Follow-up of intestinal metaplasia in the stomach: When, how and why

Gastric cancer remains the second most frequent cause of cancer-related mortality in the world. Screening programs in some Asian countries are impractical in the majority of other countries worldwide. Therefore, follow-up of precancerous lesions is advisable for secondary gastric cancer prevention. Intestinal metaplasia (IM) is recognized as a precancerous lesion for gastric cancer, increasing the risk by 6-fold. IM is highly prevalent in the general population, being detected in nearly 1 of every 4 patients undergoing upper endoscopy. The IM prevalence rate is significantly higher in patients with Helicobacter pylori (H. pylori) infection, in first-degree relatives of gastric cancer patients, in smokers and it increases with patient age. IM is the "breaking point" in the gastric carcinogenesis cascade and does not appear to regress following H. pylori eradication, although the cure of infection may slow its progression. Gastric cancer risk is higher in patients with incomplete-type IM, in those with both antral and gastric body involvement, and the risk significantly increases with IM extension over 20% of the gastric mucosa. Scheduled endoscopic control could be cost-effective in IM patients, depending on the yearly incidence of gastric cancer in IM patients, the stage of gastric cancer at diagnosis discovered at surveillance, and the cost of endoscopy. As a pragmatic behavior, yearly endoscopic control would appear justified in all IM patients with at least one of these conditions: (1) IM extension > 20%; (2) the presence of incomplete type IM; (3) first-degree relative of gastric cancer patients; and (4) smokers. In the remaining IM patients, a less intensive (2-3 years) could be proposed.     

Higher gastric cycloxygenase-2 expression and precancerous change in Helicobacter pylori-infected relatives of gastric cancer patients.

PURPOSE: This study was conducted to determine whether relatives of gastric cancer patients (GCF) showed greater gastric cycloxygenase-2 (COX-2) expression or a greater incidence of precancerous lesions after Helicobacter pylori infection and whether H. pylori eradication could reduce COX-2 expression. EXPERIMENTAL DESIGN: Three hundred subjects were enrolled in this study: half were relatives of 50 H. pylori-infected gastric cancer patients, and half were relatives of 50 H. pylori-infected duodenal ulcer (DU) patients (controls). Each relative underwent endoscopy to detect H. pylori infection and related gastric histology. One hundred and twenty GCFs were found to have H. pylori infection. After H. pylori eradication, 90 of the 120 GCFs were followed up with annual endoscopy examinations over the next 2 years. Gastric COX-2 intensity in all of the specimens collected from these patients was immunochemically stained and graded from 0 to 4. RESULTS: H. pylori infection, gastric atrophy, and intestinal metaplasia (IM) were more prevalent in GCFs than in relatives of H. pylori-infected patients with DUs (P < 0.05). H. pylori-infected GCFs also showed a greater COX-2 intensity than H. pylori-infected relatives of patients with DUs (89.1% versus 62.7%, P < 0.001; relative risk: 4.9; 95% confidence interval: approximately 2.34-10.29). Among the H. pylori-infected GCFs, COX-2 intensity correlated with atrophy and IM (P < 0.001). After H. pylori eradication, gastric COX-2 expression disappeared only in those relatives without IM (P < 0.001). CONCLUSIONS: GCFs are more likely to show greater gastric COX-2 expression and a higher incidence of precancerous lesions after H. pylori infection than the relatives of H. pylori-infected patients with only DUs. H. pylori eradication can reverse gastric COX-2 expression in patients without IM but not in patients with IM.     

Risk of Gastric Cancer in Children with Helicobacter pylori Infection

Background: Helicobacter pylori (H. pylori) is the most common chronic infectious agent in the stomach.Most importantly, it may lead to atrophy, metaplasia and cancer. The aim of this study was to investigate theincidence of H. pylori infection and to detect early mucosal changes that may lead to malignant degenerationin children. Materials and Methods: Children who underwent upper gastrointestinal endoscopy were included.Familial history of gastric cancer was noted. Endoscopic examinations were performed by a single pediatricgastroenterologist. A minimum of three biopsy samples were collected during endoscopy. The patients wereaccepted as H. pylori infected if results of biopsies and rapid urease test were both positive. Biopsies wereevaluated for the presence and degree of chronic inflammation, the activity and severity of gastritis, glandularatrophy and intestinal metaplasia. Results: A total of 750 children (388 boys, 362 girls) were evaluated in ourstudy, with a mean age of 10.1 years. A total of 390 patients (52%) were found to be infected with H. pylori.Among the H. pylori infected patients, 289 (74%) were diagnosed to have chronic superficial gastritis, 24 (6.2%)had gastric atrophy. Most strikingly, intestinal metaplasia was observed in 11 children, all were in the H. pyloripositive group. There was no difference in the mean of age, gender and socioeconomic class between H. pyloriinfected and non-infected groups. The frequency of gastric cancer in family members (4 in number) was higherin patients with H. pylori infection. No gastric cancer case was reported from the parents of non-infected children.The worst biopsy parameters (atropy and metaplasia) were improved after H. pylori eradication on controlendoscopy. Conclusions: The current study shows a higher prevalence of familial history of gastric cancer in H.pylori infected children. Intestinal metaplasia was also higher in the infected children. Eradication of H. pyloriinfection for this risk group may prevent subsequent development of gastric cancer.     

Prospective long-term endoscopic and histologic follow-up of gastric lymphoproliferative disease of early stage IE low-grade B-cell mucosa-associated lymphoid tissue type following Helicobacter pylori eradication treatment.

Long-term endoscopic and histologic follow-up of Stage IE gastric lymphoproliferative disease of the low-grade B-cell mucosa-associated lymphoid tissue (MALT) type following cure of H. pylori was undertaken. Clinical and endoscopic features (age, race, endoscopic appearance, cure of H. pylori and duration of follow-up) were also evaluated as potential prognostic indicators for complete or near-complete regression of low-grade MALT lymphoma. Sixty-eight MALT lymphoma patients prospectively underwent H. pylori eradication. follow-up at periodic intervals with endoscopy and extensive mucosal biopsy protocol on 65 patients ranging from 12 weeks up to 73 months (mean +/- SD of 22.5+/-15.8 months) has been completed. H. pylori was eradicated in 89.2% of MALT lymphoma patients with complete histologic regression noted in 58.5%, near-complete regression in 18.5%, partial in 4.6%, and no change in 18.5%. Univariate analysis revealed two factors predictive of complete and/or near complete MALT lymphoma regression, H. pylori cure (p=0. 001) and duration of follow-up (p=0.001). Stepwise logistic regression also demonstrated that both H. pylori cure (p<0.0001) and duration of follow-up (p<0.02) were independently associated with complete and near complete MALT lymphoma regression. Age, race, and endoscopic appearance were not predictive of regression. We conclude that this lymphoproliferative disease predictably undergoes complete to near-complete histologic regression at variable rates following cure of H. pylori in a majority of patients.     

Endoscopic Diagnosis for H. pylori Infection: White Light Imaging (WLI) vs. Image-Enhanced Endoscopy (IEE)

Helicobacter pylori infection is a class I carcinogen that can lead to gastric cancer. Early diagnosis and eradication of H. pylori infection are important to eliminate the risk of gastric cancer. Several invasive diagnostic techniques require biopsy samples, resulting in avoidable injury and medical expense. Furthermore, due to the localized distribution of H. pylori, random biopsies are not always reliable in diagnosing H. pylori infection. This article aimed to review endoscopic findings and new endoscopic options for the diagnosis of H. pylori infection. Using conventional white light imaging (WLI) and image-enhanced endoscopy (IEE), the endoscopic features associated with histological changes have increasingly become apparent. Real-time endoscopy is essential to make a diagnosis of H. pylori infection and allow targeted biopsy. Image-enhanced endoscopy (IEE), such as narrow-band imaging (NBI), linked color imaging (LCI), and blue laser imaging (BLI), enhances visualization of the surface vascular pattern and provides accurate diagnostic performance in H. pylori infection, as well as gastric neoplastic lesions, compared to conventional white light endoscopy. In conclusion, the new endoscopic technologies could be used in current practice with conventional white light endoscopy for accurate and real-time diagnosis of H. pylori infection and pre-cancerous lesions.     

Complete remission of primary high-grade B-cell gastric lymphoma after cure of Helicobacter pylori infection.

PURPOSE: Treatment of low-grade gastric mucosa-associated lymphoid tissue lymphoma by eradication of Helicobacter pylori is reported to result in complete lymphoma remission in approximately 75% of cases. The effect that cure of the infection has on the course of a primary high-grade gastric lymphoma is largely uncertain. The aim of this study was to report the effect of cure of H pylori infection exerted in patients with high-grade B-cell gastric lymphoma. PATIENTS AND METHODS: Eight patients (4 males and 4 females; age range, 26 to 85 years) with H pylori infection and high-grade lymphoma received eradication therapy before planned treatment. The effect of H pylori eradication on the course of high-grade lymphoma was assessed by analysis of surgical specimens (n = 2) or endoscopic biopsies (n = 6). RESULTS: H pylori eradication was successful in all patients and led to complete remission of the lymphoma in seven patients. One patient has experienced partial remission. Two patients were referred to surgery, one of whom (stage II(1E)) had lymph node involvement, and the histologic work-up of the resected stomach revealed residual infiltrates of a low-grade lymphoma, which prompted consolidation chemotherapy. In one patient (initially stage I(1E)), abdominal lymphoma developed 6 months after eradication therapy, which regressed completely after chemotherapy. In four patients, no further treatment was given. Six patients continue in complete remission (range, 6 to 66 months). CONCLUSION: Primary high-grade B-cell gastric lymphoma in stages I(E) through II(E1) associated with H pylori may regress completely after successful cure of the infection. Prospective trials are needed to investigate this treatment in larger numbers of patients.     

Efficacy of Helicobacter pylori eradication on the chronic mucosal inflammation of the remnant stomach after distal gastrectomy for early gastric cancer

Although eradication of Helicobacter pylori (Hp) after early gastric carcinoma has been recommended, very limited studies have been reported and the method differs from standard therapy. Here, we attempted the eradication of Hp in the remnant stomach after surgery for primary gastric cancer with the standardized method. We examined efficacy and the safeness of the treatment. Thirty-three H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based triple therapies. After eradication, endoscopic and histological changes were classified on the basis of the Updated Sydney System. The eradication rate in the remnant stomach was 90.9% (30 out of 33 cases) after triple therapy. Temporal minor side effects were notified in 3 cases. After eradication, the remnant stomach showed significant decreases in inflammation- and activity-scores. Moreover, significant improvement in glandular atrophy to normal mucosa was found. In conclusion, PPI-based standard therapy is just as effective for Hp eradication in the remnant stomach than it is in the non-operative stomach. Eradication therapy could be performed safely and resulted in a significant improvement in inflammation and atrophy of the mucosal layer in the remnant stomach after early gastric cancer surgery.     

Helicobacter pylori infection and gastric diseases--pathogenesis and effects of eradication

H. pylori infection is associated with major gastroduodenal diseases, i.e. peptic ulcer, cancer and MALT lymphoma in the stomach. The pathogenesis of H. pylori in these diseases has been elucidated. Non-atrophic diffuse antral gastritis is correlated with duodenal ulcer and multifocal atrophic gastritis is correlated with both gastric ulcer and cancer. It is well known that Japanese tend to have multifocal atrophic gastritis. H. pylori eradication therapy dramatically reduces the recurrence rates of gastroduodenal ulcers in humans and bacterial eradication for peptic ulcer patients has been recommended in many countries. Mongolian gerbils have provided an excellent model of gastric carcinogenesis and H. pylori enhanced (promoted) chemical carcinogen-induced carcinogenesis in the stomach using this model. H. pylori eradication reduced the incidence of gastric cancer in the Mongolian gerbil model. It was a recently discovered that a transforming clone carrying the translocation t (11;18) (q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. In the early stage, the tumor can be successfully treated by eradication, but at a later stage additional genetic abnormality in the lymphoma may show no response to H. pylori eradication therapy.     

Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis

This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> eradication therapy for the remnant stomach after gastrectomy

BACKGROUND: The remnant stomach after surgery for gastric cancer is at high risk for the metachronous development of multiple gastric cancers. Here, we report on eradication therapy of Helicobacter pylori in the remnant stomach, comparing the eradication rate with that in unoperated stomachs. We examined gross and histological changes after treatment. METHODS: Forty H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based dual and triple therapies. After eradication, histological changes were classified on the basis of the updated Sydney system. RESULTS: The eradication rate in the remnant stomach was 70% (14 of 20) after dual therapy and 90% (18 of 20) after triple therapy, using per-protocol analysis, and these rates were comparable to the rates of 70% (186 of 264) and 88% (58 of 66), respectively, in nonsurgery patients. After eradication, three sites in the remnant stomach showed similar histological changes: significant decreases in inflammation and activity scores (P < 0.001) and no significant changes in glandular atrophy and intestinal metaplasia scores. CONCLUSION: PPI-based therapy was as effective for H. pylori eradication in the remnant stomach as in the unoperated stomach, and eradication therapy resulted in a significant decrease in inflammatory cell infiltration of the mucosal layer.     

Metachronous gastric MALT lymphoma and early gastric cancer: is residual lymphoma a risk factor for the development of gastric carcinoma?

BACKGROUND: Helicobacter pylori plays a major role in the pathogenesis of primary gastric MALT lymphoma (GML) and gastric carcinoma. The occurrence of these two diseases metachronously in a same patient is a rare event. PATIENTS AND METHODS: Gastric biopsies and gastrectomy resection specimens of four patients who developed GML and early gastric cancer (EGC) were analysed by morphology, immunohistochemistry and molecular biology. RESULTS: Four patients (three males and one female; mean age 48 years) were diagnosed with GML. Helicobacter pylori infection was observed in three cases. Two patients had localized disease (stages IE and IIE, respectively) and were treated with H. pylori eradication therapy followed by an alkylating agent for one patient. Two patients had disseminated disease (stage IV), and were treated with an alkylating agent. Three cases were t(11;18) positive. All patients achieved initially complete lymphoma remission. Long-term endoscopic surveillance detected an EGC at the same location as the lymphoma in all patients at a mean time of 9.5 years (range 2.5-17 years) after lymphoma diagnosis. Gastrectomy specimens showed residual GML in all cases. CONCLUSION: Prolonged residual GML could constitute an additional risk factor for the development of gastric carcinoma. Long-term endoscopic surveillance is mandatory in patients treated conservatively for gastric MALT lymphoma.     

Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: incidence and pathological characteristics

We used Helicobacter pylori sero-positivity and mucosal atrophy as detected by the serum pepsinogen method to identify H. pylori infection-negative gastric cancer patients with or without atrophy. One hundred and six of 748 (14.2%) primary gastric cancer patients were infection-negative by a serum antibody detection system. Further, 121 (16.2%) of the 748 were negative for gastric mucosal atrophy by the pepsinogen method, of whom 15/748 (2.0%) were H. pylori-negative by pepsinogen I level (>70 ng/mL) and pepsinogen I/II ratio (>3.0). Twenty-seven of 782 (3.6%) gastric cancer patients were H. pylori-negative by antibodies and severe atrophy as determined by pepsinogen I level (<30 ng/mL) and pepsinogen I/II ratio (<2.0). H. pylori-negative gastric cancer patients with severe atrophy likely had a previous infection. These results indicate that the actual number of H. pylori-negative patients is 2.0% at minimum and 10.6% (14.2% minus 3.6%) at maximum in the general Japanese population. Five of 15 (33%) cases displaying neither anti-H. pylori antibodies nor atrophy were intestinal-type and 10 (67%) were diffuse-type adenocarcinomas. Thirteen surgical patients with primary gastric cancer displaying neither antibodies nor mucosal atrophy were further analyzed for pathological and phenotypic characteristics. The mucin phenotype was divided into four gastric, five gastric and intestinal, two intestinal and two null types, independent of histological classification. Intestinal phenotype elements were detected by Cdx2 immunohistochemical methods in nine of 13 (70%) cases examined. We conclude that a small fraction of gastric cancer patients displayed multifactorial carcinogenesis without H. pylori infection, indicating that gastric cancer risk still exists in the absence of H. pylori infection, at an incidence of 2.0% at minimum and 10.6% at maximum in the general Japanese population.     

Levels of malondialdehyde-deoxyguanosine in the gastric mucosa: relationship with lipid peroxidation, ascorbic acid, and Helicobacter pylori.

Helicobacter pylori infection is associated with elevated gastric mucosal concentrations of the lipid peroxidation product malondialdehyde and reduced gastric juice vitamin C concentrations. Malondialdehyde can react with DNA bases to form the mutagenic adduct malondialdehyde-deoxyguanosine (M(1)-dG). We aimed to determine gastric mucosal levels of M(1)-dG in relation to H. pylori infection and malondialdehyde and vitamin C concentrations. Patients (n = 124) attending for endoscopy were studied. Levels of antral mucosal M(1)-dG were determined using a sensitive immunoslot-blot technique; antral mucosal malondialdehyde was determined by thiobarbituric acid extraction, and gastric juice and antral mucosal ascorbic acid and total vitamin C were determined by high-performance liquid chromatography. Sixty-four H. pylori-positive patients received eradication therapy, and endoscopy was repeated at 6 and 12 months. Levels of M(1)-dG did not differ between subjects with H. pylori gastritis (n = 85) and those with normal mucosa without H. pylori infection (n = 39; 56.6 versus 60.1 adducts/10(8) bases) and were unaffected by age or smoking habits. Malondialdehyde levels were higher (123.7 versus 82.5 pmol/g; P < 0.001), gastric juice ascorbic acid was lower (5.7 versus 15.0 micromol/ml; P < 0.001), and antral mucosal ascorbic acid was unchanged (48.0 versus 42.7 micromol/g) in H. pylori gastritis compared with normal mucosa. Multiple regression analysis revealed that M(1)-dG increased significantly with increasing levels of malondialdehyde, antral ascorbic acid, and total antral vitamin C. M(1)-dG levels were unchanged 6 months (63.3 versus 87.0 adducts/10(8) bases; P = 0.24; n = 38) and 12 months (66.7 versus 77.5 adducts/10(8) bases; P = 0.8; n = 13) after successful eradication of H. pylori. M(1)-dG thus is detectable in gastric mucosa, but is not affected directly by H. pylori.     

Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia

Loss of Sonic Hedgehog (Shh) and aberrant CDX2 expression are early changes correlating with the presence of intestinal metaplasia that occur in the gastric mucosa prior to neoplastic transformation. The aim of this study was to compare the improvement in corpus gastritis with Shh and CDX2 expression after H. pylori eradication between subjects at high risk for gastric cancer and controls. The usefulness of serum pepsinogen levels as a predictor of resolved corpus gastritis was also examined. Seventy patients with endoscopic resection for early gastric cancer and 30 controls were studied. Expression of Shh and CDX2 were evaluated by immunostaining. Serum levels of pepsinogen I before eradication in the patients scored as having improvement of corpus atrophy were significantly higher than in the patients without improvement (<0.01). Residual inflammation at the corpus lesser curve was more frequently detected in the cancer group than in the controls (OR 4.6 95% C.I. 1.6-13.5) and in the mucosa with incomplete intestinal metaplasia rather than in those without incomplete intestinal metaplasia (OR 7.6 95% C.I. 2.4-24.3). Atrophy, expression of Shh and CDX2 at the corpus lesser curve significantly improved in mucosa without incomplete intestinal metaplasia (p < 0.01), but not in mucosa with incomplete intestinal metaplasia. In conclusion, H. pylori eradication prior to development of incomplete intestinal metaplasia improves corpus gastritis and may prevent gastric cancer. Pepsinogen I may be a useful marker in patients with a residual higher risk of gastric cancer after H. pylori eradication.     

Management of Helicobacter pylori infection: gastroenterological and surgical perspectives

Diagnosis and treatment of Helicobacter pylori is a crucial point in the management of the different gastroduodenal disorders. Management involves the general practitioner and different specialists such as internists, gastroenterologists and surgeons. Among the most frequent H. pylori-related gastroduodenal disorders of medical interest are some diseases such as dyspepsia and gastroesophageal reflux, where the role of the bacterium is not well defined and therefore the importance H. pylori eradication is still controversial. On the contrary, the relationship of H. pylori and gastric and duodenal peptic ulcer is widely and definitively proven, and there are no doubts regarding the importance of curing the bacterium in these disorders. However, the surgical aspect of peptic ulcer, in particular the relevance and management of its complications, has not been widely investigated so far. In fact, the prevalence of H. pylori in perforated, bleeding and stenotic peptic ulcers seem to be lower that in non-complicated peptic ulcer, and whenever H. pylori eradication virtually prevents the re-bleeding of peptic ulcer in all cases, the effect of curing the bacterium in perforated and stenotic ulcers is still largely unknown. The management of H. pylori infection after gastric surgery is also still controversial. Most studies suggest that H. pylori can persist after gastric surgery whenever its incidence is much lower than that before operation. However it seems most unlikely that the infection plays a major role in the development of ulcer recurrence after gastric surgery or in the induction of gastric carcinoma. In any case, there are no convincing data that its cure may prevent the occurrence of gastric carcinoma following gastrectomy procedures.     

Helicobacter pylori and Arteriosclerosis

Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B?? (VB??) and folic acid. However, deficiency of VB?? and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB?? and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB?? and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB?? and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their arterioscleroses, measured by pulse wave velocity (PWV), were investigated and compared. The levels of homocysteine were significantly high in the elderly persons and those with H. pylori infection. On the contrary, the levels of VB?? and folic acid were low in these persons. The results of PWV showed a positive correlation with the levels of gastrin and homocysteine and an inverse correlation with the levels of VB?? and folic acid. Persons with a negative result of H. pylori infection showed a lower degree of arteriosclerosis than those with a positive result who were of the same age group. Persons with a positive result of H. pylori infection tended to show an improvement from arteriosclerosis after eradication therapy without a significant difference. 1 ) It is suggested that severity of atrophy of the gastric mucosa are correlated with the severity of arteriosclerosis. 2 ) It is hypothesized that H. pylori infection may induce arteriosclerosis.     

Strategies for gastric cancer in the modern era

Gastric cancer is one of the most common neoplasms in Japan, and it is also the second leading cause of cancer-related deaths worldwide. Nowadays, infection with Helicobacter pylori (H. pylori) is a known risk factor for the development of gastric cancer. Therefore, gastric cancer should be considered as an infectious disease, and in fact, prophylactic eradication of H. pylori may prevent the development of metachronous gastric carcinoma. Before the role of H. pylori was understood, a different approach was used. Recently even after the cancer has developed, some newer therapeutic approaches have been pursued. These newer treatments have been summarized as "minimally invasive therapies" and use endoscopic or laparoscopic techniques. In addition, robotic approaches are being developed that seem to hold a great potential to change the surgical approach. Since basic understanding and treatment of the disease have both changed significantly over the last decade, we present a review of current advances in gastric cancer research and therapy.     

Age and severity of mucosal lesions influence the performance of serologic markers in Helicobacter pylori-associated gastroduodenal pathologies

OBJECTIVE: The course of Helicobacter pylori infection and antibody response to CagA in patients with preneoplastic lesions and gastric cancer has not been thoroughly studied. We aimed to study H. pylori infection and antibody response to CagA in patients with non-atrophic gastritis, preneoplastic lesions, and gastric cancer. METHODS: We studied patients attending one Oncology Hospital and one General Hospital in Mexico City. Diagnosis was based on endoscopy and histopathology in biopsies from six stomach regions. H. pylori infection was assessed by histology and serology, and antibodies against CagA were measured with immunoassay. RESULTS: We included 618 patients, 368 with non-atrophic gastritis, 126 with precancerous lesions, and 65 with gastric cancer; in addition, 59 patients with duodenal ulcer were studied. Detection of infection and IgG against CagA had a significant increase from non-atrophic gastritis to mild and up to advanced stages of metaplasia (P < 0.05), followed by decreased infection and IgG to CagA in patients with gastric cancer (P < 0.05). However, infection and CagA antibodies were associated with young gastric cancer cases. Duodenal ulcer showed a significant association with infection detected by histology and serology, particularly among women, and a trend to associate with IgG to CagA. CONCLUSIONS: This study shows that H. pylori infection and CagA are risk markers for intestinal metaplasia. The prevalence of these risk markers decreases in gastric cancer, probably reflecting that infection decreases after advanced atrophy and metaplasia in the gastric mucosa. State of the disease, age, and sex influence the association of H. pylori infection and IgG response to CagA with gastroduodenal diseases.     

Helicobacter pylori eradication and gastric preneoplastic conditions: a randomized, double-blind, placebo-controlled trial.

Helicobacter pylori causes gastric adenocarcinoma; whether treatment of H. pylori infection prevents this cancer remains unknown. In a randomized, double-blind, placebo-controlled trial of H. pylori eradication, we determined whether treatment for H. pylori decreases gastric cancer risk, using preneoplastic conditions as surrogate markers. A total of 248 healthy volunteers (age >40 years) randomly received H. pylori treatment (omeprazole, amoxicillin, clarythromycin; n = 122) or matched placebo (n = 126) for 1 week. Endoscopy was performed at baseline and at 6 weeks and 1 year. Seven biopsies from each endoscopy were reviewed by two pathologists using the revised Sydney classification. Outcome measures were both a consensus "worst biopsy" diagnosis and a weighted index score that incorporated degrees of severity of preneoplasia from all biopsies. We compared change in these outcomes over time between the two treatment groups. H. pylori cure rates for compliant subjects in the treatment arm were 79.2% and 75.7% at 6 weeks and 1 year, respectively. No statistically significant change in the worst biopsy diagnosis was observed from 6 weeks to 1 year between placebo and treated subjects (for improvement/worsening, placebo, 19.4%/10.5%; treatment, 22.5%/8.3%; P = 0.74). Change in index score was favorably greater in treatment compared with placebo subjects (intention-to-treat analysis, P = 0.03); this finding was particularly evident in the antrum. H. pylori eradication gave more favorable gastric histopathologies over 1 year than no treatment. Such incomplete regression suggests but does not prove that eradication of H. pylori decreases cancer risk.     

Cost-effectiveness analysis between primary and secondary preventive strategies for gastric cancer.

OBJECTIVE: The present study is done to assess the relative cost-effectiveness, optimal initial age, and interscreening interval between primary and secondary prevention strategies for gastric cancer. METHODS: Base-case estimates, including variables of natural history, efficacy of intervention, and relevant cost, were derived from two preventive programs targeting a high-risk population. Cost-effectiveness was compared between chemoprevention with (13)C urea breath testing followed by Helicobacter pylori (H. pylori) eradication and high-risk surveillance based on serum pepsinogen measurement and confirmed by endoscopy. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The incremental cost-effectiveness ratio (ICER) for once-only chemoprevention at age 30 years versus no screening was U.S. $17,044 per life-year gained. Eradication of H. pylori at later age or with a periodic scheme yielded a less favorable result. Annual high-risk screening at age of 50 years versus no screening resulted in an ICER of U.S. $29,741 per life-year gained. The ICERs of surveillance did not substantially vary with different initial ages or interscreening intervals. Chemoprevention could be dominated by high-risk surveillance when the initial age was older than 44 years. Otherwise, chemoprevention was more cost-effective than high-risk surveillance, either at ceiling ratios of U.S. $15,762 or up to U.S. $50,000. The relative cost-effectiveness was most sensitive to the infection rate of H. pylori and proportion of early gastric cancer in all detectable cases. CONCLUSIONS: Early H. pylori eradication once in lifetime seems more cost-effective than surveillance strategy. However, the choice is still subject to the risk of infection, detectability of early gastric cancer, and timing of intervention.