Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.

Association of Sleep Dysfunction and Emotional Status With Gastroesophageal Reflux Disease in Korea

BACKGROUND/AIMS: Sleep disturbances and emotional dysfunction are commonly associated with gastroeophageal reflux disease (GERD). The aims of this study were to evaluate GERD symptoms and disturbance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD) patients, and to compare sleep dysfunction, depressive mood, anxiety and quality of life (QOL) among the control, ERD and NERD patients in Korea. METHODS: The Korean subjects were enrolled between 2010 and 2012, classified into 3 groups; the control group with no symptom and normal endoscopic findings, the ERD group with erosive esophagitis and the NERD group with more than one episode of heartburn or acid regurgitation per week, positive response to proton pump inhibitor, and normal endoscopic findings. Questionnaire included GERD symptoms, GERD impact scale (GIS) and daytime pathological sleepiness (Epworth sleepiness scale), sleep dysfunction (Pittsburgh sleep quality index, PSQI), depression and anxiety (Hospital anxiety and depression scale, HADS) and QOL (WHO quality of life scale abbreviated version, WHOQOL-BREF). RESULTS: A total of 217 subjects were enrolled as follows; control (n = 70), ERD (n = 70) and NERD (n = 77). Impact of symptom of GIS score was higher in the NERD (9.2 +/- 0.4) than in the ERD (6.5 +/- 0.3) group (P < 0.001). Sleep dysfunctions were more frequent in GERD than the control group (PSQI score [P = 0.021]). Anxiety subscale of HAD score was higher in NERD (7.0 +/- 0.5, P = 0.002) and ERD (6.2 +/- 0.7, P = 0.004) groups than control (4.3 +/- 0.7) group. WHOQOL-BREF scores in NERD (54.9 +/- 2.3) and ERD (57.8 +/- 2.4) groups were significantly lower than those in the control group (63.8 +/- 2.4) (P = 0.002; P = 0.014, respectively). CONCLUSIONS: The patients with NERD than ERD suffered more from the symptoms and disturbance in Korea. Sleep dysfunction and anxiety mood were higher and QOL was decreased in GERD, especially in NERD, suggesting that those factors might affect the severity of NERD.

The Risk Factors for Colonic Diverticular Bleeding / 대한소화기학회지

BACKGROUND/AIMS: Colonic diverticular bleeding cases account for 30-40% of the lower gastrointestinal bleeding, among which, 3-5% appear to be massive bleeding. The purpose of this study was to evaluate the risk factors for colonic diverticular bleeding diagnosed by colonoscopic examination. METHODS: Among the 1,003 patients, who were identified to have colonic diverticulosis including sleeding by diverticulitis and diverticular bleeding coding search, 216 patients had diverculosis, and they were divided into two groups: one with diverticular bleeding, and the other without bleeding. We evaluated the potential risk factors for diverticular bleeding, based on age, gender, location of diverticulum, comorbidities related to atherosclerosis, smoking, alcohol and medications, and compared them between both groups. RESULTS: Among the 216 patients, we observed colonic diverticular bleeding in 35 patients (16.2%). The mean age of the bleeding group was significantly older than that of non-bleeding group. No difference was observed regarding gender ratio. Right colonic diverticula were common in both groups, but there were higher proportion of patients with bleeding in bilateral diverticuosis. Old age, bilateral diverticulosis, presence of atherosclerosis related diseases (hypertension, diabetes mellitus, ischemic heart disease, obesity), use of aspirin, NSAIDs and calcium channel blocker, increased the risk of bleeding. In a multivariate analysis, use of aspirin and bilateral diverticulosis were identified as independent risk factors for colonic diverticular bleeding. CONCLUSIONS: Since the patients who took aspirin and/or had bilateral colonic diverticulosis increased the risk of bleeding from divertuculi. As such, caution and education of patients are required.

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

BACKGROUND/AIMS: Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages. METHODS: For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A2 (cPLA2) levels were measured after 24 hours. RESULTS: The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA2 expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05). CONCLUSIONS: NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.

Effect of a Probiotic Preparation (VSL#3) in Patients with Mild to Moderate Ulcerative Colitis / 대한소화기학회지

BACKGROUND/AIMS: Ulcerative colitis (UC) is a chronic disease that characteristically has a relapsing and remitting course. Probiotics might possibly induce remission in the treatment of active UC. Aims of our study were to assess the efficacy of VSL#3 on clinical response and colonic tissue cytokine concentration changes in patients with active UC. METHODS: Twenty-four eligible patients with mild to moderate UC received open-label VSL#3 4 sachets daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by ulcerative colitis disease activity score and colonic tissue cytokine profiling done at baseline and at week 8. RESULTS: Twenty-four patients (mean age, 43.7 years; range, 20-70 years; male/female, 15/9) were enrolled and 2 patients did not have the final endoscopic assessment. A total of 22 patients were analyzed. Intent to treat analysis demonstrated remission in 45.8% of subjects (n=11); partial response in 20.8% (n=5); no change or worse in 25.0% (n=6) of subjects. The mean ulcerative colitis disease activity index (UCDAI) scores decreased from 7.09+/-1.81 to 1.45+/-1.29 in patients with a remission (p<0.001). The mean endoscopic scores had also significantly decreased from 1.91+/-0.54 to 0.63+/-0.50 in patients with a remission (p<0.001). The concentrations of colonic cytokines did not change significantly during treatment in patients with a remission. CONCLUSIONS: Our study demonstrated that VSL#3 is effective in achieving clinical responses and remissions in patients with mild-to moderately active UC, further supporting the potential role in UC therapy.

Dual Therapy Trial Using Esomeprazole and Amoxicillin as Third-line Rescue Therapy for Helicobacter pylori Infection

BACKGROUND/AIMS: The purpose of this study was to evaluate the efficacy and tolerability of dual therapy consisting of esomeprazole and amoxicillin as a rescue therapy for Helicobacter pylori infection. METHODS: From December 2009 to August 2010, 21 patients who experienced two consecutive eradication failures were included. They received esomeprazole (40 mg, b.i.d.) and amoxicillin (1,000 mg, b.i.d.) for 14 days as a third eradication regimen. Compliance and side effects were determined from an interview. H. pylori status was evaluated using the 13C urea breath test at least 6 weeks after treatment. RESULTS: The mean age of the patients was 59 years and included 52% males. Indications for treatment were functional dyspepsia (61.9%), peptic ulcer disease (28.6%), and gastric adenoma (9.5%). H. pylori was eradicated in 14 of 21 (66.7%) patients. Minor side effects were reported in three of the 21 patients (14.3%). These side effects consisted mainly of nausea and epigastric discomfort. CONCLUSIONS: A 2-week course of dual therapy failed to show satisfactory results in third-line H. pylori eradication, but it was very safe and tolerable. Therefore, dual therapy constitutes an encouraging empirical strategy for the elderly and infirm patients with multiple previous eradication failures.

Dual Therapy Trial Using Esomeprazole and Amoxicillin as Third-line Rescue Therapy for Helicobacter pylori Infection

BACKGROUND/AIMS: The purpose of this study was to evaluate the efficacy and tolerability of dual therapy consisting of esomeprazole and amoxicillin as a rescue therapy for Helicobacter pylori infection. METHODS: From December 2009 to August 2010, 21 patients who experienced two consecutive eradication failures were included. They received esomeprazole (40 mg, b.i.d.) and amoxicillin (1,000 mg, b.i.d.) for 14 days as a third eradication regimen. Compliance and side effects were determined from an interview. H. pylori status was evaluated using the 13C urea breath test at least 6 weeks after treatment. RESULTS: The mean age of the patients was 59 years and included 52% males. Indications for treatment were functional dyspepsia (61.9%), peptic ulcer disease (28.6%), and gastric adenoma (9.5%). H. pylori was eradicated in 14 of 21 (66.7%) patients. Minor side effects were reported in three of the 21 patients (14.3%). These side effects consisted mainly of nausea and epigastric discomfort. CONCLUSIONS: A 2-week course of dual therapy failed to show satisfactory results in third-line H. pylori eradication, but it was very safe and tolerable. Therefore, dual therapy constitutes an encouraging empirical strategy for the elderly and infirm patients with multiple previous eradication failures.

Comparison between Conventional 4 L Polyethylene Glycol and Combination of 2 L Polyethylene Glycol and Sodium Phosphate Solution as Colonoscopy Preparation / 대한소화기학회지

BACKGROUND/AIMS: Effective bowel preparation is essential for accurate diagnosis of colon disease. We investigated efficacy and safety of 2 L polyethylene glycol (PEG) solution with 90 mL sodium phosphate (NaP) solution compared with 4 L PEG method. METHODS: Between August 2009 and April 2010, 526 patients were enrolled who visited Seoul National University Bundang Hospital for colonoscopy. We allocated 249 patients to PEG 4 L group and 277 patients to PEG 2 L with NaP 90 mL group. Detailed questionnaires were performed to investigate compliance, satisfaction and preference of each method. Bowel preparation quality and segmental quality were evaluated. Success was defined as cecal intubation time less than 20 minutes without any help of supervisors. RESULTS: Both groups revealed almost the same baseline characteristics except the experience of operation. PEG 4 L group's compliance was lower than PEG 2 L with NaP 90 mL group. Success rate and cecal intubation time was not different between two groups. Overall bowel preparation quality of PEG 2 L with NaP 90 mL group was better than PEG 4 L group. Segmental bowel preparation quality of PEG 2 L with NaP 90 mL group was also better than PEG 4 L group in all segments, especially right side colon. Occurrence of hyperphosphatemia was higher in PEG 2 L with NaP 90 mL group than PEG 4 L group. However, significant adverse event was not reported. CONCLUSIONS: PEG 2 L with NaP 90 mL method seems to be more effective bowel preparation than PEG 4 L method.

Comparison of Direct Medical Care Costs Between Erosive Reflux Disease and Non-erosive Reflux Disease in Korean Tertiary Medical Center

BACKGROUND/AIMS: Gastroesophageal reflux disease is one of the most common and frequent chronic disease requiring considerable cost. We investigated the medical care costs in the erosive reflux disease (ERD) and non-erosive reflux disease (NERD). METHODS: The risk factors and the direct medical care costs were analyzed retrospectively in the ERD (178 patients) and NERD (183 patients) groups for a follow up period of 2 years. RESULTS: Logistic regression analysis showed that the ERD was more frequent in the groups of male gender, alcohol consumption, higher body mass index (> or =25 kg/m2), hiatal hernia, and higher triglyceride levels (> or =150 mg/dL). The direct medical care costs per person for 2 years were found to be $384.8 (ERD) and $412.9 (NERD) without statistically significant differences (p = 0.364). However, 9.3% (17/183) of the NERD patients had visited the emergency room compared to 3.4% (6/178) of the ERD patients (p = 0.029). In addition, more NERD patients were hospitalized than ERD patients (p = 0.006), and because of the longer hospitalization period, the medical costs in NERD patients were higher than ERD patients (p = 0.038). CONCLUSIONS: In spite of the different risk factors for ERD and NERD, total direct medical care costs were similar between the ERD and NERD group. However, more visits to emergency room and longer hospitalization period with more hospitalization costs in NERD patients account for the differences in medical service and usage distribution between the 2 groups.

Optimal Cut-off Value of PIVKA-II for Diagnosis of Hepatocellular Carcinoma: Using ROC Curve / 대한간학회지

BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist-II (PIVKA-II), also known as des-carboxyprothrombin (DCP), can be used as an alternative tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma (HCC). The aims of the present study were to compare PIVKA-II levels between the patients with HCC and patients with non-HCC chronic liver disease, to evaluate the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the receiver operating characteristic (ROC) curve. METHODS: A total of 227 consecutive patients with HCC (n=42) or chronic liver disease (n=185) were enrolled in this study. HCC was diagnosed histologically or by imaging such as computed tomography, magnetic resonance imaging or angiography. The serum PIVKA-II and AFP levels were measured by electrochemiluminoimmunoassay with using the Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. RESULTS: The PIVKA-II level in the HCC patients was significantly higher than the non-HCC chronic liver disease patients (903.0+/-1156.7 vs. 111.7+/-211.0 mAU/ mL, respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%. CONCLUSIONS: PIVKA-II was as useful surveillance tool for differentiating HCC from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a significant cut-off value for diagnosis of hepatocellular carcinoma.

A Case of Severe Skin Eruption Caused by Lamivudine in a Patient with Chronic Hepatitis B / 대한소화기학회지

Lamivudine is widely used for the treatment of chronic hepatitis B infection because of it's remarkable antiviral efficacy and safety. We report a case of severe skin eruption caused by lamivudine. A 47-year-old female was admitted because of jaundice and itching sensation. She was diagnosed as chronic hepatitis B infection a few years ago but did not receive any specific treatment. Laboratory data showed acute deterioration of chronic hepatitis B infection. We prescribed lamivudine as a rescue therapy. Her general condition improved and lab data showed improvement in liver function test thereafter. However, she complained of severe skin eruption and itching sensation a few days after the discharge. We stopped lamivudine because the symptoms did not improve despite the use of anti-histamine. Skin biopsy showed interface dermatitis. After stopping lamivudine, her symptoms improved. However, the skin eruption developed again after lamivudine was restarted. Adefovir was used instead, and the patient did not experience any further skin problems since then.

A Case of Metastasis-induced Acute Pancreatitis Improved by Chemotherap / 대한소화기학회지

Pancreatic metastases are found in up to 40% of patients with small cell lung cancer, but metastasis-induced acute pancreatitis is rare. Treatment of metastasis-induced acute pancreatitis is initially supportive, but failure of conservative management are common. There are few reports on aggressive treatment with chemotherapy which lead to rapid clinical improvement and prolongation of survival in patients with metastasis-induced acute pancreatitis. We experienced a case of metastasis-induced acute pancreatitis in a patient with small cell lung cancer. Despite conservative treatment with dietary restriction and intravenous fluid supply, serum amylase levels increased persistently with severe abdominal pain. After chemotherapy with irinotecan and carboplatin, abdominal pain and serum amylase levels resolved dramatically.