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The present study aimed to elucidate the association between post-vascular–phase (Kupffer-phase) images from contrast-enhanced ultrasonography (CEUS) with perfluorobutane microbubbles and metastatic recurrences after the resection of hepatocellular carcinoma (HCC). The study examined 73 patients with solitary HCC ≤5 cm in diameter who underwent CEUS before resection. HCC was defined as irregular type (including an irregular defect on Kupffer-phase images) or non-irregular type. Intrahepatic metastatic recurrence was defined as >3 intrahepatic recurrences. Metastatic recurrence included both extrahepatic and intrahepatic recurrences. Frequencies of microscopic portal invasion and intrahepatic metastasis were significantly higher in the irregular group than in the non-irregular group. Cumulative 5-y metastatic recurrence rates in the irregular and non-irregular groups were 43% and 7% (p = 0.028), respectively. Multivariate analyses identified Kupffer-phase findings as a factor significantly related to metastatic recurrence. In conclusion, HCCs with an irregular defect during Kupffer-phase CEUS are characterized by more frequent microscopic vascular invasion and intrahepatic metastasis and are significantly associated with metastatic recurrence after 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.

Background and Aim The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of the present 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, whereas 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

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.

Critical recurrences after radiofrequency ablation for hepatocellular carcinoma (HCC), such as intrahepatic metastases or dissemination, and extrahepatic metastases or seeding, which are difficult to treat radically, almost certainly lead to primary cancer death. The present study aimed to clarify whether the arterial tumor enhancement pattern on contrast-enhanced computed tomography (CECT) is associated with critical recurrence and cancer death after RFA for small HCC. Between April 2001 and September 2011, 226 patients with initial small hypervascular HCC (≤3 cm in diameter and ≤3 tumors) were treated by RFA. Arterial tumor enhancement patterns on CECT before RFA were categorized by whether non-enhanced areas were included inside the tumor stain. The heterogeneous enhancement group included 44 patients, and the homogeneous enhancement group included 182 patients. The cumulative 5-year critical recurrence rates of the heterogeneous and homogeneous enhancement groups were 42 and 22 % (p = 0.005), respectively. Univariate analysis for factors related to critical recurrence showed significant differences in sex, arterial enhancement pattern, and response to antiviral therapy. These factors were independent on multivariate analysis. The cumulative 5-year primary cancer death rates of the heterogeneous and homogeneous enhancement groups were 29 and 13 % (p = 0.002), respectively. Univariate analysis for factors related to primary cancer death showed significant differences in arterial enhancement pattern and response to antiviral therapy. These factors were independent on multivariate analysis. Arterial heterogeneous tumor enhancement on CECT is associated with critical recurrence and cancer death after RFA for small HCC.

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

BACKGROUND/AIMS The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon α-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, α-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

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.

Hepatocellular carcinoma (HCC) frequently develops in cirrhotic liver and is one of the most common malignancies worldwide. The tumor volume doubling time (TVDT) reflects the natural tumor growth rate and is an indicator of the biological malignant potential of a tumor. The present study aimed to elucidate the association between the serological and histological indices of HCC and TVDT. TVDT was analyzed for 53 HCCs by measuring the enlargement of the tumor diameter on dynamic computed tomography. Differences in TVDT were compared among histological grades of HCC differentiation. The α-fetoprotein (AFP) doubling time (T2AFP) for 44 HCCs with AFP levels >200 ng/ml was calculated and the differences in T2AFP were compared according to the histological grade of HCC differentiation and positivity for Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3). Among these 44 HCCs, the correlation between T2AFP and TVDT was analyzed for the 27 tumors for which TVDT could be calculated. The mean ± standard deviation (SD) TVDT in Edmondson grade 1 (Ed1), Ed2 and Ed3 HCC was 138.3±110.3, 94.9±91.5 and 32.2±20.8 days, respectively (P

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.

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

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 (

In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33-5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.

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

A 67-year-old woman with compensated cirrhosis type B associated with hepatocellular carcinoma was started on sorafenib for multiple pulmonary metastases. The patient developed right upper quadrant pain and high fever 4 weeks later. Imaging revealed marked enlargement of the gallbladder without calculi. Following percutaneous transhepatic gallbladder aspiration, her symptoms resolved, but the gallbladder remained enlarged. Laparoscopic cholecystectomy was performed. Arteriolar occlusion with intimal thickening in the muscular layer of the gallbladder was seen sporadically. The fact that this patient had no risk factors for acalculous cholecystitis suggested that the cholecystitis resulted from ischemia, implying a strong causal relationship with sorafenib.

Aim: Continuation of pegylated interferon (PEG-IFN) plus ribavirin at the recommended dose is difficult in elderly patients and/or patients with cytopenia or complications. Whether the therapeutic efficacy of low-dose PEG-IFN plus ribavirin therapy could be predicted based on virological response within 2 weeks of therapy initiation was evaluated. Methods: A total of 106 patients with a high viral load of genotype-1b hepatitis C virus (HCV) underwent low-dose PEG-IFN plus ribavirin therapy. PEG-IFN alpha 2b (0.75 µg/kg per week) and ribavirin (600–800 mg/day) were administered for 48 weeks. Results: Sustained virological response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On univariate analysis of SVR-contributing factors, significant differences were noted in the white blood cell count, platelet count, fibrosis markers, and viral reduction within 2 weeks from therapy initiation. On multivariate analysis, the platelet count and the reduction in the HCV core antigen level at week 2 were independent factors. The positive predictive value (PPV) and the negative predictive value (NPV) for SVR based on a 1-log or greater HCV-RNA level reduction at week 2 were 65% and 90%, respectively, and those based on HCV core antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2-log or greater reduction of the RNA level were 86% and 67%, respectively, and those based on the core antigen level were 93% and 69%, respectively. Conclusion: Evaluation of viral reduction at week 2 after therapy initiation is useful for predicting SVR to low-dose PEG-IFN plus ribavirin therapy.

Aim: To clarify the clinical features of and risk factors for extrahepatic seeding, a major complication following radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Methods: Our prospective database of 351 nodules in 257 patients with HCC who had undergone RFA between April 2001 and April 2008 was reviewed. The following variables were assessed to identify the risk factors for extrahepatic seeding: age, sex, viral markers, Child–Pugh class, tumor size, number of tumors, RFA indication (tumor size ≤3 cm, number of tumors ≤3), tumor biopsy prior to RFA, degree of histological differentiation, tumor markers, tumor location, number of sessions, and combined transcatheter arterial chemoembolization. Results: The median follow-up period was 36.5 months, during which the rate of seeding after was 5.1% and the 5-year cumulative seeding rate was 8.4%. The survival rate after neoplastic seeding was 21% at 5 years. Univariate analysis of the risk factors for neoplastic seeding showed significant differences in tumor size, RFA indication, subcapsular lesion, number of sessions, tumor biopsy prior to RFA, and des-gamma-carboxy prothrombin value. However, multivariate analysis showed that the only independent risk factor was RFA indication. Conclusions: The prognosis of patients with neoplastic seeding was poor. In particular, RFA performed for HCC not satisfying the RFA indication showed a high risk of seeding, and careful consideration should be given to the optimal treatment method and avoiding direct puncture of subcapsular tumors.

AIM Evaluation of malignant potential is important to determine the treatment strategy for small hepatocellular carcinoma (HCC). The aim of the present study was to establish a method of assessing the malignant potential of small hypervascular HCC using B-mode ultrasonography. METHODS One hundred and thirteen arterial hypervascular HCC nodules under 3 cm diagnosed by biopsy or surgical resection (20.5 ± 6.3 mm) were classified into two groups ultrasonographically: type 1 with (n = 27) and type 2 without (n = 86) a halo. Type 2 was categorized into three subgroups: type 2a, homogenous hyperechoic (n = 9); type 2b, hypoechoic with a smooth margin (n = 35); and type 2c, hypoechoic with an irregular or unclear margin (n = 42). RESULTS The mean diameter of type 2a nodules was significantly smaller than that of other HCC types (P

To establish a method of assessing the malignant potential of hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI).For 69 nodules [12 Edmondson (Ed)-I, 48 Ed-II, 9 Ed-III] in 54 HCC patients, signal intensity patterns and enhancement patterns of gadopentate dimeglumine (Gd-DTPA) dynamic studies were correlated with histological differentiation and serum lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) level, which is an indicator of poor prognosis.Hypointensity on T1-weighted imaging was seen in 17, 72, and 89% of Ed-I, Ed-II, and Ed-III HCCs, respectively (P 0.001). Meanwhile, hyperintensity on T2-weighted imaging was seen in 42, 88, and 89% (P 0.005). Tumor stain during the arterial phase of Gd dynamic MRI was seen in 75, 86, and 89%. Tumor stain washout during the portal phase was seen in 43% of Ed-II and 100% of Ed-III HCCs (P 0.005). In the Ed-II and Ed-III HCCs, hypointensity on T1-weighted imaging was seen in 65% of AFP-L3-negative HCCs and 90% of AFP-L3-positive HCCs (P = 0.071). Washout of tumor stain during the portal phase was seen in 39% of AFP-L3-negative HCCs and 75% of AFP-L3-positive HCCs (P 0.05).Although hyperintensity of tumor on T2-weighted imaging and arterial hypervascularity of tumor are considered to be useful for differential diagnosis between well differentiated HCCs and moderately/poorly differentiated HCCs, hypointensity of tumor on T1-weighted imaging and tumor stain washout during the portal phase of Gd-DTPA dynamic MRI reflected poorer histological differentiation of HCCs and correlated with AFP-L3 levels.

A 53-year-old woman was admitted because of a giant pancreatic tumor. Hypercalcemia and a high serum parathyroid hormone-related peptide (PTHrP) level were observed. A hypoglycemic attack occurred during pancreatectomy, and the surgical specimen revealed a PTHrP-secreting glucagonoma. Liver metastases developed 1 and 5.5 years later, and bone metastases appeared 6 years after surgery. Her serum PTHrP concentrations remained normal after surgery, despite re-elevation of the serum glucagon concentration after recurrence. The clinical course of this case illustrates the process of development of neuroendocrine tumors secreting two or more hormones.

Two patients developed segmental, diffuse intrahepatic recurrence after percutaneous radiofrequency ablation (RFA) to treat a primary, solitary, and small (2.5 cm) hepatocellular carcinoma (HCC). Despite the size of the HCC, levels of the tumor markers (α-fetoprotein, α-fetoprotein-L3%, and des-γ-carboxyprothrombin) were all elevated before RFA, and tumors in both patients were contiguous with a major branch of the portal vein. Tumor biopsies of both patients revealed moderately differentiated HCC but diagnostic imaging showed an area of reduced tumor blood flow, suggesting a poorly differentiated component. Since early detection of post-RFA malignancies by standard ultrasonography and contrast-enhanced computed tomography was difficult, the most sensitive indicator of recurrence in these two patients was the elevated tumor markers. The diffuse intrahepatic recurrence was thought to be caused by increased intratumoral pressure during RFA, resulting in the dissemination of cancer cells through the contiguous portal vein. The clinical course of these tumors indicate that the choice of RFA should be carefully considered when treating specific subtype of HCC that is adjacent to main portal vein branch and involves a possible poorly differentiated component and that surgical resection or combinations of RFA with other treatment modalities such as transcatheter arterial chemoembolization should be considered as alternative treatment strategies.

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.

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.

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.

To investigate the effects of Japanese apricot (JA) consumption on gastroesophageal reflux disease (GERD)-related symptoms.Participants included individuals living in Minabe-cho, a well-known JA-growing region, who received specific medical check-ups by the local community health service in 2010. GERD-related symptoms were examined in 1303 Japanese individuals using a validated questionnaire, the Frequency Scale for Symptoms of GERD (FSSG), which consists of 7 questions associated with acid reflux symptoms and 5 questions asking about gastrointestinal dysmotility symptoms. Each question was answered using a 4-point scale, with higher scores indicating more severe GERD-related symptoms. Subjects were divided into two groups according to their intake of dried and pickled JA: daily intake (≥ 1 JA daily) (392 subjects) and none or occasional intake (1 JA daily) (911 subjects). FSSG scores were compared between subjects who consumed JA daily and those who did not. Next, subjects were stratified by age, gender and Helicobacter pylori (H. pylori) status for subanalyses.Those who ate JA daily were significantly older than those who did not (60.6 ± 10.5 years vs 56.0 ± 11.0 years, P0.001). Total FSSG scores were significantly lower in subjects with daily JA intake than in those with none or only occasional intake (2.13 ± 3.14 vs 2.70 ± 3.82, P = 0.005). In particular, subjects who consumed JA daily showed significantly improved FSSG dysmotility scores compared with subjects who did not (1.05 ± 1.58 vs 1.46 ± 2.11, P0.001). In contrast, the FSSG reflux score did not differ between subjects with and without daily intake of JA (1.08 ± 1.90 vs 1.24 ± 2.11, P = 0.177). Subanalysis indicated that improvement in dysmotility by JA intake was specifically observed in non-elderly (1.24 ± 1.68 vs 1.62 ± 2.22, P = 0.005) and H. pylori-negative subjects (0.99 ± 1.58 vs 1.57 ± 2.06, P0.001). GERD patients (total FSSG score ≥ 8) were less frequently observed among subjects with daily intake of JA as compared to those without daily intake of JA (6.1% vs 9.7%, P = 0.040).Daily JA intake may improve digestive dysmotility symptoms, resulting in relief of GERD symptoms. The effect is more obvious in non-elderly and H. pylori-negative subjects.

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.

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.

Background and study aims: Early gastric cancers show gastric and/or intestinal phenotypes with specific mucin production profiles, and the phenotypes can vary with tumor progression. The aim of this study was to evaluate the correlation between tumor invasion patterns and phenotypes in the mucosa and submucosa of early gastric cancers. Methods: Phenotypic expressions of 44 endoscopically resected gastric cancers with submucosal invasion were evaluated immunohistochemically using MUC5AC and MUC6 as gastric and MUC2 and CD10 as intestinal phenotypic markers. Results: Cancers were classified into two patterns by invasion pattern: 19 collapsing pattern (C-pattern) tumors had cancer cells that invaded to the submucosa with expansive destruction of the muscularis mucosae, while 25 passing-through pattern (P-pattern) tumors formed focal cancer cell aggregations in the submucosa without massive destruction of the muscularis mucosae. Cancers with C-pattern invasion were likely to show similar phenotypes between the mucosa and submucosa, while phenotypes of cancers with P-pattern invasion were likely to differ between the two layers (rate of the same phenotypes: C-pattern 68% vs. P-pattern 28%, p = 0.008). Of 22 cancers with P-pattern invasion that included the intestinal phenotype component in the mucosa, 13 (59%) expressed the gastric phenotype alone in the submucosa. Conclusions: Phenotype presentation in the mucosa and submucosa differ by the invasion pattern in early gastric cancer. Tumors with P-pattern invasion are likely to express the gastric phenotype in the submucosa, regardless of phenotype in the mucosa, suggesting that such cancers might achieve submucosal invasion prior to intestinalization occurring in the mucosa.

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. J. Clin. Apheresis, 2011. © 2011 Wiley-Liss, Inc.

The aim of the present study was to predict sustained virological response (SVR) to telaprevir with pegylated interferon (PEG-IFN) and ribavirin using viral response within 2 weeks after therapy initiation. Thirty-six patients with genotype 1 hepatitis C virus (HCV) and high viral load were treated by telaprevir-based triple therapy. SVR was achieved in 72% (26/36) of patients. Significant differences between the SVR group and non-SVR group were noted regarding response to prior PEG-IFN plus ribavirin, interleukin (IL)28B polymorphism, amino acid substitution at core 70, cirrhosis, hyaluronic acid level, and HCV-RNA reduction within 2 weeks. Setting 4.56 logIU/mL as the cut-off value for HCV-RNA reduction at 2 weeks, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 77%, 86%, 95%, 50%, and 79%, respectively, and for neither the IL28B minor allele nor core 70 mutant were 80%, 71%, 91%, 50%, and 78%, respectively. In conclusion, evaluation of viral reduction at 2 weeks or the combination of IL28B polymorphism and amino acid substitution at core 70 are useful for predicting SVR to telaprevir with PEG-IFN and ribavirin therapy.

Background Pegylated interferon (PEG-IFN) plus ribavirin therapy is still recommended for elderly and/or cirrhotic patients. This study examined whether sustained virological response (SVR) to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/or cirrhotic patients could be predicted based on viral reduction within 2 weeks after therapy initiation or interleukin IL-(28B) polymorphism and viral mutations. Methods Participants comprised 115 elderly (≥65 years) and/or cirrhotic patients with genotype-1b and high viral load. Reduced doses of PEG-IFN-α2a (90 μg/kg/week) and ribavirin (400-800 mg/day) were administered for 48-72 weeks based on virological response of each patient. Results SVR was achieved in 34% (39/115), and treatment was discontinued in 15% (17/115). Univariate analysis identified age, α-fetoprotein, fibrosis marker, interferon sensitivity-determining region (ISDR), IL-28B polymorphism and level of viral reduction within 2 weeks as factors contributing significantly to SVR. However, no significant differences were noted in core amino acid substitutions. Multivariate analysis identified age, hyaluronic acid, ISDR and viral reduction as factors independently associated with SVR. Positive predictive value (PPV) and negative predictive value (NPV) of SVR based on the level of viral reduction at 2 weeks (cutoff level, 1.7 log IU/ml) were 83% and 84%, respectively. The PPV of SVR based on IL-28B major and ISDR mutant was 70%, and the NPV of SVR based on IL-28B minor and wild-type ISDR was 89%. Conclusions Evaluations of viral reduction at 2 weeks or both IL-28B and ISDR are useful to predict SVR to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/ or cirrhotic patients.

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.

AIM: To develop a new continuous suction mouthpiece (CSM) and evaluate its usefulness for screening esophagogastroduodenoscopy (EGD). METHODS: A total of 196 patients who were scheduled to undergo screening EGD were assigned to one of two groups: a group using the CSM and a group using a conventional mouthpiece. Extent of salivary flow, frequency of saliva suction, number of choking episodes during the examination, and incidence of aspiration pneumonia after the examination were evaluated and compared between the two groups. Adverse events during and after EGD were also examined. In addition, the oral cavity was meticulously examined after the EGD. RESULTS: The same number of patients was randomly allocated to each group. There were no significant differences between the two groups in sex, age, biopsy procedure, duration of procedure and depth of sedation. Aspiration pneumonia and other significant adverse events were not observed in either group. The grade of extent of salivary flow was significantly lower in patients with the CSM than in patients with the conventional mouthpiece (P < 0.001). Although there was no significant difference, less frequent suctioning and fewer choking episodes were observed in patients with the CSM than in patients with the conventional mouthpiece (P = 0.082 and P = 0.084, respectively). In addition, there were no patients in the CSM group who required saliva suctioning during the procedure. CONCLUSION: Use of the CSM during screening EGD can reduce the extent of salivary flow. The device is expected to reduce complications and contamination with saliva.

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.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.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.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.

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.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.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.The HCV core antigen level at 1 week after therapy initiation is the most useful predictor for SVR.

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.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.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.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.

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.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.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, P0.001). The number of subjects in the reflex-positive group with a high FSSG dyspepsia score (2.27 ± 2.57 vs 1.23 ± 1.84; P0.001), acid reflux symptom score (1.96 ± 2.22 vs 1.34 ± 2.14; P0.01) or an esophageal hiatal hernia (14.8% vs 4.6%; P0.001) 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.Based on FSSG questionnaire responses on upper gastrointestinal symptoms, dyspepsia symptoms, in particular, are related to presence of vomiting reflexes during EGD.

In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33–5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.

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.

Endoscopic ultrasonography (EUS) was performed on a patient being treated for chronic pancreatitis because a submucosal tumor was observed in the stomach during gastrointestinal endoscopy. As internal pulsatile blood flow on Doppler was present, the diagnosis of an aneurysm was made. The pseudoaneurysm of the left gastric artery was embolized with histoacryl and lipiodol and the splenic artery was embolized with coils at the location of the pseudoaneurysm to prevent hemorrhage. Follow up EUS confirmed the cessation of blood flow from the pseudoaneurysm. Clinicians encountering a gastric submucosal tumor-like protrusion in a patient with chronic pancreatitis should use EUS to investigate the possibility of a pseudoaneurysm, which must be treated as quickly as possible once identified.

Continuation of pegylated interferon (PEG-IFN) plus ribavirin at the recommended dose is difficult in elderly patients and/or patients with cytopenia or complications. Whether the therapeutic efficacy of low-dose PEG-IFN plus ribavirin therapy could be predicted based on virological response within 2 weeks of therapy initiation was evaluated. A total of 106 patients with a high viral load of genotype-1b hepatitis C virus (HCV) underwent low-dose PEG-IFN plus ribavirin therapy. PEG-IFN alpha 2b (0.75 µg/kg per week) and ribavirin (600-800 mg/day) were administered for 48 weeks. Sustained virological response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On univariate analysis of SVR-contributing factors, significant differences were noted in the white blood cell count, platelet count, fibrosis markers, and viral reduction within 2 weeks from therapy initiation. On multivariate analysis, the platelet count and the reduction in the HCV core antigen level at week 2 were independent factors. The positive predictive value (PPV) and the negative predictive value (NPV) for SVR based on a 1-log or greater HCV-RNA level reduction at week 2 were 65% and 90%, respectively, and those based on HCV core antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2-log or greater reduction of the RNA level were 86% and 67%, respectively, and those based on the core antigen level were 93% and 69%, respectively. Evaluation of viral reduction at week 2 after therapy initiation is useful for predicting SVR to low-dose PEG-IFN plus ribavirin therapy.

To clarify the clinical features of and risk factors for extrahepatic seeding, a major complication following radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Our prospective database of 351 nodules in 257 patients with HCC who had undergone RFA between April 2001 and April 2008 was reviewed. The following variables were assessed to identify the risk factors for extrahepatic seeding: age, sex, viral markers, Child-Pugh class, tumor size, number of tumors, RFA indication (tumor size ≤3 cm, number of tumors ≤3), tumor biopsy prior to RFA, degree of histological differentiation, tumor markers, tumor location, number of sessions, and combined transcatheter arterial chemoembolization. The median follow-up period was 36.5 months, during which the rate of seeding after was 5.1% and the 5-year cumulative seeding rate was 8.4%. The survival rate after neoplastic seeding was 21% at 5 years. Univariate analysis of the risk factors for neoplastic seeding showed significant differences in tumor size, RFA indication, subcapsular lesion, number of sessions, tumor biopsy prior to RFA, and des-gamma-carboxy prothrombin value. However, multivariate analysis showed that the only independent risk factor was RFA indication. The prognosis of patients with neoplastic seeding was poor. In particular, RFA performed for HCC not satisfying the RFA indication showed a high risk of seeding, and careful consideration should be given to the optimal treatment method and avoiding direct puncture of subcapsular tumors.

Evaluation of malignant potential is important to determine the treatment strategy for small hepatocellular carcinoma (HCC). The aim of the present study was to establish a method of assessing the malignant potential of small hypervascular HCC using B-mode ultrasonography. One hundred and thirteen arterial hypervascular HCC nodules under 3 cm diagnosed by biopsy or surgical resection (20.5 ± 6.3 mm) were classified into two groups ultrasonographically: type 1 with (n = 27) and type 2 without (n = 86) a halo. Type 2 was categorized into three subgroups: type 2a, homogenous hyperechoic (n = 9); type 2b, hypoechoic with a smooth margin (n = 35); and type 2c, hypoechoic with an irregular or unclear margin (n = 42). The mean diameter of type 2a nodules was significantly smaller than that of other HCC types (P 0.05). Overall, moderately differentiated HCC was the predominant histological type, except for type 2a, all of which were well-differentiated HCC. The percentage of poorly differentiated HCC was significantly higher in type 2c nodules (19%) than in other HCC types (P 0.01). The percentage of Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3) positivity was significantly higher in type 2c nodules (55%) than in other HCC types (P 0.01). Classification on B-mode ultrasonography was correlated with the histological differentiation and serum level, an indicator of a poor prognosis. The malignant potential of type 2a is the lowest and that of type 2c is the highest, both histologically and serologically. Assessment of the malignant potential of small, hypervascular HCC is possible by B-mode ultrasonography.

Although CD57+ lymphocytes are closely correlated with prognosis in various cancers, the role of subsets of CD57+ cells in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is unclear. In the present study, peripheral blood (PB) from HCV-related HCC patients was analyzed. Plasma cytokine levels and in vitro cytokine-producing capabilities were analyzed with enzyme-linked immunosorbent assays, and CD57+ cell subsets were studied using a multi-color FACS system. Interferon (IFN)-γ was undetectable in the plasma of patients with tumors at any stage, whereas the plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-10 and IL-18, but not that of IL-12, were significantly higher in stage IV patients compared to patients with earlier-stage tumors. In contrast, the IFN-γ-producing capability of PB was highest in stage I patients and gradually decreased with tumor progression. The IL-10-, IL-18- and IL-12-producing capabilities of PB increased from stage I to III. However, PB-TNF-α, IL-10- and IL-18-producing capabilities were reduced in stage IV patients, probably due to repeated anti-cancer treatments. The percentage of CD4+CD57+αβTCR+ cells (CD4+CD57+ T cells) in peripheral blood lymphocytes (PBLs) increased with tumor progression. Moreover, the percentage of CD4+CD57+ T cells in PBLs and the ratio of CD4+CD57+ T cells to CD4+αβTCR+ cells (CD4+ T cells), but not that of CD4+CD57+ T cells to CD57+αβTCR+ cells (CD57+ T cells), showed a significant inverse correlation with PB-IFN-γ-producing capability. The present results suggest that an increase in CD4+CD57+ T cells controls the capability of PB to produce the anti-tumor cytokine IFN-γ and that PB-IFN-γ production is impaired with HCC tumor progression.

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.

AIM: To evaluate the association of Helicobacter pylori (H.pylori)-related chronic gastritis stage with upper gastrointestinal symptoms and gastroesophageal reflux disease (GERD). METHODS: Subjects underwent upper gastrointestinal endoscopy, a questionnaire using a frequency scale for symptoms of GERD (FSSG), and measurements of serum H.pylori-antibody and pepsinogen (PG) levels. They were classified into the following 4 groups in terms of H.pylori-related chronic gastritis stage: Group A (n = 219), H.pylori(-)PG(-); Group B (n = 310), H.pylori(+)PG(-); Group C (n = 279), H.pylori(+)PG(+); and Group D (n = 17), H.pylori(-)PG(+). RESULTS: Reflux esophagitis occurred in 30.6% of Group A, 14.5% of Group B, 6.8% of Group C, and 0% of Group D (P < 0.001). Scores for acid reflux symptoms decreased significantly with chronic gastritis stage (from Group A to D) (P < 0.05), while scores for dysmotility symptoms did not differ significantly. The prevalence of non-erosive reflux disease (NERD) did not differ among groups. However, in subjects with GERD, the prevalence of NERD tended to increase with chronic gastritis stage (P = 0.081). CONCLUSION: Acid reflux symptoms and the prevalence of reflux esophagitis can be assessed by measuring both serum H.pylori-antibody and PG levels.

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.

We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG).A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers.The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data.Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.