Determinación de Helicobacter spp. en mucosa gástrica glandular de muías a través de la prueba de la actividad de la ureasa e histopatología / Determination of Helicobacter spp. in glandular gastric mucosa of mules through the test of urease activity and histopathology

RESUMEN La información sobre la presentación y los factores predisponentes del síndrome de úlcera gástrica en mulas (SUGM) es escasa en comparación con el síndrome de úlcera gástrica en equinos (SUGE) y asnales. Debido a la naturaleza multifactorial de este síndrome, la helicobacteriosis ha sido estudiada en otras especies. El objetivo de este trabajo fue establecer la presencia de Helicobacter spp. en mucosa gástrica de mulas a través de la prueba rápida de la ureasa (PRU) y de análisis histopatológico. Menos del 27% de las muestras reaccionaron a la PRU, con tiempos prolongados de reacción, y al Agar Urea (prueba de oro), con menor porcentaje de positividad. La histopatología reveló procesos inflamatorios crónicos, sin presencia de bacterias curvoespiraladas. Las PRU no fueron conclusivas en la determinación de Helicobacter spp., comportamiento similar reportado en equinos. Se requieren exámenes diagnósticos más específicos y procedimientos complementarios orientados a explorar por regiones del estómago en la consideración del número de muestras representativas.

ABSTRACT Information on the presentation and predisposing factors of Mule Gastric Ulcer Syndrome (MGUS) is scarce, compared to Equine Gastric Ulcer Syndrome (EGUS) and donkeys. Within the multifactorial nature of this syndrome, helicobacteriosis has been studied in other species. The objective of this work was to establish the presence of Helicobacter spp. in gastric mucosa of mules, through the rapid urease test (RUT) and histopathological analysis. Less than 27% of the samples reacted to RUTs, with prolonged reaction times, and Urea Agar (gold test), with a lower percentage of positivity. Histopathology revealed chronic inflammatory processes, without the presence of curved-spiral bacteria. The RUTs were not conclusive in the determination of Helicobacter spp., a similar behavior reported in horses. More specific diagnostic tests and complementary procedures are required to explore the regions of the stomach in consideration of the number of representative samples.

Associação de alterações anatomopatológicas com o Helicobacter spp. por meio de análise imuno-histoquímica em estômagos de leitões / Association of anatomopathological changes with the Helicobacter spp. through immunohistochemical analysis in piglets stomachs

O objetivo deste trabalho foi relacionar os achados anatomopatológicos das lesões gástricas subclínicas de ocorrência natural em leitões com a presença, ou não, de Helicobacter spp. por meio da imuno-histoquímica. Foram utilizados 48 leitões de linhagem genética comercial. Os animais foram adquiridos em uma granja comercial, com peso médio de 34 Kg e idade média de 79 dias; após o abate, seus estômagos foram coletados e avaliados. Avaliações histopatológicas e imuno-histoquímicas foram realizadas em amostras das regiões anatômicas aglandular e glandular. Macroscopicamente, 34 (70,83%) leitões apresentaram lesões na região aglandular, enquanto que em 14 animais (29,17%) não foram encontradas alterações nesta região. Dos estômagos com lesão, 14 foram classificados como grau 1, seis como grau 2 e 14 como grau 3. Microscopicamente, 44 amostras (91,66%) apresentaram paraqueratose. Deste total, 22 apresentaram a forma discreta, 20 a moderada e dois a acentuada. Na avaliação macroscópica da porção glandular, 41 (85,4%) animais apresentaram alteração em pelo menos uma das três regiões, e em somente sete (14,6%) não foram encontradas lesões em nenhuma delas. Em 14 deles, houve aumento da atividade mucípara, em dois, houve erosão e, em cinco, hiperemia. As lesões na região glandular do estômago foram mais extensas no antro e no cárdia, seguidas do fundo. Em relação à análise imuno-histoquímica, 21 (43,8%) amostras tiveram resultados negativos em todas as regiões, e 24 (50%) foram positivas em pelo menos uma delas, sendo que nenhuma foi positiva em todas. Os achados anatomopatológicos demonstraram relação estatística com a bactéria e, sua imunomarcação não associada à lesão em certas regiões gástricas, demonstra seu caráter saprofítico e oportunista.

The aim of this study was to relate the anatomopathological findings of naturally occurring subclinical gastric lesions in piglets, with or without Helicobacter spp. through immunohistochemistry. Forty-eight piglets of commercial genetic lineage were used. The animals were acquired in a commercial farm, with an average weight of 34 kg and an average age of 79 days, and after slaughter, their stomachs were collected and evaluated. Samples from the glandular and aglandular anatomical regions were evaluated. Macroscopically, 34 (70.83%) samples had lesions on aglandular region, while 14 (29.17%) nothing had. Of the injured stomachs, 14 were classified as grade 1, six as grade 2 and 14 as grade 3. Microscopically, 44 samples (91.66%) showed parakeratosis. Of these, 22 showed a discreet manner, 20 moderate and two severe. In the glandular region, in 41 (85.4%) samples there was a change in at least one of the three regions, and only seven animals (14.6%) showed no change in any of the three. Fourteen samples showed increased muciparous activity, two showed erosion and five hyperemia. The lesions were higher in antral regions and cardic, followed the fundus. In relation to immunohistochemistry, 21(43.8%) samples were negative in all areas, 24 (50%) were positive in at least one, and none were positive in all. The anatomopathological findings showed a statistical relationship with the bacteria, and its immunostaining, not associated with gastric lesions in certain regions, demonstrates its saprophytic and opportunistic character.

Comparison of 7- and 14-Day Eradication Therapy for Helicobacter pylori with First- and Second-Line Regimen: Randomized Clinical Trial

Helicobacter pylori testing in a population of Korean patients with pernicious anemia

No abstract available.

Evaluating Diagnostic Tests for Helicobacter pylori Infection Without a Reference Standard: Use of Latent Class Analysis

Evaluation of diagnostic tests requires reference standards, which are often unavailable. Latent class analysis (LCA) can be used to evaluate diagnostic tests without reference standards, using a combination of observed and estimated results. Conditionally independent diagnostic tests for Helicobacter pylori infection are required. We used LCA to construct a reference standard and evaluate the capability of non-invasive tests (stool antigen test and serum antibody test) to diagnose H. pylori infection compared with the conventional method, where histology is the reference standard. A total of 96 healthy subjects with endoscopy histology results were enrolled from January to July 2016. Sensitivity and specificity were determined for the LCA approach (i.e., using a combination of three tests as the reference standard) and the conventional method. When LCA was used, sensitivity and specificity were 83.8% and 99.4% for histology, 80.0% and 81.9% for the stool antigen test, and 63.6% and 89.3% for the serum antibody test, respectively. When the conventional method was used, sensitivity and specificity were 75.8% and 71.1% for the stool antigen test and 77.7% and 60.7% for the serum antibody test, respectively. LCA can be applied to evaluate diagnostic tests that lack a reference standard.

Eradication Rates of 10-day Sequential Therapy for Helicobacter pylori: Results of an 8-year Prospective Study Conducted at a Tertiary Korean Hospital / 대한소화기학회지

BACKGROUND/AIMS: The Helicobacter pylori (H. pylori) eradication rate of standard triple therapy is unsatisfactory in Korea, and sequential therapy (SQT) has been suggested to be a practical first-line alternative regimen. The aim of this prospective study was to document changes in annual eradication rates of SQT. METHODS: A total of 983 H. pylori-positive subjects were enrolled from 2010 to 2018 and their data were subjected to intention-to-treat (ITT) and per-protocol (PP) analysis. All subjects received 10-day sequential therapy consisting of 40 mg esomeprazole and 1 g amoxicillin b.i.d for 5 days followed by 40 mg esomeprazole b.i.d, 500 mg clarithromycin b.i.d and 500 mg metronidazole t.i.d for 5 days. The 13C-urea breath test, rapid urease test (CLO test®), and histology were used to confirm eradication. Compliance and side effects were also investigated. RESULTS: ITT and PP eradication rates of SQT were 69.9% (687 of 983) and 87.1% (657 of 754), respectively. The annual eradication rate of ITT remained consistent over the 8-year study period (p for trend=0.167), whereas PP analysis showed the eradication rate increased (p for trend=0.042). The overall adverse event rate for SQT was 41.7% (410 subjects). CONCLUSIONS: Despite high antibiotic resistance rates in Korea, the eradication rate of SQT did not decrease over the 8-year study period.

Risk of Peptic Ulcer Bleeding Associated with Helicobacter pylori Infection, Nonsteroidal Anti-inflammatory Drugs, and Low-dose Aspirin Therapy in Peptic Ulcer Disease: A Case-control Study

BACKGROUND/AIMS: The association between Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin therapy as a risk factor for peptic ulcer bleeding (PUB) remains unclear. This study investigated the risk of PUB associated with H. pylori infection and NSAID or low-dose aspirin therapy in patients with PUD. MATERIALS AND METHODS: This case-control study investigated 340 patients with PUB between 2012 and 2016. The control group comprised age and sex-matched patients with endoscopically documented non-bleeding ulcers. Using logistic regression analysis, the adjusted odds ratio (AOR) was calculated for the risk of PUB. RESULTS: Of the patients investigated, 57.9% in the study group and 51.8% in the control group were diagnosed with H. pylori infection (P=0.106). Logistic regression analysis showed synergistic interaction between H. pylori infection and low-dose aspirin therapy. Multivariate analysis showed that low-dose aspirin (AOR 3.92, P < 0.001), NSAIDs (AOR 2.98, P=0.001), warfarin (AOR 14.57, P=0.011), gastric ulcer (compared with duodenal ulcer) (AOR 1.65, P=0.01), and smoking (AOR 1.97, P=0.004) increased the risk of PUB compared with the risk of PUD. CONCLUSIONS: Both NSAIDs and aspirin are independent risk factors for bleeding in patients with PUD. Additionally, low-dose aspirin therapy concomitant with H. pylori infection produced a synergistic effect. Therefore, H. pylori eradication may be crucial in aspirin users. Moreover, a proton pump inhibitor should be prescribed in patients with a history of bleeding ulcers who need long-term NSAID treatment.

Periodic Methylation Patterns in the Background Mucosa of Gastric Cancer

BACKGROUND/AIMS: Gastrointestinal glandular stem cells renew every 8 years. New stem cells with impeded housekeeping gene methylation have unstable phenotypes and are prone to transform into malignant cells. Age-related changes in methylation in the gastric mucosa were evaluated to define the period of cancer-prone stem cell replacement. MATERIALS AND METHODS: Endoscopic biopsy specimens of normal-appearing gastric mucosa were obtained from 148 Helicobacter pylori-negative controls, 124 H. pylori-positive controls, and 69 gastric cancer patients with closed-type mucosal atrophy. Methylation-variable sites of two stomach-specific genes (TFF2 and TFF3) and four housekeeping genes (CDH1, ARRDC4, MMP2, and CDKN2A) were analyzed using radioisotope-labeled methylation-specific polymerase chain reaction. Age-related methylation was evaluated depending on the gastric mucosal atrophy at 2-year intervals. RESULTS: TFF2 methylation peaked periodically at 40 to 41, 48 to 49, 56 to 57, and 64 to 65 years of age in H. pylori-negative controls. Periodic peaks of TFF2 methylation were also found in H. pylori-positive controls. Housekeeping-gene methylation troughed at 48 to 49, 56 to 57, and 68 to 69 years of age in cancer patients. Trough methylation of CDH1 and ARRDC4 was lower in cancer patients than in H. pylori-positive controls. CONCLUSIONS: Methylation peaks of stomach-specific TFF2 in controls and methylation troughs of housekeeping genes in cancer patients were found every 8 years. Periodic methylation patterns may be used to identify individuals at high risk for gastric cancer.

Changes in Helicobacter pylori Immunoglobulin G Levels and Gastric Mucosal Atrophy after Successful Eradication of Helicobacter pylori

BACKGROUND/AIMS: Limited information is available about the relationship between Helicobacter pylori (H. pylori) immunoglobulin (Ig) G and serum pepsinogen (pepsinogen [PG], a marker of gastric mucosal atrophy) concentrations after H. pylori eradication. MATERIALS AND METHODS: Eligible patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer from August 2007 to March 2013 in a tertiary-referral center, and whose serum H. pylori IgG and PG concentrations were measured at the time of performing ESD and one year post-ESD, were selected. Successful H. pylori eradication was achieved after ESD in all the patients. According to the decrease in serum H. pylori IgG concentration after bacterial eradication, the patients were categorized as group 1 (IgG concentration decreased by <50%), and group 2 (IgG concentration decreased by ≥50%). RESULTS: Of the 106 patients, 25 (23.6%) were classified into group 1 and 81 (76.4%) into group 2. One year after H. pylori eradication, the serum PG II concentration was significantly decreased in group 2 (12.46±8.18 vs. 8.28±6.11, P=0.024). Although the serum PG I/II ratio of group 2 was higher than that of group 1 (8.32±4.52 ng/mL vs. 6.39±4.04 ng/mL), the difference was not significant (P=0.058). One year after successful eradication, elevated serum PG I/II ratio was observed in 21 patients (84%) in group 1 and in 77 patients (95.1%) in group 2 (P=0.087). The mean serum PG I/II ratio was also elevated in both groups. Serum PG II concentration was significantly decreased in group 2. CONCLUSIONS: A notable decrease in the concentration of H. pylori IgG antibody after bacterial eradication might reflect gastric mucosal atrophy. However, our study showed no statistically significant difference.

Can Eradication of Helicobacter pylori Improve the Symptoms of Functional Dyspepsia?

No abstract available.

Helicobacter pylori Infection and the Kyoto Classification of Gastritis

Estimating the risk of Helicobacter pylori (H. pylori)-induced gastric cancer during endoscopic examination is important. Owing to recent advances in gastrointestinal endoscopy, the gross appearance of the background gastric mucosa has enabled discrimination of subjects with active, chronic, and past H. pylori infection from those with no history of infection. To provide subjective criteria for H. pylori infection-related endoscopic findings with increased risk of gastric cancer, the Kyoto classification of gastritis was proposed at the 85th annual meeting of the Japanese Society for Gastrointestinal Endoscopy in May 2013 in Kyoto. The main contents focus on determining the gastric cancer risk by scoring the endoscopic findings of the background gastric mucosa from 0 to 8. These important findings are not described in the Kyoto Global Consensus Conference proceedings published in English. To better estimate the gastric cancer risk during screening endoscopy in an H. pylori-prevalent population, knowledge of the Japanese version of the Kyoto classification is important. This new classification emphasizes the discrimination of subjects with H. pylori infection by assessing 19 endoscopic findings (presence of atrophy, intestinal metaplasia, diffuse redness, spotty redness, mucosal swelling, enlarged folds, sticky mucus, chicken skin-like nodularity, foveolar-hyperplastic polyp, xanthoma, depressed erosion, regular arrangement of collecting venules, fundic gland polyp, linear red streak, raised erosion, hematin deposit, multiple white and flat-elevated lesions, patchy redness, and map-like redness). In this review, the validity of the Kyoto classification is summarized in conjunction with several suggestions to resolve emerging H. pylori infection-related problems in Korea.

A Randomized Double-blind Comparative Study of the Efficacy of Helicobacter pylori Eradication Therapy and Motilitone® for Functional Dyspepsia

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is one of the etiologies of functional dyspepsia (FD). The aim of this study was to compare the efficacy of H. pylori eradication therapy and motilitone monotherapy in patients with FD. MATERIALS AND METHODS: We prospectively performed a multicenter randomized double-blind study between August 2014 and June 2017. FD patients with H. pylori infection randomly received either the standard triple therapy or motilitone. Global and individual symptom improvements, and changes in quality of life score were assessed. RESULTS: We failed to enroll as many candidates as we had planned. A study to evaluate the efficacy of medications in FD patients according to the Rome III criteria is difficult to perform in Korea because of the early medication therapy at local hospitals and reluctance to discontinue digestive medications. Of the 35 patients enrolled, 30 (18 in the H. pylori eradication group and 12 in the motilitone group) completed the trial. The success rate of H. pylori eradication was 44.4% (8/18). The symptom improvement rate using the 7-point Likert scale at week 12 was 66.7% (12/18) in the H. pylori eradication group and 91.7% (11/12) in the motilitone group (P=0.193). At week 12, the symptom improvement rate was not significantly different between the patients with successful eradication (87.5%, 7/8) and those in the motilitone group (91.7%, 11/12; P=1.000). CONCLUSIONS: Eradication therapy could be an effective treatment for H. pylori-positive FD. However, our results should be cautiously interpreted, as we failed to recruit the intended number of subjects.

Lower Risk of Gastric Atrophy and Intestinal Metaplasia in Patients with MALT Lymphoma despite Helicobacter pylori Infection

BACKGROUND/AIMS: Atrophic gastritis and intestinal metaplasia are sequential consequences of chronic Helicobacter pylori (H. pylori) infection. These conditions are well known to increase the risk of gastric adenocarcinoma development. Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is also a malignant consequence of H. pylori infection, but the relationship between gastric MALT lymphoma and atrophic gastritis-intestinal metaplasia has not been a focus of interest. We investigated the clinical characteristics of atrophic gastritis and intestinal metaplasia in patients with gastric MALT lymphoma. MATERIALS AND METHODS: A study was conducted by reviewing the electronic medical records of patients diagnosed as having gastric MALT lymphoma at an academic institute, the Yeouido St. Mary's Hospital, Seoul, Korea, between January 2001 and December 2018. RESULTS: Fifty-eight subjects were enrolled consecutively during the study period and analyzed retrospectively. The patients' mean age was 56.9 years old. The male-to-female ratio was 1.15 (31/27). On histological examination, background atrophic gastritis and intestinal metaplasia were detected in 26.8% (15/58) of cases. Serum pepsinogen I, II and gastrin levels, as serological markers of atrophy, were evaluated in 28 subjects. Three (5.2%) of the 28 cases were compatible with serological atrophic gastritis (pepsinogen I/II ratio of <3 and pepsinogen I level of <70 ng/mL). CONCLUSIONS: In patients with gastric MALT lymphoma, the prevalence of background mucosal atrophy or intestinal metaplasia was 26.8% on histological examination and 5.2% on serological analyses. These rates are lower than those in patients with gastric adenocarcinoma. This result suggests a different carcinogenic pathway of gastric MALT lymphoma from that of adenocarcinoma.

Inhibitory Effects of β-caryophyllene on Helicobacter pylori Infection: A Randomized Double-blind, Placebo-controlled Study / 대한소화기학회지

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infections, which cause a variety of gastrointestinal symptoms, are common in South Korea. Recent reports have shown a decline in the H. pylori eradication rates. β-caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species, such as cloves, basil, and cinnamon. β-caryophyllene has been reported to have anti-inflammatory and anti-bacterial effects. This study investigated the inhibitory effects of β-caryophyllene on H. pylori and its potential role as an alternative gastrointestinal drug. METHODS: This 8-week, randomized double-blind, placebo-controlled trial categorized subjects into a β-caryophyllene group (33 patients who received 126 mg/day of β-caryophyllene) and a placebo group (33 patients who received a placebo preparation). The inflammation level of H. pylori infiltration and the eradication rates were evaluated endoscopically and with the urea breath test (UBT) in both groups before and after administering the medication. The serum cytokine levels (tumor necrosis factor-α, and interleukin [IL]-1β and IL-6) were compared in both groups before and after administering the medication. RESULTS: Complete eradication was not observed in either group. Moreover, there was no significant change in the UBT and updated Sydney score. On the other hand, the β-caryophyllene group showed significant improvement in nausea (p=0.025) and epigastric pain (p=0.018), as well as a decrease in the serum IL-1β levels (p=0.038). CONCLUSIONS: β-caryophyllene improves dyspepsia symptoms and can be considered a useful supplementary treatment for gastrointestinal disease.

Changes in the Treatment Strategies for Helicobacter pylori Infection in Children and Adolescents in Korea / 대한소아소화기영양학회지

The policies developed for the treatment of Helicobacter pylori infection in adults may not be the most suitable ones to treat children and adolescents. Methods used to treat children and adolescents in Europe and North America may not be appropriate for treating children and adolescents in Korea due to differences in epidemiological characteristics of H. pylori between regions. Moreover, the agreed standard guidelines for the treatment of H. pylori infection in children and adolescents in Korea have not been established yet. In this study, the optimal treatment strategy for H. pylori infection control in children and adolescents in Korea is discussed based on these guidelines, and recent progress on the use and misuse of antimicrobial agents is elaborated. Non-invasive as well as invasive diagnostic test and treatment strategy for H. pylori infection are not recommendable in children aged less than ten years or children with body weight under 35 kg, except in cases of clinically suspected or endoscopically identified peptic ulcers. The uncertainty, whether enough antimicrobial concentrations to eradicate H. pylori can be maintained when administered according to body weight-based dosing, and the costs and adverse effects outweighing the anticipated benefits of treatment make it difficult to decide to eradicate H. pylori in a positive non-invasive diagnostic test in this age group. However, adolescents over ten years of age or with a bodyweight of more than 35 kg can be managed aggressively as adults, because they can tolerate the adult doses of anti-H. pylori therapy. In adolescents, the prevention of future peptic ulcers and gastric cancers is expected after the eradication of H. pylori. Bismuth-based quadruple therapy (bismuth-proton pump inhibitor-amoxicillin/tetracycline-metronidazole) with maximal tolerable doses and optimal dose intervals of 14 days is recommended, because in Korea, the antibiotic susceptibility test for H. pylori is not performed at the initial diagnostic evaluation. If the first-line treatment fails, concomitant therapy plus bismuth can be attempted for 14 days as an empirical rescue therapy. Finally, the salvage therapy, if needed, must be administered after the H. pylori antibiotic susceptibility test.

Up-Regulation of MiR-1915 Inhibits Proliferation, Invasion, and Migration of Helicobacter pylori-Infected Gastric Cancer Cells via Targeting RAGE

PURPOSE: Helicobacter pylori (HP)-infected gastric cancer (GC) is known to be a fatal malignant tumor, but the molecular mechanisms underlying its proliferation, invasion, and migration remain far from being completely understood. Our aim in this study was to explore miR-1915 expression and its molecular mechanisms in regulating proliferation, invasion, and migration of HP-infected GC cells. MATERIALS AND METHODS: Quantitative real-time PCR and western blot analysis were performed to determine miR-1915 and receptor for advanced glycation end product (RAGE) expression in HP-infected GC tissues and gastritis tissues, as well as human gastric mucosal cell line GES-1 and human GC cell lines SGC-7901 and MKN45. CCK8 assay and transwell assay were performed to detect the proliferation, invasion, and migration capabilities. MiR-1915 mimics and miR-1915 inhibitor were transfected into GC cells to determine the target relationship between miR-1915 and RAGE. RESULTS: MiR-1915 was under-expressed, while RAGE was over-expressed in HP-infected GC tissues and GC cells. Over-expressed miR-1915 could attenuate cellular proliferation, invasion, and migration capacities. RAGE was confirmed to be the target gene of miR-1915 by bioinformatics analysis and luciferase reporter assay. Moreover, HP-infected GC cellular proliferation, invasion, and migration were inhibited after treatment with pcDNA-RAGE. CONCLUSION: MiR-1915 exerted tumor-suppressive effects on cellular proliferation, invasion, and migration of HP-infected GC cells via targeting RAGE, which provided an innovative target candidate for treatment of HP-infected GC.

Clinical Efficacy of Radiotherapy in Helicobacter pylori Negative or Unresponsive to Eradication Therapy Primary Gastric Mucosa-Associated Lymphoid Tissue Lymphoma / 대한소화기학회지

BACKGROUND/AIMS: The eradication of Helicobacter pylori (H. pylori) is an effective treatment in gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with H. pylori infection. However, the treatment strategy in gastric MALT lymphoma patients who are H. pylori-negative or unresponsive to H. pylori eradication therapy remains controversial. In this study, we investigated the clinical efficacy of treatments other than H. pylori eradication therapy in these groups of patients. METHODS: This was a retrospective single-center study based on the medical records of patients diagnosed with gastric MALT lymphoma at Yeungnam University Medical Center between January 2005 and December 2016. Patients were treated with H. pylori eradication therapy, chemotherapy, or radiotherapy according to their H. pylori infection status and stage of gastric MALT lymphoma. RESULTS: Of the 68 eligible patients, 50 were enrolled in the study. Of the 42 patients with H. pylori-positive gastric MALT lymphoma, 36 (81.7%) were treated with H. pylori eradication therapy as primary treatment and 25 (69.4%) achieved a complete response (CR). Patients without a CR after H. pylori eradication therapy (n=11, 30.6%) received radiotherapy as a secondary treatment. Two patients with H. pylori-positive gastric MALT lymphoma and eight with H. pylori-negative gastric MALT lymphoma received radiotherapy as the primary treatment. CR was achieved in all 21 patients treated with radiotherapy as primary or secondary treatment. The 5-year progression-free survival rate after radiotherapy was 92.9%. CONCLUSIONS: Radiotherapy may be a worthwhile treatment option in patients with H. pylori-negative MALT lymphoma or H. pylori-positive MALT lymphoma that is not responsive to H. pylori eradication therapy.

Effect of 7-day Bismuth Quadruple Therapy versus 14-day Moxifloxacin Triple Therapy for Second-line Helicobacter pylori Eradication Therapy / 대한소화기학회지

BACKGROUND/AIMS: Both bismuth-containing quadruple therapy and moxifloxacin-containing triple therapy have been suggested as second-line eradication therapy for Helicobacter pylori (H. pylori) infection. We aimed to evaluate the efficacy of 14-day moxifloxacin-containing triple therapy (14-EAM) in second-line H. pylori eradication in comparison to 7-day bismuth-containing quadruple therapy (7-RBMT). METHODS: From January 2011 to December 2015, a total of 569 patients who failed to respond to first-line triple therapy and who subsequently received second-line 7-RBMT or 14-EAM were retrospectively enrolled. The eradication rates were identified using per-protocol (PP) analysis. H. pylori eradication was confirmed by a 13C-urea breath test (UBiT-IR300®; Otsuka Electronics, Co., Ltd., Osaka, Japan) or a rapid urease test (CLOtest®; Delta West, Bentley, Australia) at least 4 weeks after completion of eradication therapy. RESULTS: A total of 487 and 82 patients received 7-RBMT and 14-EAM, respectively. PP eradication rates were 93.6% (366/391; 95% CI, 91.0–95.9%) with 7-RBMT and 73.8% (48/65; 95% CI, 63.1–84.6%) with14-EAM (p < 0.001). Therefore, the eradication rates with 7-RBMT were significantly higher than with 14-EAM according to the PP analysis. The adverse event rate was 17.1% (67/391) with 7-RBMT and 7.7% (5/65) with 14-EAM (p=0.065). In terms of risk factors, multivariate analysis revealed that 14-EAM (OR, 5.47; 95% CI, 2.74–10.93) was related to H. pylori eradication failure. CONCLUSIONS: 7-RBMT may be an effective second-line therapy in patients who failed to respond to first-line triple therapy in Korea, where there is a high prevalence of H. pylori infection.

Influence of Helicobacter pylori Infection on Endoscopic Findings of Gastric Adenocarcinoma of the Fundic Gland Type

PURPOSE: Gastric adenocarcinoma of the fundic gland type (chief cell predominant type) (GA-FG-CCP) was first reported as a rare adenocarcinoma found in the normal fundic mucosa. Recent studies have proposed the possibility that GA-FG-CCPs were also generated in the atrophic mucosa after Helicobacter pylori (HP) eradication therapy. However, little is known on the endoscopic findings of GA-FG-CCP generated in the atrophic mucosa due to its extreme rarity. MATERIALS AND METHODS: A total of 8 patients who underwent endoscopic submucosal resection and were diagnosed with GA-FG-CCP generated in the HP-uninfected mucosa (4 cases, HP-uninfected group) or HP-eradicated atrophic mucosa (4 cases, HP-eradicated group) were retrospectively analyzed, and their endoscopic findings, including magnifying endoscopy with narrow band imaging (M-NBI), and pathological features were compared. RESULTS: While GA-FG-CCPs in the 2 groups displayed similar macroscopic appearance, M-NBI demonstrated that characteristic microvessels (tapered microvessels like withered branches) were specifically identified in the HP-eradicated group. Pathological investigation revealed that a decreasing number of fundic glands and thinned foveolar epithelium covering tumor ducts were thought to lower the thickness of the covering layer over tumor ducts in the HP-eradicated group. Moreover, dilation of vessels just under the surface of the lesions contributed to the visualization of microvessels by M-NBI. CONCLUSIONS: The change in background mucosa due to HP infection influenced the thickness of the covering layer over the tumor ducts and M-NBI finding of GA-FG-CCP.

β-carotene Inhibits Expression of c-Myc and Cyclin E in Helicobacter pylori-infected Gastric Epithelial Cells

BACKGROUND: Helicobacter pylori infection is a major risk factor in the development of gastric cancer. H. pylori infection of gastric epithelial cells increases the levels of reactive oxygen species (ROS), activates oncogenes, and leads to β-catenin-mediated hyper-proliferation. β-Carotene reduces ROS levels, inhibits oxidant-mediated activation of inflammatory signaling and exhibits anticancer properties. The present study was carried out to determine if β-carotene inhibits H. pylori-induced cell proliferation and the expression of oncogenes c-myc and cyclin E by reducing the levels of β-catenin and phosphorylated glycogen synthase kinase 3β (p-GSK3β). METHODS: Gastric epithelial AGS cells were pre-treated with β-carotene (5 and 10 μM) for 2 hours prior to H. pylori infection and cultured for 6 hours (for determination of the levels of p-GSK3β, GSK3β, and β-catenin) and 24 hours (for determination of cell viability and protein levels of c-myc and cyclin E). Cell viability was determined by the MTT assay and protein levels were determined via western blot-based analysis. RESULTS: β-Carotene inhibited H. pylori-induced increases in the percentage of viable cells, phosphorylated GSK3β (p-GSK3β), and the levels of β-catenin, c-myc and cyclin E. CONCLUSIONS: β-Carotene inhibits H. pylori-induced hyper-proliferation of gastric epithelial cells by suppressing β-catenin signaling and oncogene expression.