (ESD) is one of the curative endoluminal surgical procedures for gastric epithelial neoplasms. There has been little research on bleeding after gastric ESD. OBJECTIVE To investigate cases of post-ESD bleeding and to verify whether a second-look endoscopy after ESD is effective in the prevention of delayed bleeding. DESIGN A retrospective study with consecutive data. SETTING A single tertiary referral center. SUBJECTS A total of 454 gastric epithelial neoplasms (386 early gastric cancers and 68 gastric adenomas). INTERVENTIONS ESD and second-look endoscopy. MAIN OUTCOME MEASUREMENTS Predictors on post-ESD bleeding by univariate analysis, incidence of post-ESD bleedings, and the timing of those before and after second-look endoscopy. RESULTS Post-ESD bleeding occurred in 26 (5.7%) lesions. Gross type (flat or depressed type) was the only factor influencing post-ESD bleeding. All cases of post-ESD bleeding occurred within 14 days after ESD (median 2; range 0-14), and bleeding tended to occur from the lower and upper stomach earlier and later, respectively. In 19 lesions with delayed bleeding more than 24 hours after ESD, the maximum delayed bleeding rates before and after the second-look endoscopy were 2.8% and 2.5%, respectively. LIMITATIONS A retrospective, single-center analysis. CONCLUSIONS A second-look endoscopy after gastric ESD may contribute little to the prevention of delayed bleeding.

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGEAL SQUAMOUS CELL NEOPLASMS

Endoscopic submucosal dissection (ESD) has gradually gained acceptance as one of the standard treatments for early esophageal cancer, as well as for early gastric cancer in Japan, but standardization of the knowledge is still incomplete. The final goal to perform ESD is not to resect the lesion in an en bloc fashion, but to save the patient from esophageal cancer‐related death. Thus, the indications should be considered based on the entire patient, not just the target lesion itself, and pre‐, peri‐ and postoperative management of the patient is also very important, as well as technical aspects of ESD. In terms of the techniques of ESD, owing to refinement of the procedural strategy, invention of the devices, and the learning curve, acceptable safety and favorable middle‐term efficacy have been obtained. We believe that ESD will become a standard treatment for early esophageal cancer not only in Japan but also worldwide in the near future.

Lifestyle factors affecting gastroesophageal reflux disease symptoms: a cross-sectional study of healthy 19864 adults using FSSG scores

BackgroundGastroesophageal reflux disease (GERD) is a very common disorder worldwide, comprised of reflux esophagitis (RE) and non-erosive reflux disease (NERD). As more than half of GERD patients are classified into the NERD group, precise evaluation of bothersome epigastric symptoms is essential. Nevertheless, compared with many reports targeting endoscopic reflux esophagitis, large-scale studies focusing on GERD symptoms have been very scarce.MethodsTo elucidate lifestyle factors affecting GERD symptoms, 19,864 healthy adults in Japan were analyzed. Sub-analyses of 371 proton pump inhibitor (PPI) users and 539 histamine H2-receptor antagonist (H2RA) users were also performed. Using the FSSG (Frequency Scale for the Symptoms of GERD) score as a response variable, 25 lifestyle-related factors were univariately evaluated by Students t-test or Pearsons correlation coefficient, and were further analyzed with multiple linear regression modelling.ResultsAverage FSSG scores were 4.8 ± 5.2 for total subjects, 9.0 ± 7.3 for PPI users, and 8.2 ± 6.6 for H2RA users. Among the total population, positively correlated factors and standardized coefficients (β) for FSSG scores are inadequate sleep (β = 0.158), digestive drug users (β = 0.0972 for PPI, β = 0.0903 for H2RA, and β = 0.104 for others), increased body weight in adulthood (β = 0.081), dinner just before bedtime (β = 0.061), the habit of midnight snack (β = 0.055), lower body mass index (β = 0.054), NSAID users (β = 0.051), female gender (β = 0.048), lack of breakfast (β = 0.045), lack of physical exercise (β = 0.035), younger age (β = 0.033), antihyperglycemic agents non-users (β = 0.026), the habit of quick eating (β = 0.025), alcohol drinking (β = 0.025), history of gastrectomy (β = 0.024), history of cardiovascular disease (β = 0.020), and smoking (β = 0.018). Positively correlated factors for PPI users are female gender (β = 0.198), inadequate sleep (β = 0.150), lack of breakfast (β = 0.146), antihypertensive agent non-users (β = 0.134), and dinner just before bedtime (β = 0.129), whereas those for H2RA users are inadequate sleep (β = 0.248), habit of midnight snack (β = 0.160), anticoagulants non-users (β = 0.106), and antihypertensive agents non-users (β = 0.095).ConclusionsAmong many lifestyle-related factors correlated with GERD symptoms, poor quality of sleep and irregular dietary habits are strong risk factors for high FSSG scores. At present, usual dose of PPI or H2RA in Japan cannot fully relieve GERD symptoms.

Non-exposed endoscopic wall-inversion surgery as a novel partial gastrectomy technique

In gastric full-thickness resection employing both endoscopy and laparoscopy, intraabdominal contamination or even possibly tumor seeding is unavoidable as a result of iatrogenic perforation and the resultant spread of gastric juice. To minimize contamination and resected tissue volume, we developed a new technique without perforation termed non-exposed endoscopic wall-inversion surgery (NEWS), and present here the preliminary results. In a clinical observation cohort study, NEWS was attempted in six patients with gastric SMT to investigate the procedure, mortality, and morbidity. NEWS consists of several steps: marking around a tumor on the mucosal as well as the serosal surface, submucosal injection of sodium hyaluronate with indigo carmine dye, circumferential seromuscular dissection with suture closure under laparoscopy, and circumferential mucosubmucosal incision under gastric endoscopy. The resected specimen is then retrieved perorally. Perforation occurred as a result of misidentification and technical inadequacy in the first three patients. After modification of the devices, the entire procedure was successfully achieved in the latter three. There were no complications in any of our six cases. NEWS allows en bloc full-thickness resection, theoretically avoiding contamination and tumor dissemination into the peritoneal cavity.

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.

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).

Technical feasibility of endoscopic submucosal dissection for early gastric cancer in patients taking anti-coagulants or anti-platelet agents

BACKGROUND Endoscopic submucosal dissection is a novel technique that is expected to be a curative treatment for early gastric cancers. Anti-coagulants and anti-platelet agents are widely used, especially in elderly patients, to prevent thromboembolic disease. However, the feasibility of endoscopic submucosal dissection for such patients has not been investigated. AIMS To determine the feasibility of endoscopic submucosal dissection for patients using anti-coagulant and anti-platelet agents via retrospective investigation of clinical outcomes. METHODS Of 408 patients with 444 early gastric cancers consecutively treated by endoscopic submucosal dissection from January 2000 to December 2007 in our hospital, 47 patients with 56 early gastric cancers were receiving anti-coagulants or anti-platelet agents. All patients were classified into groups for high and low risk of thromboembolism. In 44 low-risk patients, these agents were stopped for 1 week before and after treatment. Only three high-risk patients underwent intravenous heparin replacement during the cessation period. RESULTS Comparison with other patients showed no significant differences in complete en-bloc resection (96.4%) or perforation (1.8%). Postoperative bleeding requiring endoscopic treatment occurred for six early gastric cancers (10.7%) in the anti-coagulant and anti-platelet group; this frequency was slightly higher than that observed for other patients (5.2%). The healing of endoscopic submucosal dissection ulcers was not delayed by anti-coagulant and anti-platelet treatment (91% in the scarring stage) when checked at the 8th week after endoscopic submucosal dissection. CONCLUSION The clinical outcomes of endoscopic submucosal dissection for early gastric cancers in patients receiving anti-coagulants or anti-platelet agents indicated that endoscopic submucosal dissection for low-risk patients could be a reliable technique with equivalent efficacy and risk in comparison with that for other early gastric cancer patients.