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The global challenge of a healthy stomach
Best Practice & Research Clinical Gastroenterology 28 (2014) 949e951
Contents lists available at ScienceDirect
Best Practice & Research Clinical Gastroenterology
Preface
The global challenge of a healthy stomach The stomach is a multitasking organ that fulfils not only digestive and endocrine functions, but also represents one of the most important barriers between environmental pathogens and the human system. A healthy stomach is essential for the personal well-being, therefore gastric diseases are a substantial burden on global health care systems. Neuroendocrine stimuli, inflammatory mediators and vegetative signalling all have a role in the delicate balance of maintaining an intact gastric barrier. Until thirty years ago, modification of dietary habits and lifestyle factors were the only means by which to preserve a healthy stomach, and interference with acid secretion the main nonsurgical therapeutic approach in the treatment of gastric disease. The description of Helicobacter pylori (H. pylori) in 1983 by Robin Warren and Barry Marshall, as well as the proof of the association of this infection to gastroduodenal ulcer disease and acknowledgement of its role in gastric carcinogenesis in 1994, changed the clinical picture dramatically [1]. Both national and international guidelines on stomach-related diseases now focus on diagnosis and management of H. pylori infection. The increasingly accumulating evidence for the potential of gastric cancer prevention by H. pylori eradication gives further hope for future therapeutic directions [2,3]. However, the influence of H. pylori infection is, to a certain extent, dependent on regional factors like ethnicity of the host and local environmental conditions. Availability of diagnostic and therapeutic means, as well as regulations of the local health care system, play a further role. This is reflected in the distinct recommendations in guidelines produced from the East and the West. The Maastricht IV consensus report serves as the main guidance in Europe and the West and the 2nd AsiaePacific Consensus guidelines for the East [4,5]. It is consistently agreed that testing for H. pylori should only be undertaken when eradication is the consequence of a positive result, although there might be a shift of this approach towards population-based ‘screen-and-eradicate’ in the future when H. pylori eradication is more widely accepted for gastric cancer prevention. In guidelines from various countries eradication is indicated in patients with peptic ulcer disease, mucosa associated lymphoid tissue (MALT) lymphoma of the stomach and investigated non-ulcer dyspepsia [4e13]. There is discordance concerning ‘test-and-treat’ strategy in non-investigated dyspepsia, with the AsiaePacific consensus stating that test-and-treat is generally acceptable and Maastricht IV confirming this only in areas with a regional H. pylori prevalence higher than 20% [4,5]. In patients without alarm symptoms or family history for gastric cancer, the current German, South Korean and Chinese guidelines don't justify this indication over endoscopy as primary diagnostic approach, whereas the British consider it as an option, the US and the Brazilian guidelines recommend it with regards to the patients' age for patients older than 55 years and 35 years, respectively [7,11]. It has been estimated that the number needed to treat one H. pylori positive non-ulcer dyspepsia patient effectively for his symptoms is 15, which seems to be cost-effective compared to other strategies in the US [14,15]. A further indication for test-and-treat would be long-term intake of NSAIDs and Aspirin. This is a ‘must do’ indication in the US whereas other guidelines from Asia and Europe recommend this e and additional PPI therapy e only in patients with a history of previous ulcers or including acute ulcer bleeding [4,5,7,10]. There is agreement for H. pylori testing in patients with idiopathic thombocytopenic http://dx.doi.org/10.1016/j.bpg.2014.09.008 1521-6918/© 2014 Elsevier Ltd. All rights reserved.
950
Preface / Best Practice & Research Clinical Gastroenterology 28 (2014) 949e951
purpura and unexplained iron deficiency anaemia; however, other extragastric diseases are controversely debated, including vascular, respiratory, neurological and dermatological diseases [16e19]. The effect of H. pylori eradication on gastro-oesophageal reflux disease is discussed ambiguously. While the British and Chinese guidelines explicitly state that widespread H. pylori eradication might lead to an increase of oesophageal adenocarcinomas and cancer at the oesophagogastric junction, guidelines from the US, Germany, Brazil, Japan and South Korea regard the influence of H. pylori eradication on the outcome and severity of reflux disease as negligible [6e9,11,20]. The international European and AsiaePacific guidelines add the recommendation to test for H. pylori infection in any reflux patient who will receive long-term PPI treatment, as this can aggravate gastric atrophy [4,5]. Concerning the diagnostic methodology, non-invasive tests should be preferred if there is no indication for endoscopy. Only in Japan, serology is accepted as a reliable routine test-method, whereas, according to the European guidelines, serum-based tests should only be applied in case of an acute bleeding event, diagnosis of gastric malignancy, advanced mucosal atrophy or current intake of PPI or antibiotics [4,8]. Classic triple therapy, consisting of one PPI and two antibiotics, remains standard first-line treatment if local resistance rates for both Clarithromycin and Metronidazole are respected. However, the Japanese guidelines recommend lower doses of the administered drugs compared to other countries [8]. The length of treatment varies between seven and 14 days, but only in the US is the two-weeks regimen strictly advised [7]. If there is any contraindication for a classic first line triple, more recent guidelines respect the renaissance of Bismuth-based quadruple schemes as alternatives. There is no significant difference between the recommended second-line treatments, including comments on the usefulness and necessity of H. pylori culture and resistance testing in case of eradication failure. Recommendations for H. pylori test-and-treat with the aim of gastric cancer prevention is much more emphasised in regions with higher incidence for gastric adenocarcinomas when compared with low incidence regions, e.g. Germany. A clear focus is directed on an individual risk profile and focuses on patients with a remnant stomach who received previously curative therapy for gastric cancer, firstdegree relatives of gastric cancer patients, and patients with specific pattern of high-risk gastritis [4]. The point of no return in the cascade of mucosal alterations at which eradication can still prevent further progression of preneoplastic conditions is still under debate [21]. In countries with high incidence, like Japan and South Korea, radiological or endoscopic screening is a local health care standard due to the lack of a reliable non-invasive marker for non-invasive gastric cancer screening. For cost-effectiveness this is now more often combined with a serological prescreening for mucosal atrophy by assessment of serum pepsinogens, an approach that is not yet accepted within organised screening programs in low-incidence countries in the West. The European consensus guidelines for the management of precancerous conditions and lesions in the stomach (MAPS) are the first significant attempt to implement these approaches in Europe, in order to encourage screening and follow-up of high risk individuals in a standardised way, as is already happening for colorectal cancer screening or in patients with Barrett's oesophagus [22]. The suggested algorithm of combining the serological pre-screening for gastric diseases with colorectal cancer screening to enable broad availability and acceptance is being validated in several European multi-centre studies at present. The Healthy Stomach Initiative (www.hsinitiative.org) aims to bring these strategies forward, to combine experiences from East and West, and to initiate a comprehensive effort to fight gastric cancer. Founded in 2011, this common interest group unites international experts in the pathogenesis, diagnosis and management of gastric diseases from 35 countries. The main targets are the coordination of international trials for gastric cancer prevention, joint efforts for educational programmes to increase public awareness of gastric diseases as well as promotion of the importance of the healthy stomach as a multifunctional organ. In the spirit of this approach we would like to provide within this edition a comprehensive overview of factors that have an impact on gastric physiology, as well as new insights into the pathogenesis, diagnostic procedures and clinical management of inflammatory and oncological diseases of the stomach. Pharmacological and endogenous factors that modulate gastric barrier function will be reviewed as well as the impact of the gastrointestinal microbiome. The interaction between H. pylori and its individual host is addressed as well as the importance of additional inflammatory conditions of the stomach. An update on malignant diseases of the stomach includes modern endoscopic techniques and molecular high-throughput methods for diagnosis and subtyping of stomach cancer, as well as comments on recent consensus statements and the above-mentioned screening approaches.
Preface / Best Practice & Research Clinical Gastroenterology 28 (2014) 949e951
951
References [1] Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1(8390):1311e5. [2] Fuccio L, Zagari RM, Eusebi LH, Laterza L, Cennamo V, Ceroni L, et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med 2009;151(2):121e8. [3] Li WQ, Ma JL, Zhang L, Brown LM, Li JY, Shen L, et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. J Natl Cancer Inst 2014;106(7). [4] Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infectionethe Maastricht IV/Florence consensus report. Gut 2012;61(5):646e64. [5] Fock KM, Katelaris P, Sugano K, Ang TL, Hunt R, Talley NJ, et al. Second AsiaePacific consensus guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 2009;24(10):1587e600. [6] Fischbach W, Malfertheiner P, Hoffmann JC, Bolten W, Bornschein J, Gotze O, et al. S3-guideline “Helicobacter pylori and gastroduodenal ulcer disease” of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021/001. Z Gastroenterol 2009;47(12):1230e63. [7] Talley NJ, Vakil N. Guidelines for the management of dyspepsia. Am J Gastroenterol 2005;100(10):2324e37. [8] Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter 2010;15(1):1e20. [9] Kim SG, Jung HK, Lee HL, Jang JY, Lee H, Kim CG, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol 2014;29(7):1371e86. [10] Liu WZ, Xie Y, Cheng H, Lu NH, Hu FL, Zhang WD, et al. Fourth Chinese National consensus report on the management of Helicobacter pylori infection. J Dig Dis 2013;14(5):211e21. [11] Coelho LG, Maguinilk I, Zaterka S, Parente JM, do Carmo Friche Passos M, Moraes-Filho JP. 3rd Brazilian Consensus on Helicobacter pylori. Arq Gastroenterol 2013;50(2). [12] Hunt R, Fallone C, Veldhuyzan van Zanten S, Sherman P, Smaill F, Flook N, et al. Canadian Helicobacter Study Group Consensus Conference: update on the management of Helicobacter pyloriean evidence-based evaluation of six topics relevant to clinical outcomes in patients evaluated for H. pylori infection. Can J Gastroenterol 2004;18(9):547e54. [13] Mason JM, Delaney B, Moayyedi P, Thomas M, Walt R. Managing dyspepsia without alarm signs in primary care: new national guidance for England and Wales. Aliment Pharmacol Ther 2005;21(9):1135e43. [14] Holmes KP, Fang JC, Jackson BR. Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and management in uninvestigated dyspepsia assuming a high resource intensity practice pattern. BMC Health Serv Res 2010;10:344. [15] Moayyedi P, Deeks J, Talley NJ, Delaney B, Forman D. An update of the cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am J Gastroenterol 2003;98(12):2621e6. [16] Weigt J, Malfertheiner P. Influence of Helicobacter pylori on gastric regulation of food intake. Curr Opin Clin Nutr Metab Care 2009;12(5):522e5. [17] Kowalski M, Pawlik M, Konturek JW, Konturek SJ. Helicobacter pylori infection in coronary artery disease. J Physiol Pharmacol 2006;57(Suppl. 3):101e11. [18] Kountouras J, Tsolaki M, Gavalas E, Boziki M, Zavos C, Karatzoglou P, et al. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 2006;66(6):938e40. [19] Charlett A, Dobbs RJ, Dobbs SM, Weller C, Ibrahim MA, Dew T, et al. Blood profile holds clues to role of infection in a premonitory state for idiopathic Parkinsonism and of gastrointestinal infection in established disease. Gut Pathog 2009;1(1):20. [20] Allum WH, Blazeby JM, Griffin SM, Cunningham D, Jankowski JA, Wong R. Guidelines for the management of oesophageal and gastric cancer. Gut 2011;60(11):1449e72. [21] Bornschein J, Malfertheiner P. Helicobacter pylori and gastric cancer. Dig Dis 2014;32(3):249e64. [22] Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O'Connor A, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012;44(1):74e94.
Jan Bornschein, MD* Dept. of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK Marcis Leja, MD Faculty of Medicine, University of Latvia, Riga East University Hospital, Riga, Latvia Corresponding author. Dept. of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. Tel.: þ49 3916713100; fax: þ49 3916713105. E-mail address: [email protected] (J. Bornschein)
Contents lists available at ScienceDirect
Best Practice & Research Clinical Gastroenterology
Preface
The global challenge of a healthy stomach The stomach is a multitasking organ that fulfils not only digestive and endocrine functions, but also represents one of the most important barriers between environmental pathogens and the human system. A healthy stomach is essential for the personal well-being, therefore gastric diseases are a substantial burden on global health care systems. Neuroendocrine stimuli, inflammatory mediators and vegetative signalling all have a role in the delicate balance of maintaining an intact gastric barrier. Until thirty years ago, modification of dietary habits and lifestyle factors were the only means by which to preserve a healthy stomach, and interference with acid secretion the main nonsurgical therapeutic approach in the treatment of gastric disease. The description of Helicobacter pylori (H. pylori) in 1983 by Robin Warren and Barry Marshall, as well as the proof of the association of this infection to gastroduodenal ulcer disease and acknowledgement of its role in gastric carcinogenesis in 1994, changed the clinical picture dramatically [1]. Both national and international guidelines on stomach-related diseases now focus on diagnosis and management of H. pylori infection. The increasingly accumulating evidence for the potential of gastric cancer prevention by H. pylori eradication gives further hope for future therapeutic directions [2,3]. However, the influence of H. pylori infection is, to a certain extent, dependent on regional factors like ethnicity of the host and local environmental conditions. Availability of diagnostic and therapeutic means, as well as regulations of the local health care system, play a further role. This is reflected in the distinct recommendations in guidelines produced from the East and the West. The Maastricht IV consensus report serves as the main guidance in Europe and the West and the 2nd AsiaePacific Consensus guidelines for the East [4,5]. It is consistently agreed that testing for H. pylori should only be undertaken when eradication is the consequence of a positive result, although there might be a shift of this approach towards population-based ‘screen-and-eradicate’ in the future when H. pylori eradication is more widely accepted for gastric cancer prevention. In guidelines from various countries eradication is indicated in patients with peptic ulcer disease, mucosa associated lymphoid tissue (MALT) lymphoma of the stomach and investigated non-ulcer dyspepsia [4e13]. There is discordance concerning ‘test-and-treat’ strategy in non-investigated dyspepsia, with the AsiaePacific consensus stating that test-and-treat is generally acceptable and Maastricht IV confirming this only in areas with a regional H. pylori prevalence higher than 20% [4,5]. In patients without alarm symptoms or family history for gastric cancer, the current German, South Korean and Chinese guidelines don't justify this indication over endoscopy as primary diagnostic approach, whereas the British consider it as an option, the US and the Brazilian guidelines recommend it with regards to the patients' age for patients older than 55 years and 35 years, respectively [7,11]. It has been estimated that the number needed to treat one H. pylori positive non-ulcer dyspepsia patient effectively for his symptoms is 15, which seems to be cost-effective compared to other strategies in the US [14,15]. A further indication for test-and-treat would be long-term intake of NSAIDs and Aspirin. This is a ‘must do’ indication in the US whereas other guidelines from Asia and Europe recommend this e and additional PPI therapy e only in patients with a history of previous ulcers or including acute ulcer bleeding [4,5,7,10]. There is agreement for H. pylori testing in patients with idiopathic thombocytopenic http://dx.doi.org/10.1016/j.bpg.2014.09.008 1521-6918/© 2014 Elsevier Ltd. All rights reserved.
950
Preface / Best Practice & Research Clinical Gastroenterology 28 (2014) 949e951
purpura and unexplained iron deficiency anaemia; however, other extragastric diseases are controversely debated, including vascular, respiratory, neurological and dermatological diseases [16e19]. The effect of H. pylori eradication on gastro-oesophageal reflux disease is discussed ambiguously. While the British and Chinese guidelines explicitly state that widespread H. pylori eradication might lead to an increase of oesophageal adenocarcinomas and cancer at the oesophagogastric junction, guidelines from the US, Germany, Brazil, Japan and South Korea regard the influence of H. pylori eradication on the outcome and severity of reflux disease as negligible [6e9,11,20]. The international European and AsiaePacific guidelines add the recommendation to test for H. pylori infection in any reflux patient who will receive long-term PPI treatment, as this can aggravate gastric atrophy [4,5]. Concerning the diagnostic methodology, non-invasive tests should be preferred if there is no indication for endoscopy. Only in Japan, serology is accepted as a reliable routine test-method, whereas, according to the European guidelines, serum-based tests should only be applied in case of an acute bleeding event, diagnosis of gastric malignancy, advanced mucosal atrophy or current intake of PPI or antibiotics [4,8]. Classic triple therapy, consisting of one PPI and two antibiotics, remains standard first-line treatment if local resistance rates for both Clarithromycin and Metronidazole are respected. However, the Japanese guidelines recommend lower doses of the administered drugs compared to other countries [8]. The length of treatment varies between seven and 14 days, but only in the US is the two-weeks regimen strictly advised [7]. If there is any contraindication for a classic first line triple, more recent guidelines respect the renaissance of Bismuth-based quadruple schemes as alternatives. There is no significant difference between the recommended second-line treatments, including comments on the usefulness and necessity of H. pylori culture and resistance testing in case of eradication failure. Recommendations for H. pylori test-and-treat with the aim of gastric cancer prevention is much more emphasised in regions with higher incidence for gastric adenocarcinomas when compared with low incidence regions, e.g. Germany. A clear focus is directed on an individual risk profile and focuses on patients with a remnant stomach who received previously curative therapy for gastric cancer, firstdegree relatives of gastric cancer patients, and patients with specific pattern of high-risk gastritis [4]. The point of no return in the cascade of mucosal alterations at which eradication can still prevent further progression of preneoplastic conditions is still under debate [21]. In countries with high incidence, like Japan and South Korea, radiological or endoscopic screening is a local health care standard due to the lack of a reliable non-invasive marker for non-invasive gastric cancer screening. For cost-effectiveness this is now more often combined with a serological prescreening for mucosal atrophy by assessment of serum pepsinogens, an approach that is not yet accepted within organised screening programs in low-incidence countries in the West. The European consensus guidelines for the management of precancerous conditions and lesions in the stomach (MAPS) are the first significant attempt to implement these approaches in Europe, in order to encourage screening and follow-up of high risk individuals in a standardised way, as is already happening for colorectal cancer screening or in patients with Barrett's oesophagus [22]. The suggested algorithm of combining the serological pre-screening for gastric diseases with colorectal cancer screening to enable broad availability and acceptance is being validated in several European multi-centre studies at present. The Healthy Stomach Initiative (www.hsinitiative.org) aims to bring these strategies forward, to combine experiences from East and West, and to initiate a comprehensive effort to fight gastric cancer. Founded in 2011, this common interest group unites international experts in the pathogenesis, diagnosis and management of gastric diseases from 35 countries. The main targets are the coordination of international trials for gastric cancer prevention, joint efforts for educational programmes to increase public awareness of gastric diseases as well as promotion of the importance of the healthy stomach as a multifunctional organ. In the spirit of this approach we would like to provide within this edition a comprehensive overview of factors that have an impact on gastric physiology, as well as new insights into the pathogenesis, diagnostic procedures and clinical management of inflammatory and oncological diseases of the stomach. Pharmacological and endogenous factors that modulate gastric barrier function will be reviewed as well as the impact of the gastrointestinal microbiome. The interaction between H. pylori and its individual host is addressed as well as the importance of additional inflammatory conditions of the stomach. An update on malignant diseases of the stomach includes modern endoscopic techniques and molecular high-throughput methods for diagnosis and subtyping of stomach cancer, as well as comments on recent consensus statements and the above-mentioned screening approaches.
Preface / Best Practice & Research Clinical Gastroenterology 28 (2014) 949e951
951
References [1] Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1(8390):1311e5. [2] Fuccio L, Zagari RM, Eusebi LH, Laterza L, Cennamo V, Ceroni L, et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med 2009;151(2):121e8. [3] Li WQ, Ma JL, Zhang L, Brown LM, Li JY, Shen L, et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. J Natl Cancer Inst 2014;106(7). [4] Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infectionethe Maastricht IV/Florence consensus report. Gut 2012;61(5):646e64. [5] Fock KM, Katelaris P, Sugano K, Ang TL, Hunt R, Talley NJ, et al. Second AsiaePacific consensus guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 2009;24(10):1587e600. [6] Fischbach W, Malfertheiner P, Hoffmann JC, Bolten W, Bornschein J, Gotze O, et al. S3-guideline “Helicobacter pylori and gastroduodenal ulcer disease” of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021/001. Z Gastroenterol 2009;47(12):1230e63. [7] Talley NJ, Vakil N. Guidelines for the management of dyspepsia. Am J Gastroenterol 2005;100(10):2324e37. [8] Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter 2010;15(1):1e20. [9] Kim SG, Jung HK, Lee HL, Jang JY, Lee H, Kim CG, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol 2014;29(7):1371e86. [10] Liu WZ, Xie Y, Cheng H, Lu NH, Hu FL, Zhang WD, et al. Fourth Chinese National consensus report on the management of Helicobacter pylori infection. J Dig Dis 2013;14(5):211e21. [11] Coelho LG, Maguinilk I, Zaterka S, Parente JM, do Carmo Friche Passos M, Moraes-Filho JP. 3rd Brazilian Consensus on Helicobacter pylori. Arq Gastroenterol 2013;50(2). [12] Hunt R, Fallone C, Veldhuyzan van Zanten S, Sherman P, Smaill F, Flook N, et al. Canadian Helicobacter Study Group Consensus Conference: update on the management of Helicobacter pyloriean evidence-based evaluation of six topics relevant to clinical outcomes in patients evaluated for H. pylori infection. Can J Gastroenterol 2004;18(9):547e54. [13] Mason JM, Delaney B, Moayyedi P, Thomas M, Walt R. Managing dyspepsia without alarm signs in primary care: new national guidance for England and Wales. Aliment Pharmacol Ther 2005;21(9):1135e43. [14] Holmes KP, Fang JC, Jackson BR. Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and management in uninvestigated dyspepsia assuming a high resource intensity practice pattern. BMC Health Serv Res 2010;10:344. [15] Moayyedi P, Deeks J, Talley NJ, Delaney B, Forman D. An update of the cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am J Gastroenterol 2003;98(12):2621e6. [16] Weigt J, Malfertheiner P. Influence of Helicobacter pylori on gastric regulation of food intake. Curr Opin Clin Nutr Metab Care 2009;12(5):522e5. [17] Kowalski M, Pawlik M, Konturek JW, Konturek SJ. Helicobacter pylori infection in coronary artery disease. J Physiol Pharmacol 2006;57(Suppl. 3):101e11. [18] Kountouras J, Tsolaki M, Gavalas E, Boziki M, Zavos C, Karatzoglou P, et al. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 2006;66(6):938e40. [19] Charlett A, Dobbs RJ, Dobbs SM, Weller C, Ibrahim MA, Dew T, et al. Blood profile holds clues to role of infection in a premonitory state for idiopathic Parkinsonism and of gastrointestinal infection in established disease. Gut Pathog 2009;1(1):20. [20] Allum WH, Blazeby JM, Griffin SM, Cunningham D, Jankowski JA, Wong R. Guidelines for the management of oesophageal and gastric cancer. Gut 2011;60(11):1449e72. [21] Bornschein J, Malfertheiner P. Helicobacter pylori and gastric cancer. Dig Dis 2014;32(3):249e64. [22] Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O'Connor A, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012;44(1):74e94.
Jan Bornschein, MD* Dept. of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK Marcis Leja, MD Faculty of Medicine, University of Latvia, Riga East University Hospital, Riga, Latvia Corresponding author. Dept. of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. Tel.: þ49 3916713100; fax: þ49 3916713105. E-mail address: [email protected] (J. Bornschein)