Serum pepsinogen levels can quantify the risk of development of metachronous gastric cancer after endoscopic resection.

We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and that H. pylori eradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association with H. pylori eradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence of H. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated. H. pylori eradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC (p = 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83 vs. 69%, p = 0.04). H. pylori eradication after ER did not affect MGC development (p = 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47-12.25, p = 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless of H. pylori status.

Hypointense hepatocellular carcinomas on apparent diffusion coefficient mapping: Pathological features and metastatic recurrence after hepatectomy.

AIM: The present study aimed to evaluate pathological features of hepatocellular carcinomas (HCC) appearing hypointense on the apparent diffusion coefficient (ADC) map, and to elucidate the association between the signal intensity on the ADC map and metastatic recurrences after hepatectomy. METHODS: In total, 52 consecutive patients with initial hypervascular HCC (solitary lesion ≤5 cm in diameter) without vascular invasion on imaging were examined by diffusion-weighted magnetic resonance imaging before hepatectomy. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense or non-hypointense. Intrahepatic metastatic recurrence was defined as more than three intrahepatic recurrences. RESULTS: The 52 HCC were evaluated as 26 hypointense and 26 non-hypointense tumors. No significant differences between the hypointense and non-hypointense groups were seen for age, sex, etiology, tumor size and tumor marker levels. However, in resected specimens, significant differences between the two groups were noted for histological grade and microscopic portal invasion. The percentages of poorly differentiated HCC and microscopic portal invasion in the hypointense group were significantly higher than those in the non-hypointense group. The cumulative 3-year metastatic recurrence rates of the hypointense and non-hypointense groups on the ADC map were 56% and 13% (P = 0.001), respectively. Multivariate analyses indicated that hypointensity on the ADC map was the only independent factor related to metastatic recurrence. CONCLUSION: Hypointense HCC on ADC mapping are characterized by poor histological differentiation and more frequent microscopic portal invasion, and are significantly associated with metastatic recurrences after hepatectomy.

Contribution of Contrast-Enhanced Sonography With Perfluorobutane Microbubbles for Diagnosis of Recurrent Hepatocellular Carcinoma.

OBJECTIVES: The role of contrast-enhanced sonography in the diagnosis of recurrent hepatocellular carcinoma is still unclear. This study aimed to clarify the usefulness and limitations of contrast-enhanced sonography with a perfluorobutane microbubble contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) after contrast-enhanced computed tomography (CT) for diagnosis of recurrent hepatocellular carcinoma and to establish its optimal use. METHODS: A total of 514 patients, who were suspected to have recurrent hepatocellular carcinoma on contrast-enhanced CT, underwent contrast-enhanced sonography. Of 514 suspicious lesions, 484 were diagnosed as recurrent hepatocellular carcinomas, including 142 recurrent hepatocellular carcinomas measuring 1 cm or smaller in diameter. The largest lesion was evaluated in each patient. A final diagnosis of recurrent hepatocellular carcinoma after contrast-enhanced CT was reached on the basis of the typical hallmarks of hepatocellular carcinoma on any of the other contrast imaging modalities or by resected tissue or tumor enlargement during follow-up. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of contrast-enhanced CT were 68%, 93%, 99%, 15%, and 70%, respectively, and the values of contrast-enhanced sonography were 91%, 100%, 100%, 31%, and 91%, excluding 60 unassessable lesions on contrast-enhanced sonography. The diagnostic rate for recurrent hepatocellular carcinoma on contrast-enhanced sonography for lesions with an atypical enhancement pattern on contrast-enhanced CT was 71%. On multivariate analysis of factors contributing to the unassessability of contrast-enhanced sonography, lesion size, location, and abdominal wall thickness were independent factors. CONCLUSIONS: Although the assessability of contrast-enhanced sonography depends on lesion size, location, and abdominal wall thickness, contrast-enhanced sonography after contrast-enhanced CT is useful for confirmative diagnosis of small recurrent hepatocellular carcinoma with an atypical enhancement pattern on contrast-enhanced CT, even for lesions measuring 1 cm or smaller in diameter.

Kupffer Imaging by Contrast-Enhanced Sonography With Perfluorobutane Microbubbles Is Associated With Outcomes After Radiofrequency Ablation of Hepatocellular Carcinoma.

OBJECTIVES: An ultrasound contrast agent consisting of perfluorobutane microbubbles (Sonazoid; Daiichi Sankyo, Tokyo, Japan) accumulates in Kupffer cells, which thus enables Kupffer imaging. This study aimed to elucidate the association of defect patterns of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography with outcomes after radiofrequency ablation (RFA). METHODS: For this study, 226 patients with initial hypervascular hepatocellular carcinoma, who could be evaluated by contrast-enhanced sonography with Sonazoid before RFA, were analyzed. Patients were divided into 2 groups according to the tumor defect pattern during the Kupffer phase. The irregular-defect group was defined as patients with hepatocellular carcinoma that had a defect with an irregular margin, and the no-irregular-defect group was defined as patients with hepatocellular carcinoma that had either a defect with a smooth margin or no defect. Critical recurrence was defined as more than 3 intrahepatic recurrences, vascular invasion, dissemination, or metastasis. RESULTS: The irregular-defect and no-irregular-defect groups included 86 and 140 patients, respectively, and had cumulative 5-year critical recurrence rates of 49% and 17% (P < .01). Multivariate analysis indicated that the tumor diameter, lens culinaris agglutinin- reactive α-fetoprotein level, and defect pattern were independent factors related to critical recurrence. The cumulative 5-year overall survival rates for the irregular-defect and no-irregular-defect groups were 46% and 61% (P< .01). Multivariate analysis indicated that the Child-Pugh class, tumor diameter, lens culinaris agglutinin-reactive α-fetoprotein level, and defect pattern were independent factors related to survival. CONCLUSIONS: The defect pattern of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography is associated with critical recurrence and survival after RFA.

Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication.

OBJECTIVES: The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of this study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. METHODS: This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. RESULTS: Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan-Meier curves indicated that patients without IM before ESD never developed metachronous cancer, while patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log-rank test, p = 0.031 and p < 0.001, respectively). Multivariate analysis indicated that emergence of map-like redness after HP eradication was the only predictive factor for development of metachronous cancer (hazard ratio, 3.61; 95% confidence interval, 1.41-9.21; p = 0.007). CONCLUSIONS: Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.

Argon plasma coagulation is effective for prevention of recurrent esophageal varices after endoscopic injection sclerotherapy: Single-center case-control study.

BACKGROUND AND AIM: Esophageal varices are usually treated with endoscopic injection sclerotherapy (EIS) or endoscopic band ligation (EBL). However, frequent recurrences of varices after those procedures have been problematic. Argon plasma coagulation (APC) after EIS may be effective for preventing varix recurrence and, in recent years, we have routinely carried out APC after EIS. The aim of the present study was to verify the effectiveness of APC for preventing recurrence of varices after EIS. METHODS: A case-control study was carried out using a historical control cohort in a single center. The varix recurrence rate in 62 patients (34 men and 28 women, median age; 69 years) who underwent APC after EIS for hemorrhagic or risky esophageal varices (APC group) was compared with that of control patients who did not undergo APC after EIS (control group). Age-, sex-, and liver function-matched two control subjects were selected for one case subject (control group). Recurrence of varices was defined as rupture of varices or reappearance of risky varices. RESULTS: The 1-year and 2-year recurrence rates of the APC group were 9.7% and 11.3%, respectively. In contrast, the rates of the control group were 29.0% and 34.7%, respectively. Kaplan-Meier curves showed a significantly lower recurrence rate in the APC group (P = 0.013, log-rank test). No APC-related severe adverse events were observed. CONCLUSION: APC after EIS was safe and could significantly prevent recurrence of esophageal varices. Therefore, the addition of APC should be routinely carried out after EIS.

Video capsule endoscopy as the initial examination for overt obscure gastrointestinal bleeding can efficiently identify patients who require double-balloon enteroscopy.

BACKGROUND: Both double-balloon enteroscopy (DBE) and video capsule endoscopy (VCE) have similar diagnostic yields for patients with overt obscure gastrointestinal bleeding (OGIB). However, the choice of initial modality is still controversial. The aim of this study was to show the clinical outcome of the strategy of initial VCE, followed by DBE. METHODS: Eighty-nine consecutive overt OGIB patients who had undergone VCE as the initial examination were analyzed. The interpreters of VCE evaluated the necessity of performing DBE, and the antegrade or retrograde route was chosen, depending on the transit time of the capsule. RESULTS: Thirty-seven patients (42 %) underwent DBE depending on the findings of VCE. Of these, bleeding sites in the small bowel were identified in 29 patients with the initially selected route (21 antegrade and 8 retrograde). The remaining 8 later underwent DBE by the other route, but 7 had no bleeding lesion, which was confirmed by second-look VCE. One remaining patient had a jejunal varix found by VCE, but DBE from either side could not reach the lesion. The sensitivity and negative predictive value of VCE were 100 %, both for the presence of small bowel lesions and the requirement of hemostasis in the small bowel; this indicated that VCE never misses relevant findings in the small bowel, and that negative VCE findings correspond to the lack of necessity for further examination. CONCLUSIONS: VCE as the initial examination can efficiently identify overt OGIB patients who require DBE. The strategy of initial VCE for overt OGIB appears to be reasonable.

Signal intensity of small hepatocellular carcinoma on apparent diffusion coefficient mapping and outcome after radiofrequency ablation.

AIM: It has been reported that the apparent diffusion coefficient (ADC) value of hepatocellular carcinomas (HCC) on diffusion-weighted magnetic resonance imaging (MRI) is associated with their histological grade. The present study aimed to evaluate whether the signal intensity of small hypervascular HCC on the ADC map is related to the treatment outcome of radiofrequency ablation (RFA). METHODS: Between February 2008 and August 2012, 136 consecutive patients with initial small hypervascular HCC (≤3 tumors and ≤3 cm in diameter) were examined by diffusion-weighted MRI before RFA. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense and non-hypointense. Critical recurrence was defined as more than three intrahepatic recurrences, recurrence with vascular invasion, seeding, dissemination and/or extrahepatic metastasis. RESULTS: The median follow up was 619 days. The cumulative 2-year recurrence rates of the hypointense and non-hypointense on the ADC map groups were 79% and 50% (P < 0.001), respectively, with cumulative 2-year local recurrence rates of 18% and 7% (P = 0.014) and cumulative 2-year critical recurrence rates of 38% and 13% (P = 0.005), respectively. The cumulative 3-year survival rates were 60% and 82% (P = 0.007), respectively. On multivariate analysis, hypointensity on the ADC map was the strongest independent factor related to recurrence and survival after RFA. CONCLUSION: The signal intensity of HCC on the ADC map was strongly associated with outcome after RFA. These results suggest that treatment strategy should be determined carefully even for small HCC when they appear hypointense on the ADC map.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer.

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Prediction of efficacy to pegylated interferon-α-2b plus ribavirin in patients with genotype 2 hepatitis C virus using viral response within 2 weeks.

AIM: Rapid virological response (RVR), defined as serum hepatitis C virus (HCV) RNA negativity at 4 weeks, is the most useful predictor of sustained virological response (SVR) to standard pegylated interferon (PEG IFN) plus ribavirin therapy for patients infected with genotype 2 HCV. The aim of the present study was to predict SVR using viral response within 2 weeks of therapy initiation. METHODS: Of 64 HCV genotype 2 patients with a high viral load treated with standard PEG IFN-α-2b plus weight-based ribavirin for 24 weeks, 58 patients whose adherence was more than 67% were analyzed. RNA and core antigen levels were measured at four time points: the day of therapy initiation, the following day, and at 1 and 2 weeks. RESULTS: SVR was achieved in 73% (47/64) of patients. Univariate analysis of SVR contributing factors showed significant differences with age, bodyweight, white blood cell count, platelet count, fibrosis marker levels, baseline core antigen level and viral response. The area under the receiver-operator curve (AUC) of the core antigen level at 1 week (AUC, 0.940) was the highest among the significant SVR predicting factors. Setting 100 fmol/L as the cut-off value for core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for predicting SVR were 100%, 86%, 96%, 100% and 97%, respectively, and for predicting RVR were 66%, 93%, 97%, 46% and 72%, respectively. CONCLUSION: The HCV core antigen level at 1 week after therapy initiation is the most useful predictor for SVR.

Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis.

BACKGROUND: Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer. METHODS: Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Satα) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II. RESULTS: Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation. CONCLUSIONS: Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.

Low-dose pegylated interferon-alpha-2a monotherapy in elderly and/or cirrhotic patients infected with hepatitis C virus genotype-2 or genotype-1 low level infection.

AIM: Elderly and/or cirrhotic patients with hepatitis C virus (HCV) are at high risk of adverse effects during interferon therapy. The aim of the present study was to evaluate the efficacy, safety and predictive factors for sustained virological response (SVR) of low-dose pegylated interferon-α-2a (PEG IFN-α-2a) monotherapy in elderly and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level infection. METHODS: Sixty-four elderly (≥65 years) and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level (<5 logIU/mL) infection underwent low-dose PEG IFN-α-2a (90 µg/week) monotherapy for 24 weeks. Sixty patients were available for efficacy assessment. RESULTS: SVR was achieved in 78.3%. SVR rates according to genotype-1 low, genotype-2 low and genotype-2 high viral load were 90.0%, 87.1% and 57.9%, respectively. The discontinuation rate was 12.5%. PEG IFN-α-2a was interrupted or discontinued in four patients because of severe thrombocytopenia (<25 000/mm(3) ). The baseline platelet counts of all these patients were less than 70 000/mm(3) . On univariate analysis of factors contributing to SVR, significant differences were noted in viral load, platelet count, γ-glutamyltransferase, ferritin, α-fetoprotein level and rapid viral response (RVR). On multivariate analysis, RVR was the only independent factor (P = 0.010, odds ratio = 47.27). The positive and negative SVR-predictive values based on RVR were 95% and 82%, respectively. CONCLUSION: Low-dose PEG IFN-α-2a monotherapy was effective and tolerable in elderly and/or cirrhotic patients with genotype-2 or genotype-1 low HCV level infection. However, a baseline platelet count of more than 70 000/mm(3) is needed for safety. RVR can predict SVR accurately.

Usefulness of a continuous suction mouthpiece during percutaneous endoscopic gastrostomy: a single-center, prospective, randomized study.

BACKGROUND: No mouthpiece has been designed to control salivary flow during endoscopic procedures. A new continuous suction mouthpiece (CSM) was developed, and its usefulness for percutaneous endoscopic gastrostomy (PEG) was evaluated. PATIENTS AND METHODS: Seventy-two patients who were scheduled to undergo PEG or the exchange of a gastrostomy button or tube were assigned to one of two groups: the group using the CSM and the group using the conventional mouthpiece. Aspiration pneumonia, procedure duration, extent of salivary flow, frequency of saliva suction, and number of choking episodes during the procedures were evaluated and compared between the two groups. RESULTS: The same number of patients was randomly allocated to each group. There were no significant differences between the two groups in sex, age, procedure type, duration of procedure,depth of sedation, and indication for the procedure. The grade of salivary flow was significantly lower in patients with the CSM than in patients with the conventional mouthpiece (P < 0.001). Significantly fewer suctions and choking episodes were observed in patients with the CSM than in patients with the conventional mouthpiece (P = 0.013, and P = 0.015, respectively). Aspiration pneumonia and other significant adverse events were not observed in either group. CONCLUSIONS: CSM reduced the number of episodes associated with salivary flow in PEG-related procedures. The device is expected to reduce complications such as aspiration not only in PEG but in other upper endoscopic procedures.

A case of esophageal carcinoma on esophageal varices treated by endoscopic submucosal dissection after endoscopic injection sclerotherapy.

Esophageal varices (EVs) are often treated using endoscopic injection sclerotherapy. Endoscopic submucosal dissection (ESD) has been used for early esophageal epithelial neoplasia worldwide. We report a case of early esophageal squamous cell carcinoma (ESCC) that occurred over EVs, in which the EVs were treated with endoscopic injection sclerotherapy before the early ESCC was treated with endoscopic submucosal dissection. Argon plasma coagulation was finally performed to prevent the recurrence of varices. No serious complications, such as severe bleeding or perforation, were observed. Histopathological examination revealed submucosal veins occluded with an organized thrombus for which endoscopic injection sclerotherapy with an intravariceal injection of sclerosant had been performed, but no fibrosis was observed outside the blood vessels. This explains that the injected sclerosant into EVs did not cause any tissue reaction like fibrosis in the submucosa surrounding the vein, which may have made endoscopic submucosal dissection safer and easier. Varices have not recurred, and ESCC has also not recurred for 5 years. We demonstrated a successful treatment of ESCC on EVs and no submucosal fibrosis other than inside the occluded vessels and verified it histologically.

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

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

Relationship between vomiting reflex during esophagogastroduodenoscopy and dyspepsia symptoms.

AIM: Although frequent vomiting reflexes during esophagogastroduodenoscopy (EGD) causes suffering in patients, very few studies have investigated the characteristics of subjects who frequently develop vomiting reflexes. This study examined the incidence of the vomiting reflex and related factors, especially upper gastrointestinal symptoms, among individuals undergoing transoral EGD. METHODS: Subjects included 488 consecutive adults (mean age, 56.1 ± 8.9 years) who underwent transoral EGD for gastric cancer screening between February 2010 and March 2011. All procedures were performed by an endoscopist with 15 years of experience. Based on a questionnaire survey using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), symptoms (dyspepsia and acid reflux symptoms) and the number of vomiting reflexes during EGD were recorded. RESULTS: Of the 488 subjects, 271 (56%) developed vomiting reflexes (mean, 4.2 times). This reflex-positive group was younger (54.3 ± 9.5 years) than the reflex-negative group (58.3 ± 7.7 years, P < 0.001). The number of subjects in the reflex-positive group with a high FSSG dyspepsia score (2.27 ± 2.57 vs 1.23 ± 1.84; P < 0.001), acid reflux symptom score (1.96 ± 2.22 vs 1.34 ± 2.14; P < 0.01) or an esophageal hiatal hernia (14.8% vs 4.6%; P < 0.001) was significantly higher than in the reflex-negative group. Multivariate analysis also showed a significant correlation between these four factors and the occurrence of vomiting reflexes. Using an FSSG dyspepsia score of 1 as the cut-off offered 68% sensitivity and 57% specificity for predicting the occurrence of vomiting reflexes. CONCLUSION: Based on FSSG questionnaire responses on upper gastrointestinal symptoms, dyspepsia symptoms, in particular, are related to presence of vomiting reflexes during EGD.

Elevated risk of colorectal adenoma with Helicobacter pylori-related chronic gastritis: a population-based case-control study.

This study investigated correlations between Helicobacter pylori infection or chronic atrophic gastritis (CAG) and risk of colorectal adenoma in a population-based case-control study. Subjects comprised asymptomatic, middle-aged, male Japanese factory workers who participated in an annual health check-up program, including cancer screening with colonoscopy. We selected 239 colorectal adenoma cases based on histological evaluation and 239 age-matched adenoma-free controls, and evaluated colorectal adenoma risk according to stage of H. pylori-related chronic gastritis as determined by serum tests for H. pylori antibody titer and pepsinogen. Subjects with colorectal adenoma were more likely to be smokers and have hypercholesterolemia. H. pylori infection was a risk factor for adenoma as a whole (crude odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.44-3.55). Analysis of distal adenoma cases showed that adenoma risk was significantly increased in the presence of H. pylori infection, but there was no further increase in risk with CAG. In contrast, proximal adenoma risk increased stepwise with the presence and progression of H. pylori-related chronic gastritis and showed a maximal and significant increase with CAG (crude OR: 4.51, 95% CI: 1.43-14.2). Subjects with more extensive and severe gastritis showed still higher risk not only for proximal but also for distal adenoma. H. pylori-related chronic gastritis is likely to be involved in the development of colorectal neoplasms, and its progression appears to increase the risk, particularly for proximal adenomas. Knowing the H. pylori-related chronic gastritis stage will probably be useful for evaluation of risk for colorectal neoplasia.

Mucosal healing of esophageal involvement of Crohn's disease with granulocyte/monocyte adsorption.

We report a case of a 16-year-old male who suffered from Crohn's disease (CD) with esophageal involvement, showing remarkable improvement with granulocyte/monocyte adsorption (GMA). The patient had been diagnosed as ileocolic CD and was treated with 5-aminosalicylate. He was admitted to our hospital with symptoms of fever, diarrhea, and odynophagia. Endoscopic examinations revealed that the exacerbation of ileocolic ulcers, and advent of ulcers in esophagus. Because of the patient's refusal to receive corticosteroids, immunomodulators, or biologics, he underwent GMA twice a week. After 10 sessions of GMA, he entered remission with significant decrease in clinical activity. In addition, endoscopic examinations showed remarkable improvement of ileocolic ulcers and disappearance of esophageal lesions. No adverse events were observed. GMA could be effective for manifestations of CD in gastrointestinal tract other than ileum or colon.

Preventive effects of etodolac, a selective cyclooxygenase-2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori-negative precancerous lesion.

The present study investigated the preventive effects of etodolac, a selective cyclo-oxygenase (COX)-2 inhibitor, on metachronous cancer development after endoscopic resection of early gastric cancer. Among 267 early gastric cancer patients who underwent endoscopic resection, 47 patients with extensive metaplastic gastritis were selected based on endoscopic findings and our previously described criteria of serum pepsinogen (PG) test-positive and Helicobacter pylori antibody-negative conditions. Nonrandomized etodolac treatment (300 mg/day) was administered to 26 patients (Group A), while the remaining 21 patients were untreated (Group B). No significant differences in age, sex distribution, lifestyle factors or extent of metaplastic gastritis at baseline were identified between groups. Patients were followed for metachronous cancer development with endoscopy every 6-12 months for up to 5 years. Mean (standard deviation) follow-up period was 4.2 (0.9) years. In Group B, 5 cancers developed (incidence rate = 6,266/100,000 person-years), significantly more than the 1 cancer in Group A (incidence rate = 898/100,000 person-years; p < 0.05). Long-term etodolac treatment did not influence the extent of metaplastic gastritis as revealed by endoscopic findings or by serum PG levels, but effectively reduced metachronous cancer development in patients with extensive metaplastic gastritis. These results strongly suggest that chemoprevention of cancer in the metaplastic stomach is possible by controlling COX-2 expression.

Eradication of Helicobacter pylori prevents cancer development in subjects with mild gastric atrophy identified by serum pepsinogen levels.

A longitudinal cohort study was conducted in Helicobactor pylori-infected middle-aged Japanese males to evaluate the preventive effects of H. pylori eradication on the development of gastric cancer according to the extent of chronic atrophic gastritis (CAG). The extent of CAG was monitored by baseline serum pepsinogen (PG) levels. We followed 3,656 subjects with persistent H. pylori infection and 473 subjects with successful H. pylori eradication for cancer development for a mean (SD) of 9.3 (0.7) years. Groups with and without extensive CAG were categorized based on PG test-positive criteria to detect extensive CAG of PG I