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.

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.

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.

Pretreatment alanine transaminase level may not be the most important predictor of HBeAg loss in the older patient.

BACKGROUND: Elevated pretreatment alanine aminotransferase (ALT) over two times the upper limit of normal reference range has been accepted as a marker for predicting HBeAg loss and an indicator for initiating antiviral therapy. Recently, several opinions argued that in patients aged over 40 years, the treatment should be started if they have elevated serum hepatitis B virus (HBV) DNA without elevated ALT. However, initiating treatment in these patients might be argued against by the concept that the rate of HBeAg loss depends on the pretreatment ALT. AIM: This study was conducted to investigate the usefulness of pretreatment ALT in predicting HBeAg loss in patients aged over 40 years under lamivudine treatment. METHODS: We retrospectively analyzed 820 HBeAg-positive patients treated with lamivudine. The patients with hepatocellular carcinoma at or after initiating the lamivudine treatment and patients with evident liver cirrhosis were excluded. Three hundred fifty-five patients met the criteria and were divided into two groups: 40 years of age (Group 2). RESULTS: Analysis using the Kaplan-Meier method and the log rank test showed that the cumulative rate of HBeAg loss was not different in the two groups. Multivariate modelling indicated that an elevated pretreatment ALT level was a predictor of HBeAg loss in Group 1 (P<0.05), whereas it failed to act as a predictor in Group 2. CONCLUSION: Antiviral therapy might not need to be deferred until the ALT level increases in order to enhance the chance of HbeAg loss in HBV DNA-(+) patients aged over 40 years.

[A case of pulmonary thromboembolism in active ulcerative colitis].

Inflammatory bowel disease often involves extra-intestinal organs. Cerebral thrombosis, portal vein thrombosis and pulmonary thrombosis have been reported. Deep vein thrombosis and pulmonary thromboembolism are significant causes of mortality in patients with inflammatory bowel disease. A 48-year-old woman was diagnosed as inflammatory bowel disease on colonoscopy and histology. We used hydrocortisone and mesalazine for the treatment of disease. Nineteen days later, she complained of abrupt dyspnea. Pulmonary CT angiography revealed a thromboembolism in right pulmonary arteries. After the treatment of heparin therapy, follow-up pulmonary CT angiography showed significant improvement of previously thrombosed pulmonary arteries.

[A case of pseudomembranous colitis associated with rifampicin therapy in a patient with rectal cancer and gastrointestinal tuberculosis].

Pseudomembranous colitis (PMC) is known to be associated with the administration of antibiotics which alter normal gastrointestinal flora and allow overgrowth of Clostridium difficile. Most cases of rifampicin-induced PMC are seen in patients with pulmonary tuberculosis, but not with gastrointestinal tuberculosis. We report a case of PMC associated with rifampicin therapy in a patient with gastrointestinal tuberculosis. A 65-year-old female patient with rectal cancer and gastrointestinal tuberculosis was admitted due to abdominal pain and diarrhea. She was treated with anti-tuberculosis agents containing rifampicin. On colonoscopic examination, mucoid exudates and yellowish plaque lesions were observed. Anti-tuberculosis agents were stopped, and the patient was treated with metronidazole. Symptoms were relieved and did not recur when all the anti-tuberculosis agents except rifampicin were started again. When a patient complains of abdominal pain or diarrhea while taking rifampicin, the physician should consider the possibility of rifampicin-associated PMC.

[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.

[Concurrent chemoradiotherapy compared with concurrent chemoradiotherapy with surgery in locally advanced resectable esophageal cancer].

BACKGROUND/AIMS: This study was designed to compare the survival rates between patients with localized esophageal cancer who were treated with concurrent chemoradiation therapy without surgery and patients who were treated with concurrent chemoradiation therapy including surgery. METHODS: Eighty-eight patients from January 1997 to December 2005 with locally advanced resectable esophageal cancer were selected and retrospectively analyzed. Survival period was defined as the time to death from the date of diagnosis or mid-monitor period of December 2005. Sixty-one patients were treated with chemoradiation therapy alone while twenty-seven patients were treated with chemoradiation therapy in addition to surgery as for curative intention. As for radiation therapy, 5,000-5,500 cGY was used. 5-Fluouracil and cisplatin were used for chemotherapy. The primary end point was overall survival time. The secondary end point was overall progression free survival time. RESULTS: There was no significant difference in tissue type, location and clinical staging, but the median age was significantly younger in the group treated with surgery (63.4 years) than the group treated without surgery (68.8 years). Median period analyzed was 17.3 months. Five year survival rate for the group with chemoradiation alone was 7.4% and 4% for the group with surgery. The median survival rate was 11+/-3 months for the group with chemoradiation alone and 10+/-6 months for the group with surgery, in which there was no statistical difference (p=0.697). CONCLUSIONS: There was no significant increase in survival rate in patients who were treated by chemoradiation with surgery compared with chemoradiation alone. Further analysis in terms of prospective study is needed.

[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.

[A case of colon obstruction developed as a complication of acute pancreatitis].

In acute pancreatitis, colonic complications such as mechanical obstruction, ischemic necrosis, hemorrhage, and fistula are rare but their outcomes are fatal. It is known that colonic obstruction in acute pancreatitis is more likely found in splenic flexure and transverse colon caused by severe inflammation of body and tail of pancreas leading to pressure necrosis. A 43-year-old man presented with abdominal distension lasting for 2 weeks. The patient had been admitted to our institution 6 weeks prior to the current admission, and the abdominal CT scan performed during the first admission revealed the pancreatic enlargement with peri-pancreatic fatty infiltration and fluid collection. At that time he was diagnosed as acute pancreatitis. The conservative management resulted in clinical improvement so that the patient was discharged. Upon the second admission, abdominal CT scan revealed multiple pseudocysts in the tail portion of pancreas with concominant wall thickening and narrowing of the proximal descending colon, and a dilatation of the bowel proximal to the splenic flexure. An obstruction of the descending colon as a complication of acute pancreatitis was suspected and the patient underwent left hemicolectomy. Abdominal distension was relieved after the operation and he was discharged on the 15th hospital days.

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.

Metachronous gastric MALT lymphoma and early gastric cancer: a case report.

Metachronous association between gastric lymphoma and early gastric cancer is a rare event. Recent studies have suggested that a relationship exists between gastric mucosa-associated lymphoid tissue (MALT) lymphoma and gastric carcinoma although the mechanism is unknown. Herein, we report a 53-year-old man who visited to our hospital due to melena. Esophagogastroduodenoscopy (EGD) revealed a MALT lymphoma on the greater curvature of lower body. The patient received anti-Helicobacter pylori eradication therapy, followed by 6 cycles of chemotherapy and radiation therapy, and achieved complete remission 12 months after the therapy. Three years later, he revisited our hospital with epigastric pain. EGD revealed an early gastric cancer on the anterior wall of proximal antrum, nearly opposite to the previous lymphoma site, and a partial gastrectomy was performed. To the best of our knowledge, this is the first case report of metachronous MALT lymphoma and subsequent gastric carcinoma in Korea.

[A case of primary jejunal adenocarcinoma diagnosed by enteroscopy using pediatric colonoscope].

A 39-year-old man presented with dizziness and melena for 2 months. Abdominal CT scan showed constrictive wall thickening with enhancement and proximal loop dilatation of the jejunum. On endoscopic examination, there was large amount of bile stained fluid in duodenum. Enteroscopy using pediatric colonoscope demonstrated an encircling mass with obstruction approximately 20 cm distal to the ligament of Treitz. Endoscopic jejunal biopsy showed moderately differentiated adenocarcinoma. Small intestinal adenocarcinoma is uncommonly encountered in clinical practice. Because small intestine is relatively inaccessible via routine endoscopy, diagnosis of small intestinal neoplasm is often delayed for several months after the onset of symptoms. Most of the patients are diagnosed in advanced stage. Therefore, when a small bowel neoplasm is suspected, enteroscopy is the most useful study. If enteroscope is not available, enteroscopy using pediatric colonoscope may permit earlier preoperative diagnosis. We report a case of primary jejunal adenocarcinoma diagnosed by endoscopic biopsy using pediatric colonoscope.

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.

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.

Expression of Ki-67, p53, and K-ras in chronic pancreatitis and pancreatic ductal adenocarcinoma.

AIM: To examine surgical specimens of pancreas with either chronic pancreatitis or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia in pancreas represent precursor lesions for pancreatic cancer. METHODS: We examined expression of Ki-67, CEA, p53, and K-ras, in the surgical specimens of pancreas with adenocarcinomas (n=11) and chronic pancreatitis (n=12). Cellular proliferation was assessed by Ki-67 proliferation index using the proliferation marker Ki-67. In specimens with pancreas cancer, we divided pancreas epithelium into normal (n=7), ductal hyperplasia (n=3), dysplasia (n=4), and cancerous lesion (n=11) after hematoxylin and eosin staining, Ki-67, and CEA immunohistochemical staining. In cases with chronic pancreatitis, the specimen was pathologically examined as in cases with pancreas cancer, and they were also determined as normal (n=10), ductal hyperplasia (n=4), or dysplasia (n=5). p53 and K-ras expression were also studied by immunohistochemical staining. RESULTS: In pancreatic cancer, the Ki-67 index was 3.73+/-3.58 in normal site, 6.62+/-4.39 in ductal hyperplasia, 13.47+/-4.02 in dysplasia and 37.03+/-10.05 in cancer tissue, respectively. Overall, p53 was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 14 (0%), 0 of 7 (0%), 7 of 9 (78%), and 10 of 11 (91%), respectively, and K-ras was positive in 0 of 8 (0%), 1 of 3 (33%), 4 of 6 (67%), 4 of 5 (80%), respectively. CONCLUSION: Our results favorably support the hypothesis that ductal hyperplasia and dysplasia of the pancreas might be precursor lesions for pancreas cancer. Further evaluation of oncogenes by the molecular study is needed.

Littoral cell angioma (LCA) associated with liver cirrhosis.

A littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. A 60-year-old man, with multiple nodules in imaging study and liver cirrhosis graded as Child-Pugh classification class A, was transferred for splenomegaly. A thrombocytopenia was found on hematological evaluation. Because there was no evidence of hematological and visceral malignancy, a splenectomy was performed for a definitive diagnosis. The histological and immunohistochemical features of the splenic specimens were consistent with a LCA. After the splenectomy, the thrombocytopenia recovered to the normal platelet count. There has been no previous report of a LCA combined with liver cirrhosis. Herein, the first case of a LCA in Korea, diagnosed and treated by a splenectomy, is reported.

Detection of Helicobacter pylori antigen in stool by enzyme immunoassay.

Invasive techniques for diagnosis of Helicobacter pylori (H. pylori) infection require an endoscopic examination which is expensive and inconvenient and may cause complications. Stool cultures for H. pylori or a direct detection of H. pylori antigen in stools by PCR are expensive, tedious, and have a low sensitivity. We recently used an enzyme immunoassay (EIA) to detect H. pylori antigen in stool specimens. A total of 41 patients were seen at Inha University Hospital, Inchon, Korea between September and October 1998. There were 26 men and 15 women who had an average age of 37.6 years which ranged from 5 to 71 years in the present study. All of these patients came to the hospital complaining of an upper abdominal discomfort and were subjected to endoscopy and biopsies. Fifteen had a gastric ulcer, 13 had a duodenal ulcer, 1 had an early gastric cancer, and there were 12 chronic gastritis patients as shown by endoscopy. The biopsy specimens were examined by histology, CLO test, and cultures and these results were used as gold standards. Stool specimens were tested for the H. pylori antigen by EIA. A dual wavelength cut-off of 0.100 that was recommended by the manufacturer gave a good performance (87.1% sensitivity, 100% specificity, 100% positive predictive value, 71.4% negative predictive value, and a 90.2% efficiency). But the adjusted cut-off value using the receiver operating characteristic curve improved the performance of the test (using the cut-off value of 0.024, the sensitivity, specificity, PPV, NPV, and efficiency were 100%, 90.0%, 96.9%, 100%, and 97.6% respectively). Re-evaluation of the cut-off value may be needed for Korean patients. This technique is non-invasive, rapid, easy-to-use, and shows good performance characteristics for diagnosis of H. pylori infections. Therefore, this technique may be a substitute for gastric endoscopy especially in children and some patients who are unable to tolerate an endoscopic examination and it may be substituted for a serologic test in epidemiological research.

Successful cyclophosphamide therapy in recurrent eosinophilic colitis associated with hypereosinophilic syndrome.

Eosinophilic colitis is a relatively rare complication of hypereosinophilic syndrome which is characterized by abdominal pain and bloody diarrhea and is usually treated with steroids and hydroxyurea. However, no standard regimen exists in cases of intractable disease despite several treatment attempts with Interferon-alpha, cyclosporin, etoposide, and vincristine, etc. We here report a case of a 43-year-old woman with recurrent eosinophilic colitis as a complication of hypereosinophilic syndrome who was successfully treated with cyclophosphamide.

[A case of common bile duct stone formed around a surgical clip after laparoscopic cholecystectomy].

Laparoscopic cholecystectomy has now rapidly replaced open cholecystectomy. Rarely a calculus may arise from a metallic surgical clip migrated into the common bile duct (CBD) after this surgical procedure was performed. We report a 50-year-old man with CBD stone formed around a surgical clip, who had undergone a laparoscopic cholecystectomy because of acute calculous cholecystitis 14 months before. Abdominal CT revealed a single stone in mildly dilated CBD. A high density core within the CBD stone, was suspected to be a surgical clip. The stone was removed using a retrieval balloon catheter and basket after endoscopic sphincterotomy.