PPI Administration Research Articles

Effects of administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer.

In ulcerative early gastric cancer, improvement and exacerbation of ulceration repeat as a malignant cycle. Moreover, early gastric cancer combined with ulcer is associated with a low curative resection rate and high risk of adverse events. The aim of this study was to investigate the ulcer healing rate and clinical outcomes with the administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer. A total of 136 patients with differentiated early gastric cancer with ulcer who met the expanded indications for endoscopic submucosal dissection were reviewed between June 2005 and June 2014. Eighty-one patients were given PPI before endoscopic submucosal dissection and 55 patients were not given PPI. The complete ulcer healing rate was significantly different between the two groups (59.3% vs. 23.6%, P<0.001). The procedure time was 38.1±35.7 and 50.8±50.2min (P=0.047). However, no significant differences were detected in the en bloc resection rate, complete resection rate, and adverse events including bleeding and perforation. Multivariate analysis showed that administration of PPI (OR=10.83, P<0.001) and mucosal invasion (OR=24.43, P<0.001) were independent factors that predicted complete healing of ulceration. The calculated accuracy for whether complete healing of the ulcer after PPI administration can differentiate mucosal from submucosal invasion was 75.3%. Administration of PPI before ESD in differentiated EGC meeting the expanded criteria is effective to heal the ulcer lesion and reduce the mean procedure time. Complete healing of the ulcer after PPI administration suggests mucosal cancer.

Peritoneal delivery of sodium pyrophosphate blocks the progression of pre-existing vascular calcification in uremic apolipoprotein-E knockout mice.

Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n=18-19/group). Treatment was initiated 8weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65mg/kg or low dose, 0.33mg/kg per day), oral sevelamer (3% in diet), or placebo treatment for 8weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC.

Prospective Assessment of Prescribing Pattern of Intravenous Proton Pump Inhibitors in an Indian Tertiary-Care Teaching Hospital

Context: Inappropriate use of intravenous proton pump inhibitors (IV PPIs) has been a major challenge for private health-care setups. Inappropriate prescribing may result in increased shortages of IV PPIs in hospitals, therapeutic burden, adverse effects, and treatment costs. Therefore, the study was sought to determine drug utilization patterns (appropriateness and inappropriateness) of IV PPIs in an Indian tertiary-care teaching hospital. Aims: To assess the drug utilization pattern of IV PPIs in a tertiary-care teaching hospital. Settings and Design: This was a prospective observational study. Methods and Material: This study was conducted over a period of one month. Patients who were ≥18 years of age, who were admitted in the internal medicine, surgery, or gastroenterology wards, and who were receiving IV PPIs were included in the study. Paediatric patients and outpatients were not enrolled in the study. Ddemographics, past medication and surgery, current medical condition and medication, dose, dosing interval, duration of therapy, length of stay, and endoscopic details of each patient was collected from patients' case notes, treatment charts, and laboratory/diagnostic test reports, and evaluated for appropriateness regarding indication. Statistical analysis: Chi square test (χ 2 ) was used to analyze the data. Results: Prospective assessment involved 611 patients over a 1-month period. For prophylaxis (stress ulcer, pre-operative and postoperative prophylaxis) and treatment, IV PPIs were prescribed inappropriately to 289 (89.2%) internal medicine and 97 (34.04%) surgery ward patients. Prolonged therapy was found in patients who received IV PPIs for stress ulcer prophylaxis. Conclusion: This study revealed significant inappropriateness of PPI administration with particular reference to indication to use, duration of therapy, and changeover of therapy in an Indian tertiary-care teaching hospital.

The curative effect of triple lumen feeding tube on upper gastrointestinal tract perforation after en- doscopy

Objective To explore the curative effect of triple lumen feeding tube on upper gastroin-testinal tract perforation after endoscopic operation.Methods A total of 1 12 patients with upper gastrointes-tinal perforation after endoscopic operation were involved in this prospective control test.The remission rate of abdominal pain and abdominal distension,gastric pH,lesion healing time,length of stay and the success rate of conservative treatment were compared between the control group (indwelling traditional gastric tube and intravenous use of omeprazole injection)and the experimental group (intestinal administration of PPI through triple lumen feeding tube).Results The remission rate of abdominal pain of the experimental group was 61. 3% at 6 hours,and 83. 2% at 12 h,which were significantly higher than those of the control group (P 0. 05 ).Con-clusion The curative effect of triple lumen feeding tube on upper gastrointestinal tract perforation after endo-scopic operation is ideal. Key words: Esophageal perforation ; Proton pump inhibitors ; Omeprazole ;

Sa1881 The Effect of Low Dose PPI Administration for Prevention of Upper GI Bleeding in Chronic Kidney Disease Patients Receiving Aspirin

Sa1881 The Effect of Low Dose PPI Administration for Prevention of Upper GI Bleeding in Chronic Kidney Disease Patients Receiving Aspirin

Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease

Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.

Sa1625 The Evaluation of Portal Hypertensive Enteropathy Using Capsule Endoscopy in Cirrhotic Patients: a Multicenter Study

significantly reduced the number of such lesions at week 10. In NSAID irsogladine group, the number of mucosal breaks was significantly smaller than that at week 2 and 6 compared to NSAID PPI group. Conclusions: In concludion, long-term PPI administration did not show any preventive efficacy for small intestinal lesions induced by NSAIDs although it is a standard medication for NSAIDs induced gastrointestinal lesions. Small intestinal lesions at week 6 are less severe as compared to those at week 2 by small intestinal mucosal adaptation. On the other hand, irsogladine prevented small intestinal lesions by NSAIDs and showed therapeutic benefit for such lesions achieved with NSAIDs and PPIs.

Mo1599 MicroRNA Expression Profiles in UC-Associated Neoplastic and Adjacent Non-Dysplastic Mucosa

We have published that proton pump inhibitor could prevent colitis-associated cancer (Kim et al, Cancer Prevention Res, 2010), but question remains how PPI-induced hypergastrinemia contributed to significant cancer preventive outcomes in spite of proliferative and antiapoptotic action of gastrin beyond a central role of acid secretion. Therefore, there might be counterbalance or unexpected augmentation in cancer preventive action of PPI and gastrin, for which we investigated the effects of gastrin alone or combination with PPI on either colitis associated cancer or intestinal polyposis. Treatment of HCT116 cells with 100nM gastrin led to significantly increased proliferation, confirming trophic effects of gastrin and exogenous gastrin significantly increased the number of intestinal polyposis in Min mice as well as promoted carcinogenesis in two-stage colitic cancer mice. Gastrin treatment induced the progression of G1/S phase and increased the expressions of CDK4 and cyclin D1 as well as increased nuclear translocation of β-catenin associated with increased levels of Tcf4 and Lef1, whereas the inhibition of gastrin receptor by either YM022 or transient transfection of siRNA CCK-2R abrogated these cellular proliferations. Based on these mechanisms that pantoprazole treatment significantly abolished the gastrin-induced proliferation through attenuating gastrin induced β-catenin signaling accompanied with significant subG1 increments, combination of gastrin and PPI led to paradoxically significant prevention of colitis-associated cancer as well as significantly decreased intestinal polyposis. Our study can explain why in spite of longstanding PPI administration, the risk of colon cancer did not increase as Cohort study had documented and imposes anticipating cancer preventive action of PPI.

Mo1597 Augmented Prevention of Colitis-Associated Cancer and Attenuated Intestinal Polyposis With Proton Pump Inhibitor and PPI-Induced Hypergastrinemia

We have published that proton pump inhibitor could prevent colitis-associated cancer (Kim et al, Cancer Prevention Res, 2010), but question remains how PPI-induced hypergastrinemia contributed to significant cancer preventive outcomes in spite of proliferative and antiapoptotic action of gastrin beyond a central role of acid secretion. Therefore, there might be counterbalance or unexpected augmentation in cancer preventive action of PPI and gastrin, for which we investigated the effects of gastrin alone or combination with PPI on either colitis associated cancer or intestinal polyposis. Treatment of HCT116 cells with 100nM gastrin led to significantly increased proliferation, confirming trophic effects of gastrin and exogenous gastrin significantly increased the number of intestinal polyposis in Min mice as well as promoted carcinogenesis in two-stage colitic cancer mice. Gastrin treatment induced the progression of G1/S phase and increased the expressions of CDK4 and cyclin D1 as well as increased nuclear translocation of β-catenin associated with increased levels of Tcf4 and Lef1, whereas the inhibition of gastrin receptor by either YM022 or transient transfection of siRNA CCK-2R abrogated these cellular proliferations. Based on these mechanisms that pantoprazole treatment significantly abolished the gastrin-induced proliferation through attenuating gastrin induced β-catenin signaling accompanied with significant subG1 increments, combination of gastrin and PPI led to paradoxically significant prevention of colitis-associated cancer as well as significantly decreased intestinal polyposis. Our study can explain why in spite of longstanding PPI administration, the risk of colon cancer did not increase as Cohort study had documented and imposes anticipating cancer preventive action of PPI.

Mo1081 Is Proton Pump Inhibitor (PPI) Therapy for Reflux Esophagitis (RE) Sufficient? a Multicenter Retrospective Real-World Survey of Japanese Re Patients Treated With PPIs

BACKGROUND and AIM: Randomized controlled trials had shown a high efficacy of PPIs in healing and maintenance therapy for RE. However, their efficacy needs to be reassessed using recent real-life evidence because factors that may contribute to refractory RE, such as advanced age and absence of H. pylori infection, are becoming more prevalent in Japan. We retrospectively surveyed endoscopic findings of RE before and after ≥8 weeks of PPI administration, and analyzed factors that may affect endoscopic healing. METHOD: This multicenter retrospective survey in 41 institutions in Japan included adult (≥20 years) patients with RE defined as grade A-D by Los Angeles classification and treated for ≥8 weeks with a PPI (omeprazole, lansoprazole, or rabeprazole), who then underwent second endoscopy. Patients with malignancy, esophageal stricture, eosinophilic esophagitis, achalasia, malabsorption, or history of gastrointestinal resection or vagotomy were excluded. Using medical records for endoscopies between August 2005 and July 2010, eligible records were reviewed and analyzed for endoscopic findings, duration and dose of PPI use, comorbidities,

Protocolo de seguimiento de la infección por Helicobacter pylori

When eradication of H. pylori is indicated, triple therapy using proton pump inhibitors, amoxicillin and clarithromycin remains the treatment of choice in Spain. Seven days is the most common duration for triple therapies, but longer regimens (10-14 days) should be used in patients with MALT lymphoma or uninvestigated dyspepsia. PPI administration should be maintained until healing in complicated peptic ulcers or in large gastric ulcers (4 to 8 weeks usually). As 20% of failures of first line therapy is to be expected, to plan a rescue therapy from the start is recommend. The rescue therapy is based in avoiding antibiotic previously used with high rates of resistance. Bismuth based quadruple therapy and levofloxacin-based triple therapy are both valid options. Correct adherence is the key point for the overall success of treatment.

Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia

The high rate of cardiovascular mortality in patients with end-stage renal disease (ESRD) is a significant barrier to improved life expectancy. Unique in this population is the marked development and aggressive worsening of vascular calcification (VC). Pyrophosphate (PPi), an endogenous molecule, appears to naturally inhibit soft tissue calcification, but may be depressed in chronic kidney disease (CKD) and ESRD. Although once thought to be a promising therapeutic, PPi's very short half-life in circulation curtailed earlier studies. We tested the possibility that a slow, continuous entry of PPi into the circulation and prevention of VC might be achieved by daily peritoneal dialysis (PD). Pharmacokinetic studies were first carried out in rats with renal impairment resulting from a 5/6 nephrectomy. Efficacy studies were then performed in the apolipoprotein E gene knockout mouse model overlaid with CKD. PPi was delivered by means of a permanent peritoneal catheter in a solution simulating PD, but without the timed removal of spent dialysate. von Kossa's staining followed by semiquantitative morphological image processing, with separation of inside (intimal) and outside (presumed medial) lesions, was used to determine aortic root calcification. In comparison to an intravenous bolus, delivery of PPi in a PD solution resulted in a slower, extended delivery over >4 h. Next, the efficacy studies showed that a 6-day/week PD-simulated administration of PPi resulted in a dose-dependent inhibition of aortic calcification in both intimal and medial lesions. A dose-response effect on total aortic calcification was also documented, with a full inhibition seen at the highest dose. A limited peritoneal catheter-related inflammation was observed, as expected, and included the placebo-treated control groups. This inflammatory response could have masked a lower level PPi-specific adverse effect, but none was observed. Our findings suggest potential for PPi, administered during PD, to prevent the development of VC and to potentially extend the life of ESRD patients.

Adverse effects of proton pump inhibitor drugs: clues and conclusions

To review evidence relating to the strength of associations that have appeared in largely observational studies, between high-dose or long-term use of proton pump inhibitor drugs and certain possibly attributable side-effects, which emerge from studies confounded by other variables. In retrospective studies not designed to assess safety, evidence of causality is generally lacking. The associations of fractures of hip, wrist, forearm and other sites appear weak and only slightly higher than the risks in control populations matched for age. They may increase with drug exposure, but probably do so only in individuals in whom other risk factors are also operational (smoking, alcohol, poor nutrition, steroids, etc.). The risks of Clostridium difficile colitis, other enteric infections, small bowel bacterial overgrowth and possibly spontaneous bacterial peritonitis also appear increased. Impaired gastric secretion may adversely affect the absorption of various nutrients, but their clinical impact is ill defined. Potentially more important are the consequences of hypergastrinemia, including rebound hypersecretion of acid, and possible development of various cancers, including carcinoid tumors. Effects of other drugs, including clopidogrel, on metabolism are reviewed, but clouded by uncertainties. The safety of long-term PPI administration needs serious prospective study.

Medical and Endoscopic Treatment in Peptic Ulcer Bleeding: a National German Survey

Peptic ulcers are the leading cause of upper gastrointestinal (GI) bleeding. The aim of this study was the evaluation of the recent clinical practice in drug therapy and endoscopic treatment of ulcer bleedings in Germany and to compare the results with the medical standard. A structured questionnaire (cross-sectional study) was sent to 1371 German hospitals that provide an emergency service for upper GI bleeding. The project was designed similar to a nationwide inquiry in France in 2001. Forty-four questions concerning the following topics were asked: hospital organisation, organisation of emergency endoscopy service, endoscopic and drug therapy of ulcer bleeding, endoscopic treatment of variceal bleeding. Return of the questionnaires was closed in August 2004. Response rate was 675 / 1371 (49 %). Mean hospitals size was < 200 beds, 49 % (n = 325) had basic care level. 92 % provided a 24-hour endoscopy service, specialized nurses were available in 75 %. Fiberscopes were used only in 15 %. A mean of 10 +/- 12 (range: 0 - 160) bleeding cases/month were treated, 6 +/- 6 cases per month (60 %) were ulcer bleedings. Endoscopy was performed in 72 % immediately after stabilization but in all cases within 24 hours. The Forrest classification was used in 99 % whereas prognostic scores were applied only in 3 %. Forrest Ia,/Ib/IIa/IIb/IIc/III ulcers were indications for endoscopic therapy in 99 %/ 99 %/ 90 %/ 58 %/ 4 %/ 2 % respectively. Favoured initial treatment was injection (diluted epinephrine, mean volume 17 +/- 13 mL/lesion) followed by clipping. In re-bleedings, 93 % tried endoscopic treatment again. Scheduled re-endoscopy was performed in 63 %. PPI were used in 99.6 %, 85 % administered standard dose twice daily. PPI administration was changed from intravenous to oral with the end of fasting in nearly all hospitals. PPI administration schemes can be improved. Indications for Helicobacter pylori eradication followed rational principles. Medical and endoscopic treatment of bleeding ulcers reached a high standard, although some therapeutic strategies leave room for improvement. Bigger hospitals tend to be closer to the medical standard.

Clinical and cost impact of intravenous proton pump inhibitor use in non-ICU patients

To assess the appropriateness of the indication and route of administration of proton-pump-inhibitors (PPIs) and their associated cost impact. Data collection was performed prospectively during a 6-mo period on 340 patients who received omeprazole intravenously during their hospital stay in non-intensive care floors. Updated guidelines were used to assess the appropriateness of the indication and route of administration. Complete data collection was available for 286 patients which were used to assess intravenous (IV) PPIs utilization. Around 88% of patients were receiving PPIs for claimed stress ulcer prophylaxis (SUP) indication; of which, only 17% met the guideline criteria for SUP indication, 14% met the criteria for non-steroidal-anti-inflammatory drugs-induced ulcer prophylaxis, while the remaining 69% were identified as having an unjustified indication for PPI use. The initiation of IV PPIs was appropriate in 55% of patients. Half of these patients were candidates for switching to the oral dosage form during their hospitalization, while only 36.7% of these patients were actually switched. The inappropriate initiation of PPIs via the IV route was more likely to take place on the medical floor than the surgical floor (53% vs 36%, P = 0.003). The cost analysis associated with the appropriateness of the indication for PPI use as well as the route of administration of PPI revealed a possible saving of up to $17,732.5 and $14,571, respectively. This study highlights the over-utilization of IV PPIs in non-intensive care unit patients. Restriction of IV PPI use for justified indications and route of administration is recommended.

S1605 A Long-Term PPI Administration Induces Atrophic Corpus Gastritis and Promotes Development of Atypical Glands in Mongolian Gerbils Infected with Helicobacter pylori

S1605 A Long-Term PPI Administration Induces Atrophic Corpus Gastritis and Promotes Development of Atypical Glands in Mongolian Gerbils Infected with Helicobacter pylori

Appendix 1: Transatlantic and pacific dosage and administration of a PPI (lansoprazole)

Appendix 1: Transatlantic and pacific dosage and administration of a PPI (lansoprazole)

Motion – Laparoscopic Nissen Fundoplication Is More Cost-Effective than Oral PPI Administration: Arguments against the Motion

Discussion of the cost effectiveness of medical and surgical treatments of gastroesophageal reflux disease (GERD) is plagued by a number of logical fallacies. Several of these defects in reasoning are reviewed. For example, it is inappropriate to compare the costs of therapies unless they are equally effective. The relative cost effectiveness of various treatment options is difficult to determine because monetary expenditures and gains in health status cannot easily be measured in commensurate units. Not everything can be translated into incremental cost effectiveness ratios. Two decision analyses from European investigators seemed to show that Nissen fundoplication was more cost effective than long term acid-suppression therapy, but they failed to consider the costs of surgical complications and failures. The most comprehensive decision analysis, employing a Markov chain model, found that the two treatment options were roughly equivalent, at least during the first seven years of follow-up. Decision analyses often do not reflect actual practice patterns and cannot provide solutions to problems that cannot be solved by appropriate medical reasoning. Moreover, results that are reported by specialized surgical centres probably cannot be duplicated by less experienced surgeons. The increasing incidence of esophageal adenocarcinoma has been erroneously attributed to the use of potent acid-suppressant medications, but the actual cause has been shown to be the decreased prevalence of Helicobacter pylori. There are no significant differences in the incidence of this tumour after medical or surgical therapy of GERD. It is unlikely, however, that arguments will convince proponents of one treatment or another to change their opinions.

Motion--Laparoscopic Nissen fundoplication is more cost effective than oral PPI administration: arguments for the motion.

Gastroesophageal reflux disease is a mechanical disorder of the foregut. While medications can only provide symptom relief, surgery can correct the pathophysiological abnormality of the lower esophageal sphincter. The costs of medical and surgical therapy are much greater than the costs of medication or hospitalization alone. In the case of medical therapy, one must consider the costs of serial monitoring and of failed treatment. The effectiveness of treatment also depends on patient-related factors, including weight, socioeconomic factors, smoking, alcohol use, dietary habits and the use of nonsteroidal anti-inflammatory drugs. Surgical results depend on the experience and skill of the surgeon, as well as the attributes of the institution in which the procedure is undertaken. Therefore, studies that come from specialized centres may not be applicable to the community. Data from the author's facility indicate that laparoscopic Nissen fundoplication is the most cost effective option when it is undertaken by experienced surgeons on otherwise healthy patients who have documented gastroesophageal reflux disease.

EFFECTS OF LONG-TERM ADMINISTRATION OF HISTAMINE H2 RECEPTOR ANTAGONIST AND H+/K+ATPase INHIBITOR ON THE REGULATION KINETICS OF GASTRIC ACID SECRETION BY GASTRIN

Histamine H2 receptor antagonist (H2-RA) and H+/K+ ATPase inhibitor (PPI) were used in treating chronic peptic ulcers and acute gastric mucosal lesions. Recently, in treating peptic ulcers, long-term administration of these drugs developed the pyloric gland gastrin cell hyperplasia and also increased the serum gastrin concentration, etc.Therefore, in order to verify the occurrence of these problems after administration of the drugs, the author has focused on studying the relationship between the serum gastrin concentration and histological changes in the antral mucosa. In this study, male Wistar rats weighing 180-200g were used and the following were assessed : 1) changes of G-cell counts in the pyloric gland 2) gastric acid secretion and 3) changes in the status of gastrin secretion following long-term administration of H2-RA and PPI given for 4 or 8 weeks were evaluated. After 4 weeks administration of these drugs, gastrin cell proliferation was seen in the rats. In the groups given triple doses of these drugs, hypergastrinemia was obtained at the same time. On the other hand, when administration of the drugs was stopped for the same period, gastrin cell proliferation and hypergastrinemia were disappeared. It can therefore be concluded that there is the potential for recovery when administration of these drugs is stopped for a period equal to that of their administration. In treating peptic ulcers it is emphasized to remember that the changes in the gastric : mucosa and gastric acid secretion are reversible.