IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling.

BACKGROUND: Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion. METHODS: Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay. RESULTS: Interleukin-22 and its receptor were expressed in α-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. CONCLUSIONS: Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.

REG Iα is a biomarker for predicting response to chemotherapy with S-1 plus cisplatin in patients with unresectable stage IV gastric cancer.

BACKGROUND: The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC. METHODS: A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry. RESULTS: Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells. CONCLUSION: In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.

The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma.

BACKGROUND AND STUDY AIMS: Conventional colonoscopy can result in unnecessary biopsy or endoscopic resection due to its inability to distinguish adenomas from hyperplastic polyps. This study therefore evaluated the efficacy of high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) in discriminating colon adenoma from hyperplastic polyps. PATIENTS AND METHODS: This was a prospective multicenter study in patients undergoing AFI and NBI examinations. HRE, AFI, and NBI images were classified into two groups based on morphological characteristics, the predominant color intensities, and the visibility of meshed capillary vessels, respectively. Each of the endoscopic photographs were independently evaluated by a single endoscopist. The images were then assessed by three specialists and three residents, the latter having performed < 500 colonoscopies and < 30 NBI and AFI examinations. Diagnostic test statistics were calculated to compare the accuracy in differentiating colon adenoma from hyperplastic polyps for each method. RESULTS: A total of 183 patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps with an accuracy of 84.9 % and 88.4 %, respectively, whereas HRE exhibited an accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9 %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and residents, AFI and NBI dramatically improved the diagnostic accuracy of residents from 69.1 % to 86.1 % and 84.7 %, respectively. CONCLUSIONS: Both AFI and NBI are considered to be feasible tools that can discriminate colon adenoma from hyperplastic polyps, and their use may be particularly beneficial for less-experienced endoscopists.

K-ras mutations and cell kinetics in Helicobacter pylori associated gastric intestinal metaplasia: a comparison before and after eradication in patients with chronic gastritis and gastric cancer.

BACKGROUND: Helicobacter pylori related gastric intestinal metaplasia (IM) is considered to be a precancerous lesion. AIMS: To identify the effects of H pylori eradication on K-ras mutations, cell kinetics in IM and histological changes in patients with and without gastric cancers in a one-year prospective study. METHODS: Patients included group A (n = 39), chronic gastritis, and group B (n = 53), intestinal-type early gastric cancer patients who had all undergone endoscopic mucosal resection (n = 25) or surgical resection (n = 28). K-ras codon 12 mutations in IM were examined, followed by DNA sequencing analysis. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and using the TUNEL method, respectively. RESULTS: The incidence of K-ras mutations in the cancer was only 3.8%. The mutant K-ras in IM was observed more frequently in group A (46.2%) than in group B patients (1.9%) (p<0.005). After eradication, the K-ras mutations significantly declined to 12.8% in group A (p<0.005). The mutation pattern of K-ras codon 12 before eradication was that GGT was mainly changed to AGT (50%) in group A. AGT transformation was not affected by treatment. Apoptosis in IM showed an increase after H pylori eradication in both groups (p<0.05 in group A) although no histological improvement in IM was observed. The monocyte score was significantly higher in group A than in group B (p<0.05); the score improved significantly after eradication. CONCLUSIONS: K-ras mutations in IM do not always play a role in gastric carcinogenesis but cell kinetics, especially apoptosis, in IM may contribute to it. There are early events in K-ras mutations which are influenced by H pylori infection; some mutations may also be selected by eradication. These unstable K-ras mutations in IM may be related to lymphocyte infiltration caused by H pylori infection.

Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials.

BACKGROUND: Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases. AIM: To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU). METHODS: Patients aged ≥20 years with ≥1 endoscopically-confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU. RESULTS: For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8% (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of vonoprazan to lansoprazole was confirmed [difference = -0.3% (95% CI -4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and 98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non-inferiority to lansoprazole was not confirmed [difference = -2.8% (95% CI -6.400, 0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated patients; levels returned to baseline after treatment in both groups. CONCLUSIONS: Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non-inferior with respect to GU healing and has similar efficacy for DU healing.

Acotiamide improves stress-induced impaired gastric accommodation.

BACKGROUND: Gastric accommodation is a reflex reaction related to gastric reservoir function. Psychological stress, such as anxiety, inhibits gastric accommodation in humans. Acotiamide enhances the effect of acetylcholine in the enteric nervous system, enhances gastric contractility, and accelerates delayed gastric emptying. However, the effect of acotiamide on stress-induced impaired gastric accommodation remains unclear. Therefore, we examined the effect of acotiamide on gastric accommodation and stress-induced impaired gastric accommodation using a conscious guinea pig model. METHODS: A polyethylene bag was inserted through the distal region of the gastric body into the proximal stomach of 5-week-old male Hartley guinea pigs. Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after oral administration of a liquid meal. In the stress model, animals were subjected to water-avoidance stress. Acotiamide (Z-338) or nizatidine was administered subcutaneously. Fecal output was determined as the number of fecal pellets. KEY RESULTS: Administration of the liquid meal significantly decreased intrabag pressure, indicating induction of gastric accommodation. Acotiamide treatment prolonged liquid meal-induced gastric accommodation and significantly increased the number of fecal pellets compared to controls. Water-avoidance stress significantly inhibited liquid meal-induced gastric accommodation. Pretreatment with acotiamide significantly improved stress-induced impaired gastric accommodation. The number of fecal pellets in the acotiamide group increased significantly compared to controls. Acotiamide, but not nizatidine, significantly decreased gastric emptying. CONCLUSIONS & INFERENCES: Acotiamide prolongs gastric accommodation and improves stress-induced impaired gastric accommodation, indicating a potential role for acotiamide in the treatment of functional dyspepsia through its effects on gastric accommodation reactions.

Impairment of gastric accommodation induced by water-avoidance stress is mediated by 5-HT2B receptors.

BACKGROUND: Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5-HT2B receptors in a guinea pig model of stress-induced impairment of GA. METHODS: Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water-avoidance stress. The role of 5-HT2B receptors in impairment of GA was investigated by administering a 5-HT2B receptor agonist (BW723C86) or antagonist (SB215505), the traditional Japanese medicine rikkunshito (RKT), a muscarinic M3 receptor antagonist (1,1-dimethyl-4-diphenylacetoxypiperidium iodide [4-DAMP]), or a nitric oxide synthase inhibitor (Nω -nitro-L-arginine [L-NNA]). KEY RESULTS: In normal animals, liquid meal-induced GA was inhibited by BW723C86, but was not affected by SB215505. The inhibition of GA by BW723C86 was reversed by co-administration of 4-DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB215505 and RKT significantly suppressed stress-induced impairment of GA. After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L-NNA was suppressed by SB215505 or RKT. At a dose that did not affect GA in normal animals, BW723C86 exacerbated the impairment of GA in stressed animals. CONCLUSIONS AND INFERENCES: Stress-induced impairment of GA may be mediated by an increased responsiveness of 5-HT2B receptors, and activation of the 5-HT2B receptor signaling pathway may have an inhibitory effect on nitric oxide function.

Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis.

Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO's criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.

A new rapid technique for detection of microorganisms using bioluminescence and fluorescence microscope method.

The MicroStar-RMDS-SPS (RMDS; R apid M icrobe D etection S ystem) enables detection and determination of the number of microorganisms trapped on a membrane filter based on the ATP-bioluminescence method. However, this system could not provide information about the identity of contaminating species based on the measurement results. Therefore, we developed a new technique for observing microcolonies of contaminants using a fluorescence microscope (Micro Scanner). The coordinates in the image data of the RMDS were converted to the coordinates of the sample stage of the microscope, and a microcolony could be easily observed. A single yeast cell and a microcolony consisting of 20-30 lactic acid bacterial cells could be observed on a membrane filter after measurement using the RMDS.

Behavior of mono-, di-, and trihydroxyoctadecenoic acids during mashing and methods of controlling their production.

The behavior of mono-, di-, and trihydroxyoctadecenoic acids was investigated during laboratory-scale mashing under various conditions with a view to controlling their production. Using a malt in which the lipoxygenase activity was at only a trace level (less than 0.01 U/g) or starting the mashing at a higher temperature than that conventionally used (65 degrees C instead of 48 degrees C) significantly decreased the production of these hydroxy fatty acids. Lowering the pH of the mash to inhibit lipoxygenase activity and preventing O2 uptake by the mash using carbon dioxide were also effective in reducing the amounts of these acids produced during mashing. From the viewpoint of industrial-scale beer production, the prevention of O2 uptake by the mash was selected as an appropriate method for reducing oxidation during wort production without affecting the subsequent brewing process or the taste of the finished beer. After introducing oxidation prevention procedures, the content of trihydroxyoctadecenoic acids decreased by about 30% and the foam stability and taste were improved in commercial products brewed using less than 25% malts.

Alcohol consumption as a major risk factor in the development of early esophageal cancer in patients with head and neck cancer.

OBJECTIVE: To clarify the incidence of concomitant esophageal cancers in patients with head and neck cancer (HNC), and to investigate which risk factors are responsible for this association. PATIENTS AND METHODS: From 1994 to 2000, 134 patients with HNC underwent upper gastrointestinal endoscopy using the 0.8% Lugol stain method to detect esophageal cancer. A case-control study was designed to compare HNC patients with and without esophageal cancer. Logistic-regression analysis was used to obtain odds ratios of risk factors. RESULTS: Out of 134 patients with HNC, Lugol unstained area was detected in 42 patients. Biopsy specimens revealed squamous cell carcinoma in 17 (12.7%), dysplasia in 9 patients (6.6%), and normal in the others. Gastric carcinoma was also detected in 7 patients (5.2%). The estimated depth of cancer invasion was mucosa in 9 patients, submucosa in 5 patients, and proper muscle or deeper in 3 patients. In the results of statistical analysis, high alcohol consumption of more than 75 g per day increased the risk of esophageal cancer (odds ratio: 20.2, p<0.01). Intake of hard liquor showed a high odds ratio (whisky: 28.7, p<0.05, shochu: 12.7, p<0.05). The amount of cigarette smoking was not related to this association. CONCLUSION: High incidence of esophageal cancer was found in the patients with HNC. A high alcohol consumption level, and in particular hard liquor, participated in the development of esophageal cancer in the patients with HNC. But cigarette smoking was not related to this association.

Study on the treatment of tracheobronchial stenosis using expandable metallic stents.

The purpose of this study is to clarify the clinical usefulness of Gianturco-Z stent (G-Z stent) for the management of malignant and benign tracheobronchial stenosis. Seventy-three stents were used in 30 patients. In 20 cases, we used the so-called "stent-in-stent" method. Twenty-four patients were grade 5, and 6 were grade 4 according to the Hugh-Jones classification of respiratory status. The technical success rates, clinical condition, respiratory status, blood gas analysis, survival rate, and complications were reviewed on the basis of the patients'medical records and radiographs. All stents were successfully placed in the appropriate position. After the procedure, respiratory status improved in 97% (29/30) of the patients. PaO(2) increased statistically (p<0.05), and PaCO(2) decreased one week after the treatment. Mean survival of 30 patients after stent placement was 123 days. Mean survival in 9 malignant patients treated in combination with radiotherapy (182 days) was statistically longer (p<0.01) than in those treated without radiotherapy (65 days, n=20). The tracheobronchial burn patient who received a combination of stent placement and post operative radiotherapy survived 540 days. No major complications were encountered during or after the procedure. Only 3 minor complications were observed: 1 stent migration, 1 partial rupture of the stent, and 1 stent deformation. G-Z stent treatment with the "stent-in-stent" technique is useful for palliation of malignant and benign tracheobronchial stenosis, and should contribute to improving the quality of life in patients with advanced cancer.

[Helical CT guided lumar sympathetic ganglion block].

Helical CT scan was used as a guide for lumbar sympathetic ganglion block. By examining anatomical location of the block site with the sequential fluoroscope pictures of helical CT scan, we succeeded in the block of sympathetic ganglion easily. It is possible by the use of sequential CT picture to reduce the risk of puncturing essential organ such as the kidney, descending aorta, inferior vena cava and so on. Moreover, we can expect that application of helical CT scan will raise the success rate of block and will decrease the time necessary for the performance of block.

[Macroscopic classification and kinetic alternations in the superficial lesion of colorectal neoplasms].

To clarify relation between macroscopic appearance and the mode of tumor growth in the superficial lesion of colorectal neoplasms, we compared their colonoscopic findings with histological architecture of tumor cells. Macroscopic type was classified into the superficial elevated lesion (II a, n = 42, mean 5.14mm) and the superficial depressed lesion (n = 42, mean 3.84mm). The latter was further divided into 3 subtypes; subtype A, an irregular depression with high marginal elevation (Dep (A), n = 20); subtype B, an irregular depression with irregular marginal elevation (Dep (B), n = 7); subtype C, a clear and wide depression without marginal elevation (Dep (C), n = 15). Histological architecture was evaluated by the transmucosal growth index (TGI) of tumor cells, which is a ratio of tumor width contacting with the muscularis mucosae against that of tumor surface, and by the distribution of proliferating cells detected by Ki-67 antibody (MIB-1). In adenomas TGI increased with a degree of central depression (IIa < Dep(A) < Dep(C)). In carcinomas TGI was high irrespective of their macroscopic forms. Ki-67 labeling indices tended to increase with histological atypia. Adenomas with severe atypia showed a high labeling consistent with carcinomas. In both adenomas and carcinomas, Ki-67 positive cells were mainly noted in upper third of neoplastic glands in II a, Dep (A) and Dep (B) neoplasms. By contrast, Dep (C) neoplasms lost a preferential distribution of proliferating cells, which reached the whole neoplastic glands. These results suggest that Dep (C) adenomas and carcinomas have a unique histopathological architecture in terms of a high TGI and an enlarged distribution of proliferating cells, implying a high malignant potential.

[Intramucosal growth patterns of superficial colorectal carcinomas].

Intramucosal growth patterns of minute superficial colorectal carcinomas removed by endoscopic surgery were analyzed on these microscopic views by using two dimension morphometrical system. Superficial colorectal carcinomas were classified into 2 types based on endoscopic findings; superficial elevated type 21 cases and superficial depressed type 30 cases. Main factors determining growth pattern in mucosa depended on size in superficial elevated type and ratio of transmucosal growth in superficial depressed type. PG type and NPG type showed the same growth pattern in terms of ratio of transmucosal growth and mucosal thickness of central depressive area to the horizontal size. Accordingly, intramucosal growth patterns were different between superficial elevated type and superficial depressed type in minute lesions. And, PG type and NPG type could be included as superficial depressed type.

[An infradian rhythm of weight increment velocity in patients with Crohn's disease during nutritional therapy].

We examined the rhythm of weight velocity in eight patients with Crohn's disease. In this paper we used the spline smoothing technique to study the cycle in the weight increment velocity curves derived from individual data during nutritional therapy. As a result of the weight measurement at four-day intervals, an infradian rhythm with the average cycle of 9.6 +/- 0.7 was recognized in all of the subjects in terms of the weight increment velocity. This rhythm was especially conspicuous in three adolescent patients with serious nutritional lesion. The cycle of the rhythm was unaffected by any of the following factors: energy intake, contents of nutritional therapy, medical examination during the period. Our findings of a common cycle in the process of convalescence from a low nutritious stage in patients with Crohn's disease suggest that, in others as well, the weight increment velocity might have an infradian rhythm with a kind of inherent periodicity.

[Mucin-producing tumor of the pancreas: surgery or follow-up?].

Clinicopathological studies were carried out in 35 cases of mucin-producing tumor of the pancreas. In addition, natural history and serial pancreatogram changes were studied in 12 long-term follow-up cases. 83% of the main duct type and branch duct type greater than 4 cm were malignant, whereas hyperplasia cases were found in the branch duct type of 3 cm or less in size without marked dilation of the main duct and excrescent nodules. 33% of carcinoma cases were accompanied by parenchymal invasion and all those cases were of polypoid type of 2.5 cm or more in size. In long-term follow-up cases, all 3 cases of the main duct type showed progression of pancreatograms. In contrast, 8 of 9 cases of the branch duct type remained unchanged. These results suggest that surgical resection is mandatory in the main duct type and that the branch duct type where hyperplasia is highly suspected can be followed up.

[Evaluation of early colorectal cancer with submucosal invasion based on histological architecture].

To clarify the clinicopathological features of tumors with submucosal invasion, especially superficial elevated and sessile ones, histological architectures of 32 cases of submucosal invasive cancers were analyzed. They were classified into 3 types based on cross-section view: PG and NPG of Shimoda's classification and PG'. Histological architectures were drawn in accordance with these findings. In 7 PG-Ca which consisted of PG only, no apparent correlation was found between the tumor sizes and invasion depth of submucosal layer. However, 12 NPG-Ca which consisted of NPG only and 12 Mixed-Ca which include various cross-section views both showed massive invasion into the submucosa with 1 cm or more in tumor size. Therefore these two types were similar in biological behavior in terms of invasion depth. And degree of submucosal invasion tended to increase in the order of PG-Ca, Mixed-Ca and NPG-Ca. Examinating histological architectures of the Mixed-Ca tumors in details, all of these cancers were consisted of both PG and PG'. Of the 12 Mixed-Ca, 91.7% were proved to be PG dominant type. Macroscopically, I s and II a contained 88.9% and 40.0% of Mixed-Ca, respectively. In conclusion, these results suggest that PG' is a subtype of PG, and PG-Ca have a correlation between tumor invasion and alteration from PG to PG' in histological architectures among submucosal cancers. It is important to clarify morphological features of PG' in margin of I s and II a tumors in diagnosing the depth of early colorectal cancers.

[Usefulness of new triple therapy containing PPI].

The guideline on the management of H. pylori was developed by the Japanese Society for Helicobacter Research in 2000, and new triple therapy with lansoprazole, amoxicillin and clarithromycin is recommended. At first, we determined the eradication ratio and the frequency of adverse effects, considering difference of genetic polymorphism in metabolizing enzyme of PPI, CYP2C19. No significant difference was shown among the groups of different metabolizing activity in the two points of view. Next, resistance to antibiotics of H. pylori were determined in the eradication-failure cases and compared before and after the therapy. The result did not showed that strains newly acquired the resistance during the therapy. We emphasis that the new triple therapy can be performed without considering the genetic difference or antibacterial resistance until now and that we should examine how eradication is completely performed.