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Hossa K, Małecka-Wojciesko E. Advances in Gastroesophageal Reflux Disease Management: Exploring the Role of Potassium-Competitive Acid Blockers and Novel Therapies. Pharmaceuticals (Basel) 2025; 18:699. [PMID: 40430518 PMCID: PMC12115254 DOI: 10.3390/ph18050699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 04/29/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients' quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD.
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Affiliation(s)
| | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-419 Lodz, Poland;
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Kang SJ, Lee KJ. Association of Proton Pump Inhibitor Use With Gastric Cancer in Regions With High Prevalence of Gastric Cancer: Systematic Review and Meta-analysis. J Neurogastroenterol Motil 2025; 31:178-185. [PMID: 40205895 PMCID: PMC11986659 DOI: 10.5056/jnm24145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 02/05/2025] [Indexed: 04/11/2025] Open
Abstract
Background/Aims Although the association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer has been postulated in casecontrol and cohort studies, it remains still controversial. We aim to evaluate association of PPI use with gastric cancer in regions with high prevalence of gastric cancer, particularly in patients who underwent eradication of Helicobacter pylori, by systemic review and meta-analysis. Methods Comprehensive literature search through the PubMed, Embase, and Cochrane database was performed in October 2023. We used random effects model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) between PPI use and gastric cancer. The Cochran Q-statistic and the I2 test were employed for evaluating potential heterogeneity between studies. Results Two case-control and 6 cohort studies were identified. PPI use was significantly associated with the development of gastric cancer (OR, 2.02; 95% CI, 1.35-3.01). In subgroup analysis carried out according to the study design, sample size, and adjustment of confounding factors (age, sex, and H. pylori), such association was significant. A meta-analysis of 4 studies performed in patients with H. pylori eradication history showed that the use of PPIs was significantly associated with an elevated incidence of gastric cancer (OR, 2.10; 95% CI, 1.48-2.97). Conclusions Long-term use of PPIs is associated with an increased risk of gastric cancer in Asian regions with high prevalence of gastric cancer, particularly in subjects who have eradication history of H. pylori. Optimization of long-term PPI use seems to be necessary in regions where gastric cancer is prevalent.
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Affiliation(s)
- Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
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Rossi CM, Lenti MV, Santacroce G, Merli S, Vanoli A, Di Sabatino A. Eosinophilic oesophagitis in adults: from symptoms to therapeutic options. Intern Emerg Med 2025; 20:655-665. [PMID: 39729261 DOI: 10.1007/s11739-024-03846-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 12/15/2024] [Indexed: 12/28/2024]
Abstract
Eosinophilic oesophagitis (EoE) is a chronic and progressive immune-mediated condition, typically affecting young atopic male adults and potentially leads to organ dysfunction and fibrosis. The clinical spectrum widely varies -from non-troublesome dysphagia to food impaction- and hence the rate of misdiagnosis and diagnostic delay are high, especially when presenting with minor symptoms, such as heartburn and acid regurgitation. There have been several major therapeutic breakthroughs for the management of EoE in recent years. Highly effective conventional agents with oesophagus-specific formulations (i.e. orodispersible budesonide) and a biological agent (i.e. dupilumab) now have a formal indication. Oesophageal dilation may be indicated in case of strictures, which are more common in longstanding and untreated disease. Therefore, the early diagnosis of this disorder and specialist referral is if of great importance. The evaluation of alarm signs and typical presentation patterns should allow a more straightforward recognition. The emergency and internal medicine doctors should actively be involved in this process and take part to the multidisciplinary care of patients with EoE, to allow better patient care and clinical outcomes.
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Affiliation(s)
- Carlo Maria Rossi
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università Di Pavia, Viale Golgi 19, 27100, Pavia, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università Di Pavia, Viale Golgi 19, 27100, Pavia, Italy
| | - Giovanni Santacroce
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università Di Pavia, Viale Golgi 19, 27100, Pavia, Italy
| | - Stefania Merli
- First Department of Internal Medicine, Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università Di Pavia, Viale Golgi 19, 27100, Pavia, Italy
| | | | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy.
- First Department of Internal Medicine, Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università Di Pavia, Viale Golgi 19, 27100, Pavia, Italy.
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Authors, Collaborators. S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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Perazella MA. Proton Pump Inhibitors and Kidney Disease: What Gives? KIDNEY360 2024; 5:1374-1376. [PMID: 39325592 PMCID: PMC11441802 DOI: 10.34067/kid.0000000000000521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]
Affiliation(s)
- Mark A Perazella
- Section of Nephrology, Yale School of Medicine, New Haven, Connecticut
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Ito T, Ramos-Alvarez I, Jensen RT. Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B 12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients. Int J Mol Sci 2024; 25:7286. [PMID: 39000391 PMCID: PMC11242121 DOI: 10.3390/ijms25137286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | | | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA
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Prabhu K, Warricker F, Almilaji O, Williams E, Snook J. Role of prescribed medication in the development of iron deficiency anaemia in adults-a case-control study. BMJ Open Gastroenterol 2024; 11:e001305. [PMID: 38926132 PMCID: PMC11217774 DOI: 10.1136/bmjgast-2023-001305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 06/07/2024] [Indexed: 06/28/2024] Open
Abstract
OBJECTIVE To estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA), specifically considering oral anticoagulants (OACs), antidepressants, antiplatelet agents, proton pump inhibitors (PPIs) and non-steroidal anti-inflammatories. DESIGN A case-control study involving the analysis of community repeat prescriptions among subjects referred with IDA, and unmatched controls referred as gastroenterology fast-tracks for other indications. Multivariable logistic regression modelling was used to calculate ORs for the association between IDA presentation and each medication class, adjusted for age, sex and coprescribing. For those classes showing significance, it was also used to calculate risk differences between those in the IDA group with or without haemorrhagic lesions on investigation. RESULTS A total of 1210 cases were analysed-409 in the IDA group, and 801 in the control group. Significant associations were identified between presentation with IDA and long-term exposure to PPIs (OR 3.29, 95% CI: 2.47 to 4.41, p<0.001) and to OACs (OR 2.04, 95% CI: 1.29 to 3.24, p=0.002). IDA was not associated with long-term exposure to any of the other three drug classes. In contrast to the relationship with PPIs, the association with OACs was primarily in the IDA sub-group with haemorrhagic lesions. CONCLUSION Long-term exposure to PPIs and OACs are independently associated with the risk of developing IDA. There are grounds for considering that these associations may be causal, though the underlying mechanisms probably differ.
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Affiliation(s)
| | | | - Orouba Almilaji
- Department of Health Service Research and Policy, London School of Hygiene & Tropical Medicine, London, UK
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Smaoui H, Chtourou L, Jallouli D, Jemaa SB, Karaa I, Boudabbous M, Moalla M, Gdoura H, Mnif L, Amouri A, Akrout R, Ayadi F, Baklouti S, Tahri N. Effect of long-term proton pump inhibitors on phosphocalcium metabolism and bone mineral density. Future Sci OA 2024; 10:FSO977. [PMID: 38841182 PMCID: PMC11152587 DOI: 10.2144/fsoa-2023-0198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 02/14/2024] [Indexed: 06/07/2024] Open
Abstract
Aim: Although Proton pump inhibitors (PPIs) are well-tolerated, their long-term use may be associated with decreased bone mass. Methods: This is a case-control study including patients treated with PPIs (>1 year) and control subjects who have not received PPIs treatment. Results: A total of 90 patients and 90 matched controls were included. PPIs use was associated with hypocalcemia and hypomagnesemia. Vitamin D3 deficiency and hyperparathyroidism were associated with PPIs use. Long-term PPIs use was significantly associated with decreased bone density. Risk factors of decreased bone mineral density (BMD) included age >50 years, menopause, lack of sun exposure, double PPIs dose, daily intake, post-meal intake and association with a mucoprotective agent. Conclusion: Our results highlight the risk of decreased BMD in patients on long-term PPIs treatment.
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Affiliation(s)
- Hend Smaoui
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Lassaad Chtourou
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Dana Jallouli
- Laboratory of Biochemistry, Habib Bourguiba University Hospital, Sfax, Tunisia
| | - Samar Ben Jemaa
- Department of Rhumatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Iheb Karaa
- Laboratory of Biochemistry, Habib Bourguiba University Hospital, Sfax, Tunisia
| | - Mouna Boudabbous
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Manel Moalla
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Hela Gdoura
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Leila Mnif
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Ali Amouri
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Rim Akrout
- Department of Rhumatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Fatma Ayadi
- Laboratory of Biochemistry, Habib Bourguiba University Hospital, Sfax, Tunisia
| | - Sofien Baklouti
- Department of Rhumatology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Nabil Tahri
- Department of Gastroenterology & Hepatology, Hedi Chaker University Hospital, Sfax, Tunisia
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9
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Schene MR, Bevers MSAM, van der Vijgh WJF, Driessen JHM, Vranken L, van der Velde RY, Willems HC, Wyers CE, van den Bergh JP. PPI use is not associated with bone microarchitecture and strength assessed with HR-pQCT after three-years follow-up in patients visiting the Fracture Liaison Service. Bone 2024; 182:117066. [PMID: 38438097 DOI: 10.1016/j.bone.2024.117066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/30/2024] [Accepted: 02/29/2024] [Indexed: 03/06/2024]
Abstract
BACKGROUND The use of proton pump inhibitors (PPIs) has been associated with an increased fracture risk in observational studies. However, the reported association between PPI use and bone mineral density (BMD), bone microarchitecture, and bone strength is inconsistent. This study aims to assess the association between PPI use and bone microarchitecture and strength using high-resolution peripheral quantitative CT (HR-pQCT) in a three-year follow-up study in patients with a recent fracture visiting the Fracture Liaison Service (FLS). METHODS This three-year prospective cohort study included FLS patients aged ≥ 50 years with a recent fracture (median age 62 [IQR 56-69] years, 68.7 % females) and without anti-osteoporosis treatment indication. HR-pQCT scans (distal radius and tibia) were obtained at baseline (T0) and three-year follow-up (T3). Volumetric bone mineral density and bone area, microarchitecture, and strength (micro-finite element analysis) were determined. The association between three-year continuous PPI use and the percentage change in HR-pQCT parameters between T0 and T3 was assessed using sex-stratified multivariate linear regression analyses. Covariates included age, BMI, vitamin-D deficiency (< 50 nmol/l), glucocorticoid use, and cardiovascular co-morbidity (males and females) fracture type (major/hip vs. all others, only males) and probable sarcopenia (only females). RESULTS In total, 282 participants had available medication data throughout follow-up, of whom 20.6 % were continuous PPI users. In both males and females with complete HR-pQCT follow-up data (males: N = 69 radius, N = 84 tibia; females: N = 147 radius, N = 168 tibia), PPI use was not associated with the percentage change of any of the bone microarchitecture or strength parameters between T0 and T3 at the radius and tibia as compared to non-use. CONCLUSION Compared to non-use, PPI use was not associated with the change of bone microarchitecture and strength in FLS patients at three years of follow-up. These results do not support that an altered bone microarchitecture or strength may contribute to the increased fracture risk associated with PPI use, as reported in observational studies.
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Affiliation(s)
- M R Schene
- Department of Internal Medicine, VieCuri Medical Center, P.O. Box 1926, 5900 BX Venlo, the Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Amsterdam UMC location University of Amsterdam, Internal Medicine and Geriatrics, Meibergdreef 9, Amsterdam, Netherlands
| | - M S A M Bevers
- Department of Internal Medicine, VieCuri Medical Center, P.O. Box 1926, 5900 BX Venlo, the Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - W J F van der Vijgh
- Department of Internal Medicine, VieCuri Medical Center, P.O. Box 1926, 5900 BX Venlo, the Netherlands
| | - J H M Driessen
- Department of clinical pharmacy, CARIM School of Cardiovascular Disease, Maastricht University, Maastricht, the Netherlands; Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center +, P.O. Box 616, 6200 MD Maastricht, the Netherlands
| | - L Vranken
- Department of Internal Medicine, VieCuri Medical Center, P.O. Box 1926, 5900 BX Venlo, the Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
| | - R Y van der Velde
- Department of Internal Medicine, VieCuri Medical Center, P.O. Box 1926, 5900 BX Venlo, the Netherlands
| | - H C Willems
- Amsterdam UMC location University of Amsterdam, Internal Medicine and Geriatrics, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Bone Center, Movement Sciences Amsterdam, the Netherlands
| | - C E Wyers
- Department of Internal Medicine, VieCuri Medical Center, P.O. Box 1926, 5900 BX Venlo, the Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Internal Medicine, Maastricht University Medical Center +, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
| | - J P van den Bergh
- Department of Internal Medicine, VieCuri Medical Center, P.O. Box 1926, 5900 BX Venlo, the Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Department of Internal Medicine, Maastricht University Medical Center +, P.O. Box 616, 6200 MD Maastricht, the Netherlands
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10
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Weir MR. Proton Pump Inhibitors and Kidney Disease: Fact or Fiction? Am J Nephrol 2024; 55:499-508. [PMID: 38583423 DOI: 10.1159/000538755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/05/2024] [Indexed: 04/09/2024]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are commonly prescribed medications for dyspepsia and gastroesophageal reflux. There are concerns about their use in the development of chronic kidney disease (CKD). SUMMARY The available published literature fails to support an association with PPI and the development of CKD. Placebo-controlled trials demonstrate no difference in the incidence of CKD between placebo and PPI. If one examines the data according to the Bradford Hill perspective incorporating temporal relationship, the strength of association, dose-response relationship, replacement of findings, cessation of exposure, specificity of the association, and consistency with other knowledge, one can only conclude that there is no consistent relationship between PPI use and the development of CKD, or its progression. KEY MESSAGES There is insufficient evidence to link PPI exposure with the development or progression of CKD.
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Affiliation(s)
- Matthew R Weir
- Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Soria-Chacartegui P, Navares-Gómez M, Molina-Jiménez F, Laserna-Mendieta EJ, Arias-González L, Majano P, Casabona S, Lucendo AJ, Abad-Santos F, Santander C, Zubiaur P. Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis. Int J Mol Sci 2024; 25:3685. [PMID: 38612496 PMCID: PMC11011338 DOI: 10.3390/ijms25073685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/20/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.
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Affiliation(s)
- Paula Soria-Chacartegui
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
| | - Marcos Navares-Gómez
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
| | - Francisca Molina-Jiménez
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
| | - Emilio J. Laserna-Mendieta
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Gastroenterology Department, Hospital General de Tomelloso, 13700 Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Laura Arias-González
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Gastroenterology Department, Hospital General de Tomelloso, 13700 Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Pedro Majano
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Cellular Biology Department, Faculty of Biology, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Sergio Casabona
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alfredo J. Lucendo
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Gastroenterology Department, Hospital General de Tomelloso, 13700 Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Francisco Abad-Santos
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Cecilio Santander
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Pablo Zubiaur
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
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12
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Sumi K, Inoue H, Ando R, Fujiyoshi MRA, Fujiyoshi Y, Tanabe M, Shimamura Y, Onimaru M. Long-term efficacy of antireflux mucosectomy in patients with refractory gastroesophageal reflux disease. Dig Endosc 2024; 36:305-313. [PMID: 37332095 DOI: 10.1111/den.14617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/15/2023] [Indexed: 06/20/2023]
Abstract
OBJECTIVES Minimally invasive treatments have been applied for gastroesophageal reflux disease (GERD), but the long-term results are controversial. Antireflux mucosectomy (ARMS) is a simple endoscopic procedure that does not require the insertion of a foreign body. We provide the first report on the long-term results of ARMS. METHODS This was a single-center, single-arm trial, prospective study of 88 patients with proton pump inhibitor (PPI)-refractory GERD who underwent ARMS between June 2012 and June 2017. Primary outcomes were the rates of long-term effectiveness and PPI discontinuation. Secondary outcomes were to compare patients' preoperative background characteristics, questionnaire, and multichannel intraluminal impedance and pH monitoring data to examine the predictive factors of ARMS. The clinical course was reviewed, including the need for additional treatment after ARMS. RESULTS Antireflux mucosectomy produced a long-term effect in 68.3% of the patients, and PPI could be discontinued in 42% of patients. There were significant differences in age, intensity of preoperative symptoms, and acid-related indicators. Forty-five percent (27/60) had reflux hypersensitivity and ARMS provided long-term effectiveness in 81% of these patients. There was no significant difference in subjective symptom assessment between those with short-term and long-term efficacy. Additional treatment was administered in 23% (14/60) and scheduled at 1-2 years' follow-up. CONCLUSIONS Antireflux mucosectomy showed long-term efficacy, and many of the cases with short-term effects were able to maintain them. In addition, ARMS is also effective in patients with reflux hypersensitivity, and provides a treatment option that bridges the gap between surgical and medical treatment.
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Affiliation(s)
- Kazuya Sumi
- Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
| | - Haruhiro Inoue
- Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
| | - Ryohei Ando
- Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
| | | | - Yusuke Fujiyoshi
- Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
| | - Mayo Tanabe
- Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
| | - Yuto Shimamura
- Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
| | - Manabu Onimaru
- Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan
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13
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Bavbek S, Kepil Özdemir S, Bonadonna P, Atanaskovic-Markovic M, Barbaud A, Brockow K, Laguna Martinez J, Nakonechna A, Pagani M, Arcolacı A, Lombardo C, Torres MJ. Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper. Allergy 2024; 79:552-564. [PMID: 38013608 DOI: 10.1111/all.15961] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 11/08/2023] [Indexed: 11/29/2023]
Abstract
Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.
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Affiliation(s)
- Sevim Bavbek
- Division of Immunology and Allergy, Department of Chest Diseases, School of Medicine, Ankara University, Ankara, Turkey
| | - Seçil Kepil Özdemir
- Department of Chest Diseases, Allergy and Immunology Unit, İzmir Faculty of Medicine, Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, University of Health Sciences, İzmir, Turkey
| | | | - Marina Atanaskovic-Markovic
- Department of Allergology and Pulmonology, Faculty of Medicine, University of Belgrade, University Children's Hospital, Belgrade, Serbia
| | - Annick Barbaud
- Département de dermatologie et allergologie, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Sorbonne Université, Hôpital Tenon, Paris, France
| | - Knut Brockow
- Department of Dermatology and Allergy Biederstein, Faculty of Medicine, Technical University of Munich, Munich, Germany
| | - Jose Laguna Martinez
- Allergy Unit, Allergo-Anaesthesia Unit, Faculty of Medicine, Hospital Central de la Cruz Roja, Alfonso X El Sabio University, Madrid, Spain
| | - Alla Nakonechna
- Allergy and Clinical Immunology Department, University of Liverpool, Royal Preston Hospital, Lancashire Teaching Hospitals, NHS Foundation Trust, Liverpool, UK
| | - Mauro Pagani
- Medicine Department, Medicine Ward Mantova Hospital, ASST di Mantova, Mantova, Italy
| | | | - Carla Lombardo
- Division of Dermatology and Allergy, APSS - Trento Hospital, Trento, Italy
| | - Maria J Torres
- Allergy Unit, Regional University Hospital of Malaga, IBIMA-UMA-ARADyAL, Malaga, Spain
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14
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Martín de Argila de Prados C, López Cardona J, Argüelles-Arias F. Safe use of proton-pump inhibitors. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:475-479. [PMID: 37522310 DOI: 10.17235/reed.2023.9834/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/01/2023]
Abstract
Proton pump inhibitors (PPIs) are one of the most commonly prescribed drug groups in developed countries. Their approved indications include gastroesophageal reflux disease, peptic ulcer disease, and prophylaxis against NSAID-induced gastroenteropathy in specific scenarios. Since their introduction into clinical practice, their usage has significantly increased, leading to concerns about possible inappropriate prescribing, which can result in a higher risk of side effects and increased economic costs. Consequently, in recent years, literature linking PPIs to various adverse effects has emerged, with some supported by robust evidence, while others are based on lower-quality evidence, requiring cautious interpretation. Among the adverse effects of PPIs, significant ones include an increased risk of fragility fractures, deficiencies in certain micronutrients such as vitamin B12 and magnesium, a higher incidence of enteric infections, especially Clostridioides difficile, complications in cirrhotic patients, and pharmacological interactions with other medications. In clinical practice, it is essential to periodically evaluate the rationale for prescribing these drugs and consider discontinuing them if there is no appropriate indication. Despite PPIs being generally safe medications, it is crucial to be aware of their potential adverse effects and appropriate indications to ensure their proper use.
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Affiliation(s)
| | - Julia López Cardona
- Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
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15
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Autorinnen/Autoren, Collaborators:. S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
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16
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Choudhury A, Jena A, Jearth V, Dutta AK, Makharia G, Dutta U, Goenka M, Kochhar R, Sharma V. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2023; 17:479-487. [PMID: 37060552 DOI: 10.1080/17474124.2023.2204229] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 04/14/2023] [Indexed: 04/16/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPI) may impact the absorption of vitamin B12. We performed a systematic review to ascertain if PPI use increases risk of vitamin B12 deficiency. METHODS Electronic databases (PubMed, Embase, Scopus) were searched on first of September 2022. We selected studies that compared the frequency of vitamin B12 deficiency in PPI users and non-users. Pooled Odds Ratio (OR) was calculated for the occurrence of vitamin B12 deficiency in PPI users compared to non-users. The risk of bias was assessed using the Newcastle Ottawa scale. RESULTS Twenty-five studies were included. The pooled OR of vitamin B12 deficiency among PPI users (2852 participants) was higher than non-users (28070 participants) (OR 1.42, 95% CI: 1.16-1.73; I2 = 54%). Overall risk of PPI use among vitamin B12 deficient individuals was higher than those without deficiency (OR 1.49, 1.20-1.85; I2 = 68%). Most studies found no difference between serum vitamin B12 levels among PPI users compared to non-users. CONCLUSION Although the pooled OR of vitamin B12 deficiency was slightly increased in PPI users, but there was significant heterogeneity, and the pooled OR was too low to imply an association clearly. Better-designed prospective studies in long-term users may clarify the issue. REGISTRATION This study was not registered on PROSPERO.
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Affiliation(s)
- Arup Choudhury
- Department of Medicine, Nagaon Medical College and Hospital, Nagaon, Assam, India
| | - Anuraag Jena
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vaneet Jearth
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Amit K Dutta
- Department of Gastroenterology, Christian Medical College, Vellore, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Science, Delhi, India
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Mahesh Goenka
- Institute of Gastrosciences and Liver, Apollo Multispecialty Hospitals, Kolkata, India
| | - Rakesh Kochhar
- Director of Gastroenterology, Fortis Hospital, Mohali, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Losurdo G, Caccavo NLB, Indellicati G, Celiberto F, Ierardi E, Barone M, Di Leo A. Effect of Long-Term Proton Pump Inhibitor Use on Blood Vitamins and Minerals: A Primary Care Setting Study. J Clin Med 2023; 12:2910. [PMID: 37109245 PMCID: PMC10146626 DOI: 10.3390/jcm12082910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 03/09/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin D insufficiency may occur in such patients. MATERIALS AND METHODS We recruited patients using a PPI (pantoprazole) for >12 months. The control group was represented by subjects attending the general practitioner not taking any PPI in the last 12 months. We excluded subjects using nutritional supplements or with diseases interfering with micronutrient blood levels. All subjects underwent blood sampling with full blood count, iron, ferritin, vitamin D, calcium, sodium, potassium, phosphate, zinc and folate. RESULTS We recruited 66 subjects: 30 in the PPI group and 36 in the control group. Long-term pantoprazole users had lower red blood cell count but similar hemoglobin. We did not find any significant difference in blood iron, ferritin, vitamin B12 and folate. Vitamin D deficit was observed more frequently in the PPI group (100%) than in controls (30%, p < 0.001), with blood levels lower in pantoprazole consumers. No differences in calcium, sodium and magnesium were observed. Pantoprazole users had lower phosphate levels than controls. Finally, a non-significant trend for zinc deficiency was found in PPI users. CONCLUSIONS Our study confirms that chronic PPI users may encounter alterations in some micronutrients involved in bone mineral homeostasis. The effect on zinc levels deserves further investigation.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Precision Medicine and Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
- Ph.D. Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Precision Medicine Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | | | - Giuseppe Indellicati
- Section of Gastroenterology, Department of Precision Medicine and Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Francesca Celiberto
- Section of Gastroenterology, Department of Precision Medicine and Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
- Ph.D. Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Precision Medicine Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Precision Medicine and Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Precision Medicine and Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Precision Medicine and Jonic Area, University “Aldo Moro” of Bari, 70124 Bari, Italy
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18
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Mechanisms and clinical management of eosinophilic oesophagitis: an overview. Nat Rev Gastroenterol Hepatol 2023; 20:101-119. [PMID: 36253463 DOI: 10.1038/s41575-022-00691-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/14/2022] [Indexed: 02/03/2023]
Abstract
Since the first description of eosinophilic oesophagitis (EoE) less than three decades ago, we have observed a striking increase in the number of patients diagnosed with EoE and the understanding of its clinical and immunopathogenic background. Nonetheless, a plethora of open questions await elucidation. In this Review, we discuss the current state of knowledge regarding the underlying mechanisms, particularly environmental factors and their interaction with genetic susceptibility. Subsequently, we discuss how to translate these factors into the diagnostic and therapeutic management of this chronic, immune-mediated disorder. Finally, we dissect the still long list of unmet needs, such as reasons for and handling refractory EoE and atypical clinical presentations. These open questions can guide us through future research steps and potentially foster reconsideration of the diagnostic guidelines of EoE.
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19
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Song JH, Kim YS, Choi SY, Yang SY. Association between gastroesophageal reflux disease and coronary atherosclerosis. PLoS One 2022; 17:e0267053. [PMID: 35594317 PMCID: PMC9122211 DOI: 10.1371/journal.pone.0267053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 03/31/2022] [Indexed: 11/18/2022] Open
Abstract
Background and aim Gastroesophageal reflux disease (GERD) typically presents with symptoms of heartburn and acid regurgitation but occasionally manifests as atypical chest pain. Coronary artery disease (CAD) and GERD share some risk factors, such as smoking and obesity. The aims of this study were to evaluate the association between GERD and coronary atherosclerosis and to assess the risk factors for coronary atherosclerosis in GERD patients. Methods A total of 16616 subjects who underwent upper gastrointestinal endoscopy from 2003 to 2017 and a cardiac computed tomography (CT) scan within one year were included in this study. Coronary atherosclerosis was evaluated by the coronary artery calcium score (CACS). The severity of GERD was evaluated based on endoscopic findings using the Los Angeles classification. Results The proportion of high CACSs (≥100) increased significantly in subjects with severe GERD (p = 0.008). However, the presence of a high CACS did not increase the risk of GERD (OR = 1.007, 95% CI 0.857–1.182), nor did that of GERD increase the risk of a high CACS (OR = 1.018, 95% CI 0.865–1.198). The risk factors for a high CACS in GERD patients included age (OR = 1.087, 95% CI 1.066–1.109), male sex (OR = 5.645, 95% CI 2.561–12.446), hypertension (OR = 1.800, 95% CI 1.325–2.446), and hypercholesterolemia (OR = 1.684, 95% CI 1.213–2.338). Conclusions Although the presence of a high CACS did not increase the risk of GERD or vice versa, the proportion of high CACSs was significantly higher in subjects with severe GERD. Therefore, it might be helpful to assess the CACS in GERD patients with multiple risk factors.
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Affiliation(s)
- Ji Hyun Song
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Young Sun Kim
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
- * E-mail:
| | - Su-Yeon Choi
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Sun Young Yang
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
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20
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Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a clinical and pathological disorder, characterized by symptoms of esophageal dysfunction, and eosinophil-predominant inflammation restricted to the esophagus. Treatment outcomes include symptomatic remission, histological and endoscopic normalization and improving quality of life. Besides dietary modifications and endoscopic dilation, drugs available are swallowed topical corticosteroids (STCs) with reduced bioavailability and proton pump inhibitors (PPI). AREAS COVERED Herein, the authors review the current treatment strategies for EoE in adults, providing the reader with their expert perspectives. The authors give discussion to the value of PPIs as a first-line therapy for EoE, in addition to the use of STCs. The current development of new formulations of STCs targeting the esophagus and novel therapies aimed at blocking molecular pathways are also discussed. Finally, the authors briefly look at the value of monoclonal antibodies targeting IL-5RA, IL-13, IL-4 or Siglec8, and oral S1PR agonists to the treatment of EoE. EXPERT OPINION Viscose formulations of STC designed to coat the esophagus and new effervescent orodispersible tablets provide increased effectiveness at low doses. Investigational therapies that target several Th2-associated diseases seem useful in EoE. Comparative effectiveness and cost-utility analyses will help to position them in a complex therapeutic scenario.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology. Hospital General de Tomelloso, Tomelloso, Spain.,Instituto de Investigación Sanitaria La Princesa, Spain.,Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM).,Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
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21
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Chinzon D, Domingues G, Tosetto N, Perrotti M. SAFETY OF LONG-TERM PROTON PUMP INHIBITORS: FACTS AND MYTHS. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:219-225. [PMID: 35830032 DOI: 10.1590/s0004-2803.202202000-40] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/06/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Frequent use and long-term maintenance of these drugs drew the attention of researchers for sporadic adverse effects reports. OBJECTIVE The purpose of this narrative review is to discuss appropriate data and causality related to these adverse events and PPIs. METHODS A narrative review was conducted by systematizing information about safety and adverse events on PPIs from 2015 to 2020. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating the following situations: a) gastric cancer; b) micronutrients deficiency; c) acid rebound; d) infections; e) fractures; f) dementia; g) kidney disease; and h) sudden death and cardiovascular changes. RESULTS Recent studies have potentially associated PPIs with some adverse events as osteoporosis-related fractures. There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron. Furthermore, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports. For kidney diseases, studies consistently suggest that the use of PPI may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease. Another additional question is whether chronic PPI use would also lead to the onset of gastric cancer. The abrupt discontinuation of PPIs is also related to increased gastric acid production above pre-PPI treatment levels; this phenomenon is called acid rebound. CONCLUSION The key to mitigate adverse effects is the rational use of PPIs at the lowest effective dose and in the shortest possible duration. Although these adverse effects have a potential clinical impact, their causal association is still subject to validation.
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Affiliation(s)
- Decio Chinzon
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | - Gerson Domingues
- Faculdade de Medicina da Universidade do Estado do Rio Janeiro, Departamento de Gastroenterologia, Rio de Janeiro, RJ, Brasil
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22
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Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022; 117:559-587. [PMID: 35354777 DOI: 10.14309/ajg.0000000000001680] [Citation(s) in RCA: 229] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 02/04/2022] [Indexed: 02/07/2023]
Abstract
Barrett's esophagus (BE) is a common condition associated with chronic gastroesophageal reflux disease. BE is the only known precursor to esophageal adenocarcinoma, a highly lethal cancer with an increasing incidence over the last 5 decades. These revised guidelines implement Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the definition and diagnosis of BE, screening for BE and esophageal adenocarcinoma, surveillance of patients with known BE, and the medical and endoscopic treatment of BE and its associated early neoplasia. Important changes since the previous iteration of this guideline include a broadening of acceptable screening modalities for BE to include nonendoscopic methods, liberalized intervals for surveillance of short-segment BE, and volume criteria for endoscopic therapy centers for BE. We recommend endoscopic eradication therapy for patients with BE and high-grade dysplasia and those with BE and low-grade dysplasia. We propose structured surveillance intervals for patients with dysplastic BE after successful ablation based on the baseline degree of dysplasia. We could not make recommendations regarding chemoprevention or use of biomarkers in routine practice due to insufficient data.
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Al-Marhabi A, Hashem A, Zuberi BF, Onyekwere C, Lodhi I, Mounir M, Alkhowaiter S, Al Awadhi S, Naidoo VG, Hamada Y. The views of African and Middle Eastern Gastroenterologists on the management of mild-to-moderate, non-erosive gastro-esophageal reflux disease (GERD). Expert Rev Gastroenterol Hepatol 2022; 16:217-233. [PMID: 35184616 DOI: 10.1080/17474124.2022.2043744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 02/15/2022] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Gastro-esophageal reflux disease (GERD) is a common gastrointestinal disorder that occurs when backflow of the gastric contents into the esophagus results in troublesome symptoms. Though GERD has been extensively studied in Western populations, literature on the management of GERD in patients in Africa and Middle East (AME) is scarce. AREAS COVERED In this review, we provide an overview of the management of mild-to-moderate GERD in AME. Here we focus on the efficacy and safety of currently available treatments for GERD to help physicians and community pharmacists appropriately manage patients with mild-to-moderate GERD in the primary healthcare setting, detailing specific situations and patient scenarios that are relevant to the region, including management of GERD during Ramadan and post-bariatric surgery. EXPERT OPINION Under-appreciation of the burden of GERD in the region has resulted in a lack of consensus on management. Barriers that currently prevent the adoption of treatment guidelines in the primary healthcare setting may include lack of availability of local guidelines and referral systems, a paucity of region-specific research, and dogmatic adherence to traditional practice. By increasing awareness, strengthening knowledge, and by more effective utilization of resources, physicians and pharmacists could optimize GERD management strategies to better support patients.
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Affiliation(s)
- Ahmed Al-Marhabi
- Department of Internal Medicine, College of Medicine, Imam AbdulRahman Bin Faisal University, Khobar, Kingdom of Saudi Arabia
| | - Ahmed Hashem
- Endemic Medicine Department, Cairo University, Egypt
- Department of Medicine & Gastroenterology, Saudi German Hospital Jeddah, Jeddah, Kingdom of Saudi Arabia
| | - Bader Faiyaz Zuberi
- Department of Medicine & Gastroenterology, Dow University of Health Sciences, Karachi, Pakistan
| | - Charles Onyekwere
- Department of Medicine, Lagos State University College of Medicine, Lagos, Nigeria
| | - Imran Lodhi
- Global Medical Sciences, Reckitt Healthcare, London, UK
| | - Mohamed Mounir
- Regional Medical Affairs, Reckitt Benckiser (Arabia) FZE, Dubai, United Arab Emirates
| | - Saad Alkhowaiter
- Gastroenterology, King Saud University, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia
| | - Sameer Al Awadhi
- Digestive Diseases Unit, Rashid Hospital, Dubai, United Arab Emirates
| | - Vasudevan G Naidoo
- Department of Gastroenterology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
- Department of Gastroenterology, University of KwaZulu-Natal, Durban, South Africa
| | - Yasser Hamada
- Endemic Medicine Department, Cairo University, Egypt
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Feo-Ortega S, Lucendo AJ. Evidence-based treatments for eosinophilic esophagitis: insights for the clinician. Therap Adv Gastroenterol 2022; 15:17562848211068665. [PMID: 35069803 PMCID: PMC8777364 DOI: 10.1177/17562848211068665] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 12/03/2021] [Indexed: 02/04/2023] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Left untreated, EoE progresses to fibrous remodeling and stricture formation that impairs quality of life. Therefore, EoE requires either repeated treatments or maintenance therapy. Current guidelines recommend swallowed topical corticosteroids (STCs), proton-pump inhibitors (PPIs), or dietary intervention as initial options to induce and maintain long-term disease remission. Impractical exclusive elemental diets and suboptimal allergy testing-directed food avoidance paved the way for empirical elimination diets. These are moderately effective and highly reproducible in inducing EoE remission and allow for identification of specific food triggers. Step-up strategies, including two- and four-food rather than six-food elimination diets, should be considered as initial approaches for dietary treatment in patients of all ages, as they reduce the need for endoscopic procedures, shorten diagnostic processing time, and avoid unnecessary restrictions. Formulations of STC originally designed for asthma therapy are suboptimal for EoE treatment, with new effervescent orodispersible tablets and viscose formulations designed to coat the esophageal mucosa providing increased effectiveness at reduced doses. The anti-inflammatory effects of PPI in EoE are independent from gastric acid secretion inhibition; despite evidence from observational research, PPIs are the most commonly prescribed first-line therapy for EoE due to their accessibility, low cost, and safety profile. Double doses of PPI only induce remission in half of EoE patients, irrespective of the drug used or patients' age. Inflammatory rather than stricturing EoE phenotype and treatment duration up to 12 weeks increase chances of achieving EoE remission. Most responders effectively maintain long-term remission with standard PPI doses. Finally, endoscopic dilation should be considered in patients with reduced esophageal caliber or persistent dysphagia despite histological remission. This article provides a state-of-the-art review and updated discussion of current therapies and newly developed options for EoE.
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Affiliation(s)
- Sara Feo-Ortega
- Pediatric Gastroenterology Unit, Hospital
General de Tomelloso, Tomelloso, Spain, and Instituto de Investigación
Sanitaria de Castilla-La Mancha (IDISCAM)
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Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021. J Gastroenterol 2022; 57:267-285. [PMID: 35226174 PMCID: PMC8938399 DOI: 10.1007/s00535-022-01861-z] [Citation(s) in RCA: 122] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 02/03/2022] [Indexed: 02/06/2023]
Abstract
In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.
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Yang M, He Q, Gao F, Nirantharakumar K, Veenith T, Qin X, Page AT, Wong MCS, Huang J, Kuo ZC, Xia B, Zhang C, He Y, Meng W, Yuan J, Pan Y. Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials. BMC Med 2021; 19:316. [PMID: 34856983 PMCID: PMC8641218 DOI: 10.1186/s12916-021-02180-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. METHODS This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). RESULTS We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. CONCLUSIONS Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.
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Affiliation(s)
- Man Yang
- The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Qiangsheng He
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
| | - Fang Gao
- Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Krish Nirantharakumar
- Institute of Applied Health Research, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK
| | - Tonny Veenith
- Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Xiwen Qin
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Science, Monash University, Melbourne, Australia
- School of Population and Global Health, Faculty of Medicine, Density and Health Sciences, University of Western Australia, Perth, Australia
| | - Amy T Page
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Science, Monash University, Melbourne, Australia
| | - Martin C S Wong
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Junjie Huang
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Zi Chong Kuo
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
| | - Bin Xia
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
| | - Changhua Zhang
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
| | - Yulong He
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China
| | - Wenbo Meng
- The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu, China.
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
| | - Jinqiu Yuan
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
| | - Yihang Pan
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
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Kamal H, Sadr-Azodi O, Engstrand L, Brusselaers N. Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study. Hepatology 2021; 74:2021-2031. [PMID: 34018229 DOI: 10.1002/hep.31914] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 05/14/2021] [Accepted: 05/16/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. APPROACH AND RESULTS Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180 days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3 years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5 years of PPIs use, ruling out confounding by indication. CONCLUSIONS In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.
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Affiliation(s)
- Habiba Kamal
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Omid Sadr-Azodi
- Unit of Surgery, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Department of Surgery, Capio Saint Göran Hospital, Stockholm, Sweden
| | - Lars Engstrand
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
- Global Health Institute, Antwerp University, Antwerp, Belgium
| | - Nele Brusselaers
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
- Global Health Institute, Antwerp University, Antwerp, Belgium
- Department of Head and Skin, Ghent University Hospital, Ghent, Belgium
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Kang S, Cho SJ. Proton Pump Inhibitors and Gastric Cancer. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Concerns have been raised regarding the long-term use of proton pump inhibitors (PPIs) as an important risk factor for gastric cancer in clinical practice. PPIs can cause hypergastrinemia at clinical doses, and hypergastrinemia has been reported to induce malignant neoplasms in the stomach in previous animal studies. In humans, the proliferation of enterochromaffin-like (ECL) cells induced by hypergastrinemia is suspected as a potential mechanism of gastric cancer. Meanwhile, persistent Helicobacter pylori (H. pylori) infection causes gastric atrophic change, which itself is a major cause of gastric cancer, and it can further increase the risk of gastric cancer by strengthening corpus atrophy through interaction with PPIs. Recent epidemiologic studies have reported an important link between long-term PPI intake and gastric cancer risk even after successful eradication of H. pylori. However, due to the methodological limitations of observational clinical studies, the causal relationship is still not clear, and a recent big data-based study reported that long-term PPI use was not related to gastric cancer incidence. Taken together, despite the potential detrimental effects of PPIs, it is currently difficult to draw a definite conclusion about its association with gastric cancer. To minimize the possibility of gastric cancer in H. pylori-infected patients or precancerous lesions in long-term PPI users, long-term PPI administration should be limited to the minimum effective dose, and antibacterial treatment for H. pylori should be considered.
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Medina AL, Troendle DM, Park JY, Thaker A, Dunbar KB, Cheng E. Eosinophilic esophagitis, Barrett's esophagus and esophageal neoplasms in the pediatric patient: a narrative review. Transl Gastroenterol Hepatol 2021; 6:32. [PMID: 34423153 DOI: 10.21037/tgh-20-223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 07/31/2020] [Indexed: 01/07/2023] Open
Abstract
There are several esophageal disorders that can occur in the pediatric population. Eosinophilic esophagitis (EoE) is an eosinophil predominant inflammatory disease of the esophagus that was first characterized in the early 1900's. EoE is the most common pediatric esophageal inflammatory condition after gastroesophageal reflux disease (GERD). Longstanding GERD is a known risk factor for the development of Barrett's esophagus (BE) in both children and adults. BE is associated with the development of dysplasia and, if left undiagnosed, may progress to the development of esophageal adenocarcinoma (EAC). EAC and esophageal squamous cell carcinoma (ESCC) comprise the majority of childhood esophageal malignant neoplasms. The prevalence of EoE continues to rise within the pediatric population. On the other hand, both BE and esophageal neoplasms remain extremely rare in children. The relationship between a chronic inflammatory condition like EoE to BE and/or esophageal neoplasms remains unclear. The current research of these disease entities is prioritized to further understanding the disease pathogenesis and disease progression, exploring new diagnostic modalities, and developing novel treatments or less invasive therapeutic options. The focus of the following narrative review is to provide a summary of the current clinical practices, future research and their implications on these various esophageal disorders.
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Affiliation(s)
- Annette L Medina
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - David M Troendle
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jason Y Park
- Department of Pathology, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ameet Thaker
- Department of Pathology, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Kerry B Dunbar
- Division of Gastroenterology and Hepatology, Department of Medicine, Esophageal Diseases Center, Dallas VA Medical Center, VA North Texas Healthcare System, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Edaire Cheng
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Shu X, Zhu Z, Fu Y, Zhang Z, Wang J, Li X, He S, Fan H, Liu S, Zhang G, Tang J, Huang C, Du Q, Wang X, Xu B, Du Y, Chen Q, Wang B, Chen Y, Duan X, Xie Y, Huo L, Hou X, Lu N. Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial. Front Med (Lausanne) 2021; 8:690995. [PMID: 34336894 PMCID: PMC8317206 DOI: 10.3389/fmed.2021.690995] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 06/08/2021] [Indexed: 12/11/2022] Open
Abstract
Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole. Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated. Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -2.9% (95% CI, -16.5-10.7%), and -0.5% (95% CI, -13.5-12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -1.8% (95% CI, -19.8-16.3%), and 5.1% (95% CI, -12.2-22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group. Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.
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Affiliation(s)
- Xu Shu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhenhua Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yu Fu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhenyu Zhang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jiangbin Wang
- Department of Gastroenterology, China–Japan Union Hospital of Jilin University, Changchun, China
| | - Xing Li
- Department of Gastroenterology, Jiangxi Pingxiang People's Hospital, Pingxiang, China
| | - Shuixiang He
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Huizhen Fan
- Department of Gastroenterology, Yichun People's Hospital, Yichun, China
| | - Side Liu
- Department of Gastroenterology, Nanfang Hospital, Nanfang Medical University, Guangzhou, China
| | - Guoxin Zhang
- Department of Gastroenterology, Jiangsu Province Hospital, Nanjing, China
| | - Jianhua Tang
- Department of Gastroenterology, Ganzhou People's Hospital, Ganzhou, China
| | - Caibin Huang
- Department of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Qin Du
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoyan Wang
- Department of Gastroenterology, The Third Hospital of Central South University, Changsha, China
| | - Baohong Xu
- Department of Gastroenterology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Yiqi Du
- Department of Gastroenterology, Changhai Hospital, Shanghai, China
| | - Qikui Chen
- Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bangmao Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
| | - Ying Chen
- Clinical Development, Xuanzhu Biopharmaceutical Co., Ltd., Beijing, China
| | - Xianghui Duan
- Statistics, Xuanzhu Biopharmaceutical Co., Ltd., Beijing, China
| | - Yong Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Lijuan Huo
- Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaohua Hou
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nonghua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Sarnaik MK, Modi S, Pisipati Y, Vaidya S, Syed Gaggatur N, Sange AH, Srinivas N, Sange I. Proton Pump Inhibitors: Exploring Cardiovascular Complications and Prescription Protocol. Cureus 2021; 13:e16744. [PMID: 34354892 PMCID: PMC8328806 DOI: 10.7759/cureus.16744] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/29/2021] [Indexed: 11/05/2022] Open
Abstract
Proton pump inhibitors (PPIs) are among the most extensively prescribed medications internationally for gastroesophageal reflux disease treatment and the prevention of gastrointestinal bleeding. Their efficiency, ease of availability, and low side effect profile offer several advantages over other treatment modalities. Long-term use and inappropriate prescribing habits have increased the presence of this class of drugs, prompting several studies to reassess their adverse effects. This article explored the possibility of a relationship between PPIs and cardiovascular adverse effects while highlighting the current prescription guidelines for PPIs. We further examined the need for more research into the etiology of PPI-related cardiovascular adverse effects and strategies to alleviate these risks.
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Affiliation(s)
| | - Srimy Modi
- Internal Medicine, K. J. Somaiya Medical College, Mumbai, IND
| | | | - Sarayoo Vaidya
- Internal Medicine, M S Ramaiah Medical College, Bangalore, IND
| | | | - Aliya H Sange
- Internal Medicine, Dubai Medical College, Dubai, ARE
| | - Natasha Srinivas
- Internal Medicine, BGS Global Institute of Medical Sciences, Bangalore, IND
| | - Ibrahim Sange
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Medicine, K. J. Somaiya Medical College, Mumbai, IND
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Daniels MS, Park BI, McKay DL. Adverse Effects of Medications on Micronutrient Status: From Evidence to Guidelines. Annu Rev Nutr 2021; 41:411-431. [PMID: 34111363 DOI: 10.1146/annurev-nutr-120420-023854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Recent dietary reference intake workshops focusing on nutrient requirements in chronic disease populations have called attention to the potential adverse effects of chronic medication use on micronutrient status. Although this topic is mostly ill defined in the literature, several noteworthy drug-nutrient interactions (DNIs) are of clinical and public health significance. The purpose of this narrative review is to showcase classic examples of DNIs and their impact on micronutrient status, including those related to antidiabetic, anticoagulant, antihypertensive, antirheumatic, and gastric acid-suppressing medications. Purported DNIs related to other drug families, while relevant and worthy of discussion, are not included. Unlike previous publications, this review is primarily focused on DNIs that have sufficient evidence supporting their inclusion in US Food and Drug Administration labeling materials and/or professional guidelines. While the evidence is compelling, more high-quality research is needed to establish clear and quantitative relationships between chronic medication use and micronutrient status. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Michael S Daniels
- Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Massachusetts 02111, USA; , .,Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts 02111, USA;
| | - Brian I Park
- Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Massachusetts 02111, USA; , .,Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts 02111, USA;
| | - Diane L McKay
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts 02111, USA;
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Use of Proton Pump Inhibitors vs Histamine 2 Receptor Antagonists for the Risk of Gastric Cancer: Population-Based Cohort Study. Am J Gastroenterol 2021; 116:1211-1219. [PMID: 34074826 DOI: 10.14309/ajg.0000000000001167] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 12/29/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) are commonly prescribed medications. Long-term use of PPIs has been suspected to have a provocative effect on gastric cancer. This study was to determine the association between PPI vs histamine 2 receptor antagonist (H2RA) use and the risk of gastric cancer in a region where the risk of this malignancy is high. METHODS A population-based cohort study using the Korean National Health Insurance Services Database. The participants with first prescription of PPIs and H2RA with normal esophagogastroduodenoscopy finding from 2004 through 2015 were collected. Among them, 50% of participants were systematic stratified randomly sampled. There were 122,118 users of PPIs or H2RAs who use medication more than cumulative defined daily dose of 180 days. The users were followed up from long-term use threshold until gastric cancer, death from non-gastric cancer cause, gastric surgery, or study end (December 2017). RESULTS After calculating propensity score weights, we included 39,799 PPI and 38,967 H2RA users. Among the new PPI and H2RA users, we identified 411 cases of incident gastric cancer from 182,643 person-years of follow-up observation and 397 cases from 178,846 person-years of follow-up observation, respectively. Compared with H2RA users, PPI users did not experience significantly different gastric cancer incidence (adjusted hazard ratio, 1.01; 95% confidence interval, 0.88-1.16; P = 0.89). Sensitivity analyses confirmed that gastric cancer incidence did not differ between PPI and H2RA users. DISCUSSION In this large study, long-term treatment with PPIs vs H2RAs did not show higher risk of gastric cancer even in a high-risk region.
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Multiple Micronutrients, Including Zinc, Selenium and Iron, Are Positively Associated with Anemia in New Zealand Aged Care Residents. Nutrients 2021; 13:nu13041072. [PMID: 33806205 PMCID: PMC8066767 DOI: 10.3390/nu13041072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/30/2022] Open
Abstract
Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.
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Labenz J. [Conservative Therapy of Reflux Disease and its Limits]. Zentralbl Chir 2021; 146:176-187. [PMID: 33598907 DOI: 10.1055/a-1309-2368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Gastrooesophageal reflux disease (GORD) is common. Proton pump inhibitors (PPI) are regarded as first line therapy for all clinical manifestations. However, their efficacy is inadequate for at least 30% of patients and they are occasionally poorly tolerated. Moreover, some patients would prefer an alternative therapy. Alginate cause mechanical reflux inhibition by forming a gelatinous layer in the so-called acid pocket, an acid reservoir that forms on the surface of the chyme in the gastric corpus immediately after food intake. They may be used an alternative to treat the symptoms of uncomplicated GORD and as an add-on to PPIs if these do not improve symptoms adequately. If the reflux symptoms persist or if reflux oesophagitis does not heal, differentiated diagnostic testing must be performed, using endoscopy and functional analysis. Extraoesophageal manifestations of GORD include cough, compulsive clearing of the throat, problems with the voice and globus sensation. These often do not respond to antireflux therapy. Recent data indicate that these are complex hypersensitivity syndromes and that reflux is only one of several possible triggers.
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Affiliation(s)
- Joachim Labenz
- Innere Medizin, Diakonie Klinikum, Jung-Stilling-Krankenhaus Siegen, Deutschland
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Moayyedi P, El-Serag HB. Current Status of Chemoprevention in Barrett's Esophagus. Gastrointest Endosc Clin N Am 2021; 31:117-130. [PMID: 33213791 DOI: 10.1016/j.giec.2020.08.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Candidates for chemoprevention in Barrett's esophagus have long been suggested and there has been observational data to support many drugs, including statins, hormone replacement therapy, metformin, proton pump inhibitor therapy, and aspirin. Proton pump inhibitor therapy and aspirin are the most promising agents. Data suggest that aspirin and proton pump inhibitor therapy can decrease the risk of neoplastic progression in Barrett's esophagus. Further, the combination of aspirin and proton pump inhibitor therapy decrease all-cause mortality by approximately 33%. Future guideline groups need to evaluate the evidence rigorously, but the combination of proton pump inhibitor therapy and aspirin is promising.
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Affiliation(s)
- Paul Moayyedi
- McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
| | - Hashem B El-Serag
- Baylor College of Medicine Medical Center, McNair Campus (Clinic), 7200 Cambridge Street, 8th Floor, Suite 8B, Houston, TX 77030, USA
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Perry IE, Sonu I, Scarpignato C, Akiyama J, Hongo M, Vega KJ. Potential proton pump inhibitor-related adverse effects. Ann N Y Acad Sci 2020; 1481:43-58. [PMID: 32761834 DOI: 10.1111/nyas.14428] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/31/2020] [Accepted: 06/12/2020] [Indexed: 12/11/2022]
Abstract
Proton pump inhibitors (PPIs) are one of the most common medications taken by patients worldwide. PPIs are used to treat acid-related disorders, including gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection, and nonsteroidal anti-inflammatory drug/stress ulceration. For some of these diseases, long-term treatment is necessary. With such prolonged use, concern and investigation into potential adverse effects has increased. In addition, data are available regarding potential anticancer effects of PPIs, especially regarding solid tumors. The aim of this review is to assess the literature on PPIs with regard to common concerns, such as drug-drug interactions, the intestinal microbiome, dementia and central nervous system disease, and osteoporosis, as well as to highlight potential negative and positive impacts of the drug in cancer.
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Affiliation(s)
- Issac E Perry
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, Georgia
| | - Irene Sonu
- Division of Gastroenterology and Hepatology, Stanford University, Redwood City, California
| | - Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta
- Faculty of Medicine, Chinese University of Hong Kong, ShaTin, Hong Kong
| | - Junichi Akiyama
- Division of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Michio Hongo
- Department of Comprehensive Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
- Department of Medicine, Kurokawa General Hospital, Kurokawa, Miyagi, Japan
| | - Kenneth J Vega
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, Georgia
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Kanno T, Moayyedi P. Who Needs Gastroprotection in 2020? CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2020; 18:557-573. [PMID: 33199955 PMCID: PMC7656506 DOI: 10.1007/s11938-020-00316-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Accepted: 10/23/2020] [Indexed: 02/07/2023]
Abstract
Purpose of review Peptic ulcer disease (PUD) is a recognized complication of non-steroidal anti-inflammatory drugs (NSAIDs). Stress ulcers are a concern for intensive care unit (ICU) patients; PUD is also an issue for patients taking anticoagulation. Helicobacter pylori test and treat is an option for patients starting NSAID therapy, and proton pump inhibitors (PPIs) may reduce PUD in NSAID patients and other high-risk groups. Recent findings There are a large number of trials that demonstrate that Helicobacter pylori eradication reduces PUD in NSAID patients. PPI is also effective at reducing PUD in this group and is also effective in ICU patients and those on anticoagulants. The effect is too modest for PPI to be recommended in everyone, and more research is needed as to which groups would benefit the most. Increasing age, past history of PUD, and comorbidity are the most important risk factors. Summary H. pylori test and treat should be offered to older patients starting NSAIDS, while PPIs should be prescribed to patients that are at high risk of developing PUD and at risk of dying from PUD complications.
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Affiliation(s)
- Takeshi Kanno
- Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 Japan
- Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Ontario Canada
| | - Paul Moayyedi
- Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Ontario Canada
- Audrey Campbell Chair of Ulcerative Colitis Research, Division of Gastroenterology, Department of Medicine, McMaster University, 1280 Main St. W. HSC 3V3, Hamilton, ON L8S 4K1 Canada
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[Gastro-oesophageal reflux disease-update 2021]. Internist (Berl) 2020; 61:1249-1263. [PMID: 33112963 DOI: 10.1007/s00108-020-00890-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Gastro-oesophageal reflux disease (GORD), a highly prevalent disease, is defined by troublesome symptoms and/or oesophageal lesions caused by reflux of gastric content. A diagnostic gold standard does not exist. A reliable diagnosis may be difficult in individual cases. Patients' history, endoscopic findings and pH-impedance monitoring contribute to the evaluation of gastro-oesophageal reflux and its consequences. High-resolution manometry may add important information on the pathophysiology of the disease and may help to rule out motility disorders as the leading cause of the symptoms. Proton pump inhibitors (PPI) are the drugs of first choice. In patients with insufficient PPI response, optimization of PPI therapy and/or combination with drugs having another mechanism of action are the available options. If PPIs are not sufficiently effective, not tolerated, or not wished antireflux procedures may be offered in specialized centers taking pathophysiological data into account.
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Trinh VQH, Shi C, Ma C. Gastric neuroendocrine tumours from long-term proton pump inhibitor users are indolent tumours with good prognosis. Histopathology 2020; 77:865-876. [PMID: 32702178 DOI: 10.1111/his.14220] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/07/2020] [Accepted: 07/21/2020] [Indexed: 12/14/2022]
Abstract
AIMS Proton pump inhibitors (PPIs) are among the most widely used medications in the United States. Most PPI users have persistent hypergastrinaemia during treatment. However, gastric neuroendocrine tumours diagnosed in long-term PPI users are rarely reported. Their clinicopathological features and prognosis are not characterised. It remains unclear whether or not they can be classified as Type III sporadic tumours. METHODS AND RESULTS We retrospectively characterised 66 gastric neuroendocrine tumours from patients without atrophic gastritis and gastrinoma from two tertiary care medical centres, including 38 tumours in patients who had used PPIs for at least 1 year and 28 tumours from patients without long-term PPI use (control group, Type III tumours). Compared to controls, tumours from long-term PPI users tended to be in the pT1-2 category (98% versus 79%, P = 0.09) and less often invaded the serosa (3% versus 18%, P = 0.08) or lymphovascular spaces (11% versus 32%, P = 0.06). Using Kaplan-Meier analysis, long-term PPI users had significantly longer overall survival than controls (P = 0.035). While three control patients developed distant metastasis and seven died, long-term PPI users were without distant metastasis (P = 0.06) or death (P = 0.002) during follow-up. However, five long-term PPI users developed additional gastric neuroendocrine tumour(s), while none of the controls did (P = 0.07). CONCLUSIONS Our results show that gastric neuroendocrine tumours of long-term PPI users are probably less aggressive compared to Type III sporadic tumours and have an indolent disease course. Our findings support the classification of gastric neuroendocrine tumours in long-term PPI users as a separate subtype.
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Affiliation(s)
- Vincent Q-H Trinh
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Chanjuan Shi
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Changqing Ma
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Dhar A, Maw F, Dallal HJ, Attwood S. Side effects of drug treatments for gastro-oesophageal reflux disease: current controversies. Frontline Gastroenterol 2020; 13:45-49. [PMID: 34966532 PMCID: PMC8666855 DOI: 10.1136/flgastro-2019-101386] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 07/28/2020] [Accepted: 07/28/2020] [Indexed: 02/06/2023] Open
Abstract
The two main drugs used in the treatment of gastro-oesophageal reflux disease are proton pump inhibitors and histamine-2 receptor antagonists and both these agents have been implicated in a number of adverse effects, leading to considerable controversies related to their long-term use. This paper is aimed at a critical review of the published literature and the clinical significance of these reported side effects, most of which are associations rather than causal.
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Affiliation(s)
- Anjan Dhar
- Gastroenterology, County Durham & Darlington NHS Foundation Trust, Darlington, UK
| | - Frances Maw
- Pharmacy, County Durham and Darlington NHS Foundation Trust, Darlington, Darlington, UK
| | - Helen Jane Dallal
- Gastroenterology, County Durham & Darlington NHS Foundation Trust, Darlington, UK
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Latest insights into the hot question of proton pump inhibitor safety - a narrative review. Dig Liver Dis 2020; 52:842-852. [PMID: 32513631 DOI: 10.1016/j.dld.2020.04.020] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/14/2020] [Accepted: 04/17/2020] [Indexed: 02/06/2023]
Abstract
Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide and their use is continuously increasing. Although they have been shown to combine high therapeutic efficacy and good safety profile in many studies, in last years we have witnessed the publication of many articles reporting the possible association of long-term PPI therapy with important unexpected adverse events and these observations have created alarmism in both patients and physicians. However, the majority of these studies are observational, retrospective and prone to residual confounding. Also, the odds ratio values are generally comprised between 1 and 2 and therefore devoid of strong clinical relevance. As it is unlikely that prospective randomized trials will be ever done to reinforce these associations, we can only attempt to distinguish clear- from unclear-defined adverse events from the available literature. Nowadays we can reasonably exclude cardiovascular diseases, community-acquired pneumonia, all-cause mortality, dementia and bone fractures from PPI-related adverse events. However, physicians should be aware of the existence of possible risks when treating their patients, especially the elderly and frail ones, with long-term PPIs, which should be prescribed only to persons with defined indications and at lowest dose and duration.
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Abstract
PURPOSE OF REVIEW Proton pump inhibitors (PPIs) are widely prescribed and have excellent short-term tolerability. Administrative database studies have highlighted that many diseases are associated with PPI therapy including pneumonia, fracture, cardiovascular disease, and all-cause mortality. This review therefore reviews the evidence of the risks and benefits of these drugs. RECENT FINDINGS There is high-to-moderate quality evidence that PPIs are effective at treating many acid-related disorders. Recent randomized trials have suggested that the associations between PPIs and various diseases are likely to be related to bias and residual confounding and these drugs appear to be safe apart from a possible increased risk of enteric infections. SUMMARY PPIs should be used at the lowest dose and for the shortest duration possible. They are still relatively well-tolerated drugs but should only be prescribed for proven indications.
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Gutiérrez Junquera C, Fernández Fernández S, Domínguez-Ortega G, Vila Miravet V, García Puig R, García Romero R, Fernández de Valderrama A, Andradas Rivas R, Alonso Vicente C, Álvarez Beltrán M, Barrio Torres J, Barros García P, Colomé Rivero G, Javier Eizaguirre Arocena F, Fernández Caamaño B, Orden Izquierdo EL, Leis Trabazo R, Lorenzo Garrido H, Medina Benítez E, Montraveta Querol M, Vecino López R. Recommendations for the diagnosis and practical management of paediatric eosinophilic oesophagitis. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2020. [DOI: 10.1016/j.anpede.2020.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Gutiérrez Junquera C, Fernández Fernández S, Domínguez-Ortega G, Vila Miravet V, García Puig R, García Romero R, Fernández de Valderrama A, Andradas Rivas R. [Recommendations for the diagnosis and practical management of paediatric eosinophilic oesophagitis]. An Pediatr (Barc) 2020; 92:376.e1-376.e10. [PMID: 32471747 DOI: 10.1016/j.anpedi.2020.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 04/05/2020] [Accepted: 04/06/2020] [Indexed: 11/26/2022] Open
Abstract
Eosinophilic oesophagitis is an emerging and chronic disorder mediated by the immune system, and is characterised by symptoms of oesophageal dysfunction and inflammation with isolated eosinophil infiltration in the oesophagus. It is more common in males and in atopic subjects, and the symptoms vary with age. In younger children, there is vomiting, abdominal pain and dietary problems, with dysphagia and food impaction in older children and adolescents. The diagnosis is based on the presence of symptoms and oesophageal inflammation with ≥ 15 eosinophils / high power field, and after ruling out other causes of oesophageal eosinophilia. Without treatment, the disease usually persists and can progress to fibrostenotic forms more common in adults. The treatment options included proton pump inhibitors, empirical elimination diets, and swallowed topical corticosteroids. Maintenance therapy is advisable after the induction treatment. Diet is the only treatment that is directed at the cause of the disease, on identifying the triggering food or foods. The response to the treatments requires a histological assessment due to the poor agreement between the symptoms and the oesophageal inflammation. The practical management of Eosinophilic oesophagitis presents with challenges, due to, among other causes, the current lack of availability of specific drugs, and to its approach with, occasionally complex, diet treatments. The present document, prepared by the Working Group on Eosinophilic Gastrointestinal Disorders of the Spanish Society of Paediatric Gastroenterology, Hepatology and Nutrition, has as its objective to help in the diagnostic and therapeutic approach to paediatric eosinophilic oesophagitis, based on the recent evidence-based consensus guidelines.
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Affiliation(s)
| | | | | | - Víctor Vila Miravet
- Gastroenterología Pediátrica, Hospital Universitario Maternoinfantil San Joan de Deu, Barcelona, España
| | - Roger García Puig
- Gastroenterología Pediátrica, Hospital Universitario Mutua Terrassa, Barcelona, España
| | - Ruth García Romero
- Gastroenterología Pediátrica, Hospital Infantil Universitario Miguel Servet, Zaragoza, España
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Tsai C, Steffen R, Kessler U, Merki H, Lipham J, Zehetner J. Postoperative Dysphagia Following Magnetic Sphincter Augmentation for Gastroesophageal Reflux Disease. Surg Laparosc Endosc Percutan Tech 2020; 30:322-326. [DOI: 10.1097/sle.0000000000000785] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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Schnoll-Sussman F, Niec R, Katz PO. Proton Pump Inhibitors: The Good, Bad, and Ugly. Gastrointest Endosc Clin N Am 2020; 30:239-251. [PMID: 32146944 DOI: 10.1016/j.giec.2019.12.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Proton pump inhibitors (PPIs) continue to be the medication of choice for treatment of acid-related disease, with few if any overt side effects seen with daily use. They are often prescribed empirically, often in high doses and with many patients being treated with multiple PPIs without an objective diagnosis. Therefore, they are believed to be overprescribed and used without indication. In this article we discuss the appropriate clinical indications for PPIs, review in detail the major associated adverse events, and put in perspective key issues in balancing benefits and risk of this exceptional (and safe) class of drug.
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Affiliation(s)
- Felice Schnoll-Sussman
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1315 York Avenue, New York City, NY 10021, USA
| | - Rachel Niec
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1315 York Avenue, New York City, NY 10021, USA
| | - Philip O Katz
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1315 York Avenue, New York City, NY 10021, USA.
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Madison AA, Woody A, Bailey B, Lustberg MB, Ramaswamy B, Wesolowski R, Williams N, Reinbolt R, VanDeusen JB, Sardesai S, Malarkey WB, Kiecolt-Glaser JK. Cognitive problems of breast cancer survivors on proton pump inhibitors. J Cancer Surviv 2020; 14:226-234. [PMID: 31933149 PMCID: PMC7183896 DOI: 10.1007/s11764-019-00815-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 10/01/2019] [Indexed: 12/20/2022]
Abstract
PURPOSE Proton pump inhibitors (PPIs) are used in cancer patients to manage treatment-related gastrointestinal symptoms and to prevent damage to the gastric mucosal lining during treatment. However, PPI use may contribute to cognitive problems. To compare PPI-users and non-users, breast cancer survivors reported cognitive problems in three studies. METHODS In Study 1, breast cancer survivors (N = 209; n = 173 non-users, n = 36 PPI-users; stages 0-IIIC) rated their cognitive function on the Kohli scale prior to cancer treatment, as well as one and two years later. In Study 2, women (N = 200; n = 169 non-users, n = 31 PPI-users, stages 0-IIIa, M = 11 months post-treatment) rated their cognitive function on the Kohli scale and BCPT checklist at three visits over a six-month period. In Study 3, participants (N = 142; n = 121 non-users, n = 21 PPI-users; stages I-IIIa, M = 4 years post-treatment) rated their cognitive function on the Kohli scale, BCPT checklist, and Functional Assessment of Cancer Therapy cognitive scale (FACT-cog). RESULTS In Study 1, PPI-users reported more severe concentration problems (p = 0.039) but not memory problems (p = 0.17) than non-users. In Study 2, PPI-users reported more severe concentration problems (p = 0.022) than non-users, but not memory problems or symptoms on the BCPT (ps = 0.11). Study 3's PPI-users reported more severe memory problems (p = 0.002), poorer overall cognitive function (p = 0.006), lower quality of life related to cognitive problems (p = 0.005), greater perceived cognitive impairment (p = 0.013), and poorer cognitive abilities (p = 0.046), but not more severe concentration problems (p = 0.16), compared to non-users. CONCLUSIONS/IMPLICATIONS PPI use may impair breast cancer survivors' memory, concentration, and quality of life.
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Affiliation(s)
- Annelise A Madison
- Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Drive, Columbus, OH, 43210, USA
- Department of Psychology, The Ohio State University, 1835 Neil Avenue, Columbus, OH, 43210, USA
| | - Alex Woody
- Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Drive, Columbus, OH, 43210, USA
| | - Brittney Bailey
- Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Drive, Columbus, OH, 43210, USA
| | - Maryam B Lustberg
- The Ohio State University Comprehensive Cancer Center, 4460 West 10th Avenue, Columbus, OH, 43210, USA
| | - Bhuvaneswari Ramaswamy
- The Ohio State University Comprehensive Cancer Center, 4460 West 10th Avenue, Columbus, OH, 43210, USA
| | - Robert Wesolowski
- The Ohio State University Comprehensive Cancer Center, 4460 West 10th Avenue, Columbus, OH, 43210, USA
| | - Nicole Williams
- The Ohio State University Comprehensive Cancer Center, 4460 West 10th Avenue, Columbus, OH, 43210, USA
| | - Raquel Reinbolt
- The Ohio State University Comprehensive Cancer Center, 4460 West 10th Avenue, Columbus, OH, 43210, USA
| | - Jeffrey B VanDeusen
- The Ohio State University Comprehensive Cancer Center, 4460 West 10th Avenue, Columbus, OH, 43210, USA
| | - Sagar Sardesai
- The Ohio State University Comprehensive Cancer Center, 4460 West 10th Avenue, Columbus, OH, 43210, USA
| | - William B Malarkey
- Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Drive, Columbus, OH, 43210, USA
- Department of Internal Medicine, The Ohio State University, 395 West 12th Avenue, Columbus, OH, 43210, USA
| | - Janice K Kiecolt-Glaser
- Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Drive, Columbus, OH, 43210, USA.
- Department of Psychiatry and Behavioral Health, The Ohio State University, 1670 Upham Drive, Columbus, OH, 43210, USA.
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Paz MFCJ, de Alencar MVOB, de Lima RMP, Sobral ALP, do Nascimento GTM, dos Reis CA, Coêlho MDPSDS, do Nascimento MLLB, Gomes Júnior AL, Machado KDC, de Menezes AAPM, de Lima RMT, de Oliveira Filho JWG, Dias ACS, dos Reis AC, da Mata AMOF, Machado SA, Sousa CDDC, da Silva FCC, Islam MT, de Castro e Sousa JM, Melo Cavalcante AADC. Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:3457890. [PMID: 32308801 PMCID: PMC7146093 DOI: 10.1155/2020/3457890] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 10/19/2019] [Accepted: 11/21/2019] [Indexed: 12/15/2022]
Abstract
Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.
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Affiliation(s)
- Márcia Fernanda Correia Jardim Paz
- Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, PI, Brazil
- Laboratory of Genetic Toxicity, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil
| | | | | | - André Luiz Pinho Sobral
- Laboratory of Genetic Toxicity, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil
- University Hospital, Teresina, PI, Brazil
| | | | | | | | | | - Antonio Luiz Gomes Júnior
- Laboratory of Genetic Toxicity, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil
- University Centre UNINOVAFAPI, Teresina, PI, Brazil
| | | | | | - Rosália Maria Torres de Lima
- Laboratory of Genetic Toxicity, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil
| | | | - Ana Carolina Soares Dias
- Laboratory of Genetics and Molecular Biology, Federal University of Maranhão, São Luís, MA, Brazil
| | - Antonielly Campinho dos Reis
- Laboratory of Genetic Toxicity, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil
| | | | | | | | - Felipe Cavalcanti Carneiro da Silva
- Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, PI, Brazil
- Department of Biological Sciences, Federal University of Piauí, Picos, PI, Brazil
| | - Muhammad Torequl Islam
- Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam
| | | | - Ana Amélia de Carvalho Melo Cavalcante
- Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, PI, Brazil
- Laboratory of Genetic Toxicity, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil
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Alkhushaym N, Almutairi AR, Althagafi A, Fallatah SB, Oh M, Martin JR, Babiker HM, McBride A, Abraham I. Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis. Expert Opin Drug Saf 2020; 19:327-334. [PMID: 31928106 DOI: 10.1080/14740338.2020.1715939] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 01/10/2020] [Indexed: 02/07/2023]
Abstract
Objectives: To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.Methods: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.Results: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12-2.72, I2 = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98-14.703, I2 = 87.9%).Conclusion: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.
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Affiliation(s)
- Nasser Alkhushaym
- Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- Department of Clinical Pharmacy, Royal Commission Health Services Program, Jubail, Saudi Arabia
| | - Abdulaali R Almutairi
- Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- SFD-Drug sector, Saudi Food and Drug Authority, Riyadh, Saudi Arabia
| | - Abdulhamid Althagafi
- Clinical Pharmacy Department, College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Saad B Fallatah
- Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- Clinical and Hospital Pharmacy Department, College of Pharmacy, Taibah University, Medina, Saudi Arabia
| | - Mok Oh
- Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
| | - Jennifer R Martin
- Arizona Health Sciences Library, The University of Arizona, Tucson, AZ, USA
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
| | - Hani M Babiker
- Department of Hematology & Oncology, College of Medicine, The University of Arizona, Tucson, AZ, USA
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
| | - Ali McBride
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- University of Arizona Cancer Center, Tucson, AZ, USA
| | - Ivo Abraham
- Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
- Department of Family and Community Medicine, College of Medicine, The University of Arizona, Tucson, AZ, USA
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