Nationwide epidemiological study on gastroesophageal reflux disease and sleep disorders in the Japanese population.

BACKGROUND: To elucidate the relationship between gastroesophageal reflux disease and sleep disorders in the Japanese population, we conducted a nationwide survey on the prevalence of heartburn, the cardinal symptom of the disease, and sleep disorders. METHODS: Questionnaires regarding the frequency of heartburn and sleep disorders were distributed and endoscopic findings were assessed among patients who visited 35 participating institutions from March through September 2005, with a target sample size of 100 consecutive endoscopy patients per institution. RESULTS: A total of 2426 patients were included in the analysis population. The prevalence of gastroesophageal reflux disease in patients was 26.5% (n = 644). Mean sleeping time was 6.5 +/- 1.2 h, and 48.3% (n = 1172) of all patients reported experiencing sleep disorders. Sleep disorders were significantly more prevalent among patients with heartburn, at 56.3% (615/1093 patients, P < 0.0001), with the number of sleep disorder events increasing with the frequency of heartburn. Conversely, those with sleep disorders reported experiencing heartburn at a significantly higher rate (approximately 75%). However, sleep disorders occurred in only 51.6% (197/382) of patients with reflux esophagitis, showing no significant difference compared with those without reflux esophagitis. No definite tendency was seen in relation to the severity of reflux esophagitis. CONCLUSIONS: In Japanese people, patients with heartburn had a significantly higher prevalence of sleep disorders than those without heartburn.

[Epidemiology of GERD in Japan].

To determine the epidemiological characteristics of Japanese patients with gastroesophageal reflux disease(GERD), we investigated the prevalences of heartburn, reflux esophagitis(RE), hiatus hernia and Barrett's mucosa, and assessed the correlations among them. In total, 15.4 % (725/4,723) of patients had heartburn twice or more per week and 42.2% had symptoms of heartburn, including those who had heartburn once or less per week, and 16.7 % (602/3,608) of patients had RE. The prevalences of hiatus hernia and Barrett' s mucosa were 49.3 % (1,263/2,560) and 20.8% (536/2,577), respectively. There was a weak correlation between RE and heartburn, but 75.5% of patients who had heartburn did not have any endoscopic abnormalities, and 40.1% of patients without endoscopic abnormalities had heartburn, suggesting the presence of endoscopy-negative GERD. Results also showed that 26.2 % of patients had RE associated with hiatus hernia, and there was a correlation between the two. There was a weak correlation between Barrett' s mucosa and RE and between Barrett' s mucosa and hiatus hernia.

Long-term outcome of endoscopic metallic stenting for benign biliary stenosis associated with chronic pancreatitis.

AIM: Endoscopic metal stenting (EMS) offers good results in short to medium term follow-up for bile duct stenosis associated with chronic pancreatitis (CP); however, longer follow-up is needed to determine if EMS has the potential to become the treatment of first choice. METHODS: EMS was performed in eight patients with severe common bile duct stenosis due to CP. After the resolution of cholestasis by endoscopic naso-biliary drainage three patients were subjected to EMS while, the other five underwent EMS following plastic tube stenting. The patients were followed up for more than 5 years through periodical laboratory tests and imaging techniques. RESULTS: EMS was successfully performed in all the patients. Two patients died due to causes unrelated to the procedure: one with an acute myocardial infarction and the other with maxillary carcinoma at 2.8 and 5.5 years after EMS, respectively. One patient died with cholangitis because of EMS clogging 3.6 years after EMS. None of these three patients had showed symptoms of cholestasis during the follow-up period. Two patients developed choledocholithiasis and two suffered from duodenal ulcers due to dislodgement of the stent between 4.8 and 7.3 years after stenting; however, they were successfully treated endoscopically. Thus, five of eight patients are alive at present after a mean follow-up period of 7.4 years. CONCLUSION: EMS is evidently one of the very promising treatment options for bile duct stenosis associated with CP, provided the patients are closely followed up; thus setting a system for their prompt management on emergency is desirable.

Generation of antitumor immunity against large colon tumors by repeated runs of electrochemotherapy.

BACKGROUND/AIMS: Electrochemotherapy, which uses two parallel electrodes for delivery of electric pulses, may be useful for treatment of tumor nodules. However, in clinical fields, tumors that are larger than the distance between the two electrodes are frequently observed, and it would be difficult in such cases to deliver electric pulses to the tumor. This study was done to define how host antitumor immunity is generated by repeated electrochemotherapy treatments, and whether it is associated with regression of even large tumor nodules. METHODOLOGY: Balb/c mice and Balb/c nude mice were inoculated subcutaneously with colon 26. Electrochemotherapy using bleomycin and electroporation (CUY21) was administered as a treatment for tumor nodules that were larger than the distance between the electrodes. RESULTS: In Balb/c mice, growth of large tumors at the start of treatment is not inhibited by a single electrochemotherapy treatment. However, complete tumor regression was obtained through repeated electrochemotherapy treatments. No tumor cure was observed among Balb/c nude mice under the same therapeutic conditions. Inflammatory cells were accumulated in the tumor tissue seven days after the third electrochemotherapy treatment. CONCLUSIONS: Repeated electrochemotherapy is a promising treatment, even for large tumors, such as are usually encountered in clinical practice, by generating T-cell dependent, antitumor immunity.

High en bloc resection rate achieved by endoscopic mucosal resection with IT knife for early gastric cancer.

BACKGROUND/AIMS: Circumferential endoscopic mucosal resection (EMR) around lesions performed by an insulation-tipped diathermic knife (IT knife) increases en bloc resection rates, suggesting the possibility of expanding indications for EMR. METHODOLOGY: Clinical outcome of EMR performed by IT knife under general anesthesia was evaluated for 26 patients with 29 early gastric cancer. RESULTS: Successful en bloc resection rates obtained by the IT knife were 100, 87.5, 90.0 and 100% for lesions < or =10 mm in size, 11-20 mm, 21-30 mm, and > or =31 mm, respectively. They were significantly higher with the IT knife than those obtained by the conventional method (IT knife method: 93.1% vs. conventional method: 28.5%, p<0.0001). Two lesions were lateral margin positive, and in three cases invasion of lesions was observed as deep as the submucosa. Distal, total, and proximal gastrectomy with D2 lymphadenectomy, respectively, was provided in 3 cases; however, no lymph node involvement was found in any of the resected specimens. Bleeding and perforation were observed in 3 cases, respectively, however, no additional surgical treatment was required for these patients. CONCLUSIONS: EMR by means of the IT knife under general anesthesia can be performed safely and adequately. It is a useful treatment modality for early gastric cancer.

[Nationwide epidemiological survey regarding heartburn and reflux esophagitis in Japanese].

The details on prevalence of heartburn and reflux esophagitis have not been clarified, since no large-scale survey has been conducted to date. Accordingly, we conducted the nationwide survey regarding prevalence of heartburn and reflux esophagitis by asking new outpatients and patients with the first endoscopy to be performed who visited the medical institutions participating in this survey to fill out the questionnaire and undergo endoscopy. The result showed that heartburn was reported from 1,994 patients (42.2%) out of 4,723, and reflux esophagitis classified as grade A-D was reported from 602 patients (16.7%) out of 3,608. Meanwhile, fat intake, sweet food and anti-inflammatory analgesics were proven to be causes of heart-burn. Furthermore, frequency of heartburn and severity of reflux esophagitis were slightly correlated, although those were not necessarily obviously related.

[The operation of Barrett's esophagus].

The purpose of operation in Barrett's esophagus is to protect against esophageal acid exposure. In Western countries antireflux surgery is positive because Barrett's esophagus is recognized as premalignancy. But in Japan many people have SSBE without intestinal metaplasia. Thus if cancer is not detected in Barrett's esophagus, it is difficult to accept surgery. Besides antireflux surgery is not always successful. So the extra-surgical treatment is more recommended than operation in Japan.

Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.

Antiangiogenic factors are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vitro and tumor growth in mice. We have demonstrated the synergistic antitumor effect of antiangiogenic genes (mouse angiostatin: pBLAST-mAngio; and mouse endostatin: p-BLAST42-mEndo XV) delivered to tumors by low-voltage electroporation in mouse colon 26 models. A synergistic antitumor effect was strongly suggested by in vivo tumor growth kinetics, as well as in survival studies with the mice. RT-PCR confirmed that the fragments of each gene were transferred by low-voltage electroporation in the tumor. Decreased microvessel density measurements in tumors also confirmed the efficacy of the synergistic antitumor effect of both genes. Significant growth inhibition was observed in mice treated with a 1:1 proportion of angiostatin and endostatin genes, and the order of the both genes transferred (first the endostatin gene, followed 1 week later by the angiostatin gene) had a profound inhibitory effect on tumor growth. These data suggest that in vivo delivery of antiangiogenic genes with low-voltage electroporation could be a possible therapeutic strategy for established solid tumors when both genes were applied in combination.

Survey on the prevalence of GERD and FD based on the Montreal definition and the Rome III criteria among patients presenting with epigastric symptoms in Japan.

BACKGROUND: The present survey aimed to clarify the prevalence of gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) in patients presenting with epigastric symptoms in Japan based on the Montreal definition and the Rome III criteria, respectively, and to determine the degree of overlap between the two disease entities and the validity of using these Western-developed diagnostic criteria in Japan. METHODS: Patients presenting with epigastric symptoms for whom the first upper gastrointestinal endoscopy was scheduled from April through August 2007 at 55 institutions were asked to complete a questionnaire to ascertain the type, frequency, and severity of epigastric symptoms. The prevalence of esophageal mucosal damage was also determined from endoscopic findings. RESULTS: A total of 1,076 patients were included in the analysis population. There was a high degree of coincidence for all symptoms, with the mean number of symptoms per patient of 2.8. With strict application of the Montreal and Rome III definitions, symptomatic GERD accounted for 15.6% (168 patients), whereas FD accounted for 10.3% (111 patients), and the overlap between GERD and FD symptoms was less than 10%. However, when frequency and severity alone were considered in more broadly defined criteria, the overlap between GERD and FD symptoms was 30-40%. CONCLUSION: A highly specific disease classification is possible when the Montreal definition and the Rome III criteria are strictly applied. On the other hand, the present survey highlighted a problem with the criteria whereby a definitive diagnosis could not be made in a substantial number of patients. This problem will require further research.

Placement of the Bravo wireless pH monitoring capsule onto the gastric wall under endoscopic guidance.

BACKGROUND: The Bravo system was designed mainly to monitor esophageal pH, and there have been no reports on gastric pH monitoring using this system. OBJECTIVE: To place the Bravo capsule on the gastric wall and monitor gastric pH. DESIGN: Experimental clinical trial with the cooperation of volunteers. SETTING: Academic medical center. PATIENTS: Eleven volunteers (9 men, 2 women; mean age 38 years; 3 had symptoms of GERD). INTERVENTIONS: The Bravo system was introduced into the esophagus and stomach along a thin endoscope and capsules were attached, one each to the esophageal and gastric walls under direct vision through the endoscope. Esophageal and gastric pHs were simultaneously monitored. RESULTS: The 2 capsules were successfully placed in 10 of the 11 subjects, and both esophageal and gastric pHs were monitored for 48 hours in 9 subjects. Mild to moderate precordial pain was observed in 7 subjects, but no other complications or side effects were observed in this study. The gastric pH of 10 subjects increased after meals and returned to baseline pH 2 hours later. Decrease of esophageal pH was observed 1 hour after a meal in the symptomatic subjects and corresponded to the time when gastric pH decreased secondary to the increase of pH with meals. CONCLUSIONS: The Bravo capsule is easily placed on the gastric wall under endoscopic assistance and enables long ambulatory monitoring of gastric pH.

Primary malignant melanoma of the esophagus treated with heavy-ion radiotherapy.

Primary malignant melanoma of the esophagus (PMME) is an uncommon but aggressive tumor with very poor prognosis. There is no established treatment plan for the disease, which may be attributed to its rarity and aggressiveness. Surgery is the choice of treatment in early cases. Radiotherapy follows surgery, and chemotherapy has an insignificant role in its treatment. Radiation with heavy ion beams is showing promising results in cancer therapy. Compared to conventional radiation, it permits selective irradiation with minimal injury to the surrounding normal tissue, and treatment with a low dose within a short interval of time is possible. We herein report a case of PMME treated with heavy ion radiation, the first case to be reported so far, and review the relevant literature.

Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin.

PURPOSE: The antitumor efficiency of electrochemotherapy using chemotherapeutic agents and high-voltage electric pulse has been reported. This study was done to define the precise nature of the involvement of antitumor immunity in the regression of tumor nodules in electrochemotherapy, and to evaluate the effectiveness of using low-voltage electroporation. METHODS: Balb/c mice and Balb/c nu/nu nude mice were inoculated subcutaneously with Colon 26 cells or Meth A cells. Electrochemotherapy using bleomycin and low-voltage electroporation (CUY21) was performed as a treatment against tumor nodules. RESULTS: Colon 26 tumors were eradicated in the mice given an intratumor (i.t.) injection of 500 microg bleomycin followed by treatment with electric fields ranging from 50 to 150 V/cm, with complete response rates ranging from 80% to 100%. The mice rejected inoculations of rechallenged Colon 26 cells, but not Meth A cells. In the Balb/c nu/nu nude mice, complete regression of the tumor was not seen after electrochemotherapy under the same therapeutic conditions that resulted in almost complete cure in the Balb/c mice. CONCLUSION: Our results suggest that the generation of T-cell-dependent, tumor-specific protective immunity might be involved in the process of tumor nodule regression in low-voltage electrochemotherapy.