Effectiveness of L-Menthol Spray Application on Lesions for the Endoscopic Clarification of Early Gastric Cancer: Evaluation by the Color Difference.

INTRODUCTION: Although L-menthol spray application on lesions has been shown to be effective for the endoscopic clarification of early gastric cancer (EGC), the currently available data are all based on subjective evaluations. OBJECTIVES: This study was aimed to objectively evaluate the effectiveness of L-menthol spray for the endoscopic classification of EGC. METHODS: Patients with EGC treated by endoscopic submucosal dissection were included. Images taken by white light imaging (WLI) and narrow band imaging (NBI) before and after spraying L-menthol directly on a lesion were saved. The primary endpoint was a change in the color difference between the EGC lesion and surrounding mucosa (ΔExy) before and after L-menthol spray application. The secondary endpoints were patient factors related to the change in ΔExy after L-menthol spray application and the pathological findings. RESULTS: Fifty cases of EGC were included in the analysis. The median ΔExy was significantly larger after L-menthol spray application than before, as assessed by either WLI (p <0.001) or NBI (p < 0.001). An increased ΔExy after L-menthol spray application was noted in 76 and 92% of patients by WLI and NBI, respectively. The percentage of patients with a ΔExy ≥5 (a level distinguishable by human eyes) was significantly larger after L-menthol spray application either by WLI (p <0.001) or NBI (p < 0.001). Pathologically, mucosal vasodilatation and stromal edema were noted after L-menthol spray application in the evaluated 2 cases. CONCLUSIONS: These results objectively demonstrate that L-menthol provides benefits in the endoscopic clarification of EGC.

Endoscopic ultrasound-guided coil deployment with sclerotherapy for isolated gastric varices: Case series of feasibility, safety, and long-term follow-up.

The purpose of the present study is to report our experience of endoscopic ultrasound-guided coil deployment with sclerotherapy (EUS-CS) for isolated gastric varices (IGV) through a case series. Eight consecutive patients who had risky IGV were prospectively enrolled. EUS-CS was performed according to the following procedures: (i) several coils were first deployed in the IGV under EUS guidance; (ii) contrast medium was subsequently injected without removing the needle; (iii) if the infused contrast medium stayed in the IGV and feeding vein, sclerosant was then injected to obliterate the IGV and feeders. Coil deployment in the IGV was successfully performed in all cases. Sclerosant was injected both into the IGV and feeders in seven patients (87.5%). There was no adverse event during the procedure. During a median follow-up of 57 months, one patient who could not inject the sclerosant into IGV and feeders had an early hemorrhagic recurrence. Our case series showed that EUS-CS could be a feasible and safe procedure for the treatment of IGV.

Japanese periodical nationwide epidemiologic survey of aberrant portal hemodynamics.

AIM: Idiopathic portal hypertension (IPH), extrahepatic portal obstruction (EHO), and Budd-Chiari syndrome (BCS) are characterized by aberrant portal hemodynamics of unknown etiology. The aim of this study was to explore trends in the descriptive epidemiology of these diseases through periodical nationwide surveys. METHODS: Nationwide epidemiologic surveys were undertaken in 1999, 2005, and 2015 using the same protocol. The survey targets were selected from all departments of gastrointestinal medicine, surgery, pediatrics, and pediatric surgery in Japan by stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of patients with IPH, EHO, and BCS during the preceding year. RESULTS: The estimated number of BCS patients increased from 280 (95% confidence interval, 200-360) in 1999 survey to 410 (300-530) in 2015 survey, whereas the number of IPH and EHO patients has remained largely unchanged during the 15 years (IPH was approximately 1000; EHO was approximately 770 in 2015 survey). The mean age at symptom onset was approximately 45 years for IPH, 30 years for EHO, and 40 years for BCS over the past 15 years. Those who described disease aggravation from the time of diagnosis accounted for approximately 10% of IPH, 15% of EHO, and 20% of BCS patients in each of the three surveys. CONCLUSIONS: In Japan, the prevalence of BCS is increasing, while those of IPH and EHO appear to be stable. Clinical characteristics, including prognoses, have remained largely unchanged in the past 15 years.

Current status of portal vein thrombosis in Japan: Results of a questionnaire survey by the Japan Society for Portal Hypertension.

AIM: To investigate the current status of portal vein thrombosis (PVT) in Japan, the Clinical Research Committee of the Japan Society of Portal Hypertension undertook a questionnaire survey. METHODS: A questionnaire survey of 539 cases of PVT over the previous 10 years was carried out at institutions affiliated with the Board of Trustees of the Japan Society of Portal Hypertension. RESULTS: The most frequent underlying etiology of PVT was liver cirrhosis in 75.3% of patients. Other causes included inflammatory diseases of the hepatobiliary system and the pancreas, malignant tumors, and hematologic diseases. The most frequent site was the main trunk of the portal vein (MPV) in 70.5%, and complete obstruction of the MPV was present in 11.5%. Among the medications for PVT, danaparoid was given to 45.8%, warfarin to 26.2%, heparin to 17.3%, and anti-thrombin III to 16.9%. Observation of the course was practiced in 22.4%. Factors contributing to therapeutic efficacy were implementation of various medications, thrombi localized to either the right or left portal vein only, non-complete obstruction of the MPV and Child-Pugh class A liver function. A survival analysis showed that the prognosis was favorable with PVT disappearance regardless of treatment. CONCLUSION: The questionnaire survey showed the current status of PVT in Japan. Any appropriate medication should be given to a patient with PVT when PVT is recognized. It is necessary to compile a large amount of information and reach a consensus on safe and highly effective management of PVT.

Conventional versus contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for diagnosis of solid pancreatic lesions: A prospective randomized trial.

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) has been used to diagnose solid pancreatic lesions (SPLs). The aim of this study was to investigate the efficacy of CEH-EUS-guided fine-needle aspiration (CEH-EUS-FNA) compared with that of conventional EUS-FNA for the diagnosis of SPLs. METHODS: Forty patients with solid pancreatic lesions who visited Fukushima Medical University between September 2013 and June 2014 were recruited for this prospective study. Twenty patients underwent CEH-EUS-FNA, and 20 patients underwent conventional EUS-FNA. The sampling rate, sensitivity, accuracy, and number of needle passes required to obtain sufficient samples were compared between the two groups. RESULTS: Patient characteristics, sampling rate, accuracy, and sensitivity were not significantly different between the two groups. The final diagnosis of patients who underwent CEH-EUS-FNA was pancreatic cancer in 19 and intraductal papillary mucinous carcinoma in one. Nineteen patients who underwent conventional EUS-FNA were finally diagnosed with pancreatic cancer and one was diagnosed as cancer of the common bile duct. There was a significant difference in the number of needle passes required. A sufficient sample was obtained on one needle pass in 60% (12/20) of CEH-EUS-FNA group compared with 25% (5/20) of the conventional EUS-FNA group. CONCLUSIONS: Fewer needle passes were required to obtain samples from solid pancreatic lesions using CEH-EUS-FNA than those required using conventional EUS-FNA. Therefore, CEH-EUS-FNA may be more efficient and safer than conventional EUS-FNA for the diagnosis of solid pancreatic lesions.

Potential application of interventional endoscopic ultrasonography for the treatment of esophageal and gastric varices.

Interventional endoscopic ultrasonography (EUS) has been developed mainly for the treatment of pancreaticobiliary disorders (e.g. cyst drainage for pancreatic pseudocysts, biliary drainage for malignant biliary obstruction, and celiac plexus neurolysis). Recently, the application of interventional EUS has been expanded to a new field, the treatment of gastrointestinal varices. There have been several studies examining this new technique for the treatment of esophageal and gastric varices. In the present review, we have summarized the current status of interventional EUS for the treatment of esophageal and gastric varices (e.g. EUS-guided coil deployment for gastric varices) and clarified the clinical feasibility of this procedure.

Guidelines for sedation in gastroenterological endoscopy.

Recently, the need for sedation in gastrointestinal endoscopy has been increasing. However, the National Health Insurance Drug Price list in Japan does not include any drug specifically used for the sedation. Although benzodiazepines are the main medication, their use in cases of gastrointestinal endoscopy has not been approved. This has led the Japan Gastrointestinal Endoscopy Society to develop the first set of guidelines for sedation in gastrointestinal endoscopy on the basis of evidence-based medicine in collaboration with the Japanese Society for Anesthesiologists. The present guidelines comprise 14 statements, five of which were judged to be valid on the highest evidence level and three on the second highest level. The guidelines are not intended to strongly recommend the use of sedation for gastrointestinal endoscopy, but rather to indicate the policy as to the choice of appropriate procedures when such sedation is deemed necessary. In clinical practice, the final decision as to the use of sedation should be made by physicians considering patient willingness and physical condition.

Diagnostic yield of endoscopic retrograde cholangiopancreatography-based cytology for distinguishing malignant and benign intraductal papillary mucinous neoplasm: systematic review and meta-analysis.

BACKGROUND AND AIM: Published studies have revealed the diagnostic yield of cytology obtained from endoscopic retrograde cholangiopancreatography (ERCP) in distinguishing malignant and benign intraductal papillary mucinous neoplasm (IPMN). However as a result of small sample sizes, the overall magnitude of benefit is unknown. Additionally, the optimal endoscopic procedure for cytology acquisition is also unclear. The aim of the present study was to evaluate the diagnostic yield of ERCP-based cytology in patients with IPMN and clarify the optimal sampling technique. METHODS: Relevant studies with a reference standard of definitive surgical histology were identified via MEDLINE and SCOPUS. Malignant IPMN included invasive adenocarcinoma, carcinoma in situ, and high-grade dysplasia. For ERCP, studies using aspiration, brush, and lavage cytology were included. The main objective was the diagnostic yield (pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) of cytology obtained from ERCP to distinguish malignant and benign IPMN. RESULTS: Meta-analysis of 13 international studies with 483 IPMN patients was conducted. Pooled sensitivity was 35.1%, specificity 97.2%, and accuracy 92.9%. Among the three ERCP techniques, lavage cytology showed the best diagnostic ability (sensitivity 45.8%, specificity 97.9%). Malignant IPMN were observed in 45.1% (218/483) of patients in ERCP studies. CONCLUSIONS: Cytology from ERCP has good specificity but poor sensitivity in distinguishing benign from malignant IPMN. Newer techniques or markers are needed to improve diagnostic yield.

Prospective evaluation of the optimal number of 25-gauge needle passes for endoscopic ultrasound-guided fine-needle aspiration biopsy of solid pancreatic lesions in the absence of an onsite cytopathologist.

INTRODUCTION: A prior study with 22-gauge needles recommended more than seven needle passes for endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) of solid pancreatic lesions (SPL) without onsite cytopathology for optimal acquisition of cytopathological diagnosis. The feasibility of this recommendation should be re-evaluated considering the later development and popularity of 25-gauge EUS-FNA needles. We aimed to determine the optimal number of needle passes for cytopathological specimen acquisition with 25-gauge needles for EUS-FNA of SPL. METHODS: A preliminary prospective study of 22 patients with an onsite cytopathology technician showed a sensitivity of 93.3% and a specificity of 100% with four needle passes that was not statistically different from five needle passes. Based on our preliminary study, we fixed the number of needle passes to four (Group A). As a control group, we carried out sampling in consecutive patients using 25-gauge needles with an onsite cytopathologist (Group B). Sampling rate, diagnostic value and complications were evaluated. RESULTS: We enrolled 20 patients in each group. Sampling rate was higher in Group B (20/20, 100%) than in Group A (19/20, 95%), but there was no statistical difference between them (P-value = 0.31). In Group A, sensitivity, specificity and accuracy were 100% among 19. In Group B, sensitivity was 94.1%, specificity 100%, accuracy 95%. There were also no statistical differences between the groups. No complications were seen. CONCLUSION: Our study suggests that four needle passes using a 25-gauge needle may be sufficient for EUS-FNA of SPL where onsite cytology is not available.

The skill qualification system for portal hypertension in Japan.

Objectives: The diverse treatments available for portal hypertension require specialized knowledge of hemodynamics and include endoscopic treatments, interventional radiology (IVR), and surgery. The Japan Society for Portal Hypertension has developed the skill qualification system (SQS) for portal hypertension and began examination in 2014. Here, the status and validity of the judgment of the SQS examination were evaluated. Methods: From 2014 to 2020, 79 applicants were evaluated by the SQS for portal hypertension. Each unedited video submitted as a candidate procedure was evaluated by two judges, and a grade of greater than 70% for the scoring items assessed by the judges was required to pass the examination. Inter-rater agreement of success/failure between the two judges was investigated by the AC1 coefficient. Results: The results of two judges differed for 11 of the 79 videos (13.9%), and five applicants (6.3%) ultimately failed the examination. The percentages of total points received by the applicants with endoscopic treatments, IVR, and surgery were 87.3%, 79.4%, and 80.8%, respectively. There were significant differences in the percentages between endoscopic treatments and IVR (P = 0.0015). The AC1 coefficients were 0.84 for the applicants overall, 0.93 for endoscopic treatments, 0.66 for IVR, and 0.72 for surgery. Similarly, there were significant differences in the AC1 coefficient between endoscopic treatments and IVR (P = 0.021). Conclusions: The SQS for portal hypertension of the Japan Society for Portal Hypertension showed high reliability for video assessments by the judges. This system may contribute to the spread and further development of safe and effective treatments for portal hypertension in Japan.

ATP assay-guided chemosensitivity testing for gemcitabine with biopsy specimens obtained from unresectable pancreatic cancer using endoscopic ultrasonography-guided fine-needle aspiration.

OBJECTIVES: This study evaluates the feasibility of chemosensitivity testing by use of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) samples and determines the optimum cut-off value for gemcitabine. METHODS: Thirty-four consecutive patients with unresectable pancreatic cancer were enrolled. Chemosensitivity (treated/control ratio: T/C ratio) was calculated as the quantity of adenosine triphosphate for a tumor treated with gemcitabine as a percentage of that for the control. To identify the cut-off value sufficient to predict 180 days of progression-free survival (PFS), the receiver operating characteristic curve and the corresponding area under the curve (AUC) were calculated. RESULTS: The success of this assay was 88.2% (30/34); therefore, 30 patients were assessable and included in the population of analyzable patients.. The response was 6.7%. Median PFS was 96 days and median overall survival was 241 days, respectively. The cut-off value was determined as 74% (AUC, 0.745; p = 0.053; 95% CI 0.485-1.005). According to this cut-off value, we predicted 180 days PFS with a sensitivity and specificity of 71.4 and 91.3%, respectively. When patients were divided into two groups at T/C ratio 74%, a significant difference was found in PFS (median 77 vs. 205 days, p = 0.0036). Moreover, T/C ratio < 74% and decrease of CA19-9 were significant and independent prognostic factors by multivariate analysis. CONCLUSION: Chemosensitivity testing by use of EUS-FNA samples in patients with unresectable pancreatic cancer is feasible. This definition emphasizes the possibility of selecting patients for whom favorable results from gemcitabine treatment can be expected.

Autoimmune neutropenia associated with autoimmune pancreatitis.

CONTEXT: We report a rare case of autoimmune neutropenia associated with autoimmune pancreatitis. CASE REPORT: A 61-year-old man was referred to our hospital with slight epigastralgia. He had been admitted to another hospital with exacerbation of diabetes and jaundice. Blood tests showed low white blood cell and neutrophil counts (1,800 µL-1 and 3%, respectively), and elevated transaminase, biliary enzyme, amylase and lipase levels. Serum IgG and IgG4 levels were elevated to 2,693 mg/dL and 454 mg/dL, respectively. Abdominal CT showed diffuse pancreatic swelling, and MRCP revealed diffuse narrowing of the main pancreatic duct and dilation of the common bile duct. An additional EUS-FNA was performed in our hospital. Laboratory data, imaging and histopathological findings confirmed the diagnosis of autoimmune pancreatitis. However, the low white blood cell count continued. For additional investigation, a bone marrow examination was performed, indicating a granulocyte maturation disorder. Moreover, anti-neutrophil antibodies were positive. Therefore, a diagnosis of autoimmune neutropenia associated with autoimmune pancreatitis was made. After steroid therapy, the anti-neutrophil antibodies disappeared and the white blood cell count was within the reference limit. No recurrence of disease has been observed since then. CONCLUSION: Autoimmune neutropenia, which is positive for anti-neutrophil antibodies, can be associated with autoimmune pancreatitis.

Complete response of anaplastic pancreatic carcinoma to paclitaxel treatment selected by chemosensitivity testing.

A 58-year-old woman was admitted to our institute in June 2007 because of obstructive jaundice. A mass in the pancreatic head and multiple swollen lymph nodes surrounding the common hepatic artery were identified using computed tomography (CT). Subsequently, endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) was done. Histopathologic results revealed anaplastic carcinoma of the pancreas. Using specimens obtained with EUS-FNA, chemosensitivity testing with adenosine triphosphate assay was performed. Testing indicated high chemosensitivity to paclitaxel (PTX). According to this result, chemotherapy using PTX was performed, and the primary lesion and lymph node metastases disappeared completely on CT. The patient has been doing well with no recurrence for 1 year and 11 months since initial chemotherapy.

General rules for recording endoscopic findings of esophagogastric varices (2nd edition).

General rules for recording endoscopic findings of esophageal varices were initially proposed in 1980 and revised in 1991. These rules have widely been used in Japan and other countries. Recently, portal hypertensive gastropathy has been recognized as a distinct histological and functional entity. Endoscopic ultrasonography can clearly depict vascular structures around the esophageal wall in patients with portal hypertension. Owing to progress in medicine, we have updated and slightly modified the former rules. The revised rules are simpler and more straightforward than the former rules and include newly recognized findings of portal hypertensive gastropathy and a new classification for endoscopic ultrasonographic findings.

Endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses with rapid on-site cytological evaluation by endosonographers without attendance of cytopathologists.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with rapid on-site evaluation (ROSE) has been reported to provide a more accurate diagnosis than EUS-FNA without such evaluation. However, even endosonographers can evaluate ROSE regarding sample adequacy. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers compared to ROSE by cytopathologists in patients with solid pancreatic masses. METHODS: Between September 2001 and October 2005, of the 73 EUS-FNA procedures with the final diagnoses, 38 procedures after the introduction of ROSE by endosonographers (September 2001-September 2003, period 1), and 35 procedures after the introduction of ROSE by cytopathologists (October 2003-October 2005, period 2) were included. The specimens were stained with Diff-Quik stain and assessed. When the on-site assessors (endosonographers or cytopathologists) indicated that the amounts of cell samples were adequate, the procedure was stopped. RESULTS: Results are presented with 95% confidence limits. The average numbers of needle passes were 4.0 +/- 1.6 and 3.4 +/- 1.5 in periods 1 and 2, respectively (P = 0.06). The specimen collection rates were 97.4 and 97.1% in periods 1 and 2, respectively (P = 0.51). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy and benign were 92.9, 100, 100, 83.3, and 94.7%, respectively, in period 1, and 93.1, 100, 100, 75.0, and 94.3%, respectively, in period 2 (P = 0.97, P = 1.0, P = 1.0, P = 0.65, P = 0.93, respectively). No complications were seen. CONCLUSIONS: For accurate diagnosis, ROSE should be performed during EUS-FNA by the endosonographer, if no cytopathologist is available.

Pancreatobiliary drainage using the EUS-FNA technique: EUS-BD and EUS-PD.

The recent progression of endoscopic ultrasonography (EUS) enables EUS-guided transmural drainage based on the EUS-guided fine-needle aspiration biopsy technique. Prior to the development of EUS-guided drainage procedures, the options for treating obstruction of the pancreatobiliary system included surgical drainage, percutaneous drainage using ultrasound and radiological guidance, and endoscopic (non EUS-guidance) transmural drainage. Today, using EUS guidance and dedicated accessories, it is possible to create bilio- or pancreato-digestive anastomosis, EUS-guided biliary drainage (EUS-BD), and EUS-guided pancreatic drainage (EUS-PD). The recent literature describes that EUS-BD and EUS-PD have acceptable success and complication rates. These procedures are anticipated for use as alternatives to surgery or percutaneous drainage when endoscopic transpapillary procedures fail.

Pancreatic lipoma diagnosed using EUS-FNA. A case report.

CONTEXT: Pancreatic mesenchymal tumors are rare, accounting for only 1-2% of pancreatic tumors. A pancreatic lipoma is an especially rare condition. This is only the second report of a pancreatic lipoma diagnosed before surgery using endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). CASE REPORT: A 75-year-old woman with a round low-density lesion which had been detected by CT was referred to our hospital. EUS revealed an oval 49x32 mm homogeneous and almost isoechoic mass (as compared to normal pancreatic parenchyma) in the pancreatic head. Its outer margin was not clearly differentiated from the parenchyma. Although a benign pancreatic lipomatous lesion was deemed most probable from information obtained using CT/MRI, a mass with malignancy such as a liposarcoma could not be ruled out as a differential diagnosis. Therefore, EUS-FNA was performed for a definitive diagnosis. Two passes were performed with on-site pathology. The results obtained from the sample analysis indicated a pancreatic lipoma consisting of mature fat cells with no atypia. CONCLUSION: Although imaging modalities are useful for the diagnosis of pancreatic lipomatous lesions, it is sometimes difficult to diagnose lipomatous malignancies mimicking benign lipoma. This case demonstrates the usefulness of EUS-FNA for the differential diagnosis of pancreatic lipomatous lesions.

Analysis of prognostic factors in patients with gastric varices after endoscopic treatment.

BACKGROUND: The prognostic factors, including gastric variceal bleeding itself, in patients with gastric varices (GV) after endoscopic treatment remain unclear. The aim of this study was to analyze prognostic factors in patients with GV after endoscopic treatment as well as to evaluate safety and efficacy of our endoscopic treatment. PATIENTS AND METHODS: This study enrolled 115 patients who underwent endoscopic treatment for GV between October 1988 and December 2003 using cyanoacrylate and 5% ethanolamine oleate. Successful hemostasis, recurrence rates, rebleeding rates, survival rates, complications and prognostic factors after the treatment were retrospectively reviewed. RESULTS: Treatment sessions for GV were performed 3.4 +/- 2.5 times. All cases, including 14 emergency cases, were treated successfully. The cumulative recurrence rates at 1, 3 and 5 years after the treatment were 7.0%, 15.6% and 20.0%, respectively, and the cumulative rebleeding rates at 1, 3 and 5 years were 3.5%, 8.7% and 14.8%, respectively. The overall survival rates were 78.3%, 63.7% and 51.5% at 1, 3 and 5 years, respectively. Grade B or C in Child-Pugh classification, emergency or elective cases, and association with hepatocellular carcinoma were identified as significant negative prognostic factors after endoscopic treatment by multivariate analysis. Although several complications were observed, there was no mortality. CONCLUSIONS: Grade B or C in Child-Pugh classification, emergency or elective situation, and association with hepatocellular carcinoma are negative prognostic factors after endoscopic treatment.

Synthetic oligodeoxynucleotides induce gastritis in mice.

To investigate whether DNA directly induces gastritis and/or peptic ulcer, we injected synthetic DNA including CpG motif (CpG-DNA) to mouse stomach. BALB/c mice were injected with either saline, acetic acid (AA), CpG-DNA, or Control-DNA. Mice were sacrificed, and sections of the stomachs were stained with hematoxylin and eosin. The lesions were histopathologically scored from 0 to 4 based on the extent of the inflammation. Populations of neutrophils and mononuclear cells infiltrated to the lesion were calculated. IFN-y mRNA expression at the injection site was analyzed by RT-PCR. The number of CpG motifs included in the complete genomes of H. pylori HP26695 and J99, Escherichia coli O157, and Salmonella Typhi was determined by genomic analysis of these bacteria. Intragastric injection with CpG-DNA induced gastritis, and statistical analysis of histological scores revealed a significant difference between saline vs CpG-DNA (p = 0.037). The population of mononuclear cells infiltrated to the lesions was significantly higher in mice injected with CpG-DNA than that injected with AA (p = 0.0061). IFN-gamma mRNA expression was detected in the CpG-DNA group. While H. pylori includes multiple CpG motifs in its genome, it has fewer than the other pathogenic gram-negative bacilli. We conclude that synthetic DNA including CpG motif directly causes gastritis in mice and induces IFN-gamma production in the stomach. Bacterial DNA including CpG motif is known to stimulate innate immunity and to cause inflammation. Thus, H. pylori genomic DNA may be one of the virulent factors involved in H. pylori infection.