Rabeprazole, amoxycillin and low- or high-dose clarithromycin for cure of Helicobacter pylori infection.

BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. RESULTS: There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.

CagA and cytotoxicity of Helicobacter pylori are not markers of peptic ulcer in Japanese patients.

BACKGROUND: The infection with cagA-positive Helicobacter pylori strains is reported to be associated with peptic ulcer disease in developed countries, but it is controversial in Asia. To investigate the relationship between the virulence factors of H. pylori and peptic ulcer disease in Japan, we compared these between ulcer and nonulcer patients. MATERIALS AND METHODS: Seventy-four strains of clinically isolated H. pylori obtained from 22 gastric ulcer (GU), 23 duodenal ulcer (DU), and 29 chronic gastritis (CG) patients were studied. The presence of vacA and cagA gene was examined by polymerase chain reaction method using two different primer sets. We evaluated the proliferation-inhibiting and lethal cytotoxicity of culture supernatants using the alamarBlue assay. RESULTS: The vacA gene was identified in all strains by the original primers. S1 strains were found in 90.9% (20/22) from GU, 95.7% (22/23) from DU, and 96.6% (28/29) from CG patients. The prevalence of cagA gene determined by the first, and second primers was 90.9% (20/22), 90.9% (20/22) in strains from GU, 87.0% (20/23), 91.3% (21/23) from DU, and 86.2% (25/29), 89.7% (26/29) from CG patients, respectively. The supernatant showed cytolethal effect in 95.5% (21/22) of strains from GU, in 100% (23/23) from DU, and in 93.1% (27/29) from CG patients. There was no significant difference in the prevalence of the virulence factors between H. pylori strains isolated from patients with peptic ulcers and those with chronic gastritis. CONCLUSIONS: These results indicate that cagA gene status and the proliferation-inhibiting and lethal cytotoxicity of supernatant are not reliable markers of ulcerogenicity of H. pylori in Japanese patients.

Biopsy sites suitable for the diagnosis of Helicobacter pylori infection and the assessment of the extent of atrophic gastritis.

OBJECTIVES: We performed this study to determine which biopsy sites in the stomach are suitable for the diagnosis of Helicobacter pylori infection and the assessment of the extent of atrophic gastritis. METHODS: Endoscopy was performed in 76 H. pylori-positive patients with histologically confirmed chronic gastritis. Biopsies were taken from the following six sites: the lesser curvatures of the mid-antrum (site 1), the angulus (site 2), the middle body (site 3), and the greater curvatures of the mid-antrum (site 4), the angulus (site 5), and the middle body (site 6) of the stomach. The extent of atrophic gastritis was assessed endoscopically as well as histologically, and patients were classified into five groups according to its extent. H. pylori status was assessed histologically. The histological severity of inflammation, activity, atrophy, and intestinal metaplasia was assessed according to the Updated Sydney System. The grades of these items were compared among the six biopsy sites in each group of patients. RESULTS: Site 6 was most reliable for the diagnosis of H. pylori infection, and site 4 was suitable for examining the status of H. pylori colonization in the antrum. Site 1, site 3, and site 6 were suitable for the assessment of the extent of atrophic gastritis. CONCLUSIONS: Our results indicate that for an accurate diagnosis and assessment, biopsies should be taken from the following four sites: the lesser curvatures of the mid-antrum (site 1) and middle body (site 3), and the greater curvatures of the mid-antrum (site 4) and middle body (site 6) of the stomach.

The value of LYM-1 cells for examining vacuole formation and loss of cell viability induced by culture supernates of Helicobacter pylori.

Some strains of Helicobacter pylori are known to produce an extracellular cytotoxin that causes vacuolation in cultured mammalian cells. Screening for such strains makes use of HeLa cells which may not be sensitive enough to detect minimal changes. The aim of this study was to develop a more sensitive cell line. Vacuole formation was examined in HeLa cells, as well as four other cell lines established in this laboratory by ammonium chloride induction. Among five cell lines tested, LYM-1 cells were most sensitive for the detection of intracellular vacuolation with this agent. Loss of cell viability of LYM-1 and HeLa cells induced by H. pylori culture supernates was also examined: LYM-1 were more sensitive than HeLa cells. Cell death was not always accompanied by vacuole formation. This suggests that the mechanism whereby cell death occurs must be different from that for vacuole formation. LYM-1 cells may be useful when measuring vacuole formation and cell death of the cultured cells induced by culture supernates of clinical isolates of H. pylori.

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection.

AIM: To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection. 99 patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole. METHODS: The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended. RESULTS: The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79-97%) and 92% in the RCM group (45 of 49; 95% CI = 84-99%). The incidence of adverse events was 16% and 18% for the two groups, respectively. CONCLUSIONS: No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2-blocker is sufficient to achieve optimal H. pylori eradication.

The efficacy and safety of one-week triple therapy with lansoprazole, clarithromycin, and metronidazole for the treatment of Helicobacter pylori infection in Japanese patients.

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of 1-week, low-dose triple therapy with lansoprazole, clarithromycin, and metronidazole (LCM) for the cure of H. pylori infection and to establish the adequate dosage of a new triple therapy for Japanese patients. MATERIALS AND METHODS: One hundred four H. pylori-positive Japanese patients were assigned alternatively to one of two groups: one to receive either 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily for 1 week (LCM1; n = 52); the other to receive 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 500 mg metronidazole twice daily for 1 week (LCM2; n = 52). H. pylori infection was assessed by smear, culture, and histological assessment (Giemsa stain) performed before and 4 weeks after cessation of the therapy. RESULTS: The overall cure rates of H. pylori infection were 92.3% (48 of 52; 95% confidence interval (CI), 85% to 100%) in LCM1 and 92.3% (48 of 52; 95% CI, 85% to 100%) in LCM2. The cure rates in the patients without prior treatment were 95.7% (44 of 46; 95% CI, 89%-100%) in LCM1 and 95.7% (45 of 47; 95% CI, 89%-100%) in LCM2. Minor side effects were observed in 7.7% of LCM1 and 9.6% of LCM2, respectively. CONCLUSION: The LCM1 regimen consisting of 30 mg lansoprazole once daily, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily (the regular doses in ordinary use in Japan) is a highly effective and safe regimen for Japanese patients. LCM1 as a new triple therapy is a promising regimen for the first-line treatment of H. pylori infection in Japanese patients.

Deficiencies of automatic endoscopic reprocessors: a method to achieve high-grade disinfection of endoscopes.

BACKGROUND: We show that disinfection using the automatic endoscopic reprocessor is not complete and propose a method for high-grade disinfection of endoscopes. METHODS: We used an automatic endoscopic reprocessor, Pyser System 83, and 2% glutaraldehyde. After each endoscopic procedure, the endoscopes were divided into three groups. Endoscopes in group A were washed only by the reprocessor. Group B endoscopes were washed by the reprocessor after the connectors were soaked in glutaraldehyde for 5 minutes. The channels, valves, connecting sections of group C endoscopes, and the connectors of the machine were sprayed with glutaraldehyde before machine-washing. Swabs were taken from all 13 parts of each endoscope and machine for microbiologic culture. RESULTS: Six endoscopes were positive, cumulatively, for bacterial contamination in group A. Among group B endoscopes, one remained contaminated. No endoscope was positive in group C. The difference between group A and C was statistically significant (p < .05). CONCLUSIONS: Machine washing by automatic endoscopic reprocessors may not achieve complete disinfection. Additional procedures are necessary. High-grade disinfection of the connectors is critical. Disinfection of the interface between the connectors is important.

Efficacy of clarithromycin in eradicating Helicobacter pylori.

We reviewed reports on the efficacy of clarithromycin in eradicating Helicobacter pylori. Reports on dual and 1-week triple therapy that included clarithromycin were analyzed to assess the eradication rates of H. pylori infection. Dual therapy with clarithromycin and a proton pump inhibitor achieved eradication rates of 38%-83%, and 1-week triple therapy with omeprazole, clarithromycin, and other antibiotics achieved eradication rates, of 80%-96%. The incidence of side effects with all regimens was low. Clarithromycin is useful for treatment of H. pylori infection. One-week triple therapy that includes clarithromycin and a proton pump inhibitor effectively eradicates H. pylori.

Endoscopic topical therapy for the treatment of Helicobacter pylori infection.

We modified a novel topical therapeutic method for the treatment of Helicobacter pylori infection to increase its effectiveness and tolerability. Sixty-six patients (with nonulcer dyspepsia, inactive ulcer, or active ulcer) were given lansoprazole (30 mg, h.s.) and pronase (18,000 tyrosine units, b.i.d.) orally for 2 days before the topical therapy. One hundred milliliters of 7% sodium bicarbonate solution containing bismuth subnitrate, amoxicillin, metronidazole (at two different regimens), and pronase was instilled into the stomach through an endoscope. A double-lumen tube with a balloon at the tip was inserted into the duodenum along with the endoscope. The balloon was inflated with 25 ml of air and was lodged postbulbarly. The solution was kept in the stomach for 2 h, and the patient's position was changed every 15 min from the sitting to the supine, prone, and right lateral position, each position being maintained twice, to expose the entire gastric mucosa. The solution was aspirated at the end of the procedure. H. pylori infection was cured in 16/22 (72.7%) of patients with nonulcer dyspepsia, in 21/26 (80.7%) of patients with inactive ulcer, and in 1/18 (5.6%) patients with active ulcer. H. pylori eradication was confirmed 4 weeks after the therapeutic procedure by smear, culture, and histology of antral and corpus biopsy specimens. Side effects (loose stools) were observed in two patients only, and one patient had loss of appetite. These effects were transient. This endoscopic topical therapy for H. pylori infection is a safe, effective, and well tolerated procedure. With further modifications of the drug regimens and the method itself, this procedure could be of interest as anti-H. pylori therapy.

Distribution of inflammation and atrophy in the stomach of Helicobacter pylori-positive and -negative patients with chronic gastritis.

OBJECTIVES: To investigate the extent of inflammation and atrophy in the stomach of Helicobacter pylori-positive and -negative patients with chronic gastritis. METHODS: Endoscopy with biopsies from the lesser curvatures of the antrum, angulus, middle body, and the greater curvature of the middle body of the stomach was performed in 59 patients with histologically confirmed chronic gastritis. The extent of atrophic gastritis was assessed endoscopically as well histologically. H. pylori status was assessed by histology as well as enzyme-linked immunosorbent assay. The histological severity of chronic and acute inflammation, glandular atrophy, and intestinal metaplasia was assessed according to the Sydney system. RESULTS: In H. pylori-positive patients, H. pylori was evenly distributed throughout the stomach when the extent of atrophic gastritis was limited to the antrum and the lesser curvature of the body, but disappeared from the antrum of patients with more extensive atrophic gastritis. The severity of acute and chronic inflammation at the greater curvature of the body increased with the extension of atrophic gastritis. In H. pylori-negative patients, the severity of chronic inflammation at the greater curvature of the body was significantly higher in patients with extensive atrophic gastritis than in those with a lesser extent of atrophic gastritis. CONCLUSION: At the greater curvature of the body, the development of atrophy is closely associated with the increase in the severity of inflammation, which is more marked in H. pylori-positive patients.

Dual therapy with lansoprazole and clarithromycin for eradication of Helicobacter pylori.

AIM: To evaluate the eradication of Helicobacter pylori by therapy with a combination of 60 mg lansoprazole and 800 mg clarithromycin. PATIENTS AND METHODS: In an open therapeutic trial, 30 H. pylori-positive patients with active ulcer disease took 30 mg lansoprazole twice a day and 400 mg clarithromycin twice a day for the first 2 weeks, followed by 30 mg lansoprazole once a day for 4-6 weeks. Endoscopy was performed both before and at the end of therapy, and 4 weeks after the end of the therapy. H. pylori was detected by using a combination of smear, culture and tissue sections. RESULTS: Complete pain relief occurred within 3 days in all patients and all ulcers were healed by the end of the therapy. The H. pylori clearance rate was 83.3% and the eradication rate was 73.3%. A minor side effect (metallic taste) was reported by only one patient (3.3%). CONCLUSIONS: Therapy with a combination of 60 mg lansoprazole and 800 mg clarithromycin is efficacious in the eradication of H. pylori and has the advantage of a low incidence of side effects and quick pain relief for patients with active ulcers.

A 1-h topical therapy for the treatment of Helicobacter pylori infection.

OBJECTIVE: A novel topical therapeutic methodology for the treatment of Helicobacter pylori infection was developed and studied in 25 patients with H. pylori to evaluate safety and efficacy. METHODS: The patients had been given lansoprazole (30 mg, hs) orally and pronase (18,000 tyrosine units, b.i.d.) for the 2 days before topical therapy. One hundred milliliters of solution with 80 ml of 7% sodium bicarbonate and 20 ml of contrast medium meglumine sodium amidotrizoate containing bismuth subnitrate (1 g), amoxicillin (2 g), metronidazole (1 g), and pronase (36,000 tyrosine units) were instilled into the stomach through a nasally introduced 16-Fr intestinal tube with a balloon at its radiopaque tip, which was inflated with approximately 25 ml of air and lodged postbulbarly at the superior duodenal angle under fluoroscopy, thus preventing leakage of the solution distally into the jejunum. The solution was kept in the stomach for 1 h, and the patient's position was changed every 15 min from the sitting to the supine, prone, and right lateral position to expose the entire gastric mucosa. The solution was suctioned at the end of the procedure. RESULTS: H. pylori infection was successfully cured in 24 (96%) patients, confirmed 4 wk after the therapeutic procedure by negative smear, culture, and histology of the antral and corpus biopsy specimens. No side effects were observed except for loose stools in one case. CONCLUSION: This 1-h topical therapy is a safe, effective, and well tolerated procedure for the treatment of H. pylori infection. With further improvements and modifications of the method itself, as well as of the drug regimens, this method may become a highly efficient modality for anti-H. pylori therapy.

Efficacy of lansoprazole in eradication of Helicobacter pylori.

Fifty-eight Helicobacter pylori-positive ulcer patients received omeprazole 20 mg (n = 15), or lansoprazole 30 mg (n = 23), lansoprazole 60 mg (n = 13), or E3810 20 mg (n = 7) q.d. Another 63 H. pylori-positive ulcer patients received lansoprazole and clarithromycin for 2 weeks. Patients received lansoprazole 30 mg and clarithromycin 400 mg (group 1, n = 22), lansoprazole 30 mg and clarithromycin 800 mg (group 2, n = 12), or lansoprazole 60 mg and clarithromycin 800 mg (group 3, n = 29). Neither proton pump inhibitor (PPI) was capable of eradication by monotherapy, but the clearance rates in the lansoprazole group were 60.9 and 69.2%, which were higher than those for omeprazole (p < 0.05). In the dual therapy, eradication rates were 50, 50, and 72.4% in groups 1, 2, and 3, respectively. Minor side effects were observed in one case each in groups 1 and 3. Lansoprazole monotherapy proved more efficacious than omeprazole monotherapy, but it was unable to eradicate H. pylori. Dual therapy with lansoprazole 60 mg and clarithromycin 800 mg was an efficacious and safe regimen for H. pylori eradication in this study.

Helicobacter pylori detected deep in gastric glands: an ultrastructural quantitative study.

To determine the presence of Helicobacter pylori deep in the gastric glands and in the parietal cell canaliculi, biopsied specimens from 15 patients were observed by electron microscopy. In the specimens, 818 H. pylori and 1,846 parietal cells were detected. Most of the H. pylori (93.9%, 768/818) were present on the mucosal surface. However, a few organisms (50/818, 6.1%) were detected deep in the mucosa. The mean number of H. pylori per specimen was 2.13 (32/818, 3.9%) and 1.20 (18/818, 2.2%), deep in the gland and in the parietal cell canaliculi, respectively. All appeared morphologically intact. Although the combination of culture and histology from biopsy tissues is usually used for isolation of H. pylori in most laboratories, such organisms are considered difficult to detect with conventional methods and to dislodge with antimicrobial therapy. Therefore, H. pylori present deep in the mucosa are suggested to be one of the factors in recrudescence after eradication therapy. In addition, H. pylori in the parietal cell canaliculi may affect parietal cell function or alter gastric physiology.

[A case report of esophageal intramural pseudodiverticulosis].

A 76 year old man with esophageal intramural pseudodiverticulosis occurring in reflux esophagitis is presented. This unusual condition characterized by multiple small outpouchings in the esophageal wall and associated with a high incidence of benign esophageal stricture. Our case demonstrated typical radiological feature by barium swallow.

[A superficial carcinoma arising from a solitary hepatic cyst].

Reported is a rare superficial papillary adenocarcinoma arising from a congenital cyst, along with a survey of pertinent cases in the world literature. A 43-year-old male with a huge hepatic cyst was admitted to hospital for further examination. Since the cystic drainage done for alcoholic fixation was seromucinous initially but later contaminated by bile, an operation was initiated for dome resection and the closure of the biliary communication. At the time of the deroofing, however, small granulomas were found. And those were confirmed as being malignant by frozen section. Thus, an extended right lobectomy was performed for therapy. From its history and nature, this was considered to be a cancer arising in a congenital hepatic cyst.

Isolation of tryptic fragment of antigen from mitochondrial inner membrane proteins reacting with antimitochondrial antibody in sera of patients with primary biliary cirrhosis.

Most of the sera from patients with primary biliary cirrhosis contains antimitochondrial antibodies, which react with four proteins of the mitochondrial inner membrane. We reported in a previous paper that when beef heart mitochondrial inner membrane proteins were digested by trypsin, a new reactive 36 kDa fragment with antimitochondrial antibody was obtained. This 36 kDa fragment derives from original 70 kDa protein because the monoclonal antibody specific to 70 kDa protein reacts with the 36 kDa band equivalent to 70 kDa band. The 36 kDa fragment was purified using an affinity column conjugated with an immunoglobulin-rich fraction of primary biliary cirrhosis serum containing antimitochondrial antibody, preparative electrophoresis and high-performance liquid chromatography using a reverse phase column. The final preparation showed a single band in sodium dodecyl sulfate polyacrylamide gel electrophoresis. Its amino acid composition is in good agreement with that of the subunit binding domain of the pyruvate dehydrogenase complex E2 from bovine heart.

[A case of hepatocellular carcinoma (HCC) with lung metastasis which responded to chemotherapy with a single use of 1-hexylcarbamoyl-5-fluorouracil (HCFU)].

To our knowledge, there has been only one report pertaining to the efficacy of HCFU for treatment of metastatic lung lesion of HCC, so we reported a case of HCC with lung metastasis which responded to chemotherapy with a single use of HCFU. A 64-year-old male was diagnosed as having HCC with lung metastasis by biochemical examination, abdominal CT, hepatic arteriogram and chest X-P. He had been treated previously with gamma-interferon and mitoxantrone, which were assessed as NC and PD, respectively. Two months after last chemotherapy, HCFU was administrated at a dose of 400 mg/body everyday for 8 months. After 4 weeks metastatic lung lesions showed remarkable regression (47% decrease) and disappeared completely 9 weeks later. The size of primary liver tumor gradually decreased during therapy and revealed marked improvement (85.7% decrease) after about 2 months of this therapy. During these periods serum levels of alpha-fetoprotein dropped from 430 ng/ml to less than 10 ng/ml. He is presently still alive and the duration of the PR attained to 35 weeks. As side effects, hypoproteinemia, anorexia and hot sensation were observed.

[Antitumoral effect of gamma-interferon in patients with hepatocellular carcinoma].

The antitumoral effect of gamma-Interferon (Re-IFN-gamma, KW-2202) on nine patients with hepatocellular carcinoma (HCC) has been investigated. gamma-IFN was administered intravenously biweekly at a dose of 8-24 x 10(6) units/day for 5 consecutive days. As all patients had measurable disease determined by an abdominal CT, the antitumoral effect was evaluated by CT, according to the criteria of Koyama and Saito, During gamma-IFN therapy, one patient, who received a total of 4.4 x 10(8) units of gamma-IFN, achieved a partial response (PR) 133 days after onset of treatment. Another patient showed a minor response (MR) 43 days after start of therapy. The duration of the PR and MR were 7.8 weeks and 10.8 weeks, respectively. Two patients were assessed as having had no change (NC), and 5 patients as still manifesting a progressive disease (PD). Marked falls in serum alpha-fetoprotein levels during therapy were observed in 2 cases of which one was graded as having obtained a PR, and the other, a NC. The toxicities observed were fever, general malaise, headaches, and joint pains, which were slight and transient in most cases. In one case, however, a therapy was stopped because of a continuous and severe shoulder pain with no metastasis. Further studies on the use of IFN, possibly in combination with other chemotherapeutic agents, should be performed in patients with HCC.

[A case of recurrent gastric cancer successfully treated with a combination of cisplatin and carmofur].

A 51-year-old man with recurrent gastric cancer was treated by combined administration of Cisplatin and Carmofur. The target sites were the abdominal lymph nodes and the area of invasion to the stomach. Cisplatin (50 mg/body/day) was given for 3 days, while Carmofur (400-800 mg/body/day) was administered daily in 1 course. After 1 course of administration, the target tumor was reduced in size and the therapy was continued. A complete response was confirmed by upper gastrointestinal roentgenography, endoscopy and echography after 8 courses of Cisplatin administration. The patient has survived for 2 years 6 months in a state of CR. This case suggests that a combination therapy of Cisplatin and Fluoropyrimidine derivatives might be effective for gastric cancer.