Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H+, K+-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.
2-Pyridinylmethylsulfinylbenzimidazoles ; Benzimidazoles ; Gastric Acid ; Genotype ; Half-Life ; Hydrogen-Ion Concentration ; Imidazoles ; Nitro Compounds ; Omeprazole ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Pyridines ; Quality of Life

PURPOSE: Polypoid lesions of the gallbladder have a range of causes. A problem exists in the selection of patients for surgery. This study examined the usefulness of laparoscopic cholecystectomy, suspected risk factors and plan of patients with gallbladder polyps. METHODS: This study examined 57 patients who underwent laparoscopy cholecystectomy with gallbladder polyps. All patients had been diagnosed preoperatively by ultrasound and abdominal computed tomography between October 2001 and October 2010. Preoperative radiologic diagnosis, age, gender, symptoms, size of polyps, number, concurrent gallstones and histological diagnosis of the polyps as well as the postoperative complications were reviewed retrospectively. The operation indications were polyps >10 mm, age above 55 years, symptomatic polyps, coincidence of a stone, focal thickening of gallbladder wall and detection during other operations. RESULTS: The number of each type of polyp lesion of the gallbladder was as follows: 26 cases (45.6%) had cholesterol polyps, 2 cases (3.6%) inflammatory polyps, 1 case (1.7%) mucosal lymphoid follicles, 12 cases (21.1%) adenomatous polyps, 1 case (1.7%) adenocarcinoma. Non-neoplastic and neoplastic polyps accounted for 50.9% and 22.8%, respectively. Forty-eight cases had an accepted operative indication and underwent surgery. The nine other cases also underwent surgery. Among those with operative indications, 27.1% had neoplastic polyps. Of the patients who had non-indication operative surgery or polyps <5 mm in size, there were non neoplastic polyps in any cases. Two of the patients developed complications; wound infection (1 case), and common bile duct obstruction (1 case). CONCLUSION: Observation and careful surgery is necessary for patients with polyps <5 mm in size, and who do not have accepted operative indications. Laparoscopic cholecystectomy can be considered an adequate treatment for patients with accepted operative indications.
Adenocarcinoma ; Adenomatous Polyps ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Cholesterol ; Common Bile Duct ; Gallbladder ; Gallstones ; Humans ; Laparoscopy ; Polyps ; Postoperative Complications ; Retrospective Studies ; Risk Factors ; Wound Infection

PURPOSE: In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. METHODS: Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. RESULTS: The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). CONCLUSION: Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts.
Aged ; Anemia ; Bile Ducts ; Cholecystectomy* ; Cohort Studies ; Gallbladder Neoplasms* ; Gallbladder* ; Humans ; Hypertension ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Risk Factors

BACKGROUND/AIMS: Many studies on infliximab have confirmed its efficacy in the remission induction and even maintenance in refractory and fistulizing Crohn's disease. We report the treatment efficacy of infliximab in Crohn's disease and ulcerative colitis refractory to steroid treatment and the complications of infliximab treatment. METHODS: We performed infliximab administration in 5 cases (3 Crohn's disease, 2 ulcerative colitis) refractory to systemic steroid treatment and 5 cases of Crohn's disease with fistula. Patients received an intravenous infusion of infliximab at 3-5 mg/kg body weight. RESULTS: In 3 cases of refractory Crohn's patients, clinical response and remission induction were obtained in 2 (67%) and 1 cases (33%). After infusion of infliximab, the occlusion of internal fistula could be found in all 2 cases. Two out of 3 cases of anal fistula were completely healed. In two cases of refractory ulcerative colitis, one case who showed clinical manifestation of toxic megacolon had improved and avoided the colectomy, but the other case did not respond to the infusion of infliximab and underwent colon resection. CONCLUSIONS: We found that administration of infliximab is an effective alternative for refractory and fistulizing Crohn's disease but further studies are necessary for refractory ulcerative colitis.
Adolescent ; Adult ; Antibodies, Monoclonal/*therapeutic use ; Colitis, Ulcerative/complications/*drug therapy ; Crohn Disease/complications/*drug therapy ; English Abstract ; Female ; Gastrointestinal Agents/*therapeutic use ; Humans ; Intestinal Fistula/complications ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha

BACKGROUND/AIMS: We performed a prospective study to compare the feasibility, safety and tolerance among ultrathin transnasal (UT-N), thin transnasal (T-N) and ultrathin oral (UT-O) esophagogastroduodenoscopy. METHODS: Two narrow diameter endoscopes (phi=5.2 mm for UT-N and UT-O, phi=6.5 mm for T-N) were used. The operator factors and patient factors were quantified by a visual analogue scale. RESULTS: The procedure was successfully completed in 100 of 100 patients in the UT-O group. The T-N group, when compared with the UT-N group, accounted for a significantly higher portion of failure (14% vs 3%, respectively, p=0.000), more cases of epistaxis (11% vs 3%, respecttively, p=0.013) and more complaints of nasal pain (17% vs 6%, p=0.016). The overall quality of the exam was significantly higher in the UT-N group (UT-N, 8.7; T-N, 8.1; UT-O, 8.2, p=0.04). The frequency of a incurring a gag reflex was significantly lower in the UT-N group (UT-N, 1.26; T-N, 1.48; UT-O, 2.94, p= 0.000). The patients' score for overall general satisfaction was higher in the UT-N group (UT-N, 8.5; T-N, 7.8; UT-O, 7.7, p=0.006). Nausea was significantly reduced the in UT-N group (UT-N, 8.2; T-N, 7.8; UT-O, 7.3, p= 0.003). Patients in the UT-N group were more willing to repeat the same procedure (UT-N, 82%; T-N, 65%; UT-O, 71%, p=0.046). CONCLUSIONS: Ultrathin transnasal endoscopy is more feasible, safe and comfortable compared with the thin transnasal endoscopy or when compared with either instrument that was passed orally.
Endoscopes ; Endoscopy ; Epistaxis ; Humans ; Nausea ; Prospective Studies ; Reflex