Involvement of non-Helicobacter pylori helicobacter infections in Helicobacter pylori-negative gastric MALT lymphoma pathogenesis and efficacy of eradication therapy

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.

Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

“…Effects of antibiotics were particularly observed in patients with localized disease [34,35]. In addition, Helicobacter species other than H. pylori have been suspected to explain the antibiotic treatment responses [36,37]. In the present study, nine H. pylori negative patients were treated with antibiotics (stage I, n = 6; stage II, n = 2; stage IV, n = 1).…”

Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma in the Gastrointestinal Tract in the Modern Era

“…Bone marrow involvement is exceedingly rare (3%) [ 18 ]. There is an increasing trend of H. pylori -negative gastric MALT lymphoma cases, accounting for 6–40% of recent cases [ 7 , 8 , 9 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Compared to H. pylori -positive cases, H. pylori -negative gastric MALT lymphomas tend to be in an advanced clinical stage [ 24 ].…”

“…In H. pylori -negative cases, non- H. pylori Helicobacters (NHPHs; also referred to as H. heilmannii ) are occasionally associated with gastric MALT lymphoma [ 46 ]. Takigawa et al reported that 55% of patients with H. pylori -negative gastric MALT lymphoma without a BIRC3-MALT1 chimeric transcript are infected with an NHPH [ 20 ]. NHPHs typically have a large spiral-shaped morphology and comprise H. suis, H. felis, H. bizzozeronii, H. salomonis, and Candidatus H. heilmannii , accounting for only 0.1% of cases in which gastric biopsy is performed [ 47 , 48 ].…”

“…Eradication therapy for H. pylori is now used as the first-line therapy for gastric MALT lymphoma, regardless of stage. Antibiotic eradication of H. pylori leads to regression and an effective cure of gastric MALT lymphoma in approximately 70–80% of patients [ 7 , 20 , 26 , 27 ]. Triple-therapy regimens combining a proton-pump inhibitor for 4 weeks plus clarithromycin with either amoxicillin or metronidazole for 10–14 days are highly effective [ 75 ].…”

“…The predictors of resistance to H. pylori eradication include the absence of H. pylori , advanced stage, proximal location, endoscopic non-superficial type, polypoid appearance, deep submucosal invasion by endoscopic ultrasonography, and the presence of t(11;18)/ BIRC3 ( API2)-MALT1 translocation [ 20 , 75 , 78 , 79 , 80 , 81 ].…”