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Kitadai Y, Takigawa H, Shimizu D, Ariyoshi M, Tsuboi A, Tanaka H, Yamashita K, Hiyama Y, Kishida Y, Urabe Y, Ishikawa A, Kuwai T, Oka S. Endoscopic features differentiating non-Helicobacter pylori Helicobacter-induced gastric mucosa-associated lymphoid tissue lymphoma with a nodular gastritis-like appearance and H. pylori-induced conventional nodular gastritis. Dig Endosc 2025. [PMID: 40347029 DOI: 10.1111/den.15042] [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: 12/02/2024] [Accepted: 04/13/2025] [Indexed: 05/12/2025]
Abstract
OBJECTIVES Conventional nodular gastritis has been known to be caused by Helicobacter pylori infection. Several cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with non-H. pylori Helicobacters (NHPH) exhibit endoscopic findings resembling nodular gastritis. Considering the differences in malignancy, distinguishing between these two conditions is crucial. This study aimed to identify the distinguishing endoscopic features of NHPH-induced gastric MALT lymphoma with nodular gastritis-like appearance (NHPHi-MNG) and H.-induced conventional nodular gastritis (HPi-NG). METHODS Between 2011 and 2022, we analyzed 17 patients with NHPHi-MNG and 50 patients with HPi-NG at Hiroshima University Hospital and evaluated nodule morphology and distribution patterns. RESULTS Compared with the HPi-NG group, the NHPHi-MNG group exhibited significantly larger nodules (2.5 vs. 2.0 mm, P < 0.05) with protruded morphology (protruded/superficial, elevated: 14/3 vs. 8/42, P < 0.05), most prominently in the gastric angulus. The variability in nodule size was significantly higher in the NHPHi-MNG group than in the HPi-NG group (0.85 vs. 0.37 mm, P < 0.05), reflecting nodule heterogeneity. The distance from the gastric angulus to the proximal end of the nodular lesions was significantly greater in the NHPHi-MNG group than in the HPi-NG group (4.4 vs. 1.7 cm, P < 0.05). The nodules in the HPi-NG group were smaller, superficial, elevated, and most prominent in the gastric antrum compared with those in the NHPHi-MNG group. They were predominantly distributed in the gastric antrum with a homogeneous morphology. CONCLUSION NHPHi-MNG and HPi-NG can be endoscopically differentiated according to nodule morphology and distribution. Recognizing these distinguishing features is essential for an accurate diagnosis.
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Affiliation(s)
- Yuki Kitadai
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hidehiko Takigawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Daisuke Shimizu
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Misa Ariyoshi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Akiyoshi Tsuboi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hidenori Tanaka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ken Yamashita
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuichi Hiyama
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshihiro Kishida
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuji Urabe
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Akira Ishikawa
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toshio Kuwai
- Gastrointestinal Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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García-Ferrús M, González A, Ferrús MA. Detection, isolation and virulence characterization of Helicobacter suis from pork products aimed to human consumption. Int J Food Microbiol 2025; 427:110936. [PMID: 39437682 DOI: 10.1016/j.ijfoodmicro.2024.110936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 10/06/2024] [Accepted: 10/10/2024] [Indexed: 10/25/2024]
Abstract
Helicobacter suis is the most common non-Helicobacter pylori gastric Helicobacter species found in humans. Infection is associated with gastritis, peptic ulcer, gastric MALT lymphoma and neurodegenerative disorders, particularly Parkinson's disease. However, the pathogenicity of this species is still a matter of research, and results of virulence studies and antibiotic susceptibility tests tend to vary between strains. Cholesterol α-glucosyltransferase (αCgT), a known H. pylori virulence factor, appears to be present in most clinical H. suis isolates. The ability to form biofilms also plays a crucial role in the pathogenesis of H. pylori. However, no reports have been published on this ability in H. suis. H. suis is considered an emerging zoonotic pathogen, with pigs being the main source of human infection. However, there is very little information on its presence in pork, mainly due to the difficulties of its culture. Therefore, our aim was to determine the prevalence of H. suis in pork products from our geographical area by PCR and Fluorescence in situ Hybridization (FISH), as well as to isolate the bacteria and determine the antibiotic susceptibility patterns, the presence of the αCgT gene and the ability of the isolates to form biofilms. Overall, H. suis was detected in 20 of the 70 (28.6 %) samples analyzed. In 3 of them, H. suis was isolated. The αCgT gene was detected in all isolates and two of them showed a multiresistance pattern. The H. suis reference strain and two of the isolates showed "strong" to "moderate" in vitro biofilm formation ability under optimal growth conditions. Our results seem to indicate that H. suis is significantly prevalent in pork products. The combination of culture with FISH and/or mPCR proved to be a rapid and specific method for the detection, identification and direct visualization of cultivable H. suis cells from pork food products.
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Affiliation(s)
- Miguel García-Ferrús
- Centro Avanzado de Microbiología Aplicada, Universitat Politècnica de València, Camino de Vera s/n, 46022 València, Spain.
| | - Ana González
- Centro Avanzado de Microbiología Aplicada, Universitat Politècnica de València, Camino de Vera s/n, 46022 València, Spain.
| | - María A Ferrús
- Centro Avanzado de Microbiología Aplicada, Universitat Politècnica de València, Camino de Vera s/n, 46022 València, Spain.
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Sim JY, Chung HS, Kim SG, Cho SJ, Kim BK, Hong JS, Kim IH. Long-term Outcomes and Prognostic Factors of Gastric MALT Lymphoma. J Gastric Cancer 2024; 24:406-419. [PMID: 39375056 PMCID: PMC11471325 DOI: 10.5230/jgc.2024.24.e36] [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: 05/20/2024] [Revised: 08/06/2024] [Accepted: 08/12/2024] [Indexed: 10/09/2024] Open
Abstract
PURPOSE This study aimed to evaluate the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, including overall survival (OS), remission, and factors associated with an aggressive disease course. MATERIALS AND METHODS Medical records of 153 patients diagnosed with gastric MALT lymphoma between 2013 and 2020 were retrospectively reviewed. Patients experiencing relapse, progression, high-grade transformation, or residual diseasewere included in the aggressive group and were compared with those in the indolent group. Additionally, the endoscopic findings of Helicobacter pylori-negative patients were reviewed. RESULTS Patient characteristics were as follows: mean age (56.9±11.2 years), sex (male, 51.0%), H. pylori infection (positive, 79.7%), endoscopic location (distal, 89.5%), endoscopic feature (superficial, 89.5%), clinical stage (stage I, 92.8%), invasion depth by endoscopic ultrasound (mucosa, n=115, 75.7%), and bone marrow result (no involvement, n=77, 100.0%). The median follow-up period was 59 months (mean, 61; range, 36-124) and the continuous remission period (n=149) was 51 months (mean, 50; range, 3-112). The 5-year survival rate was 97.7% while the 5-year continuous remission was 88.3%. Factors associated with the patients in the aggressive group were old age, sex(male), and clinical stage II or higher. H. pylori-negative patients' endoscopy revealed a high incidence of atrophic gastritis in the antrum. CONCLUSIONS The long-term prognosis of gastric MALT lymphoma appears indolent and is indicated by the 5-year OS and continuous remission rates. Aggressive disease courses are associated with old age, sex (male), and clinical stage II or higher, but are not related to OS.
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Affiliation(s)
- Jae Yeon Sim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Soo Chung
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
| | - Sang Gyun Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Soo Jeong Cho
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Bo Kyung Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jun Shik Hong
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - In Ho Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Abuduwaili M, Takigawa H, Yuge R, Teshima H, Kotachi T, Urabe Y, Ito M, Sentani K, Oue N, Oka S, Kitadai Y, Tanaka S. No significant association between non-Helicobacter pylori Helicobacter infection with gastritis-related indices and gastric cancer. Am J Med Sci 2023; 366:421-429. [PMID: 37660992 DOI: 10.1016/j.amjms.2023.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 06/24/2023] [Accepted: 08/29/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND Non-Helicobacter pylori Helicobacter (NHPH) has recently been linked to various gastric diseases. However, the relationship between NHPH infection and gastric cancer remains controversial. This study aimed to identify the effect of NHPH infection on gastritis and gastric cancer development. MATERIALS AND METHODS Formalin-fixed paraffin-embedded tissues were obtained from 73 patients with gastric cancer, of whom 21 cases were Helicobacter pylori (Hp) current infection, 37 cases were Hp previous infection, and 15 cases were Hp naïve infection, and were screened for NPHPs using polymerase chain reaction. The results were compared with NHPH infection rates in the patients with gastritis-related diseases reported in the previous study. We evaluated the association of NHPH infection with gastritis and clinicopathological features of gastric cancer. RESULTS NHPH infection rates were 4/21 (19%) in "Hp current" patients, 4/37 (11%) in "Hp previous" infection patients, and 1/15 (7%) in "Hp naïve" patients, showing no significant difference in infection rates based on Hp infection status. NHPH infection rates in gastric cancer patients were similar to those in the patients with gastritis-related diseases reported in the previous study. A comparison of NHPH-positive and negative patients showed no significant differences in atrophic gastritis status, serum gastritis markers, or clinicopathological characteristics of gastric cancer, such as localization, size, gross type, differentiation, or depth. CONCLUSIONS The association between gastric cancer and NHPH infection would have important implications for gastric cancer prevention, diagnostics, and treatment, however, no significant association was found in this particular population.
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Affiliation(s)
- Maidina Abuduwaili
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Hidehiko Takigawa
- Department of Endoscopy, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Hajime Teshima
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Takahiro Kotachi
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Yuji Urabe
- Division of Regeneration and Medicine Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan
| | - Masanori Ito
- Department of General Internal Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Naohide Oue
- Department of Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Yasuhiko Kitadai
- Department of Health and Science, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
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Lemos FFB, Silva Luz M, Rocha Pinheiro SL, Teixeira KN, Freire de Melo F. Role of non- Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma. World J Gastroenterol 2023; 29:4851-4859. [PMID: 37701138 PMCID: PMC10494762 DOI: 10.3748/wjg.v29.i32.4851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 07/18/2023] [Accepted: 08/02/2023] [Indexed: 08/25/2023] Open
Abstract
Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma, trailing behind diffuse large B-cell lymphoma and follicular lymphoma. Gastric mucosa-associated lymphoid tissue lymphoma (GML) is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori (H. pylori)-induced chronic gastritis. On the other hand, a specific subset of individuals diagnosed with GML does not exhibit H. pylori infection. In contrast to its H. pylori-positive counterpart, it was previously believed that H. pylori-negative GML was less likely to respond to antimicrobial therapy. Despite this, surprisingly, in-creasing evidence supports that a considerable proportion of patients with H. pylori-negative GML show complete histopathological remission after bacterial eradication therapy. Nonetheless, the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended. In recent years, there has been growing interest in investigating the role of non-H. pylori gastric helicobacters (NHPHs) in the pathogenesis of H. pylori-negative GML. However, additional research is required to establish the causal relationship between NHPHs and GML. In this minireview, we examined the current understanding and proposed prospects on the involvement of NHPHs in H. pylori-negative GML, as well as their potential response to bacterial eradication therapy.
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Affiliation(s)
- Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
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Matysiak-Budnik T, Priadko K, Bossard C, Chapelle N, Ruskoné-Fourmestraux A. Clinical Management of Patients with Gastric MALT Lymphoma: A Gastroenterologist's Point of View. Cancers (Basel) 2023; 15:3811. [PMID: 37568627 PMCID: PMC10417821 DOI: 10.3390/cancers15153811] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/25/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
Gastric mucosa-associated lymphoid tissue (MALT) lymphomas (GML) are non-Hodgkin lymphomas arising from the marginal zone of the lymphoid tissue of the stomach. They are usually induced by chronic infection with Helicobacter pylori (H. pylori); however, H. pylori-negative GML is of increasing incidence. The diagnosis of GML is based on histological examination of gastric biopsies, but the role of upper endoscopy is crucial since it is the first step in the diagnostic process and, with currently available novel endoscopic techniques, may even allow an in vivo diagnosis of GML per se. The treatment of GML, which is usually localized, always includes the eradication of H. pylori, which should be performed even in H. pylori-negative GML. In the case of GML persistence after eradication of the bacteria, low-dose radiotherapy may be proposed, while systemic treatments (immunochemotherapy) should be reserved for very rare disseminated cases. In GML patients, at diagnosis but even after complete remission, special attention must be paid to an increased risk of gastric adenocarcinoma, especially in the presence of associated gastric precancerous lesions (gastric atrophy and gastric intestinal metaplasia), which requires adequate endoscopic surveillance of these patients.
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Affiliation(s)
- Tamara Matysiak-Budnik
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, 44093 Nantes, France; (K.P.); (N.C.)
- Inserm, CHU Nantes, University of Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, 44000 Nantes, France
| | - Kateryna Priadko
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, 44093 Nantes, France; (K.P.); (N.C.)
- Hepato-Gastroenterology Unit, University Hospital Universita degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | | | - Nicolas Chapelle
- IMAD, Hepato-Gastroenterology & Digestive Oncology, University Hospital of Nantes, 44093 Nantes, France; (K.P.); (N.C.)
- Inserm, CHU Nantes, University of Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, 44000 Nantes, France
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Takigawa H, Yuge R, Miyamoto R, Otani R, Kadota H, Hiyama Y, Hayashi R, Urabe Y, Sentani K, Oue N, Kitadai Y, Oka S, Tanaka S. Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma. Cancers (Basel) 2023; 15:1206. [PMID: 36831547 PMCID: PMC9954119 DOI: 10.3390/cancers15041206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 02/04/2023] [Accepted: 02/08/2023] [Indexed: 02/17/2023] Open
Abstract
Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp infection using comprehensive RNA sequence analysis. Among 164 gastric MALT lymphoma patients who underwent eradication therapy as primary treatment, 36 were negative for both the API2-MALT1 fusion gene and Hp infection. Based on eradication therapy efficacy, two groups were established: complete response (CR) and no change (NC). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that cancer-related genes and infection-related genes were highly expressed in the NC and CR groups, respectively. Based on this finding and transcription factor, gene ontology enrichment, and protein-protein interaction analyses, we selected 16 candidate genes for predicting eradication therapy efficacy. Real-time PCR validation in 36 Hp-negative patients showed significantly higher expression of olfactomedin-4 (OLFM4) and the Nanog homeobox (NANOG) in the CR and NC groups, respectively. OLFM4 and NANOG could be positive and negative predictive markers, respectively, for eradication therapy efficacy against gastric MALT lymphoma that is negative for both API2-MALT1 and Hp infection.
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Affiliation(s)
- Hidehiko Takigawa
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Ryo Yuge
- Department of Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan
| | - Ryo Miyamoto
- Department of Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan
| | - Rina Otani
- Department of Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan
| | - Hiroki Kadota
- Department of Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yuichi Hiyama
- Department of Clinical Research Center, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Ryohei Hayashi
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Yuji Urabe
- Gastrointestinal Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Naohide Oue
- Department of Molecular Pathology, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Yasuhiko Kitadai
- Department of Health and Science, Prefectural University of Hiroshima, Hiroshima 734-8558, Japan
| | - Shiro Oka
- Department of Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, Japan
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Helicobacter suis-Associated Gastritis Mimicking Conventional H. pylori-Associated Atrophic Gastritis. Case Rep Gastrointest Med 2022; 2022:4254605. [PMID: 35911659 PMCID: PMC9329004 DOI: 10.1155/2022/4254605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/08/2022] [Indexed: 11/17/2022] Open
Abstract
A 45-year-old Japanese man underwent esophagogastroduodenoscopy, which revealed spotty redness at the gastric fornix, mucosal swelling, diffuse redness in the corpus, and mucosal atrophy in the gastric angle and antrum. Histological examination showed rod-shaped bacteria that appeared larger than Helicobacter pylori. The patient tested positive for rapid urease test, and serum anti-H. pylori IgG antibody test results were negative. Further examination of the bacteria revealed that H. suis antibody test was positive, and the presence of H. suis was confirmed using H. suis-specific real-time PCR. H. suis was successfully eradicated after triple therapy with vonoprazan, amoxicillin, and clarithromycin. This case reinforces the notion that non-H. pylori Helicobacter species such as H. suis and H. heilmannii may be involved in the pathogenesis of active gastritis in patients who test negative for H. pylori antibodies.
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Taillieu E, Chiers K, Amorim I, Gärtner F, Maes D, Van Steenkiste C, Haesebrouck F. Gastric Helicobacter species associated with dogs, cats and pigs: significance for public and animal health. Vet Res 2022; 53:42. [PMID: 35692057 PMCID: PMC9190127 DOI: 10.1186/s13567-022-01059-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/10/2022] [Indexed: 12/14/2022] Open
Abstract
This article focuses on the pathogenic significance of Helicobacter species naturally colonizing the stomach of dogs, cats and pigs. These gastric "non-Helicobacter (H.) pylori Helicobacter species" (NHPH) are less well-known than the human adapted H. pylori. Helicobacter suis has been associated with gastritis and decreased daily weight gain in pigs. Several studies also attribute a role to this pathogen in the development of hyperkeratosis and ulceration of the non-glandular stratified squamous epithelium of the pars oesophagea of the porcine stomach. The stomach of dogs and cats can be colonized by several Helicobacter species but their pathogenic significance for these animals is probably low. Helicobacter suis as well as several canine and feline gastric Helicobacter species may also infect humans, resulting in gastritis, peptic and duodenal ulcers, and low-grade mucosa-associated lymphoid tissue lymphoma. These agents may be transmitted to humans most likely through direct or indirect contact with dogs, cats and pigs. Additional possible transmission routes include consumption of water and, for H. suis, also consumption of contaminated pork. It has been described that standard H. pylori eradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcine H. suis strains are intrinsically less susceptible to aminopenicillins than non-human primate H. suis strains and other gastric Helicobacter species. Virulence factors of H. suis and the canine and feline gastric Helicobacter species include urease activity, motility, chemotaxis, adhesins and gamma-glutamyl transpeptidase. These NHPH, however, lack orthologs of cytotoxin-associated gene pathogenicity island and vacuolating cytotoxin A, which are major virulence factors in H. pylori. It can be concluded that besides H. pylori, gastric Helicobacter species associated with dogs, cats and pigs are also clinically relevant in humans. Although recent research has provided better insights regarding pathogenic mechanisms and treatment strategies, a lot remains to be investigated, including true prevalence rates, exact modes of transmission and molecular pathways underlying disease development and progression.
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Affiliation(s)
- Emily Taillieu
- Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
| | - Koen Chiers
- Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Irina Amorim
- Instituto de Investigação E Inovação Em Saúde (i3S), Universidade Do Porto, Porto, Portugal.,Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), Porto, Portugal.,School of Medicine and Biomedical Sciences, Porto University, Porto, Portugal
| | - Fátima Gärtner
- Instituto de Investigação E Inovação Em Saúde (i3S), Universidade Do Porto, Porto, Portugal.,Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), Porto, Portugal
| | - Dominiek Maes
- Department of Internal Medicine, Reproduction and Population Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Christophe Van Steenkiste
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp University, Edegem, Belgium.,Department of Gastroenterology and Hepatology, General Hospital Maria Middelares, Ghent, Belgium
| | - Freddy Haesebrouck
- Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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Kadota H, Yuge R, Miyamoto R, Otani R, Takigawa H, Hayashi R, Urabe Y, Oka S, Sentani K, Oue N, Kitadai Y, Tanaka S. Investigation of endoscopic findings in nine cases of Helicobacter suis-infected gastritis complicated by gastric mucosa-associated lymphoid tissue lymphoma. Helicobacter 2022; 27:e12887. [PMID: 35363918 DOI: 10.1111/hel.12887] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/05/2022] [Accepted: 03/06/2022] [Indexed: 01/16/2023]
Abstract
BACKGROUND We have previously reported that eradication therapy was more effective against Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma in non-Helicobacter pylori Helicobacter (NHPH)-positive cases than in NHPH-negative cases and that the infection status of NHPH could be a predictive marker for the efficacy of eradication therapy for H. pylori negative gastric MALT lymphoma. However, a diagnostic test for NHPH infection has not yet been clinically established. In this study, we investigated the endoscopic findings in cases of H. suis-infected gastritis associated with gastric MALT lymphoma reported at our institution. MATERIALS AND METHODS Participants were selected from cases of gastric MALT lymphoma who underwent esophagogastroduodenoscopy at Hiroshima University Hospital, who were negative for the API2-MALT1 gene, and who received eradication therapy as a first-line treatment. We examined the endoscopic findings in nine cases from this group in which H. suis infection was confirmed by polymerase chain reaction. RESULTS Endoscopic findings, such as cracked mucosa, spotty redness, nodular gastritis-like appearance, and white marbled appearance, which have been reported as characteristics of NHPH gastritis, were observed in multiple cases. The most common endoscopic findings in this study were cracked mucosa (7/9 cases), followed by spotty redness (6/9 cases), nodular gastritis-like appearance (5/9 cases), and white marbled appearance (2/9 cases). CONCLUSIONS Our study may serve as a reference for re-evaluation of the diagnostic criteria for H. suis infection and indications for eradication therapy, particularly for cases of H. pylori negative gastric MALT lymphoma, where endoscopic findings such as those seen in this study were observed in the background mucosa.
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Affiliation(s)
- Hiroki Kadota
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Ryo Miyamoto
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Rina Otani
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Hidehiko Takigawa
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Ryohei Hayashi
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Yuji Urabe
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Shiro Oka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Naohide Oue
- Department of Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Yasuhiko Kitadai
- Department of Health Sciences, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
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11
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Kuo SH, Yeh KH, Lin CW, Liou JM, Wu MS, Chen LT, Cheng AL. Current Status of the Spectrum and Therapeutics of Helicobacter pylori-Negative Mucosa-Associated Lymphoid Tissue Lymphoma. Cancers (Basel) 2022; 14:1005. [PMID: 35205754 PMCID: PMC8869919 DOI: 10.3390/cancers14041005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/12/2022] [Accepted: 02/14/2022] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori (HP)-unrelated mucosa-associated lymphoid tissue (MALT) lymphoma includes the majority of extragastric MALT lymphomas and a small proportion of gastric MALT lymphomas. Although the role of first-line antibiotics in treating HP-negative gastric MALT lymphomas remains controversial, HP eradication therapy (HPE)-like regimens may result in approximately 20-30% complete remission (CR) for patients with localized HP-negative gastric MALT lymphoma. In these patients, H. heilmannii, H. bizzozeronii, and H. suis were detected in sporadic gastric biopsy specimens. Extragastric MALT lymphoma is conventionally treated with radiotherapy for localized disease and systemic chemotherapy for advanced and metastatic diseases. However, a proportion of extragastric MALT lymphomas, such as ocular adnexal lesions and small intestinal lesions, were reported to be controlled by antibiotics for Chlamydophila psittaci and Campylobacter jejuni, respectively. Some extragastric MALT lymphomas may even respond to first-line HPE. These findings suggest that some antibiotic-responsive tumors may exist in the family of HP-negative MALT lymphomas. Two mechanisms underlying the antibiotic responsiveness of HP-negative MALT lymphoma have been proposed. First, an HPE-like regimen may eradicate the antigens of unknown bacteria. Second, clarithromycin (the main component of HPE) may have direct or indirect antineoplastic effects, thus contributing to the CR of these tumors. For antibiotic-unresponsive HP-negative MALT lymphoma, high-dose macrolides and immunomodulatory drugs, such as thalidomide and lenalidomide, have reported sporadic success. Further investigation of new treatment regimens is warranted.
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Affiliation(s)
- Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan; (S.-H.K.); (K.-H.Y.)
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan; (S.-H.K.); (K.-H.Y.)
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan;
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan;
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan;
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan;
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 704, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan; (S.-H.K.); (K.-H.Y.)
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan;
- Department of Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan
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12
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Ishikawa E, Nakamura M, Satou A, Shimada K, Nakamura S. Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma in the Gastrointestinal Tract in the Modern Era. Cancers (Basel) 2022; 14:446. [PMID: 35053607 PMCID: PMC8773811 DOI: 10.3390/cancers14020446] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/08/2022] [Accepted: 01/12/2022] [Indexed: 12/15/2022] Open
Abstract
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) typically arises from sites such as the stomach, where there is no organized lymphoid tissue. Close associations between Helicobacter pylori and gastric MALT lymphoma or Campylobacter jejuni and immunoproliferative small intestinal disease (IPSID) have been established. A subset of tumors is associated with chromosomal rearrangement and/or genetic alterations. This disease often presents as localized disease, requiring diverse treatment approaches, from antibiotic therapy to radiotherapy and immunochemotherapy. Eradication therapy for H. pylori effectively cures gastric MALT lymphoma in most patients. However, treatment strategies for H. pylori-negative gastric MALT lymphoma are still challenging. In addition, the effectiveness of antibiotic therapy has been controversial in intestinal MALT lymphoma, except for IPSID. Endoscopic treatment has been noted to usually achieve complete remission in endoscopically resectable colorectal MALT lymphoma with localized disease. MALT lymphoma has been excluded from post-transplant lymphoproliferative disorders with the exception of Epstein-Barr virus (EBV)-positive marginal zone lymphoma (MZL). We also describe the expanding spectrum of EBV-negative MZL and a close association of the disease with the gastrointestinal tract.
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Affiliation(s)
- Eri Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;
| | - Akira Satou
- Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute 480-1195, Japan;
| | - Kazuyuki Shimada
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan;
| | - Shotaro Nakamura
- Department of Gastroenterology, International University of Health and Welfare, Fukuoka 814-0001, Japan;
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13
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Tanaka T, Matsuno Y, Torisu T, Shibata H, Hirano A, Umeno J, Kawasaki K, Fujioka S, Fuyuno Y, Moriyama T, Esaki M, Kitazono T. Gastric microbiota in patients with Helicobacter pylori-negative gastric MALT lymphoma. Medicine (Baltimore) 2021; 100:e27287. [PMID: 34559138 PMCID: PMC8462607 DOI: 10.1097/md.0000000000027287] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 09/02/2021] [Indexed: 01/05/2023] Open
Abstract
To investigate the mucosal microbiota in the stomach of patients with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma by means of metagenomic analysis.Although some gastric MALT lymphomas are associated with the presence of H. pylori, other gastric MALT lymphomas occur independently of H. pylori infection. The pathogenesis of H. pylori-negative MALT lymphoma remains unclear.Mucosal biopsy specimens were collected from the gastric body from 33 MALT lymphoma patients with gastric lesions, including both H. pylori-infection naïve patients and posteradication patients, as well as 27 control participants without H. pylori infection or cancer. Subsequently, the samples were subjected to 16S rRNA gene sequencing. Quantitative insights into microbial ecology, linear discriminant analysis effect size, and phylogenetic investigation of communities by reconstruction of unobserved states softwares were used to analyze the participants' microbiota.H. pylori-negative MALT lymphoma patients had significantly lower alpha diversity (P = .04), compared with control participants. Significant differences were evident in the microbial composition (P = .04), as determined by comparison of beta diversity between the 2 groups. Taxonomic composition analysis indicated that the genera Burkholderia and Sphingomonas were significantly more abundant in MALT lymphoma patients, while the genera Prevotella and Veillonella were less abundant. Functional microbiota prediction showed that the predicted gene pathways "replication and repair," "translation," and "nucleotide metabolism" were downregulated in MALT lymphoma patients.H. pylori-negative MALT lymphoma patients exhibited altered gastric mucosal microbial compositions, suggesting that altered microbiota might be involved in the pathogenesis of H. pylori-negative MALT lymphoma.
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Affiliation(s)
- Takahide Tanaka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuichi Matsuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takehiro Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroki Shibata
- Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Atsushi Hirano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keisuke Kawasaki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shin Fujioka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuta Fuyuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | | | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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14
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Seo WC, Lee SY, Han HS. Helicobacter pylori-naive Subject with Spotty Redness in the Gastric Corpus. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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15
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Varon C, Azzi-Martin L, Khalid S, Seeneevassen L, Ménard A, Spuul P. Helicobacters and cancer, not only gastric cancer? Semin Cancer Biol 2021; 86:1138-1154. [PMID: 34425210 DOI: 10.1016/j.semcancer.2021.08.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 08/11/2021] [Accepted: 08/16/2021] [Indexed: 12/11/2022]
Abstract
The Helicobacter genus actually comprises 46 validly published species divided into two main clades: gastric and enterohepatic Helicobacters. These bacteria colonize alternative sites of the digestive system in animals and humans, and contribute to inflammation and cancers. In humans, Helicobacter infection is mainly related to H. pylori, a gastric pathogen infecting more than half of the world's population, leading to chronic inflammation of the gastric mucosa that can evolve into two types of gastric cancers: gastric adenocarcinomas and gastric MALT lymphoma. In addition, H. pylori but also non-H. pylori Helicobacter infection has been associated with many extra-gastric malignancies. This review focuses on H. pylori and its role in gastric cancers and extra-gastric diseases, as well as malignancies induced by non-H. pylori Helicobacters. Their different virulence factors and their involvement in carcinogenesis is discussed. This review highlights the importance of both gastric and enterohepatic Helicobacters in gastrointestinal and liver cancers.
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Affiliation(s)
- Christine Varon
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Lamia Azzi-Martin
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France; Univ. Bordeaux, UFR des Sciences Médicales, Bordeaux, France
| | - Sadia Khalid
- Tallinn University of Technology, Department of Chemistry and Biotechnology, Akadeemia RD 15, 12618, Tallinn, Estonia
| | - Lornella Seeneevassen
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Armelle Ménard
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Pirjo Spuul
- Tallinn University of Technology, Department of Chemistry and Biotechnology, Akadeemia RD 15, 12618, Tallinn, Estonia.
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16
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Takigawa H, Yuge R, Masaki S, Otani R, Kadota H, Naito T, Hayashi R, Urabe Y, Oka S, Tanaka S, Chayama K, Kitadai Y. Involvement of non-Helicobacter pylori helicobacter infections in Helicobacter pylori-negative gastric MALT lymphoma pathogenesis and efficacy of eradication therapy. Gastric Cancer 2021; 24:937-945. [PMID: 33638751 DOI: 10.1007/s10120-021-01172-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 02/12/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Eradication therapy is known to be effective against Helicobacter pylori-positive gastric MALT lymphoma but predicting the efficacy of eradication therapy against Helicobacter pylori-negative gastric MALT lymphoma is difficult. Recent reports have shown that non-Helicobacter pylori helicobacter infections induce gastric MALT lymphoma, and we aimed to clarify whether non-Helicobacter pylori helicobacter infections are associated with the efficacy of eradication therapy. METHODS We analyzed eradication therapy as a first-line treatment for 182 cases of gastric MALT lymphoma, classified according to Helicobacter pylori infection and API2-MALT1 mutation status. We also evaluated the non-Helicobacter pylori helicobacter infection status in 29 Helicobacter pylori-negative cases via PCR with DNA extracted from paraffin-embedded biopsy tissues. Finally, we analyzed the relationship between non-Helicobacter pylori helicobacter infection status and eradication therapy outcome. RESULTS The API2-MALT1 mutation was observed in 13/182 patients (7.1%), none of whom were cured by eradication therapy. Helicobacter pylori-negative cases had a significantly higher non-Helicobacter pylori helicobacter infection rate than Helicobacter pylori-positive cases (16/29, 55% vs. 3/29, 10%; P < 0.05). Among the Helicobacter pylori-negative cases, non-Helicobacter pylori helicobacter-positive cases had a significantly higher complete response rate than non-Helicobacter pylori helicobacter-negative cases (12/16, 75% vs. 3/13, 23%; P < 0.05). CONCLUSION Helicobacter pylori-negative and API2-MALT1-negative gastric MALT lymphoma cases exhibited a high rate of non-Helicobacter pylori helicobacter infections, which may have contributed to the success of eradication therapy. Therefore, we recommend eradication therapy as a first-line treatment for non-Helicobacter pylori helicobacter-positive gastric MALT lymphoma.
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Affiliation(s)
- Hidehiko Takigawa
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, 734-0037, Japan
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, 734-0037, Japan
| | - Satoshi Masaki
- Department of Health and Science, Prefectural University of Hiroshima, 1-1-71, Ujinahigashi, Minami-ku, Hiroshima, 734-8558, Japan
| | - Rina Otani
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, 734-0037, Japan
| | - Hiroki Kadota
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, 734-0037, Japan
| | - Toshikatsu Naito
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, 734-0037, Japan
| | - Ryohei Hayashi
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, 734-0037, Japan
| | - Yuji Urabe
- Division of Regeneration and Medicine Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, 734-0037, Japan
| | - Shiro Oka
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, 734-0037, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, 734-0037, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, 734-0037, Japan
| | - Yasuhiko Kitadai
- Department of Health and Science, Prefectural University of Hiroshima, 1-1-71, Ujinahigashi, Minami-ku, Hiroshima, 734-8558, Japan.
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17
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Rimbara E, Suzuki M, Matsui H, Nakamura M, Morimoto M, Sasakawa C, Masuda H, Nomura S, Osaki T, Nagata N, Shibayama K, Tokunaga K. Isolation and characterization of Helicobacter suis from human stomach. Proc Natl Acad Sci U S A 2021; 118:e2026337118. [PMID: 33753513 PMCID: PMC8020762 DOI: 10.1073/pnas.2026337118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Helicobacter suis, a bacterial species naturally hosted by pigs, can colonize the human stomach in the context of gastric diseases such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because H. suis has been successfully isolated from pigs, but not from humans, evidence linking human H. suis infection to gastric diseases has remained incomplete. In this study, we successfully in vitro cultured H. suis directly from human stomachs. Unlike Helicobacter pylori, the viability of H. suis decreases significantly on neutral pH; therefore, we achieved this using a low-pH medium for transport of gastric biopsies. Ultimately, we isolated H. suis from three patients with gastric diseases, including gastric MALT lymphoma. Successful eradication of H. suis yielded significant improvements in endoscopic and histopathological findings. Oral infection of mice with H. suis clinical isolates elicited gastric and systemic inflammatory responses; in addition, progression of gastric mucosal metaplasia was observed 4 mo postinfection. Because H. suis could be isolated from the stomachs of infected mice, our findings satisfied Koch's postulates. Although further prospective clinical studies are needed, H. suis, like H. pylori, is likely a gastric pathogen in humans. Furthermore, comparative genomic analysis of H. suis using complete genomes of clinical isolates revealed that the genome of each H. suis isolate contained highly plastic genomic regions encoding putative strain-specific virulence factors, including type IV secretion system-associated genes, and that H. suis isolates from humans and pigs were genetically very similar, suggesting possible pig-to-human transmission.
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Affiliation(s)
- Emiko Rimbara
- Department of Bacteriology II, National Institute of Infectious Diseases, 208-0011 Tokyo, Japan;
| | - Masato Suzuki
- Antimicrobial Research Center, National Institute of Infectious Diseases, 189-0002 Tokyo, Japan
| | - Hidenori Matsui
- Omura Satoshi Memorial Institute, Kitasato University, 108-8641 Tokyo, Japan;
| | | | - Misako Morimoto
- Department of Research Associate Product Development, Nippon Institute for Biological Science, 198-0024 Tokyo, Japan
| | - Chihiro Sasakawa
- Department of Research Associate Product Development, Nippon Institute for Biological Science, 198-0024 Tokyo, Japan
- Medical Mycology Research Center, Chiba University, 263-8522 Chiba, Japan
| | - Hiroki Masuda
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 113-8654 Tokyo, Japan
- Department of Gastrointestinal Surgery, Nippon Medical University, 113-8602 Tokyo, Japan
| | - Sachiyo Nomura
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 113-8654 Tokyo, Japan
| | - Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, 181-8611 Tokyo, Japan
| | - Noriyo Nagata
- Department of Pathology, National Institute of Infectious Diseases, 208-0011 Tokyo, Japan
| | - Keigo Shibayama
- Department of Bacteriology II, National Institute of Infectious Diseases, 208-0011 Tokyo, Japan
| | - Kengo Tokunaga
- Department of General Medicine, Kyorin University School of Medicine, 181-8611 Tokyo, Japan
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18
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Naito T, Yuge R, Tanaka S, Otani R, Kadota H, Takigawa H, Tamura T, Sentani K, Yasui W, Kitadai Y, Chayama K. Gastric mucosa-associated lymphoid tissue lymphoma in conjunction with multiple lymphomatous polyposis in the context of Helicobacter pylori and Helicobacter suis superinfection. Clin J Gastroenterol 2021; 14:478-483. [PMID: 33393060 PMCID: PMC8016757 DOI: 10.1007/s12328-020-01310-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 11/27/2020] [Indexed: 12/24/2022]
Abstract
A 53-year-old woman visited a doctor and complained of chest discomfort after meals. Esophagogastroduodenoscopy showed multiple granular elevations in the gastric body. After biopsies from the elevations, she was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. Polymerase chain reaction also detected Helicobacter pylori and H. suis. Treatment to eradicate H. pylori and H. suis was successful. Endoscopic examination after the bacterial eradication treatment showed that multiple granular elevations remained in the gastric body; however, no lymphoma cells were found during histopathological examination. Thus, we reported a case of H. pylori-positive gastric MALT lymphoma with a unique morphology associated with H. suis superinfection.
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Affiliation(s)
- Toshikatsu Naito
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan
| | - Rina Otani
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Hiroki Kadota
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Hidehiko Takigawa
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Tadamasa Tamura
- Department of Gastroenterology, Tsuchiya General Hospital, Hiroshima, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Wataru Yasui
- Department of Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Yasuhiko Kitadai
- Department of Health Science, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
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Abstract
This review covers the most important, accessible, and relevant literature published between April 2019 and April 2020 in the field of non-Helicobacter pylori Helicobacter species (NHPH). The initial part of the review covers new insights regarding the presence of gastric and enterohepatic NHPH in humans and animals, while the subsequent section focuses on the progress in our understanding of animal models, the pathogenicity and omics of these species. Over the last year, the clinical relevance of gastric NHPH infections in humans was highlighted. With regard to NHPH in animals, the ancestral source of Helicobacter suis was further established showing that Cynomolgus macaques are the common ancestor of the pig-associated H. suis population, and 3 novel Helicobacter species isolated from the gastric mucosa of red foxes were described. "Helicobacter burdigaliensis" sp nov. and "Helicobacter labetoulli" sp nov. were proposed as novel enterohepatic Helicobacter species associated with human digestive diseases. An analysis of Helicobacter cinaedi recurrent infections in humans proposed long-term antibiotic therapies. Several studies using rodent models further elucidated the mechanisms underlying the development of NHPH-related disease, as well as intestinal immunity in inflammatory bowel disease models. Omics approaches supported Helicobacteraceae taxonomy and unraveled the transcriptomic signatures of H. suis and Helicobacter heilmannii upon adherence to the human gastric epithelium. With regard to virulence, data showed that the nuclear remodeling promoted by cytolethal distending toxin of Helicobacters involves the MAFB oncoprotein and is associated with nucleoplasmic reticulum formation in surviving cells.
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Affiliation(s)
- Annemieke Smet
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.,Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Armelle Menard
- Univ. Bordeaux, INSERM, Bordeaux Research in Translational Oncology, BaRITOn, UMR1053, Bordeaux, France.,CHU de Bordeaux, Laboratoire de Bactériologie, Centre National de Référence des Campylobacters et des Hélicobacters, Bordeaux, France
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Takigawa H, Masaki S, Naito T, Yuge R, Urabe Y, Tanaka S, Sentani K, Matsuo T, Matsuo K, Chayama K, Kitadai Y. Helicobacter suis infection is associated with nodular gastritis-like appearance of gastric mucosa-associated lymphoid tissue lymphoma. Cancer Med 2019; 8:4370-4379. [PMID: 31210418 PMCID: PMC6675707 DOI: 10.1002/cam4.2314] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 05/15/2019] [Accepted: 05/16/2019] [Indexed: 01/28/2023] Open
Abstract
Most patients with gastric mucosa‐associated lymphoid tissue (MALT) lymphoma are infected with Helicobacter pylori, and eradication therapy is the first‐line treatment for localized disease with H pylori infection. However, there were several reports showing effectiveness of eradication therapy in even H pylori negative cases. Gastric MALT lymphomas are endoscopically classified into three common types: superficial, ulcerative, and elevated types. For the past 20 years, we have encountered 200 cases of localized gastric MALT lymphoma. Among them, only 4 cases (2%) showed similar macroscopic findings to those of nodular gastritis (gastric MALT lymphoma with nodular gastritis‐like appearance; M‐NGA). Here, we compared clinicopathological characteristics and prevalence of non‐H pylori Helicobacter (NHPH) infection between M‐NGA and other common types of gastric MALT lymphoma. To examine the prevalence of NHPH infection, DNA was extracted from formalin‐fixed paraffin‐embedded biopsy tissues from four cases of M‐NGA, 20 cases of common endoscopic types of gastric MALT lymphoma, and 10 cases of nodular gastritis. We used a highly sensitive polymerase chain reaction assay to detect the presence of five species of NHPH (Helicobacter suis, H felis, H bizzozeronii, H salomonis, and H heilmannii). H suis infection was detected in 4, 2, and 0 of the 4, 20, and 10 cases of M‐NGA, other types of gastric MALT lymphoma, and nodular gastritis, respectively. Other NHPH species were not detected in any cases. Complete response rate by eradication therapy was 4/4 in M‐NGA cases. Therefore, nodular gastritis‐like MALT lymphoma, which shows a very rare phenotype, is closely associated with NHPH infection, and eradication therapy may be the first‐choice treatment.
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Affiliation(s)
- Hidehiko Takigawa
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Satoshi Masaki
- Department of Health and Science, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Toshikatsu Naito
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University, Hiroshima, Japan
| | - Yuji Urabe
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University, Hiroshima, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Taiji Matsuo
- Department of Internal Medicine, Matsuonaika Hospital, Mihara, Japan
| | - Keisuke Matsuo
- Department of Internal Medicine, Matsuonaika Hospital, Mihara, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Yasuhiko Kitadai
- Department of Health and Science, Prefectural University of Hiroshima, Hiroshima, Japan
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