Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease.

BACKGROUND/AIMS: The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). METHODS: GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. RESULTS: The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. CONCLUSIONS: Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.

Ten-day empirical sequential or concomitant therapy is more effective than triple therapy for Helicobacter pylori eradication: A multicenter, prospective study.

BACKGROUND: The resistance of Helicobacter pylori to antibiotics has increased the need for new empirical, first-line treatments. However, the efficacy of sequential therapy (ST) and concomitant therapy (CT) compared with triple therapy (TT) has not been adequately evaluated. AIM: In this study, we evaluated the efficacy of these empirical three regimens. METHODS: The 517 patients enrolled in the study were prospectively randomized to receive 10 days of TT (n=171), ST (n=170), and CT (n=176) at 5 university-affiliated hospitals from May 2013 to March 2015. The post-treatment H. pylori status was determined using the (13)C-urea breath test. RESULTS: The baseline characteristics were similar among the three groups. The intention-to-treat eradication rates were 62.6%, 70.6%, and 77.8% in the TT, ST, and CT groups, respectively (p<0.01). The corresponding per-protocol eradication rates were 82.8%, 89.5%, and 94.4%, respectively (p<0.01). There were no significant differences in the compliance, side effects, and follow-up loss rates. CONCLUSION: A higher eradication rate was achieved with empirical 10-day ST, and CT than with the TT regimen, with similar rates of compliance and treatment side effects.

Refractory pseudomembranous colitis that was treated successfully with colonoscopic fecal microbial transplantation.

Pseudomembranous colitis (PMC) is a nosocomial and opportunistic infection caused by Clostridium difficile. PMC is related to the use of antibiotics leading to intestinal dysbiosis and an overgrowth of C. difficile. Metronidazole or vancomycin is considered to be the standard therapy for the management of PMC. However, PMC has a 15%-30% recurrence rate and can be refractory to standard treatments, resulting in morbidity and mortality. Here we describe a patient who experienced refractory PMC who was treated with fecal microbiota transplantation. A 69-year-old woman was admitted to the hospital with consistent abdominal pain and diarrhea, which had been present for 5 months. She was diagnosed with PMC by colonoscopy and tested positive for C. difficile toxin. Even though she took metronidazole for 10 days, followed by vancomycin for 4 weeks, her symptoms did not improve. Because of her recurrent and refractory symptoms, we decided to perform fecal microbiota transplantation. Fifty grams of fresh feces from a donor were obtained on the day of the procedure, mixed with 500 mL of normal saline, and then filtered. The filtered solution was administered to the patient's colon using a colonoscope. After the procedure, her symptoms rapidly improved and a follow-up colonoscopy showed that the PMC had resolved without recurrence.

A Case of Esophageal Fibrovascular Polyp That Induced Asphyxia during Sleep.

Esophageal fibrovascular polyps are rare, benign, submucosal tumors of the upper digestive tract that usually have an indolent course until the lesion attains a very large size. The most frequent complaints associated with these tumors include dysphagia and foreign body sensation. However, a long pedunculated polyp can regurgitate into the pharynx or oral cavity and cause asphyxia and sudden death if the larynx is occluded. We describe the case of a 51-year-old man who experienced snoring and occasional asphyxia during sleep. Upper endoscopy was performed, which indicated the presence of a pedunculated esophageal polyp that regurgitated into the vocal cords. The polyp was removed using a polypectomy snare and was confirmed to be a fibrovascular polyp based on pathologic examination findings. Three months after the excision of the polyp, the patient was found to be doing well without any further occurrence of asphyxia or sleep disturbances.

Delayed flumazenil injection after endoscopic sedation increases patient satisfaction compared with immediate flumazenil injection.

BACKGROUND/AIMS: Flumazenil was administered after the completion of endoscopy under sedation to reduce recovery time and increase patient safety. We evaluated patient satisfaction after endoscopy under sedation according to the timing of a postprocedural flumazenil injection. METHODS: In total, 200 subjects undergoing concurrent colonoscopy and upper endoscopy while sedated with midazolam and meperidine were enrolled in our investigation. We randomly administered 0.3 mg of flumazenil either immediately or 15 minutes after the endoscopic procedure. A postprocedural questionnaire and next day telephone interview were conducted to assess patient satisfaction. RESULTS: Flumazenil injection timing did not affect the time spent in the recovery room when comparing the two groups of patients. However, the subjects in the 15 minutes injection group were more satisfied with undergoing endoscopy under sedation than the patients in the immediate injection group according to the postprocedural survey (p=0.019). However, no difference in overall satisfaction, memory, or willingness to undergo a future endoscopy was observed between the two groups when the telephone survey was conducted on the following day. CONCLUSIONS: This study demonstrated that a delayed flumazenil injection after endoscopic sedation increased patient satisfaction without prolonging recovery time, even though the benefit of the delayed flumazenil injection did not persist into the following day.

Endoscopic application of EGF-chitosan hydrogel for precipitated healing of GI peptic ulcers and mucosectomy-induced ulcers.

The gastrointestinal (GI) endoscopy has become a standard diagnostic tool for GI ulcers and cancer. In this study we studied endoscopic application of epidermal growth factor-containing chitosan hydrogel (EGF-CS gel) for treatment of GI ulcer. We hypothesized that directional ulcer-coating using EGF-CS gel via endoscope would precipitate ulcer-healing. EGF-CS gel was directly introduced to the ulcer-region after ulceration in acetic acid-induced gastric ulcer (AAU) and mucosal resection-induced gastric ulcer (MRU) rabbit and pig models. The ulcer dimensions and mucosal thicknesses were estimated and compared with those in the control group. Healing efficacy was more closely evaluated by microscopic observation of the ulcer after histological assays. In the AAU model, the normalized ulcer size of the gel-treated group was 2.3 times smaller than that in the non-treated control group on day 3 after ulceration (P < 0.01). In the MRU model, the normalized ulcer size of the gel-treated group was 5.4 times smaller compared to that in the non-treated control group on day 1 after ulceration (P < 0.05). Histological analysis supported the ability of EGF-CS gel to heal ulcers. The present study suggests that EGF-CS gel is a promising candidate for treating gastric bleeding and ulcers.

Esophageal mucosal metastasis from adenocarcinoma of the distal stomach.

Dissemination of gastric cancer may usually occur by direct spread through the perigastric tissues to adjacent organ, lymphatic spread, and hematogenous spread. We report a rare case of gastric cancer with mucosal metastastic lesion on the upper esophagus that was diagnosed by endoscopy and endosonography. A biopsy of the esophageal mass was performed and the pathologic findings with immunohistochemical stain for Mucin-5AC are proved to be identical to that of gastric adenocarcinoma, suggesting metastasis from main lesion of the gastric cancer. The lesion could not be explained by lymphatic or hematogenous spread, and its metastasis mechanism is considered to be different from previous studies. We suggest that the gastroesophageal reflux of cancer cells could be one of the possible metastatic pathways for metastasis of esophagus from an adenocarcinoma of the stomach.

Peroral endoscopic myotomy for treating achalasia in an animal model: a feasibility study.

BACKGROUND/AIMS: Laparoscopic Heller myotomy with antireflux procedure is considered to be a standard treatment for achalasia. Recently, peroral endoscopic myotomy (POEM) was developed and performed on patients with achalasia. However, there is no report on POEM use in South Korea. The aim of this study was to evaluate the technical feasibility of POEM in a porcine model. METHODS: POEM was performed on two mini pigs. We performed upper endoscopy under general anesthesia. A submucosal tunnel was created and the circular muscle layer was incised using several knives. The mucosal entry was closed using resolution clips. We performed a follow-up endoscopy and sacrificed the pigs 2 weeks after the POEM. The myotomy site was evaluated grossly and histologically. RESULTS: POEM was successfully performed on the two mini pigs. No injuries to any abdominal or mediastinal structures occurred. Two weeks after the POEM, the esophageal mucosa healed without any endoscopic evidence of complications. Necropsy revealed that the circular muscle layer was completely lost and replaced with fibrotic tissue. CONCLUSIONS: We found that POEM is a technically feasible method which can be performed on an animal model. However, to ensure safe use on patients with achalasia, further studies on technical methods and long-term follow-up examinations are required.

Two cases of ileal dieulafoy lesion with massive hematochezia treated by single balloon enteroscopy.

Ileal Dieulafoy lesion is an unusual vascular abnormality that can cause gastrointestinal bleeding. It can be associated with massive, life-threatening hemorrhage and requires urgent angiographic intervention or surgery. Ileal Dieulafoy lesion is hard to recognize due to inaccessibility and normal-appearing mucosa. With advances in endoscopy, aggressive diagnostic and therapeutic approaches including enteroscopy have recently been performed for small bowel bleeding. We report two cases of massive ileal Dieulafoy lesion bleeding diagnosed and treated successfully by single balloon enteroscopy with a review of the literature.

Longer capsule endoscopy operation time increases the rate of complete examination of the small bowel.

BACKGROUND/AIMS: Wireless capsule endoscopes (CEs) have become a useful diagnostic tool for small bowel diseases, but they may fail to examine the entire small bowel. We analyzed the clinical experience of the MiRo CE in patients with suspected small bowel disease to assess whether longer operation time could increase the complete examination rate of the small bowel and diagnostic yield. METHODOLOGY: A total of 96 patients with suspected small bowel disease received CE examination at 4 tertiary hospitals in Korea. The recorded information was uploaded to a computer and analyzed by the physicians responsible for each patient. RESULTS: The average total capsule operation time was 11 hours and 39 minutes (range: 5 hours 18 minutes approximately 12 hours). In 87 (90.6%) out of 96 cases, the CE was able to explore the entire small bowel. In 32 cases (33.3%), it took more than 8 hours to reach the cecum. Capsule retention occurred in 2 cases (2.1%). The CE found meaningful small bowel lesions in 62 (64.6%) out of 96 total cases. CONCLUSIONS: A CE with a long operation time had more chance to explore the entire small bowel even in patients with suspected small bowel disease.

The ballooning time in endoscopic papillary balloon dilation for the treatment of bile duct stones.

BACKGROUND/AIMS: Endoscopic papillary balloon dilation (EPBD) is a safe and effective method for the treatment of choledocholithiasis, but previous studies have rarely reported the appropriate ballooning time (BT). We prospectively evaluated the safety and efficacy of EPBD according to BT in patients undergoing bile duct stone removal. METHODS: Seventy consecutive patients with bile duct stones were randomly assigned to receive EPBD with either conventional (n = 35, 60 seconds) or short (n = 35, 20 seconds) BT. RESULTS: EPBD alone achieved complete bile duct clearance in 67 patients (long BT, n = 33, 94.3%; short BT, n = 34, 97.1%; p = 0.808). We also found no significant difference in the rate of complete duct clearance, including procedures that used mechanical lithotripsy, between the long and short BT groups (97.1% vs. 100%; p = 0.811). Mild pancreatitis was noted in four (11.4%) patients in the long BT group and two (5.7%) patients in the short BT group, but this incidence was not significantly different. CONCLUSIONS: The study showed that EPBD using both 20-sec and 60-sec BTs is safe and effective for the treatment of bile duct stones. Short and long BTs produced comparable outcomes.

Identification of Helicobacter pylori in Gallstone, Bile, and Other Hepatobiliary Tissues of Patients with Cholecystitis.

BACKGROUND/AIMS: Bacterial infection is accepted as a precipitating factor in cholesterol gallstone formation, and recent studies have revealed the presence of Helicobacter species in the hepatobiliary system. We utilized the polymerase chain reaction (PCR) to establish the presence of bacterial DNA, including from Helicobacter species, in gallstones, bile juice, and gallbladder mucosa from patients with gallstones. METHODS: At cholecystectomy, 58 gallstones, 48 bile samples, and 46 gallbladder mucosa specimens were obtained and subjected to nested PCR using specific 16S rRNA primers of H. pylori and other bacteria. Bacterial species were identified by DNA sequencing analysis. Bacterial 16S rRNA was detected in 25 out of 36 mixed-cholesterol gallstones, 1 out of 10 pure-cholesterol gallstones, and 9 out of 12 pigmented stones. Furthermore, 16S rDNA sequencing identified Escherichia coli, Pseudomonas, Citrobacter, Klebsiella, and Helicobacter species. RESULTS: Helicobacter DNA was detected in 4 out of 58 gallstones, 6 out of 48 bile samples, and 5 out of 46 gallbladder specimens. Direct sequencing of Helicobacter amplicons confirmed strains of H. pylori in all four gallstones, five out of six bile samples, and three out of five gallbladder specimens. Almost all mixed-cholesterol gallstones appear to harbor bacterial DNA, predominantly E. coli. CONCLUSIONS: H. pylori was also found in the biliary system, suggesting that these bacteria are of etiological importance in gallstone formation.

Synchronous large-cell neuroendocrine carcinoma and adenocarcinoma of the colon.

Large-cell neuroendocrine carcinoma of the colon is a rare entity with a prognosis that is usually poor due to the high likelihood of early metastasis. A 61-year-old man had surgery for colon cancer of the transverse colon and cecum. Microscopic examination of the tumor showed that the location was the proximal transverse colon, with small nests containing rosettes and palisading patterns of large tumor cells with faintly granular cytoplasm. The immunohistochemistry was positive for synaptophysin and chromogranins. The tumors were diagnosed as a large-cell neuroendocrine carcinoma of the colon. In addition, the tumor of the cecum showed microscopic findings consistent with a well-differentiated adenocarcinoma. The immunohistochemical panel showed that the tumor was negative for neuroendocrine markers. There were no clinical findings suggestive of hormone hypersecretion. Cancer metastasis was found in the peritoneum section of the small bowel. Postoperative chemotherapy was applied. The patient was alive with good performance after, and there was no sign of tumor progression. This is the first case of a synchronous large-cell neuroendocrine carcinoma and adenocarcinoma of the colon. The patient was treated successfully with debulking surgery and systemic chemotherapy.

Primary endoscopic approximation suture under cap-assisted endoscopy of an ERCP-induced duodenal perforation.

Duodenal perforation during endoscopic retrograde cholangiopancreatography (ERCP) is a rare complication, but it has a relatively high mortality risk. Early diagnosis and prompt management are key factors for the successful treatment of ERCP-related perforation. The management of perforation can initially be conservative in cases resulting from sphincterotomy or guide wire trauma. However, the current standard treatment for duodenal free wall perforation is surgical repair. Recently, several case reports of endoscopic closure techniques using endoclips, endoloops, or fully covered metal stents have been described. We describe four cases of iatrogenic duodenal bulb or lateral wall perforation caused by the scope tip that occurred during ERCP in tertiary referral centers. All the cases were simply managed by endoclips under transparent cap-assisted endoscopy. Based on the available evidence and our experience, endoscopic closure was a safe and feasible method even for duodenoscope-induced perforations. Our results suggest that endoscopists may be more willing to use this treatment.

Three-weekly s-1 monotherapy as first-line treatment in elderly patients with recurrent or metastatic gastric cancer.

BACKGROUND/AIMS: Elderly patients with advanced gastric cancer (AGC) have generally been excluded from clinical trials, and there are few data available on the treatment of these patients. The efficacy of palliative S-1 monotherapy as a first-line treatment regimen for elderly patients has not been well elucidated. METHODS: For this study, 25 AGC patients were enrolled between January 1, 2007 and March 31, 2009; 4 cases were recurrent AGC and 21 cases were metastatic AGC at the time of diagnosis. These patients received S-1 therapy at a dose of 40 mg/m(2) twice daily for 14 days every 3 weeks. All of the patients were older than 70 years. RESULTS: The median follow-up duration, the median progression-free survival, and the overall survival time were 8.7 months (range, 4.9 to 12.5 months), 4.9 months (range, 3.5 to 6.3 months), and 10.8 months (range, 6.6 to 15.0 months), respectively. Grade 3/4 nonhematologic toxicities were rare. Grade 3/4 neutropenia was noted in two patients. The partial response rate was 21.7% and stable disease was observed in 34.8% of the patients. Two patients (8%) died due to chemotherapy-associated toxicity during treatment (septic shock/intracranial hemorrhage). CONCLUSIONS: Oral S-1 chemotherapy seems to be effective as a first-line treatment regimen for elderly patients with metastatic or recurrent AGC. However, elderly patients receiving S-1 treatment should undergo continuous toxicity monitoring, since they are highly susceptible to adverse effects.

[A case of large cell neuroendocrine carcinoma of the colon].

Neuroendocrine carcinoma of the colon can be classified into small cell carcinoma and large cell neuroendocrine carcinoma. The incidence of neuroendocrine carcinoma is so low that the guidelines for the treatment of large cell neuroendocrine carcinoma of the colon are not established. The prognosis of large cell neuroendocrine carcinoma of the colon is worse than that of conventional adenocarcinoma of the colon. We report a case of large cell neuroendocrine carcinoma of the colon that treated with right hemicolectomy and 6th sequential combination chemotherapy of 5-fluorouracil and cisplatin. There has been no evidence of the recurrence of metastasis of tumor for 6 months.

Endoscopic large-balloon sphincteroplasty without preceding sphincterotomy for the removal of large bile duct stones: a preliminary study.

BACKGROUND: Endoscopic sphincterotomy (EST) has usually been performed before large-balloon sphincteroplasty (LBS) to retrieve large bile duct stones because of the high risk of pancreatitis and some advantages of EST. However, there are no available data on the preceding EST to confirm these assertions. OBJECTIVE: We investigated the safety and efficacy of LBS without a preceding EST for the management of large bile duct stones. DESIGN: Single-institution retrospective study. SETTING: Tertiary referral center. PATIENTS: Thirty-eight patients with large bile duct stones. INTERVENTIONS: Endoscopic LBS without preceding EST. MAIN OUTCOME MEASUREMENTS: Efficacy of stone removal and complications related to the procedure. RESULTS: The overall success rate irrespective of whether mechanical lithotripsy (ML) was used was 97.4% (37/38). Complete duct clearance by LBS alone without ML was achieved in 29 (76.3%) patients. Complete stone retrieval was achieved by LBS alone in the first session in 25 (65.8%) patients. ML was required in 8 (21.1%) patients. Failure to extract a stone occurred in 1 (2.6%) patient. There was a mild degree of postprocedure pancreatitis in only 1 (2.6%) patient and asymptomatic hyperamylasemia in 3 (7.9%) patients. The maximum diameters of the stones and the balloon/stone diameter ratio had a tendency to affect complete stone retrieval in the success and failure groups: 16.7 +/- 3.9 mm vs 20.8 +/- 6.5 mm and 0.96 +/- 0.19 mm vs 0.80 +/- 0.23 mm, respectively (results are presented as mean +/- standard deviation). LIMITATIONS: Small-scale, single-arm study. CONCLUSIONS: Our data suggest that LBS without EST is safe and effective in patients with large bile duct stones.

[Durability of a sustained virologic response in combination therapy with interferon/peginterferon and ribavirin for chronic hepatitis C].

BACKGROUNDS/AIMS: The ultimate goal of antiviral therapy using interferon/pegylated interferon combined with ribavirin in chronic C-viral hepatitis is to achieve a sustained virologic response (SVR). Several studies have shown that the reappearance rate of hepatitis C virus (HCV) RNA in serum after the achievement of an SVR is less than 1%; the durability of an SVR in Korean patients is not known. The aim of this study was to determine the durability of the virologic response in chronic hepatitis C patients with an SVR to antiviral therapy. METHODS: A total of 156 patients who were treated successfully with interferon/peginterferon and ribavirin were evaluated retrospectively. Patients received either subcutaneous conventional interferon alpha 3x10(6) units three times a week or subcutaneous pegylated interferon (alpha-2a: 180 microgram, alpha-2b: 80-100 microgram) once a week in combination with ribavirin at 600-1,200 mg daily (depending on body weight). Patients with HCV genotype 1 were treated for 48 weeks, whereas those with non-genotype 1 were treated for 24 weeks. RESULTS: Eighty-two patients underwent treatment with conventional interferon and ribavirin, whereas 74 patients were treated with pegylated interferon and ribavirin. An SVR was achieved in 73 patients (73/156, 46.8%). HCV RNA reappeared in eight patients (8/73, 11.0%; detected by qualitative PCR), including one patient with persistent viremia (1/73, 1.4%). CONCLUSIONS: Reappearance of HCV RNA after earlier achievement of an SVR might appear more frequently than previously reported. Close follow-up of these patients is recommended and the implication of temporary viremia should be determined in the future.