|
1
|
Waldum H, Modlin I. The central role of gastrin in Helicobacter pylori gastric carcinogenesis. Scand J Gastroenterol 2025:1-12. [PMID: 40411354 DOI: 10.1080/00365521.2025.2509094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2025] [Revised: 05/14/2025] [Accepted: 05/15/2025] [Indexed: 05/26/2025]
Abstract
Gastric cancer is still a prevalent and lethal cancer. Gastric hypoacidity and gastritis have long been recognized in the pathogenesis. The identification of Helicobacter(H.) pylori as the main cause of gastritis leading to peptic ulcer disease and gastric cancer was a breakthrough. H. pylori was the first bacterium accepted as a carcinogen. The mechanism was not found before H. pylori was shown to predispose to cancer only after having induced oxyntic atrophy incriminating reduced killing of microorganisms and/or secondary hypergastrinemia. H. pylori has an uncertain carcinogenic role in cardia cancer, making microbes more unlikely. Gastrin has a trophic effect on the oxyntic mucosa, particularly on the enterochromaffin like cell carrying the gastrin receptor. Every condition with long-term hypergastrinemia in whatever species predisposes to gastric neoplasia. All observations on gastric neoplasia connected to H. pylori gastritis (the protective effect of duodenal ulcer, increased risk with oxyntic atrophy and preserved risk after loss of H. pylori in complete oxyntic atrophy) may be explained by gastrin. The role of gastrin in gastric carcinogenesis is also reflected by autoimmune gastritis and profound long-term gastric acid inhibition.
Collapse
Affiliation(s)
- Helge Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Irvin Modlin
- School of Medicine, FCS (RSA) Emeritus Prof Yale University, New Haven, CT, USA
| |
Collapse
|
|
2
|
Song Y, Chen E, Chiang YJ, Yao JC, Halperin DM, Chatterjee D, Badgwell BD. Classification of Gastric Neuroendocrine Tumors and Associations With Survival. J Surg Oncol 2025; 131:204-211. [PMID: 39257200 DOI: 10.1002/jso.27876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 08/11/2024] [Indexed: 09/12/2024]
Abstract
BACKGROUND AND OBJECTIVES Not all gastric neuroendocrine tumors (GNETs) may be classified into one of the three described clinicopathologic subtypes. The purpose of this study was to better characterize GNET subtypes and associated outcomes. METHODS Patients treated for GNET at our institution (1995-2021) were identified. Pathologic specimens of tumors that could not be classified as type 1, 2, or 3 were further reviewed. GNETs were categorized as proton pump inhibitor (PPI)-associated based on changes in the background gastric mucosa consistent with PPI use. Distant metastasis at presentation (DM) and disease-specific survival (DSS) were evaluated. RESULTS Among 246 patients, there were 164 (67%) type 1, 5 (2%) type 2, 52 (21%) type 3, and 18 (7%) PPI-associated GNETs. Seven (3%) tumors remained unclassified. DM was more frequent with type 3 GNETs (38%) than type 1 (1%), type 2 (20%), or PPI-associated tumors (11%, p < 0.001). Ten-year DSS rates were 100% for type 1, 53% (95% confidence interval [CI], 38%-75%) for type 3, and 80% (95% CI, 58%-100%) for PPI-associated tumors (p < 0.001). GNET subtype, race, and DM were independently associated with DSS. CONCLUSIONS PPI-associated tumors may represent a distinct GNET subtype with intermediate outcomes. Other factors should also be considered in overall prognosis.
Collapse
Affiliation(s)
- Yun Song
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Eunise Chen
- Department of Surgery, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - James C Yao
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Daniel M Halperin
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Deyali Chatterjee
- Department of Anatomical Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Brian D Badgwell
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| |
Collapse
|
|
3
|
Nagao S, Yabuuchi Y, Tanaka K, Morihisa Y, Kobayashi T, Akiyama S, Tanke G, Wada M, Morita S, Inoue S, Hobyung C, Yamashita D, Inokuma T. Multiple Gastric Neuroendocrine Tumors Associated with Long-term Use of a Proton Pump Inhibitor and a Potassium-competitive Acid Blocker. Intern Med 2024; 63:2001-2010. [PMID: 38008447 PMCID: PMC11309866 DOI: 10.2169/internalmedicine.2857-23] [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: 08/31/2023] [Accepted: 10/09/2023] [Indexed: 11/28/2023] Open
Abstract
A 52-year-old man who had been using a proton pump inhibitor (PPI) and a potassium-competitive acid blocker (P-CAB) for 14 years underwent esophagogastroduodenoscopy and was found to have three neuroendocrine tumors (NETs) in the gastric body. Following detailed examinations, parietal cell dysfunction was excluded, and the NETs did not meet the criteria for the Rindi classification types I-III. The lesions were ultimately considered to be associated with the long-term use of the PPI and P-CAB. We performed endoscopic submucosal dissection of the lesions, with no recurrence or new lesions noted after discontinuation of the PPI and P-CAB.
Collapse
Affiliation(s)
- Soichiro Nagao
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Yohei Yabuuchi
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Kosuke Tanaka
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Yoshiki Morihisa
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Takuya Kobayashi
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Shinsuke Akiyama
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Gensho Tanke
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Masaya Wada
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Shuko Morita
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Satoko Inoue
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Chung Hobyung
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| | - Daisuke Yamashita
- Department of Pathology, Kobe City Medical Center General Hospital, Japan
| | - Tetsuro Inokuma
- Department of Gastroenterology, Kobe City Medical Center General Hospital, Japan
| |
Collapse
|
|
4
|
Sawaid IO, Samson AO. Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence. J Clin Med 2024; 13:1970. [PMID: 38610738 PMCID: PMC11012754 DOI: 10.3390/jcm13071970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 03/14/2024] [Accepted: 03/14/2024] [Indexed: 04/14/2024] Open
Abstract
Background: Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. Methods: First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Results: Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.
Collapse
Affiliation(s)
| | - Abraham O. Samson
- Azrieli Faculty of Medicine, Bar Ilan University, Safed 1311502, Israel;
| |
Collapse
|
|
5
|
Modica R, Liccardi A, Minotta R, Cannavale G, Benevento E, Colao A. Current understanding of pathogenetic mechanisms in neuroendocrine neoplasms. Expert Rev Endocrinol Metab 2024; 19:49-61. [PMID: 37936421 DOI: 10.1080/17446651.2023.2279540] [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: 05/25/2023] [Accepted: 11/01/2023] [Indexed: 11/09/2023]
Abstract
INTRODUCTION Despite the fact that important advances in research on neuroendocrine neoplasms (NENs) have been made, consistent data about their pathogenetic mechanism are still lacking. Furthermore, different primary sites may recognize different pathogenetic mechanisms. AREAS COVERED This review analyzes the possible biological and molecular mechanisms that may lead to NEN onset and progression in different organs. Through extensive research of the literature, risk factors including hypercholesterolemia, inflammatory bowel disease, chronic atrophic gastritis are evaluated as potential pathogenetic mechanisms. Consistent evidence is available regarding sporadic gastric NENs and MEN1 related duodenopancreatic NENs precursor lesions, and genetic-epigenetic mutations may play a pivotal role in tumor development and bone metastases onset. In lung neuroendocrine tumors (NETs), diffuse proliferation of neuroendocrine cells on the bronchial wall (DIPNECH) has been proposed as a premalignant lesion, while in lung neuroendocrine carcinoma nicotine and smoke could be responsible for carcinogenic processes. Also, rare primary NENs such as thymic (T-NENs) and Merkel cell carcinoma (MCC) have been analyzed, finding different possible pathogenetic mechanisms. EXPERT OPINION New technologies in genomics and epigenomics are bringing new light to the pathogenetic landscape of NENs, but further studies are needed to improve both prevention and treatment in these heterogeneous neoplasms.
Collapse
Affiliation(s)
- Roberta Modica
- Endocrinology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Napoli, Italy
| | - Alessia Liccardi
- Endocrinology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Napoli, Italy
| | - Roberto Minotta
- Endocrinology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Napoli, Italy
| | - Giuseppe Cannavale
- Endocrinology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Napoli, Italy
| | - Elio Benevento
- Endocrinology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Napoli, Italy
| | - Annamaria Colao
- Endocrinology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Napoli, Italy
- UNESCO Chair "Education for Health and Sustainable Development, " Federico II University, Naples, Italy
| |
Collapse
|
|
6
|
Waldum H, Mjønes P. The central role of gastrin in gastric cancer. Front Oncol 2023; 13:1176673. [PMID: 37941554 PMCID: PMC10628637 DOI: 10.3389/fonc.2023.1176673] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 09/19/2023] [Indexed: 11/10/2023] Open
Abstract
The prevalence of gastric cancer has markedly declined, but due to the high mortality rates associated with gastric cancer, it is still a serious disease. The preferred classification of gastric cancer is according to Lauren into either the intestinal type, which has a glandular growth pattern, or the diffuse type, which does not have glandular structures. Both types have been classified as adenocarcinomas, with the latter type based on periodic acid-Schiff (PAS) positivity presumed to reflect mucin. However, the presence of mucin in the diffuse type, in contrast to neuroendocrine/enterochromaffin-like (ECL) cell markers, has not been confirmed by immunohistochemistry and in situ hybridization. The ECL cells are probably prone to becoming cancerous because they do not express E-cadherin. Gastric cancer is unique in that a bacterium, Helicobacter pylori, is thought to be its main cause. H. pylori predisposes infected individuals to cancer only after having caused oxyntic atrophy leading to gastric hypoacidity and hypergastrinemia. No single H. pylori factor has been convincingly proved to be carcinogenic. It is probable that gastrin is the pathogenetic factor for gastric cancer due to H. pylori, autoimmune gastritis, and long-term prolonged inhibition of gastric acid secretion. Hypergastrinemia induces ECL cell hyperplasia, which develops into neuroendocrine tumors (NETs) and then into neuroendocrine carcinomas in rodents, a sequence that has also been described in humans. During carcinogenesis, the tumor cells lose specific traits, requiring that sensitive methods be used to recognize their origin. Gastric cancer occurrence may hopefully be prevented by H. pylori eradication at a young age, and by the reduced use of inhibitors of acid secretion and use of a gastrin antagonist in those with previous long-term H. pylori infection and those with autoimmune gastritis.
Collapse
Affiliation(s)
- Helge Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Patricia Mjønes
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Pathology, St. Olav’s Hospital – Trondheim University Hospital, Trondheim, Norway
| |
Collapse
|
|
7
|
Baiardi G, Calvini G, Panarello S, Fioravanti C, Stella M, Martelli A, Antonucci G, Mattioli F. Prescriptive Appropriateness: Inhospital Adherence to Proton Pump Inhibitors Deprescription Flow Chart. Pharmaceuticals (Basel) 2023; 16:ph16050635. [PMID: 37242418 DOI: 10.3390/ph16050635] [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: 03/21/2023] [Revised: 04/13/2023] [Accepted: 04/20/2023] [Indexed: 05/28/2023] Open
Abstract
The prescriptive appropriateness of Proton Pump Inhibitors (PPIs) in polypharmacy is controversial. PPIs are often overprescribed and the risk of prescribing errors and adverse drug reactions increases for each additional drug added to therapy. Hence, guided deprescription should be considered and easily implementable in ward practice. This observational prospective study evaluated the implementation of a validated PPIs deprescription flow chart to real-life internal ward activity through the presence of a clinical pharmacologist as an enhancing additional factor by assessment of inhospital prescriber's adherence to the proposed flow chart. Patients' demographics and prescribing trends of PPIs prescriptions were analyzed by descriptive statistics. The final analysis of data included ninety-eight patients (forty-nine male and forty-nine female), aging 75.6 ± 10.6 years; 55.1% of patients had home-PPIs prescriptions, while 44.9% received inhospital-PPIs prescriptions. Evaluation of prescriber's adherence to the flow chart revealed that the percentage of patients with a prescriptive/deprescriptive pathway conforming to that of the flow chart was 70.4%, with low symptomatologic recurrences. The clinical pharmacologists' presence and influence in ward activity may have contributed to this finding, since continuous training of the prescribing physicians is deemed a success-related factor in the deprescribing strategy. Multidisciplinary management of PPIs deprescription protocols shows high adherence by prescribers in real-life hospital settings and low recurrence events.
Collapse
Affiliation(s)
- Giammarco Baiardi
- Clinical Pharmacology Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
- Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy
| | - Giulia Calvini
- Clinical Pharmacology Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
- Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy
| | - Serena Panarello
- Internal Medicine Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
| | - Chiara Fioravanti
- Internal Medicine Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
| | - Manuela Stella
- Clinical Pharmacology Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
- Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy
| | - Antonietta Martelli
- Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy
| | - Giancarlo Antonucci
- Internal Medicine Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
| | - Francesca Mattioli
- Clinical Pharmacology Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
- Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy
| |
Collapse
|
|
8
|
Metastatic multiple gastric neuroendocrine tumors with a long history of proton pump inhibitor use: A case report. JOURNAL OF SURGERY AND MEDICINE 2022. [DOI: 10.28982/josam.1038661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
It is widely accepted that gastric neuroendocrine tumors (NETs) develop due to enterochromaffin-like (ECL) cell proliferation following exposure to hypergastrinemia, which causes hyperplastic-dysplastic-neoplastic changes. Here we describe the case of a 46-year-old female patient diagnosed with metastatic NETs by liver biopsy and evaluated at an external center. At our hospital, nodular structures extending from the cardia to the antrum were observed by gastroscopy, considered the primary tumor focus. Histopathological examination revealed a trabecular-insular pattern, with microNETs consisting of monotone cells with round-oval nuclei and surrounding neuroendocrine cell hyperplasia foci and fundic gland polyps. The patient had a history of regular proton pump inhibitor (PPI) use for 10 years and a serum gastrin of 9240 pg/mL. A 3-cm metastatic lesion in the left lobe of the liver was observed in whole-body imaging with octreotide. By gastrectomy, we observed a large number of nodular lesions in the corpus-antrum and a 3-cm diameter lesion in the hepatectomy material. Histopathological examination revealed NETs in multiple foci with submucosal invasion in the stomach. The Ki-67 proliferative index was 3%. Metastatic tumors of similar morphology were found in the liver and three of the greater curvature lymph nodes. We made a diagnosis of multiple gastric NETs (Grade 2). In Type I gastric NETs, the neuroendocrine cell proliferation spectrum up to NET is observed as a result of hypergastrinemia due to atrophic gastritis. Also, in experimental studies, prolonged hypergastrinemia has been reported to cause ECL cell neoplasms in animals treated with PPIs. Although our case could be accepted as Type 1 NET, the possibility of developing NET secondary to long-term PPI use should also be considered.
Collapse
|
|
9
|
Gong EJ, Bang CS, Kim DK, Lee JJ, Baik GH. Use of Proton Pump Inhibitors and the Risk for the Development of Gastric Cancers: A Nationwide Population-Based Cohort Study Using Balanced Operational Definitions. Cancers (Basel) 2022; 14:5172. [PMID: 36291956 PMCID: PMC9600864 DOI: 10.3390/cancers14205172] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/18/2022] [Accepted: 10/20/2022] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVES Previous cohort studies using national claim data in Korea have shown conflicting results about the association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer. This may be due to differences in the inclusion criteria or index dates of each study. This study aims to evaluate the association between PPI use and the risk of gastric cancer using balanced operational definitions. DESIGN A population-based cohort analysis was conducted using the Korean National Health Insurance Service database. Subjects who used PPIs or histamine-2 receptor antagonist (H2RA) for more than 60 days after Helicobacter pylori eradication were included. The study subjects were those who had never used H2RAs (PPI users) and controls were those who had never used PPIs (H2RA users). For comparison, the index dates of previous studies were adopted and analyzed. The subjects were followed until the development of gastric cancer, death, or study end. RESULTS A total of 10,012 subjects were included after propensity score matching. During a median follow-up of 6.56 years, PPI was not associated with an increased risk of gastric cancer (Hazard ratio: 1.30, 95% confidence interval: 0.75-2.27). This was consistent if the cumulative daily dose was adjusted (90/120/180 days), or if the index date was changed to the first day of PPI prescription or the last day of Helicobacter pylori eradication. There was no significant difference in mortality between both groups. CONCLUSION PPI use was not associated with an increased risk of gastric cancer.
Collapse
Affiliation(s)
- Eun Jeong Gong
- Institute of New Frontier Research, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
- Department of Internal Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24253, Gangwon-do, Korea
| | - Chang Seok Bang
- Institute of New Frontier Research, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
- Department of Internal Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24253, Gangwon-do, Korea
- Division of Big Data and Artificial Intelligence, Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Korea
| | - Dong-Kyu Kim
- Institute of New Frontier Research, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
- Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
| | - Jae Jun Lee
- Institute of New Frontier Research, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
- Division of Big Data and Artificial Intelligence, Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Korea
- Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon-si 24253, Gangwon-do, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24253, Gangwon-do, Korea
| |
Collapse
|
|
10
|
A rare case of an enterochromaffin-like neuroendocrine tumor associated with parietal cell dysfunction treated using endoscopic submucosal dissection. Clin J Gastroenterol 2022; 15:1041-1047. [DOI: 10.1007/s12328-022-01704-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/13/2022] [Indexed: 10/14/2022]
|
|
11
|
Kawaguchi K, Yashima K, Ikebuchi Y, Yoshida A, Kuwamoto S, Isomoto H. The First Case of Gastric Neuroendocrine Tumors Induced by a Proton Pump Inhibitor in von Hippel-Lindau Disease. Intern Med 2022; 61:2587-2592. [PMID: 35135919 PMCID: PMC9492478 DOI: 10.2169/internalmedicine.8701-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Von Hippel-Lindau (VHL) disease is a rare inherited familial syndrome complicated with various neoplasms, including neuroendocrine tumors (NETs). We herein report the first case of multiple gastric NETs in a 45-year-old man with VHL. He had multiple gastric polyps, and several endoscopic resected lesions were diagnosed as NETs. The serum gastrin level was elevated because he was taking a proton pump inhibitor (PPI). We suspected that gastrin had played a role in the development of NETs, and the remaining polyps were followed up with discontinuation of the PPI. The NETs gradually reduced in size until they became hard to notice on endoscopy and have remained nearly invisible for over eight years.
Collapse
Affiliation(s)
- Koichiro Kawaguchi
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Kazuo Yashima
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Yuichiro Ikebuchi
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Akira Yoshida
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| | - Satoshi Kuwamoto
- Department of Pathology, Faculty of Medicine, Tottori University, Japan
| | - Hajime Isomoto
- Division of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, Japan
| |
Collapse
|
|
12
|
Biancotti R, Dal Pozzo CA, Parente P, Businello G, Angerilli V, Realdon S, Savarino EV, Farinati F, Milanetto AC, Pasquali C, Vettor R, Grillo F, Pennelli G, Luchini C, Mastracci L, Vanoli A, Milione M, Galuppini F, Fassan M. Histopathological Landscape of Precursor Lesions of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms. Dig Dis 2022; 41:34-48. [PMID: 35816999 DOI: 10.1159/000525421] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 05/12/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Despite the important advances in research on neuroendocrine neoplasms of the gastro-entero-pancreatic tract, their precursor lesions are much less well known. SUMMARY This review analyzes the preneoplastic neuroendocrine lesions of the gastro-entero-pancreatic tract, by adopting a coherent anatomical benchmark. In particular, the settings in which neuroendocrine precursor lesions represent well-recognized pathophysiological and morphological entities (with eventual molecular correlates) have been distinguished from the ones in which the nature of preneoplastic changes is still obscure. KEY MESSAGES The aim of the paper was to summarize what is known about precursor lesions of gastro-entero-pancreatic neuroendocrine tumors, with the goal of providing a useful tool for future research aimed at obtaining a fuller understanding of the underlying biology and early development of these diseases.
Collapse
Affiliation(s)
- Rachele Biancotti
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | | | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Gianluca Businello
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Valentina Angerilli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | | | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Fabio Farinati
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Anna Caterina Milanetto
- Division of Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Claudio Pasquali
- Division of Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Roberto Vettor
- Endocrine-Metabolic Laboratory, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Center for the Study and the Integrated Management of Obesity, Padua University Hospital, Padua, Italy
| | - Federica Grillo
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Genova, Italy
- Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy
| | - Gianmaria Pennelli
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Luca Mastracci
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Genova, Italy
- Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Massimo Milione
- 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Francesca Galuppini
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy
| |
Collapse
|
|
13
|
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.
Collapse
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
| | | | | |
Collapse
|
|
14
|
Time to Classify Tumours of the Stomach and the Kidneys According to Cell of Origin. Int J Mol Sci 2021; 22:ijms222413386. [PMID: 34948181 PMCID: PMC8707540 DOI: 10.3390/ijms222413386] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/09/2021] [Accepted: 12/10/2021] [Indexed: 12/18/2022] Open
Abstract
Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By histological appearance the site of origin may often be confirmed. Using same treatment for tumours from the same organ is rational only when there is no principal heterogeneity between the tumours of that organ. Organ tumour heterogeneity is typical for the lungs with small cell and non-small cell tumours, for the kidneys where clear cell renal carcinoma (CCRCC) is the dominating type among other subgroups, and in the stomach with adenocarcinomas of intestinal and diffuse types. In addition, a separate type of neuroendocrine tumours (NETs) is found in most organs. Every cell type able to divide may develop into a tumour, and the different subtypes most often reflect different cell origin. In this article the focus is on the cells of origin in tumours arising in the stomach and kidneys and the close relationship between normal neuroendocrine cells and NETs. Furthermore, that the erythropoietin producing cell may be the cell of origin of CCRCC (a cancer with many similarities to NETs), and that gastric carcinomas of diffuse type may originate from the ECL cell, whereas the endodermal stem cell most probably gives rise to cancers of intestinal type.
Collapse
|
|
15
|
Suzuki T, Higuchi T, Kagami T, Uotani T, Yamade M, Tani S, Hamaya Y, Iwaizumi M, Osawa S, Sugimoto K, Miyajima H, Furuta T. Effects of pirenzepine on vonoprazan-induced gastric acid inhibition and hypergastrinemia. Eur J Clin Pharmacol 2021; 77:971-978. [PMID: 34059932 DOI: 10.1007/s00228-021-03162-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/14/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels. METHODS Eleven healthy volunteers were subjected to 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75 mg alone, vonoprazan 10 mg alone, and vonoprazan 10 mg plus pirenzepine 75 mg administered in a randomized crossover fashion. RESULTS Median pH 4 holding time ratios (range) achieved with pirenzepine 75 mg, vonoprazan 10 mg, and vonoprazan 10 mg plus pirenzepine 75 mg were 6.9% (2.4-32.8%), 88.4% (54.6-100%), and 84.2% (40.3-100%), respectively. Respective serum gastrin levels were 79 (75-210) pg/ml, 310 (110-870) pg/ml, and 170 (140-930) pg/ml. In cases with hypergastrinemia (gastrin ≥ 200 pg/ml) induced by vonoprazan 10 mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370 to 180 pg/ml (P = 0.028). CONCLUSION Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent.
Collapse
Affiliation(s)
- Takahiro Suzuki
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomohiro Higuchi
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takuma Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahiro Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shinya Tani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Moriya Iwaizumi
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hiroaki Miyajima
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
| |
Collapse
|
|
16
|
Tumor Classification Should Be Based on Biology and Not Consensus: Re-Defining Tumors Based on Biology May Accelerate Progress, An Experience of Gastric Cancer. Cancers (Basel) 2021; 13:cancers13133159. [PMID: 34202596 PMCID: PMC8269176 DOI: 10.3390/cancers13133159] [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: 04/28/2021] [Revised: 06/14/2021] [Accepted: 06/21/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Rational treatment of diseases including cancers depends on knowledge of their cause as well as their development. The present review is based upon more than 40 years’ work in clinical gastroenterology, gastric physiology, and pathology. The central role of hormones as well as local endocrine cells in cancer development has become apparent. Moreover, the classification of tumors should focus not only on the organ of origin but also on the cell of origin. All cells with the ability to divide may give rise to tumors. Based upon knowledge of the growth regulation of the cell of origin, prophylaxis and treatment may be tailored. Presently, there is hope for individual treatment of cancer patients based upon genetic analyses of tumors. However, with correct identification of the cell of origin, this may not be necessary. Abstract Malignant tumors are a consequence of genetic changes mainly occurring during cell division, sometimes with a congenital component. Therefore, accelerated cell divisions will necessarily predispose individuals, whether due to conditions of chronic cell destruction or hormonal overstimulation. It has been postulated that two genetic hits are necessary for the development of malignancy (Knudson). The correct view is probably that the number of genetic changes needed depends on the role the mutated genes have in proliferation and growth control. Hormones should accordingly be regarded as complete carcinogens. In this review based upon experience of gastric cancer where gastrin is central in the pathogenesis, it is argued that oxyntic atrophy—and not metaplasia as postulated by Correa—is the central precancer change in gastric mucosa. Moreover, the target cell of gastrin, the enterochromaffin-like (ECL) cell, is central in gastric carcinogenesis and most probably the cell of origin of gastric carcinomas of the diffuse type according to Lauren (a classification probable in accordance with biology). The distinction between adenocarcinomas and neuroendocrine carcinomas based upon a certain percentage of cancer cells with neuroendocrine differentiation is questioned. To make progress in the treatment of cancer, a correct classification system and knowledge of the pathogenesis are necessary.
Collapse
|
|
17
|
Abstract
INTRODUCTION Short bowel syndrome (SBS) is a rare, highly disabling, life-threatening condition due to extensive intestinal resections, characterized by diarrhea, malabsorption, and malnutrition. SBS is the main cause of intestinal failure (SBS-IF). The primary therapy for SBS-IF is intravenous supplementation (IVS) of nutrients. The pharmacological therapy aims to improve the remnant bowel function, leading to the decrease of IVS requirement. AREAS COVERED This review provides a safety perspective and discusses unmet clinical needs on pharmacotherapy for SBS, ranging from symptomatic agents traditionally used off-label to manage hypersecretion and diarrhea, to curative drugs with selective intestinotrophic properties. Real-world evidence on symptomatic drugs is lacking. Data on teduglutide - the first-in-class glucagon-like peptide-2 (GLP-2) receptor agonist approved in SBS - are mainly derived from clinical trials, with several unsettled safety issues, including the risk of malignancies. EXPERT OPINION Defining the long-term safety of drugs used for SBS is a priority; a unified list of commonly used drugs with consolidated proof of effectiveness is needed to harmonize the symptomatic pharmacological approach to SBS. GLP-2 receptor agonists are a promising curative pharmaco-therapeutic approach, although long-term safety and effectiveness deserve further real-world assessment. Pharmacovigilance and global data sharing are crucial to support safe prescribing in SBS.
Collapse
|
|
18
|
Gastritis, Gastric Polyps and Gastric Cancer. Int J Mol Sci 2021; 22:ijms22126548. [PMID: 34207192 PMCID: PMC8234857 DOI: 10.3390/ijms22126548] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/08/2021] [Accepted: 06/14/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer is still an important disease causing many deaths worldwide, although there has been a marked reduction in prevalence during the last few decades. The decline in gastric cancer prevalence is due to a reduction in Helicobacter pylori infection which has occurred for at least 50 years. The most probable mechanism for the carcinogenic effect of H. pylori is hypergastrinemia since H. pylori infected individuals do not have increased risk of gastric cancer before the development of oxyntic atrophy. When atrophy has developed, the carcinogenic process continues independent of H. pylori. Autoimmune gastritis also induces oxyntic atrophy leading to marked hypergastrinemia and development of ECL cell neoplasia as well as adenocarcinoma. Similarly, long-term treatment with efficient inhibitors of acid secretion like the proton pump inhibitors (PPIs) predisposes to ECL cell neoplasia of a different degree of malignancy. Contrasting the colon where most cancers develop from polyps, most polyps in the stomach have a low malignant potential. Nevertheless, gastric polyps may also give rise to cancer and have some risk factors and mechanisms in common with gastric cancer. In this overview the most common gastric polyps, i.e., hyperplastic polyps, adenomatous polyps and fundic gland polyps will be discussed with respect to etiology and particularly use of PPIs and relation to gastric carcinogenesis.
Collapse
|
|
19
|
Valent F, Tullio A, Kara E, Cipri C, Sciannimanico SM, Vescini F, Grimaldi F. A Retrospective Cohort Study of Histology-Proven Neuroendocrine Neoplasms in the Italian Area of Udine. Endocr Metab Immune Disord Drug Targets 2021; 21:448-457. [PMID: 32660412 DOI: 10.2174/1871530320666200713093533] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 03/12/2020] [Accepted: 05/15/2020] [Indexed: 11/22/2022]
Abstract
AIMS The aim of this study was to investigate the epidemiology of histology-proven Neuroendocrine neoplasms (NENs) in an Italian area. BACKGROUND NENs are a rare and poorly known disease and the global incidence and prevalence appear to be increasing over the past decades. OBJECTIVE The objectives of this study were to estimate the incidence and trends of NENs in a 250,000-inhabitant area in the North-East of Italy in the 1998-2018 period and to compare them with international data. METHODS This retrospective cohort study was based on the analysis of anonymous health administrative databases, linked with each other at individual patient level through an anonymous stochastic key. NENs were identified from the anatomical pathology database. The standardized incidence rate (2010ESP and US2000) ± 95% CI per 100,000 were calculated, both annually and globally, for the whole period. Incidence was also calculated for specific anatomical sites and by gender. Trends for the considered periods and sites were summarized through the annual percent change (APC) and average increase (cases per 100,000 per year). RESULTS In the 1998-2018 period, the standardized incidence rate of NENs in the area of Udine was 2.49 (APC 3.33). A total of 162 cases were observed (51.2% males). Differences in incidence and trend were observed between sexes. The obtained results were consistent with those reported in other countries, confirming a significant and steady increase in NENs incidence in the last twenty years. CONCLUSION This study provides new epidemiological data on NENs in Italy. The observed sex differences deserve further investigations.
Collapse
Affiliation(s)
- Francesca Valent
- Hygiene and Clinical Epidemiology Unit, University Hospital S. Maria della Misericordia of Udine, 33100 Udine, Italy
| | - Annarita Tullio
- Hygiene and Clinical Epidemiology Unit, University Hospital S. Maria della Misericordia of Udine, 33100 Udine, Italy
| | - Elda Kara
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia of Udine, 33100 Udine, Italy
| | - Claudia Cipri
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia of Udine, 33100 Udine, Italy
| | - Silvia M Sciannimanico
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia of Udine, 33100 Udine, Italy
| | - Fabio Vescini
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia of Udine, 33100 Udine, Italy
| | - Franco Grimaldi
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia of Udine, 33100 Udine, Italy
| |
Collapse
|
|
20
|
Lock G, Oelckers M, Clauditz TS, Schrader J. Gastric NET Subtypes: Do We Need An Additional One? ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:255-258. [PMID: 33506449 DOI: 10.1055/a-1348-2727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Depending on etiology, prognosis and malignant potential, recent S2k guideline differentiates gastric neuroendocrine tumors (gNET) in 4 types with different treatment implications.We report on a 55-year-old patient with the accidental finding of a 15 mm gNET. Apart from a prolonged use of proton pump inhibitors (PPI) for 20 years as a treatment for gastroesophageal reflux disease, there were no other associations or risk factors for gNETs. Formally, this patient would have been classified as a type III gNET, implicating gastric surgery. From a pathophysiological point of view, however, the assumed prolonged gastrin hypersecretion would have justified an assignment as a type I gNET. The gNET was resected by ESD, but histology showed an R1 situation. After cessation of PPIs, there is no recurrence so far. Besides, the initially documented numerous and large gland polyps showed an impressive regression only a few weeks after cessation of PPI.This case points to a probably underestimated gap in the present gNET classification. On the basis of present literature, the therapeutic dilemma of PPI-associated gNETs is discussed. A new assignment of PPI associated gNETs as type Ib could help to overcome this dilemma.
Collapse
Affiliation(s)
- Guntram Lock
- Klinik für Innere Medizin, Albertinen-Krankenhaus, Hamburg, Germany
| | - Michael Oelckers
- Klinik für Innere Medizin, Albertinen-Krankenhaus, Hamburg, Germany
| | | | - Jörg Schrader
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| |
Collapse
|
|
21
|
Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells. Cancers (Basel) 2020; 12:cancers12113477. [PMID: 33266504 PMCID: PMC7700139 DOI: 10.3390/cancers12113477] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/19/2020] [Accepted: 11/21/2020] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Generally, we know that cancers represent genetic changes in tumour cells, but we most often do not know the causes of cancers or how they develop. Our knowledge of the regulation of gastric acid secretion is well known, with the gastric hormone gastrin maintaining gastric acidity by stimulation of the enterochromaffin-like (ECL) cell to release histamine, which subsequently augments acid secretion. Furthermore, it seems to be a general principle that stimulation of function (which, for the ECL cell, is release of histamine) in a parallel way stimulates the proliferation of the same cell. Long-term hyperstimulation of cell division predisposes to genetic changes and, thus, development of tumours. All conditions with reduced gastric acidity result in an increased risk of gastric tumours due to elevated gastrin in order to restore gastric acidity. It is probable that Helicobacter pylori infection (the most important cause of gastric cancer), as well as drugs inhibiting gastric acid secretion induce gastric cancer in the long-term, due to an elevation of gastrin caused by reduced gastric acidity. Gastric carcinomas have been shown to express ECL cell markers, further strengthening this relationship. Abstract The stomach is an ideal organ to study because the gastric juice kills most of the swallowed microbes and, thus, creates rather similar milieu among individuals. Combined with a rather easy access to gastric juice, gastric physiology was among the first areas to be studied. During the last century, a rather complete understanding of the regulation of gastric acidity was obtained, establishing the central role of gastrin and the histamine producing enterochromaffin-like (ECL) cell. Similarly, the close connection between regulation of function and proliferation became evident, and, furthermore, that chronic overstimulation of a cell with the ability to proliferate, results in tumour formation. The ECL cell has long been acknowledged to give rise to neuroendocrine tumours (NETs), but not to play any role in carcinogenesis of gastric adenocarcinomas. However, when examining human gastric adenocarcinomas with the best methods presently available (immunohistochemistry with increased sensitivity and in-situ hybridization), it became clear that many of these cancers expressed neuroendocrine markers, suggesting that some of these tumours were of neuroendocrine, and more specifically, ECL cell origin. Thus, the ECL cell and its main regulator, gastrin, are central in human gastric carcinogenesis, which make new possibilities in prevention, prophylaxis, and treatment of this cancer.
Collapse
|
|
22
|
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.
Collapse
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
| |
Collapse
|
|
23
|
Ahmed M. Gastrointestinal neuroendocrine tumors in 2020. World J Gastrointest Oncol 2020; 12:791-807. [PMID: 32879660 PMCID: PMC7443843 DOI: 10.4251/wjgo.v12.i8.791] [Citation(s) in RCA: 132] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/26/2020] [Accepted: 07/18/2020] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological, biological, and clinical characteristics that have increased in incidence and prevalence within the last few decades. They contain chromogranin A, synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor. Ki-67 index and mitotic index correlate with cellular proliferation. Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors. Most of the gastrointestinal neuroendocrine tumors are non-functional. World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm. Gastric neuroendocrine tumors arise from enterochromaffin like cells. They are classified into 4 types. Only type I and type II are gastrin dependent. Small intestinal neuroendocrine tumor is the most common small bowel malignancy. More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve. Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs. Duodenal and jejuno-ileal neuroendocrine tumors are distinct biologically and clinically. Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver. Appendiceal neuroendocrine tumors are generally detected after appendectomy. Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis. Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000. Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy, endoscopic ultrasound, serology of biomarkers, imaging studies and functional somatostatin scans. Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.
Collapse
Affiliation(s)
- Monjur Ahmed
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
| |
Collapse
|
|
24
|
Tatsuguchi A, Hoshino S, Kawami N, Gudis K, Nomura T, Shimizu A, Iwakiri K. Influence of hypergastrinemia secondary to long-term proton pump inhibitor treatment on ECL cell tumorigenesis in human gastric mucosa. Pathol Res Pract 2020; 216:153113. [PMID: 32853950 DOI: 10.1016/j.prp.2020.153113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/22/2020] [Accepted: 07/06/2020] [Indexed: 12/13/2022]
Abstract
Proton pump inhibitor (PPI) therapy causes hypergastrinemia, which could promote the development and progression of neuroendocrine tumors (NETs). Concerns have been raised about the safety of long-term PPI use due to a possible increased risk of NETs. This study aimed to investigate the association between hypergastrinemia and the risk of NETs. Twenty outpatients presenting with serum gastrin levels greater than 400 pg/mL after long-term PPI treatment were registered in this study. Immunohistochemical analyses for chromogranin A (CgA), Ki67, gastrin and CCK/B gastrin receptor (CCKBR) were performed, and positive cell numbers were counted. There were no NET or gastric epithelial neoplasia cases observed among any of the 20 patients examined throughout the PPI treatment period. Histologically, ECL cell hyperplasia were shown in all patients. However, no relationship was found between serum gastrin levels and the number of CgA positive ECL cells. There was also no relationship between serum gastrin levels and the proportion of Ki67 positive cells or the density of CCKBR positive cells. The data indicate no relationship may exist between NETs and hypergastrinemia secondary to PPI treatment in patients having no, or mild, atrophic gastritis.
Collapse
Affiliation(s)
- Atsushi Tatsuguchi
- Department of Gastroenterology Nippon Medical School, Tokyo, Japan; Department of Analytic Human Pathology, Nippon Medical School, Graduate School of Medicine Tokyo, Japan.
| | - Shintaro Hoshino
- Department of Gastroenterology Nippon Medical School, Tokyo, Japan
| | - Noriyuki Kawami
- Department of Gastroenterology Nippon Medical School, Tokyo, Japan
| | - Katya Gudis
- Department of Gastroenterology Nippon Medical School, Tokyo, Japan
| | - Tsutomu Nomura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Akira Shimizu
- Department of Analytic Human Pathology, Nippon Medical School, Graduate School of Medicine Tokyo, Japan
| | | |
Collapse
|
|
25
|
Waldum HL. Clinical consequences of controversies in gastric physiology. Scand J Gastroenterol 2020; 55:752-758. [PMID: 32515242 DOI: 10.1080/00365521.2020.1771758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Studies on the regulation of gastric acid secretion started more than 100 years ago at an early phase of experimental physiology. In nearly the whole last century there were disputes about the interpretation of the findings: the interaction between the three principle gastric acid secretagogues acetylcholine, gastrin and histamine, the cell producing the relevant histamine which turned out to be the ECL cell, the ability of the ECL cell to divide and thus develop into tumours, the classification of gastric carcinomas and the mechanism for Helicobacter pylori carcinogenesis. The elucidation of the central role of the ECL cell and thus its main regulator, gastrin, solve all these controversies, and gives a solid base for handling upper gastrointestinal diseases.
Collapse
Affiliation(s)
- Helge L Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| |
Collapse
|
|
26
|
Abstract
Costly proton pump inhibitors have been widely prescribed since the 1990s for prevention and treatment of ulcers and gastroesophageal reflux disease. Evidence published since 2012 demonstrates risks associated with taking proton pump inhibitors for longer than 8 weeks. Primary care providers mostly deprescribe proton pump inhibitors for persons not meeting criteria for long-term use. Many patients resist discontinuation.A 3-month evidence-based practice education project was conducted by a nurse practitioner to improve primary care provider peer deprescribing successes with appropriate patients in an outpatient California-based veteran primary care clinic. Fifteen primary care providers were pretested about usual care practices between 2 comparable clinics. Five primary care providers at the smaller clinic location were educated about long-term proton pump inhibitor use risks and introduced to 3 evidence-based practice guidelines using tapering techniques with follow-up care.A Canadian 2017 evidence-based practice proton pump inhibitor deprescribing guideline was proposed for translation into practice. Primary care providers voted to pilot this guideline, dependent upon nursing support. Primary care providers denied frustration with usual care practices, even as all were willing to try an evidence-based practice change between pre- and post-test surveys. Support for peer-led evidence-based practice on-site coaching increased from 87% to 100%. Tapering behavior increased from 67% to 100%, expediting improved long-term medication cessation.
Collapse
|
|
27
|
Takeuchi T, Furuta T, Fujiwara Y, Sugimoto M, Kasugai K, Kusano M, Okada H, Suzuki T, Higuchi T, Kagami T, Uotani T, Yamade M, Sawada A, Tanaka F, Harada S, Ota K, Kojima Y, Murata M, Tamura Y, Funaki Y, Kawamura O, Okamoto Y, Fujimoto K, Higuchi K. Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study). Aliment Pharmacol Ther 2020; 51:534-543. [PMID: 31990424 DOI: 10.1111/apt.15641] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 09/10/2019] [Accepted: 01/05/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. AIMS To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. METHODS This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints. RESULTS Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. CONCLUSIONS Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).
Collapse
Affiliation(s)
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine School of Medicine, Osaka, Japan
| | - Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | - Kunio Kasugai
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Motoyasu Kusano
- Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Meabashi, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Takahiro Suzuki
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomohiro Higuchi
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takuma Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahiro Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Akinari Sawada
- Department of Gastroenterology, Osaka City University Graduate School of Medicine School of Medicine, Osaka, Japan
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka City University Graduate School of Medicine School of Medicine, Osaka, Japan
| | - Satoshi Harada
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| | - Kazuhiro Ota
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| | - Yuichi Kojima
- Endoscopic Center, Osaka Medical College Hospital, Takatsuki, Japan
| | - Masaki Murata
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | - Yasuhiro Tamura
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Yasushi Funaki
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Osamu Kawamura
- Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Meabashi, Japan
| | - Yuki Okamoto
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Kazuma Fujimoto
- Department of Internal Medicine, Saga Medical School, Saga, Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| |
Collapse
|
|
28
|
Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids-What Is the Relationship? Int J Mol Sci 2020; 21:ijms21020662. [PMID: 31963924 PMCID: PMC7014182 DOI: 10.3390/ijms21020662] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/13/2020] [Accepted: 01/16/2020] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine tumors (NETs) throughout the body are the focus of much current interest. Most occur in the gastrointestinal tract and have shown a major increase in incidence over the past 30 years, roughly paralleling the world-wide increase in the use of proton pump inhibitor (PPI) drugs. The greatest rise has occurred in gastric carcinoids (g-NETs) arising from enterochromaffin-like (ECL) cells. These tumors are long known to occur in auto-immune chronic atrophic gastritis (CAG) and Zollinger-Ellison syndrome (ZES), with or without multiple endocrine neoplasia type-1 (MEN-1), but the incidences of these conditions do not appear to have increased over the same time period. Common to these disease states is persistent hypergastrinemia, generally accepted as causing g-NETs in CAG and ZES, and postulated as having similar tumorigenic effects in PPI users. In efforts to study the increase in their occurrence, g-NETs have been classified in a number of discussed ways into different grades that differ in their incidence and apparent pathogenesis. Based on a large amount of experimental data, tumorigenesis is mediated by gastrin’s effects on the CCK2R-receptor on ECL-cells that in turn leads to hyperplasia, dysplasia, and finally neoplasia. However, in all three conditions, the extent of response of ECL-cells to gastrin is modified by a number of genetic influences and other underlying risk factors, and by the duration of exposure to the hormonal influence. Data relating to trophic effects of hypergastrinemia due to PPI use in humans are reviewed and, in an attached Appendix A, all 11 reports of g-NETs that occurred in long-term PPI users in the absence of CAG or ZES are summarized. Mention of additional suspected cases reported elsewhere are also listed. Furthermore, the risk in humans may be affected by the presence of underlying conditions or genetic factors, including their PPI-metabolizer phenotype, with slow metabolizers likely at increased risk. Other problems in estimating the true incidence of g-NETs are discussed, relating to non-reporting of small tumors and failure of the Surveillance, Epidemiology, and End Results Program (SEER) and other databases, to capture small tumors or those not accorded a T1 rating. Overall, it appears likely that the true incidence of g-NETs may be seriously underestimated: the possibility that hypergastrinemia also affects tumorigenesis in additional gastrointestinal sites or in tumors in other organ systems is briefly examined. Overall, the risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses: those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk. While the overall risk of g-NETs induced by PPI therapy is undoubtedly low, it is real: this necessitates caution in using PPI therapy for long periods of time, particularly when initiated in young subjects.
Collapse
|
|
29
|
Helgadottir H, Bjornsson ES. Problems Associated with Deprescribing of Proton Pump Inhibitors. Int J Mol Sci 2019; 20:E5469. [PMID: 31684070 PMCID: PMC6862638 DOI: 10.3390/ijms20215469] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 02/07/2023] Open
Abstract
Proton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use.
Collapse
Affiliation(s)
- Holmfridur Helgadottir
- Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
- Division of Gastroenterology and Hepatology, The National University Hospital of Iceland, 101 Reykjavik, Iceland.
| | - Einar S Bjornsson
- Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
- Division of Gastroenterology and Hepatology, The National University Hospital of Iceland, 101 Reykjavik, Iceland.
| |
Collapse
|
|
30
|
Adverse Effects of Proton Pump Inhibitors-Evidence and Plausibility. Int J Mol Sci 2019; 20:ijms20205203. [PMID: 31640115 PMCID: PMC6829383 DOI: 10.3390/ijms20205203] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 10/17/2019] [Accepted: 10/18/2019] [Indexed: 12/12/2022] Open
Abstract
Proton pump inhibitors (PPIs) have been increasingly used over the last decades and there are concerns about overuse and the numerous reported side-effects. It is uncertain whether associations between PPI use and potential side effects are causal. However, important evidence from experimental and mechanistic studies that could support a causal relationship may have been underestimated by epidemiologists and meta-analysists. In the current manuscript we review the combined epidemiological and mechanistic evidence of the adverse effects of PPI use.
Collapse
|
|
31
|
Lee L, Ramos-Alvarez I, Ito T, Jensen RT. Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. Int J Mol Sci 2019; 20:5128. [PMID: 31623145 PMCID: PMC6829234 DOI: 10.3390/ijms20205128] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/08/2019] [Accepted: 10/13/2019] [Indexed: 02/07/2023] Open
Abstract
The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.
Collapse
Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
| | | | - 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.
| |
Collapse
|
|
32
|
Waldum HL, Rehfeld JF. Gastric cancer and gastrin: on the interaction of Helicobacter pylori gastritis and acid inhibitory induced hypergastrinemia. Scand J Gastroenterol 2019; 54:1118-1123. [PMID: 31524029 DOI: 10.1080/00365521.2019.1663446] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Gastric cancer, a disease with a reduced frequency for decades, now appears to be on the rise again in young Americans. The epidemiology of gastric cancer differs between tumors in the cardia and those of the more distal parts of the stomach. The tumors are divided into the intestinal type showing glandular growth pattern and the diffuse type with a different pattern. The latter often expresses neuroendocrine and more specifically ECL-cell markers suggesting that they originate from the ECL cell, the target cell for the antral hormone, gastrin. Helicobacter pylori gastritis is accepted as the major cause of gastric cancer, but only after having induced oxyntic atrophy which reduces gastric acid secretion and thus induces hypoacidity leading to hypergastrinemia. Long-term hypergastrinemia is known to induce malignant neoplasia in the stomach of animals as well as man. Recently treatment with proton pump inhibitor after Helicobacter pylori eradication in patients with gastroesophageal reflux disease, has been reported to predispose to gastric cancer. Since profound acid inhibition is a well-known cause of gastric neoplasia, it is to be expected that Helicobacter pylori infection and profound acid inhibition has an additive or possibly potentiating effect on the development of gastric cancer.
Collapse
Affiliation(s)
- Helge L Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology , Trondheim , Norway
| | - Jens F Rehfeld
- Department of Clinical Biochemistry , Rigshospitalet, Copenhagen , Denmark
| |
Collapse
|
|
33
|
Mori H, Suzuki H. Role of Acid Suppression in Acid-related Diseases: Proton Pump Inhibitor and Potassium-competitive Acid Blocker. J Neurogastroenterol Motil 2019; 25:6-14. [PMID: 30504527 PMCID: PMC6326200 DOI: 10.5056/jnm18139] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 09/27/2018] [Accepted: 10/25/2018] [Indexed: 12/11/2022] Open
Abstract
Proton pump inhibitors are commonly utilized for the treatment of gastric acid-related diseases, such as gastroesophageal reflux disease, peptic ulcer disease, and Helicobacter pylori infection, and for the prevention of low-dose aspirin or nonsteroidal anti-inflammatory drug-induced peptic ulcers. Vonoprazan is a first-in-class potassium-competitive acid blocker, which has distinct advantages compared to other conventional proton pump inhibitors in terms of the efficacy for acid suppression. Due to its strong gastric acid suppression capabilities, vonoprazan serves as an effective drug for the treatment of gastroesophageal reflux disease and H. pylori infection.
Collapse
Affiliation(s)
- Hideki Mori
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo,
Japan
| | - Hidekazu Suzuki
- Fellowship Training Center and Medical Education Center, Keio University School of Medicine, Tokyo,
Japan
| |
Collapse
|
|
34
|
Soto-Solís R, Romano-Munive A, Santana de Anda K, Barreto-Zuñiga R. Factors related to gastric neuroendocrine tumors. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2018.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
35
|
Waldum HL, Fossmark R. Types of Gastric Carcinomas. Int J Mol Sci 2018; 19:ijms19124109. [PMID: 30567376 PMCID: PMC6321162 DOI: 10.3390/ijms19124109] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 12/15/2018] [Accepted: 12/15/2018] [Indexed: 12/16/2022] Open
Abstract
Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for Helicobacter pylori as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.
Collapse
Affiliation(s)
- Helge L Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
- Department of Gastroenterology and Hepatology, St. Olav's University Hospital, 7006 Trondheim, Norway.
| | - Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
- Department of Gastroenterology and Hepatology, St. Olav's University Hospital, 7006 Trondheim, Norway.
| |
Collapse
|
|
36
|
Kojima Y, Takeuchi T, Sanomura M, Higashino K, Kojima K, Fukumoto K, Takata K, Sakamoto H, Sakaguchi M, Tominaga K, Higuchi K. Does the Novel Potassium-Competitive Acid Blocker Vonoprazan Cause More Hypergastrinemia than Conventional Proton Pump Inhibitors? A Multicenter Prospective Cross-Sectional Study. Digestion 2018; 97:70-75. [PMID: 29393198 DOI: 10.1159/000484217] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIM The long-term administration of proton pump inhibitors (PPIs) is useful for preventing recurrent reflux esophagitis. On the other hand, several adverse reactions, such as an increase in the blood gastrin level, have been reported. The aim of the present study was to examine the increase in the blood gastrin level due to the long-term administration of conventional PPIs compared with vonoprazan. METHODS A prospective cross-sectional study was conducted. We examined the blood gastrin levels of patients taking vonoprazan or conventional PPIs in whom the grade of atrophic gastritis had been endoscopically evaluated in the last year. RESULTS The blood gastrin level was significantly higher in the vonoprazan group than that in the PPI group in patients with milder or no atrophic gastritis, irrespective of the administration periods. However, no significant difference was observed between the groups in patients with severe atrophic gastritis. CONCLUSION Vonoprazan more markedly increased the blood gastrin level compared with conventional PPIs in patients with milder or no atrophic gastritis. This indicates that vonoprazan may have stronger acid-suppressing effects in such patients than conventional PPIs. Key Message: We should be aware of the potential development of hypergastrinemia during the long-term administration of vonoprazan, especially in patients with mild or no atrophic gastritis.
Collapse
Affiliation(s)
- Yuichi Kojima
- Endoscopy Center, Osaka Medical College, Osaka, Japan.,Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Toshihisa Takeuchi
- Endoscopy Center, Osaka Medical College, Osaka, Japan.,Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Makoto Sanomura
- Department of Gastroenterology, Hokusetsu General Hospital, Osaka, Japan
| | - Ken Higashino
- Department of Gastroenterology, Shiroyama Hospital, Osaka, Japan
| | - Keishi Kojima
- Department of Internal Medicine, Sousei Hospital, Osaka, Japan
| | - Kenji Fukumoto
- Department of Internal Medicine, Taishou Hospital, Osaka, Japan
| | - Kou Takata
- Department of Gastroenterology, Shitennouji Hospital, Osaka, Japan
| | - Hiroki Sakamoto
- Department of Gastroenterology, Katsuragi Hospital, Osaka, Japan
| | - Masahiro Sakaguchi
- Department of Gastroenterology, Moriguchi Keijinkai Hospital, Osaka, Japan
| | - Kazunari Tominaga
- Premier Developmental Research of Medicine, Osaka Medical College, Osaka, Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| |
Collapse
|
|
37
|
Waldum HL, Öberg K, Sørdal ØF, Sandvik AK, Gustafsson BI, Mjønes P, Fossmark R. Not only stem cells, but also mature cells, particularly neuroendocrine cells, may develop into tumours: time for a paradigm shift. Therap Adv Gastroenterol 2018; 11:1756284818775054. [PMID: 29872453 PMCID: PMC5974566 DOI: 10.1177/1756284818775054] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2017] [Accepted: 04/03/2018] [Indexed: 02/04/2023] Open
Abstract
Stem cells are considered the origin of neoplasms in general, and malignant tumours in particular, and the stage at which the stem cells stop their differentiation determines the degree of malignancy. However, there is increasing evidence supporting an alternative paradigm. Tumours may develop by dedifferentiation from mature cells able to proliferate. Studies of gastric carcinogenesis demonstrate that mature neuroendocrine (NE) cells upon long-term overstimulation may develop through stages of hyperplasia, dysplasia, and rather benign tumours, into highly malignant carcinomas. Dedifferentiation of cells may change the histological appearance and impede the identification of the cellular origin, as seen with gastric carcinomas, which in many cases are dedifferentiated neuroendocrine tumours. Finding the cell of origin is important to identify risk factors for cancer, prevent tumour development, and tailor treatment. In the present review, we focus not only on gastric tumours, but also evaluate the role of neuroendocrine cells in tumourigenesis in two other foregut-derived organs, the lungs and the pancreas, as well as in the midgut-derived small intestine.
Collapse
Affiliation(s)
- Helge L. Waldum
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, N-7491, Norway Department of Gastroenterology and Hepatology, St. Olav’s University Hospital, Trondheim, Norway
| | - Kjell Öberg
- Department of Endocrine Oncology Uppsala University and University Hospital, Uppsala, Sweden
| | - Øystein F. Sørdal
- Department of Gastroenterology and Hepatology, St. Olav’s University Hospital, Trondheim, Norway
| | - Arne K. Sandvik
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, St. Olav’s University Hospital, Trondheim, Norway
| | - Bjørn I. Gustafsson
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, St. Olav’s University Hospital, Trondheim, Norway
| | - Patricia Mjønes
- epartment of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Pathology, St. Olav’s University Hospital, Trondheim, Norway
| | - Reidar Fossmark
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, St. Olav’s University Hospital, Trondheim, Norway
| |
Collapse
|
|
38
|
Soto-Solís R, Romano-Munive AF, Santana de Anda K, Barreto-Zuñiga R. Factors related to gastric neuroendocrine tumors. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 84:52-56. [PMID: 29705524 DOI: 10.1016/j.rgmx.2018.03.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 02/08/2018] [Accepted: 03/06/2018] [Indexed: 01/13/2023]
Abstract
INTRODUCTION AND AIMS An association between long-term use of proton pump inhibitors and the development of gastric neuroendocrine tumors has been reported, but it is still a subject of debate. The aims of the present study were to determine the presence of this association in a Mexican population and to identify the risk factors for developing gastric neuroendocrine tumors. MATERIALS AND METHODS A case-control study was conducted, in which the cases were patients with a histopathologic diagnosis of gastric neuroendocrine tumor and the controls were patients evaluated through upper endoscopy. The controls were paired by age, sex, and endoscopic examination indication. Proton pump inhibitor use was considered prolonged when consumption was longer than 5 years. RESULTS Thirty-three patients with gastric neuroendocrine tumor and 66 controls were included in the study. Eighteen (54.5%) patients in the case group were women, as were 39 (59%) of the patients in the control group. The median age of the patients in the case group was 55 years (minimum-maximum range: 24-82) and it was 54 years (minimum-maximum range:18-85) in the control group. A greater number of patients in the gastric neuroendocrine tumor group presented with gastric atrophy (p<0.0001) and autoimmune atrophic gastritis (p=0.0002), compared with the control group. No association between gastric neuroendocrine tumor and prolonged proton pump inhibitor use, sex, smoking, gastroesophageal reflux disease, Helicobacter pylori infection, diabetes mellitus, or autoimmune diseases was found in the univariate analysis. CONCLUSIONS The results of our study showed no association between proton pump inhibitor use for more than 5 years and the development of gastric neuroendocrine tumor. The presence of gastric atrophy and autoimmune atrophic gastritis was associated with gastric neuroendocrine tumor development.
Collapse
Affiliation(s)
- R Soto-Solís
- Departamento de Endoscopia, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad Social y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Ciudad de México, México; Hospital Ángeles Pedregal, Ciudad de México, México.
| | - A F Romano-Munive
- Departamento de Endoscopia, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Ciudad de México, México
| | | | - R Barreto-Zuñiga
- Departamento de Endoscopia, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Ciudad de México, México
| |
Collapse
|
|
39
|
Del Giorno R, Ceschi A, Pironi M, Zasa A, Greco A, Gabutti L. Multifaceted intervention to curb in-hospital over-prescription of proton pump inhibitors: A longitudinal multicenter quasi-experimental before-and-after study. Eur J Intern Med 2018; 50:52-59. [PMID: 29274884 DOI: 10.1016/j.ejim.2017.11.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 11/03/2017] [Accepted: 11/06/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are indicated for a restricted number of clinical conditions, and their misuse can lead to several adverse effects. Despite that, the proportion of overuse is alarmingly high. OBJECTIVE To test the efficacy of a multifaceted strategy in order to achieve a significant reduction of new PPI prescriptions at discharge in hospitalized patients. DESIGN Multicenter longitudinal quasi-experimental before-and-after study conducted from July 1st, 2014 to June 30th, 2017. PARTICIPANTS 44,973 admissions in a network of 5 public teaching hospitals of the Italian-speaking region of Switzerland. INTERVENTION Multifaceted strategy consisting in a continuous transparent monitoring-benchmarking and in capillary educational interventions applied in the internal medicine departments. To confirm the causality of the results we monitored the trend of new PPI prescriptions in the, not exposed to the intervention, surgery departments of the same hospital network. MAIN MEASURES New PPI prescriptions at hospital discharge. KEY RESULTS Over the 36month study period 44,973 patient files were analyzed. At admission, comparing internal medicine vs. surgery departments, 44.9% vs. 23.3% of patients were already being treated with a PPI. The annual rate of new PPI prescriptions, for internal medicine showed a decreasing trend: 19, 19, 18, 16% in years 2014, 2015, 2016, 2017, respectively (p<0.001, 2014 vs. 2017; p-for-trend <0.001), while an increasing rate was found in the surgery departments in the same years: 30, 29, 36, 36%, respectively (p<0.001, 2014 vs. 2017; p-for-trend <0.001). The case mix was significantly associated with the probability of new PPI prescriptions in both departments (OR1.35, 95% CI 1.26-1.44 for internal medicine and 1.24, 95% CI 1.19-1.30 for surgery). CONCLUSIONS The introduction of a multifaceted intervention significantly reduced the time trend of PPI prescriptions at hospital discharge in internal medicine departments. Further studies are needed to confirm whether the strategy proposed could contribute to optimize the in-hospital drug prescription behavior in other healthcare settings as well.
Collapse
Affiliation(s)
- Rosaria Del Giorno
- Department of Internal Medicine and Nephrology, Regional Hospital of Bellinzona and Valli, Bellinzona, Switzerland.
| | - Alessandro Ceschi
- Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
| | - Michela Pironi
- Central Pharmacy Service, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
| | - Anna Zasa
- Quality and Patient Safety Service, La Carità Hospital, Locarno, Switzerland
| | - Angela Greco
- Quality and Patient Safety Service, La Carità Hospital, Locarno, Switzerland.
| | - Luca Gabutti
- Department of Internal Medicine and Nephrology, Regional Hospital of Bellinzona and Valli, Bellinzona, Switzerland; Institute of Biomedicine, University of Southern Switzerland, Lugano, Switzerland.
| |
Collapse
|
|
40
|
Suzuki T, Kagami T, Uotani T, Yamade M, Hamaya Y, Iwaizumi M, Osawa S, Sugimoto K, Miyajima H, Furuta T. Comparison of effect of an increased dosage of vonoprazan versus vonoprazan plus lafutidine on gastric acid inhibition and serum gastrin. Eur J Clin Pharmacol 2018; 74:45-52. [PMID: 28986609 DOI: 10.1007/s00228-017-2324-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 08/21/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H2RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. AIMS The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. METHODS Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. RESULTS Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml. CONCLUSION Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.
Collapse
Affiliation(s)
- Takahiro Suzuki
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takuma Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahiro Uotani
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Moriya Iwaizumi
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hiroaki Miyajima
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
| |
Collapse
|
|
41
|
Abstract
Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.
Collapse
|
|
42
|
Leoncini E, Boffetta P, Shafir M, Aleksovska K, Boccia S, Rindi G. Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms. Endocrine 2017; 58:368-379. [PMID: 28303513 PMCID: PMC5671554 DOI: 10.1007/s12020-017-1273-x] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 02/22/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE The incidence of neuroendocrine neoplasms is increasing. This work aimed at: (i) establishing worldwide incidence trend of low-grade neuroendocrine neoplasms; (ii) defining the incidence and temporal trend of high-grade neuroendocrine neoplasms in USA utilizing the Surveillance Epidemiology and End Results database; (iii) comparing trends for low-grade vs. high-grade neuroendocrine neoplasms. METHODS We conducted a literature search on MEDLINE and Scopus databases and incidence trends were plotted for 1973-2012. The Surveillance Epidemiology and End Results database was used to identify incidence rates in USA for 1973-2012. Incidence rates were stratified according to histological grade, gender and ethnicity. Trends were summarized as annual percent change and corresponding 95% confidence interval. RESULTS 11 studies were identified involving 72,048 cases; neuroendocrine neoplasm incidence rates increased over time in all countries for all sites, except for appendix. In Surveillance Epidemiology and End Results low-grade neuroendocrine neoplasm incidence rate increased from 1.09 in 1973 to 3.51 per 100,000 in 2012. During this interval, high-grade neuroendocrine neoplasm incidence rate increased from 2.54 to 10.52 per 100,000. African Americans had the highest rates of digestive neuroendocrine neoplasms with male prevalence in high-grade. CONCLUSIONS Our data indicate an increase in the incidence of neuroendocrine neoplasms as a worldwide phenomenon, affecting most anatomical sites and involving both low-grade and high-grade neoplasms.
Collapse
Affiliation(s)
| | | | - Michail Shafir
- Departments of Surgery and Neoplastic Diseases, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA
| | | | - Stefania Boccia
- Section of Hygiene, Institute of Public Health, Rome, 00168, Italy
| | - Guido Rindi
- Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, Rome, 00168, Italy.
- European NeuroEndocrine Tumor Society (ENETS) Center of Excellence, Rome, Italy.
| |
Collapse
|
|
43
|
Takahari K, Haruma K, Ohtani H, Kiyoto S, Watanabe A, Kamada T, Manabe N, Hatano Y. Proton Pump Inhibitor Induction of Gastric Cobblestone-like Lesions in the Stomach. Intern Med 2017; 56:2699-2703. [PMID: 28924108 PMCID: PMC5675929 DOI: 10.2169/internalmedicine.7964-16] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 11/08/2016] [Indexed: 12/30/2022] Open
Abstract
Objective The long-term use of proton pump inhibitors (PPIs) may induce adverse events in many organs, including the stomach. The chronic use of PPIs has been associated with the growth of fundic gland polyps (FGPs) and of gastric black spots. This study assessed the incidence of gastric lesions with cobblestone-like appearance in PPI users. Methods The clinical characteristics and endoscopic findings of patients who underwent upper gastrointestinal endoscopy after using PPIs for at least six months were analyzed. The biopsy specimens from patients with gastric cobblestone-like lesions (GCLLs) were examined histopathologically. Patients This study analyzed 171 patients who underwent upper gastrointestinal endoscopy after more than 6 months of PPI use in Mitsugi Public General Hospital from January 1, 2015, to March 31, 2016. Results Of the 171 patients, 60 (35.1%) had GCLLs and 111 (64.9%) did not. There were no significant between-group differences in age, sex, duration of PPI use, and receipt of Helicobacter pylori eradication therapy. Atrophic gastritis of the corpus was significantly less frequent in the GCLL than in the non-GCLL group (55.0% vs. 47.8%, p=0.0097). Among the GCLL group, histological examinations of 24 patients revealed cystic dilation of the fundic gland in 19 (79.2%), parietal cell hyperplasia in 18 (75.0%), and cytoplasmic vacuolation in 7 (29.2%). Conclusion GCLLs occurred frequently in long-term PPI users, especially in patients without atrophic gastritis. The pathological findings of GCLLs included parietal cell hyperplasia and fundic gland cysts. The clinical importance of these new lesions remains uncertain, but they should be observed carefully.
Collapse
Affiliation(s)
- Kosuke Takahari
- Department of Internal Medicine, Mitsugi General Hospital, Japan
| | - Ken Haruma
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Japan
| | | | - Sho Kiyoto
- Department of Internal Medicine, Mitsugi General Hospital, Japan
| | - Akifumi Watanabe
- Department of Internal Medicine, Mitsugi General Hospital, Japan
| | - Tomoari Kamada
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Japan
| | - Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Japan
| | | |
Collapse
|
|
44
|
Johnson DA, Katz PO, Armstrong D, Cohen H, Delaney BC, Howden CW, Katelaris P, Tutuian RI, Castell DO. The Safety of Appropriate Use of Over-the-Counter Proton Pump Inhibitors: An Evidence-Based Review and Delphi Consensus. Drugs 2017; 77:547-561. [PMID: 28233274 PMCID: PMC5357248 DOI: 10.1007/s40265-017-0712-6] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The availability of over-the-counter (OTC) proton pump inhibitors (PPIs) for the short-term (2 weeks) management of frequent heartburn (≥2 days/week) has increased markedly, yet evidence-based recommendations have not been developed. A panel of nine international experts in gastroesophageal reflux disease developed consensus statements regarding the risks and benefits of OTC PPIs using a modified Delphi process. Consensus (based on ≥80% approval) was reached through multiple rounds of remote voting and a final round of live voting. To identify relevant data, the available literature was searched and summarized. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system terminology was used to rate the quality of evidence and strength of recommendations; consensus was based on ≥2/3 agreement. After 4 rounds of review, consensus was achieved for 18 statements. Notably, the available data did not directly reflect OTC use, but instead, prescription use; therefore, extrapolations to the OTC setting were often necessary. This limitation is regrettable, but it justifies performing this exercise to provide evidence-based expert opinion on a widely used class of drugs. The panel determined that using OTC PPIs according to label instructions is unlikely to mask the symptoms of esophageal or gastric cancer or adversely impact the natural history of related precursor conditions. OTC PPIs are not expected to substantially affect micronutrient absorption or bone mineral density or cause community-acquired pneumonia, Clostridium difficile infection, or cardiovascular adverse events. However, OTC PPI use may be associated with slightly increased risks for infectious diarrhea, certain idiosyncratic reactions, and cirrhosis-related spontaneous bacterial peritonitis. The available evidence does not suggest that OTC PPI use consistent with label instructions is associated with substantial health risks. To minimize potential risks, healthcare professionals and consumers must actively participate in decision making when managing reflux-related symptoms in the self-care setting.
Collapse
Affiliation(s)
- David A Johnson
- Department of Gastroenterology, Eastern Virginia Medical School, 885 Kempsville Rd, Suite 114, Norfolk, VA, 23505, USA.
| | - Philip O Katz
- Division of Gastroenterology, Einstein Medical Center, 5401 Old York Rd, Suite 363 Klein Building, Philadelphia, PA, 19141, USA.
| | - David Armstrong
- Division of Gastroenterology, McMaster University, HSC-3V3, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada
| | - Henry Cohen
- Department of Gastroenterology, National University of Uruguay, Av. Italia 2370, 11600, Montevideo, Uruguay
| | - Brendan C Delaney
- Department of Surgery and Cancer, Imperial College, Kensington, London, SW7 2AZ, UK
| | - Colin W Howden
- Division of Gastroenterology, University of Tennessee Health Science Center, 956 Court Avenue, Suite H210, Memphis, TN, 38163, USA
| | - Peter Katelaris
- Department of Gastroenterology, University of Sydney, Concord, Sydney, 2139, Australia
| | - Radu I Tutuian
- Department of Gastroenterology, University of Bern School of Medicine, Freiburgerstr 10, Bern, Switzerland
| | - Donald O Castell
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, 11 Harleston Place, Charleston, SC, 29401, USA
| |
Collapse
|
|
45
|
Anjiki H, Mukaisho KI, Kadomoto Y, Doi H, Yoshikawa K, Nakayama T, Vo DTN, Hattori T, Sugihara H. Adenocarcinoma arising in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor therapy. Clin J Gastroenterol 2017; 10:128-136. [DOI: 10.1007/s12328-017-0714-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 01/17/2017] [Indexed: 12/18/2022]
|
|
46
|
Martín-Alcolea M, Rodríguez-Hernández I, Aldea M, Rosas I, Juncà J, Granada ML. Chronic proton pump inhibition therapy in the diagnostic accuracy of serum pepsinogen I and gastrin concentrations to identify pernicious anaemia. Clin Biochem 2017; 50:481-484. [PMID: 28109748 DOI: 10.1016/j.clinbiochem.2017.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 01/17/2017] [Accepted: 01/17/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Chronic use of proton pump inhibitors (PPIs) leads to increases in gastrin and pepsinogen-I serum concentrations. AIM To asses if chronic treatment with PPIs has an effect on serum gastrin and pepsinogen-I concentrations for the diagnosis of pernicious anaemia (PA). MATERIALS AND METHODS Serum gastrin and pepsinogen-I were measured in 38 patients with PA and 74 without PA (controls); 17/38 PA patients and 36/74 controls were treated with PPIs. Receiver Operating Curves (ROC) were used to compare diagnostic accuracy of gastrin and pepsinogen-I for PA in patients under chronic treatment with PPIs and in untreated patients. RESULTS PPI treatment increased pepsinogen-I in patients and in controls, while gastrin increased only in controls. In untreated patients, a pepsinogen-I <8.3ng/mL had 95.2% sensitivity and 100% specificity, whereas a gastrin >115pg/mL had 100% sensitivity and 92.11% specificity for PA diagnosis. In PPI-treated patients, a pepsinogen I<24.1ng/mL had a lower sensitivity (82.4%) but retained 100% specificity, however the best cut-off point for gastrin, 610pg/mL, had a very low sensitivity (58%). CONCLUSIONS PPI chronic treatment decreased the diagnostic accuracy for the studied biomarkers, particularly of gastrin. In PPI-treated patients, serum pepsinogen-I concentrations >24.1ng/mL allowed rejecting a PA diagnosis with 100% specificity.
Collapse
Affiliation(s)
- Mariam Martín-Alcolea
- Department of Clinical Biochemistry, Hospital "Germans Trias i Pujol", Universitat Autonoma of Barcelona, Ctra Canyet s/n., 08916 Badalona, Barcelona, Spain
| | - Inés Rodríguez-Hernández
- Haematology-Laboratory, Hospital "Germans Trias i Pujol", Universitat Autonoma of Barcelona, Ctra Canyet s/n., 08916 Badalona, Barcelona, Spain
| | - Marta Aldea
- Department of Clinical Biochemistry, Hospital "Germans Trias i Pujol", Universitat Autonoma of Barcelona, Ctra Canyet s/n., 08916 Badalona, Barcelona, Spain
| | - Irene Rosas
- Department of Clinical Biochemistry, Hospital "Germans Trias i Pujol", Universitat Autonoma of Barcelona, Ctra Canyet s/n., 08916 Badalona, Barcelona, Spain
| | - Jordi Juncà
- Haematology-Laboratory, Hospital "Germans Trias i Pujol", Universitat Autonoma of Barcelona, Ctra Canyet s/n., 08916 Badalona, Barcelona, Spain
| | - Maria Luisa Granada
- Department of Clinical Biochemistry, Hospital "Germans Trias i Pujol", Universitat Autonoma of Barcelona, Ctra Canyet s/n., 08916 Badalona, Barcelona, Spain.
| |
Collapse
|
|
47
|
Abstract
Gastric cancer although occurring in reduced frequency is still an important disease, partly because of the bad prognosis when occurring in western countries. This decline in occurrence may mainly be due to the reduced prevalence of Helicobacter pylori (Hp) infection, which is the most important cause of gastric cancer. There exist many different pathological classifications of gastric carcinomas, but the most useful seems to be the one by Lauren into intestinal and diffuse types since these types seldom transform into the other and also have different epidemiology. During the nearly 30 years that have passed since the groundbreaking description of Hp as the cause of gastritis and gastric cancer, a continuous search for the mechanism by which Hp infection causes gastric cancer has been done. Interestingly, it is mainly atrophic gastritis of the oxyntic mucosa that predisposes to gastric cancer possibly by inducing hypoacidity and hypergastrinemia. There are many arguments in favor of an important role of gastrin and its target cell, the enterochromaffin-like cell, in gastric carcinogenesis. The role of gastrin in gastric carcinogenesis implies caution in the long-term treatment with inhibitors of gastric acid secretion inducing secondary hypergastrinemia, in a common disease like gastroesophageal reflux disease.
Collapse
Affiliation(s)
- Helge L. Waldum
- Department of Gastroenterology and Hepatology, St Olav’s Hospital, Trondheim, Norway
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- *Correspondence: Helge L. Waldum,
| | - Liv Sagatun
- Department of Gastroenterology and Hepatology, St Olav’s Hospital, Trondheim, Norway
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Patricia Mjønes
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Pathology, St Olav’s Hospital, Trondheim, Norway
- Department of Laboratory Medicine, Children and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway
| |
Collapse
|
|
48
|
Potential clinical indications for a CCK2 receptor antagonist. Curr Opin Pharmacol 2016; 31:68-75. [PMID: 27710813 DOI: 10.1016/j.coph.2016.09.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 09/19/2016] [Accepted: 09/20/2016] [Indexed: 12/15/2022]
|
|
49
|
Bojar P, Swatek J, Drabko J, Golec K, Ostrowska A, Szumilo J. Gastric neuroendocrine tumor treated with endoscopic submucosal dissection. CURRENT ISSUES IN PHARMACY AND MEDICAL SCIENCES 2016. [DOI: 10.1515/cipms-2016-0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
AbstractA case of a 59-year-old male patient with gastric neuroendocrine tumor which was misdiagnosed as adenocarcinoma, is presented. Herein, primary diagnosis was made due to the similarity of endoscopic pictures of both diseases and dues to the inappropriate interpretation of a small biopsy sample. The patient was qualified for endoscopic submucosal dissection. Microscopic examination of whole lesion, supplemented by immmunohistochemical reactions (chromogranin A, synaptophysin, cytokeratins 7 and 20, Ki67) revealed gastric neuroendocrine tumor (NET) G2.The lesson learnt is that to provide effective treatment to the patient, it is necessary to use all available methods to make a proper diagnosis and to distinguish the suspected disease from others with similar features.
Collapse
Affiliation(s)
- Pawel Bojar
- Department of Clinical Pathomorphology Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| | - Jaroslaw Swatek
- Department of Clinical Pathomorphology Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| | - Jaroslaw Drabko
- Gastromed Healthcare Center, Onyksowa 10, 20-582 Lublin, Poland
| | - Katarzyna Golec
- Department of Clinical Pathomorphology Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| | - Anna Ostrowska
- Department of Clinical Pathomorphology Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| | - Justyna Szumilo
- Department of Clinical Pathomorphology Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| |
Collapse
|
|
50
|
Akazawa Y, Fukuda D, Fukuda Y. Vonoprazan-based therapy for Helicobacter pylori eradication: experience and clinical evidence. Therap Adv Gastroenterol 2016; 9:845-852. [PMID: 27803739 PMCID: PMC5076777 DOI: 10.1177/1756283x16668093] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Stable suppression of gastric acid secretion is a crucial factor in Helicobacter pylori eradication. Vonoprazan is a potassium-competitive acid blocker recently approved for use in Japan. As vonoprazan has a long duration of action and causes rapid and strong inhibition of gastric acid secretion, it has gained clinical attention for treating erosive oesophagitis, peptic ulcers, and H. pylori infection. In this review, we discuss the recent knowledge regarding the safety and efficacy of vonoprazan, focusing on its use in H. pylori eradication. The latest literature and our clinical experience have shown that vonoprazan-based therapies have satisfactory eradication rates. Additionally, vonoprazan-based therapies are associated with similar rates of adverse events as standard triple therapies with conventional proton-pump inhibitors.
Collapse
|