Possible role of Helicobacter pylori infection in early gastric cancer development

BACKGROUND: Gastric cancer is the most frequently diagnosed malignancy in Japan. The possible relationship between Helicobacter pylori infection and gastric cancer in Japan was evaluated. METHODS: H. pylori infection was identified by the presence of anti-H. pylori IgG. The frequency of H. pylori infection was compared in 213 patients with gastric cancer and the same number of asymptomatic control subjects matched for age and sex. RESULTS: The presence of IgG antibody to H. pylori was significantly more prevalent (P < 0.001) in those with gastric cancer compared with asymptomatic control subjects (88.2% versus 74.6%). H. pylori positive rates were significantly greater in patients with the intestinal type (90.4%, P < 0.001) and diffuse type (86.4%, P < 0.05) of gastric cancer than in control subjects. Ninety-three percent of the patients with early gastric cancer tested positive for H. pylori (P < 0.001 compared with control subjects), whereas no significant difference was observed between those with advanced gastric cancer and control subjects. The intestinal type of early gastric cancer showed only the significantly increased frequency of high titer (optical density > 1.50) of H. pylori IgG antibody (P < 0.001) compared with control subjects without cancer. CONCLUSIONS: These results suggest that H. pylori infection may be associated with the development of early gastric cancer in Japan.     

Effect of Helicobacter pylori eradication on intestinal metaplasia and gastric epithelium proliferation

Gastric epithelial turnover increase in Helicobacter pylori infection has been demonstrated by interventional and non interventional methods for proliferating cell detection. We have observed a progressive hyperproliferation with the progression of Helicobacter pylori-induced mucosal lesions until the development of intestinal metaplasia. A similar result has been reported in other studies in the succession from normal mucosa to gastric carcinoma even if interventional techniques show less conspicuous differences in comparison to non interventional ones, which give an overestimated picture of proliferation. Later studies show that Helicobacter pylori-related hyperproliferation reverses after eradication. We have observed that this reversibility does not occur in areas of intestinal metaplasia, where the oncoprotein ras p21, involved in early gastric carcinogenesis, is expressed. This finding agrees with that demonstrating that hyperproliferation in intestinal metaplasia or gastric cancer is not affected by Helicobacter pylori. Other oncogenetic changes in intestinal metaplasia (i.e., p53 mutation) may further explain the persistently modified proliferative pattern of the epithelium. Recent studies suggest a lack of reversibility of intestinal metaplasia after Helicobacter pylori eradication, but this problem remains controversial. Our experience suggests that the persistence of the bacterium may increase the extent of this lesion. In conclusion the development of intestinal metaplasia is associated with an impaired regulation of gastric epithelial proliferation. Nevertheless, from the biological point of view, the progression towards carcinoma requires further DNA changes. Moreover, many questions need to be answered in order to establish clear guidelines for the clinical management.     

Pathological appearance of the stomach after endoscopic mucosal resection for early gastric cancer

BACKGROUND: The pathological findings of the resected stomach after endoscopic mucosal resection (EMR) for early gastric cancer were reviewed. EMR was indicated when a lesion consisting of well or moderately differentiated adenocarcinoma had a diameter of less than 2 cm. METHODS: Of 39 patients with early gastric cancer were treated with EMR between 1990 and 1995, 11 required additional surgery. RESULTS: Malignant tissue in the gastric wall was completely removed in four patients, while cancer cells remained in the mucosa adjacent to the scar in five and infiltrated into the submucosa in two. Most of these residual cancers were characterized by a lesion with a diameter exceeding 15 mm and by the location in the body or cardia of the stomach. Lymph node metastases were observed in one patient whose carcinoma invaded the deeper submucosal layer. Assessment of the depth of entire invasion from the endoscopically-resected specimen was correct for six of 11 patients. CONCLUSION: Gastric carcinomas to be resected by EMR should be smaller, especially if located in the body or cardia. Accurate diagnosis of the width and depth of invasion is indispensable before proceeding to EMR. Surgery may be the treatment of choice when there is submucosal invasion.     

Treatment of primary low-grade gastric lymphomas with eradication of Helicobacter pylori

There is evidence associating Helicobacter pylori (HP) with both mulosa-associated lymphoid tissue (MALT) and MALT-lymphoma. Recently, three studies including 65 patients have shown that the eradication of HP can lead to regression in about 60-70% of primary low-grade gastric B-cell MALT-lymphomas. Prolonged follow-up will be necessary to see whether these remissions are lasting, and whether eradication of HP in combination with conventional therapy is more effective than either of these treatments alone. Until then we recommend that HP is eradicated in these lymphomas before referral to standard treatment with chemotherapy and/or radiotherapy.     

Helicobacter pylori reinfection is virtually absent after successful eradication

This study examined whether reinfection or recrudescence accounts for the reappearance of Helicobacter pylori infection after apparent successful eradication. In a prospective study, 173 patients cured from H. pylori infection underwent follow-up endoscopies, with biopsies for culture and histopathology, every 3 months during the first year after treatment. Subsequently, elective half-yearly endoscopies were performed in 124 patients; the remaining 49 underwent follow-up endoscopy only in 1995. At reappearing infection, DNA profiles of pretreatment and recurrent strains were compared. After 3.5 years (range, 1.0-9.2), H. pylori infection recurred in 9 patients (5.2%). Reappearing infections were classified as endoscopically transmitted reinfection (n = 2), unclassified because of loss of pretreatment isolate (n = 1), or recrudescence (identical DNA patterns before and after treatment; n = 6). The reappearance rate of infection, discarding endoscopic transmission, was 1.2% (7/601 H. pylori-negative patient-years). There was virtually no reinfection with H. pylori after eradication in this adult Western population. These data do not rule out acquisition of H. pylori.     

A case of multiple early gastric cancer showing complete response to UFT-E after endoscopic mucosal resection

The aim of this study was to investigate whether MR imaging of trabecular bone structure using magnetic inhomogeneity measurements is related to the amount of bone mineral in human vertebrae. Weight, bone mineral content (BMCDXA), bone mineral per area (BMADXA) and bone mineral density (BMDCT) were determined in 12 defatted human lumbar vertebrae (L2-L4) by weighing, dual X-ray absorptiometry (DXA) and CT. Inhomogeneity caused by susceptibility differences between trabecular bone and surrounding water was studied with MR imaging at 1.5 T using the GESFIDE sequence. The pulse sequence determines the transverse relaxation rate R2(*) and its two components, the non-reversible transverse relaxation rate (R2) and the reversible transverse relaxation rate (R2'; i. e. relaxation rate due to magnetic susceptibility) in a single scan. Voxel size was 0.9 x 1.9 x 5.0 mm. Positive significant correlations between R2' and weight, BMCDXA, BMADXA and BMDCT were observed (r > 0.61 and p < 0.05 for all). Unexpectedly, R2 was also positively correlated with weight, BMCDXA and BMDCT (r > 0.66 and p < 0.05 for all), but not with BMADXA. Thus, R2' measurements are related to the amount of bone mineral, but they also provide information which is not obtainable from bone mineral measurements.     

Long-term effect of Helicobacter pylori eradication on gastric metaplasia in patients with duodenal ulcer

Thyroid functions were analyzed before, during and after interferon (IFN) therapy in patients with chronic hepatitis C. According to the results of routine thyroid function tests and measurements of the levels of anti-thyroid autoantibody prior to the therapy, patients were divided into 2 groups; Group A (19 patients) had at least one abnormal finding related to the thyroid, and Group B (40 patients) did not show any abnormality. Five patients (26%) in Group A and 4 (10%) in Group B showed thyroid dysfunctions which were very clearly reflected by thyrotropin (TSH) measurements. Interestingly, the time of peak TSH elevation in Group A (mean +/- SD, 4.3 +/- 0.8 months) was significantly earlier than that in Group B (6.8 +/- 0.8). Most patients in Group B were diagnosed as having destructive thyroiditis. These findings may suggest that the pathogenesis of IFN-induced thyroid dysfunction consists not only of exacerbation of pre-existing thyroid autoimmunity but also of de novo destructive changes even in the intact thyroid before IFN therapy.     

A case of reflux esophagitis after eradication of Helicobacter pylori]

Ceruminous glands are modified sweat glands, confined to the skin lining of the cartilaginous part of the external auditory meatus. Tumours arising from these glands are extremely rare. Confusion exists regarding the nomenclature 'ceruminoma' and controversies prevail on the standard way of management. Treatment often involves a multidisciplinary approach, requiring reconstruction after extensive surgical resection. A case report of adenoid cystic carcinoma of ceruminous glands is presented along with discussion of the various pathological types and a review of management.     

Beneficial effects of Helicobacter pylori eradication on migraine

BACKGROUND/AIMS: Migraine is a commonly unilateral throbbing headache, which has been associated with disorders of the vascular tone. Helicobacter pylori, the most relevant cause of gastritis and peptic ulcer, has been recently associated with a typical functional vascular disorder such as primary Raynaud phenomenon. The aim of this study was to assess the prevalence of H. pylori for patients affected by migraine and the effects of H. pylori eradication on migraine symptoms. METHODOLOGY: Two-hundred and twenty-five patients were consecutively enrolled between October 1996 and January 1997. H. pylori was assessed by 13C-urea breath test. Infected subjects were eradicated of the bacterium; frequency, intensity and duration of attacks of migraine were assessed during a 6 month follow-up period. RESULTS: H. pylori was detected in 40% of the patients. Eighty-three percent of the patients who underwent therapy were eradicated. Intensity, duration and frequency of attacks of migraine were significantly reduced in all eradicated patients. CONCLUSIONS: H. pylori is common in subjects with migraine. Bacterium eradication causes a significant decrease in attacks of migraine. The reduction of vasoactive substances produced during infection may be the pathogenetic mechanism underlying the phenomenon.     

Regression of superficial gastric MALT lymphoma with unsuccessful eradication therapy for Helicobacter pylori infection

A 51-year-old man had a reddish flat granular lesion in the stomach on endoscopic examination. Histology of biopsied specimen confirmed the diagnosis of low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) and simultaneous infection with Helicobacter pylori. He was given antibiotic treatment. Five weeks later, endoscopy and histology of biopsied specimen showed eradication of H. pylori, and the tumor had regressed. Six months later, H. pylori reemerged, but the tumor had not recurred. After the second antibiotic therapy, H. pylori has been eradicated. The lymphoma has been in remission for 14 months.     

Helicobacter pylori infection induces gastric cancer in mongolian gerbils

BACKGROUND & AIMS: Although epidemiological studies have indicated that Helicobacter pylori infection plays a crucial role in gastric carcinogenesis in humans, there is no direct proof that H. pylori is actually associated with gastric carcinogenesis. The purpose of this study was to elucidate the relationship between H. pylori infection and gastric carcinogenesis using an animal model of long-term H. pylori infection. METHODS: Mongolian gerbils were orally inoculated with H. pylori, and the sequential morphological changes in the stomach were examined for up to 62 weeks. RESULTS: H. pylori was constantly detected in all infected animals throughout the study. At the 26th week, severe active chronic gastritis, ulcers, and intestinal metaplasia could be observed in infected animals. By the end of the study, adenocarcinoma had developed in the pyloric region of 37% of the infected animals. All tumors consisted of well-differentiated intestinal-type epithelium, and their development seemed to be closely related to intestinal metaplasia. CONCLUSIONS: We have successfully demonstrated that long-term infection with H. pylori induces adenocarcinoma in Mongolian gerbils. The observations are thus highly suggestive of the involvement of H. pylori infection in gastric carcinogenesis in humans.     

Age-dependent eradication of Helicobacter pylori with dual therapy

BACKGROUND: Combined treatment using an acid-inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. METHODS: In a single-blind study, 60 H. pylori-positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. RESULTS: The overall eradication rates were 45% (intention-to-treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 +/- 1.7; 51 +/- 25%) than for omeprazole (5.4 +/- 1.1: 77 +/- 25%; P < 0.05) or lansoprazole (4.4 +/- 1.6: 68 +/- 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post-treatment H. pylori status was not dependent on those levels, or the drug-induced extent or duration of increased intragastric pH. However, H. pylori-eradicated patients were significantly (P < 0.05) older (56 +/- 13 years) than patients still H. pylori-positive (47 +/- 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75-83%) in subgroups of patients (> 50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. CONCLUSION: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.     

Is Helicobacter pylori really the cause of gastric cancer?

The goal of this study was to assess the role of examining and repetitive rhythmic activity in infants' exploration of novel objects. Sixteen 8-month-old infants played with novel toys as auditory-visual slide distractors occurred on one side at random intervals. The results showed that examining, but not repetitive activities, declined with exposure to the objects. They also showed that infants had different patterns of distractibility during examining and repetitive rhythmic activities. The infants were slower to turn to the distractor if they were examining the toy than if they were engaged in other activity, but the probability of a response did not differ. In contrast, when engaged in repetitive rhythmic activity, infants were less likely to respond to the distractor than when engaged in other activities, including examining; the speed with which they responded, however, did not differ. The results suggest that, during these two activities, the mechanisms for resisting distraction are quite different.     

Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urticaria

Helicobacter pylori, the most important cause of gastritis and peptic ulcer, recently has been associated with several extradigestive diseases. The aim of this study was to assess the prevalence of Helicobacter pylori infection and the effects of bacterium eradication in 42 consecutive patients affected by idiopathic chronic urticaria. Helicobacter pylori was assessed by [13C]urea breath test. Amoxicillin, clarithromycin, and lansoprazole were given to infected patients for seven days. Urticaria and gastrointestinal symptoms were assessed on enrollment and after eradication. Fifty-five percent of patients proved to be infected by Helicobacter pylori. Prevalence of gastrointestinal symptoms did not differ between infected and uninfected patients. Eighty-eight percent of infected patients in whom the bacterium was eradicated after therapy showed a total or partial remission of urticaria symptoms. Conversely, symptoms remained unchanged in all uninfected patients. In conclusion, Helicobacter pylori affects a high percentage of patients with idiopathic chronic urticaria; however, typical gastrointestinal symptoms do not identify infection status. Bacterium eradication is associated with a remission of urticaria symptoms, suggesting a possible role of Helicobacter pylori in the pathogenesis of this skin disorder.     

Endoscopic mucosal resection for early gastric cancer

Endoscopic therapy of gastric cancer has been mainly performed to early cancer of nonresectable cases, for example patients having severe complications, high aged group and patients refusing the operation. Recently, endoscopic mucosal resection (EMR) made it possible to do radical resection for small gastric cancer of resectable cases. 112 patients of small cancers which diagnosed as a cancer limited to the mucosa were investigated. Indication to perform EMR instead of surgery were determined pathologically as follows, 1. depressed type of cancer not accompanying with converging folds measuring 1 cm or less in size, 2. elevated type of cancer measuring 2 cm or less in size, 3. differentiated type of carcinomas. According to those indications, 112 cases with 129 lesions of early gastric cancer were resected. The incision procedure consisted in EMR using two-channel fiberscope, a large chating forceps and a snare, the tissue being ablated with a high frequency electrical current. 2-6 ml of phisocal saline was locally infused at the submucosal level before resection to do it safely. Results: Relationship between the prognosis and the histological distance from the edge of the specimen to the margin of the cancer were discussed. All of 81 cases having the distance more than 2 mm, it's called 'complete radical resection', were not recurrent, on the other hand 4 of 24 cases having the distance less than 2 mm, called 'incomplete radical resection', were recurrent at the site of resection and 12 of 24 cases obviously cancer spread to the edge of the specimen, called 'non-radical resection', were recognized the recurrence. conclusion, 1) On endoscopical resection for small gastric cancer, the distance more than 2 mm between the edge of the specimen and the margin of the cancer was necessary to get a complete radical resection. 2) Technical and mechanical problems still remained at the case of the cancer located in the angular region and gastric body.     

The impact of Helicobacter pylori eradication on peptic ulcer healing

OBJECTIVE: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status. METHODS: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients. RESULTS: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7, p < 0.01), duodenal ulcer 95% vs 76% (OR 5.6, p < 0.0001), and peptic ulcer 95% vs 76% (OR 6.6, p < 0.0001), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (< or = 6, 7-8, and 10-12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all p < 0.0001, Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94-96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7-20% improved healing rates, whereas patients becoming HP-negative did not profit. CONCLUSION: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.     

Relevance of Helicobacter pylori infection in the development of gastric tumors

The efficacy of a 6-week rehabilitation program was evaluated in 100 consecutive patients, age 15-42 years, with acute anterior cruciate ligament (ACL) injury. Arthroscopy revealed associated lesions in 82% of the patients. Except for resections on menisci with large and unstable lesions, no surgery was performed. The patients were randomly assigned to supervised training or self-monitored training after instruction. RESULTS: At the 6-week follow-up there was no difference between the groups with regard to pain at rest, pain during walking, or experience of giving-way episodes, Tegner activity level of Lysholm knee score. Only 2 of the 100 patients were observed without joint mobility restriction. The only significant difference between the groups was the improvement of muscle function in men in the supervised training group. Conclusion: Six weeks' rehabilitation is too short a time period from original injury to obtain normal mobility and restored knee function.