Japanese apricot improves symptoms of gastrointestinal dysmotility associated with gastroesophageal reflux disease.

AIM: To investigate the effects of Japanese apricot (JA) consumption on gastroesophageal reflux disease (GERD)-related symptoms. METHODS: 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. RESULTS: Those who ate JA daily were significantly older than those who did not (60.6 ± 10.5 years vs 56.0 ± 11.0 years, P < 0.001). 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, P < 0.001). 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, P < 0.001). 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). CONCLUSION: 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.

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.

Usefulness of continuous suction mouthpiece during esophagogastroduodenoscopy: A single-center, prospective, randomized study.

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.

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.

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.

Elevated risk of recurrent colorectal neoplasia with Helicobacter pylori-associated chronic atrophic gastritis: A follow-up study of patients with endoscopically resected colorectal neoplasia.

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.

Serological and histological indices of hepatocellular carcinoma and tumor volume doubling time.

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<0.05). The mean ± SD T2AFP in Ed2 and Ed3 HCC was 121.0±167.5 and 37.3±24.6 days, respectively (P<0.01). TVDT and T2AFP decreased with histological dedifferentiation of HCC. The mean ± SD T2AFP in the AFP-L3-positive and -negative groups was 63.2±101.2 and 191.9±209.9 days, respectively, with a statistically significant difference between the groups (P<0.01). A significant correlation was observed between T2AFP and TVDT (correlation coefficient, 0.70; P<0.01). A significant correlation was also observed among TVDT, serological indices and histological grades of HCC differentiation. A short T2AFP and/or AFP-L3-positivity were shown to reflect a poorly differentiated HCC histopathology and a higher malignant potential.

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.

A case of chronic pancreatitis in which endoscopic ultrasonography was effective in the diagnosis of a pseudoaneurysm.

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.

Diazepam during endoscopic submucosal dissection of gastric epithelial neoplasias.

AIM: To investigate risk factors and adverse events related to high-dose diazepam administration during endoscopic submucosal dissection for gastric neoplasias. METHODS: Between February 2002 and December 2009, a total of 286 patients with gastric epithelial neoplasia underwent endoscopic submucosal dissection in our hospital. To achieve moderate sedation, 5-7.5 mg of diazepam was administered intravenously by non-anesthesiologists. Intermittent additional administration of 2.5-5 mg diazepam was performed if uncontrollable body movement of the patient was observed. All patients were classified into groups based on the required diazepam dose: low-dose (≤ 17.5 mg, n = 252) and high-dose (> 17.5 mg, n = 79). RESULTS: Differences between the low- and high-dose diazepam groups were observed in lifetime alcohol consumption (0.30 ± 0.48 vs 0.44 ± 0.52 tons, P = 0.032), body weight (58.4 ± 10.3 vs 62.0 ± 9.9 kg, P = 0.006), tumor size (15 ± 10 vs 23 ± 18 mm, P < 0.001), lesion location (P < 0.001) and the presence of ulcerative findings (14/238 vs 18/61, P < 0.001). Multivariate analysis identified all five variables as independently related to required diazepam dosage. In terms of adverse reactions to diazepam administration, paradoxical excitement was significantly more frequent in the high-dose diazepam group (P < 0.001). CONCLUSION: Intermittent administration of diazepam enabled safe completion of gastric endoscopic submucosal dissection except in patients who were alcohol abusers or obese, or who showed complicated lesions.

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.

Management of bleeding and artificial gastric ulcers associated with endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD), an endoscopic procedure for the treatment of gastric epithelial neoplasia without lymph node metastases, spread rapidly, primarily in Japan, starting in the late 1990s. ESD enables en bloc resection of lesions that are difficult to resect using conventional endoscopic mucosal resection (EMR). However, in comparison to EMR, ESD requires a high level of endoscopic competence and a longer resection time. Thus, ESD is associated with a higher risk of adverse events, including intraoperative and postoperative bleeding and gastrointestinal perforation. In particular, because of a higher incidence of intraoperative bleeding with mucosal incision and submucosal dissection, which are distinctive endoscopic procedures in ESD, a strategy for endoscopic hemostasis, mainly by thermo-coagulation hemostasis using hemostatic forceps, is important. In addition, because of iatrogenic artificial ulcers that always form after ESD, endoscopic hemostasis and appropriate pharmacotherapy during the healing process are essential.

Ultrasonogram of hepatocellular carcinoma is associated with outcome after radiofrequency ablation.

AIM: To investigate the association between B-mode ultrasound classification of small hepatocellular carcinoma (HCC) and outcome after radiofrequency ablation (RFA). METHODS: Ninety-seven cases of HCC treated using RFA between April 2001 and March 2006 were reviewed. Ultrasound images were classified as follows: type 1, with halo (n = 29); and type 2, without halo (n = 68). Type 2 was further categorized into three subgroups: type 2a, homogenous hyperechoic (n = 9); type 2b, hypoechoic with smooth margins (n = 43); and type 2c (n = 16), hypoechoic with irregular or unclear margins. Patients with type 2a HCC were excluded from analysis due to the small number of cases. RESULTS: Two year recurrence rates for type 2b, type 1 and type 2c were 26%, 42% and 69%, respectively, with significant differences between type 2b and type 2c (P < 0.01), and between type 1 and type 2c (P < 0.05). Five year survival rates were 89%, 43% and 65%, respectively. Survival was significantly longer for type 2b than for other types (type 1 vs type 2b, P < 0.01; type 2b vs type 2c, P < 0.05). On univariate analysis, factors contributing to recurrence were number of tumors, tumor stage, serum level of lens culinaris agglutinin-reactive alpha-fetoprotein and ultrasound classification (P < 0.05). Factors contributing to survival were tumor stage and ultrasound classification (P < 0.05). Multivariate analysis identified ultrasound classification as the only factor independently associated with both recurrence and survival (P < 0.05). CONCLUSION: B-mode ultrasound classification of small HCC is a predictive factor for outcome after RFA.

Transnasal and standard transoral endoscopies in the screening of gastric mucosal neoplasias.

AIM: To compare the diagnostic performances of transnasal and standard transoral esophagogastroduodenoscopy (EGD) in gastric cancer screening of asymptomatic healthy subjects. METHODS: Between January 2006 and March 2010, a total of 3324 subjects underwent examination of the upper gastrointestinal tract by EGD for cancer screening, with 1382 subjects (41.6%) screened by transnasal EGD and the remaining 1942 subjects (58.4%) by standard transoral EGD. Clinical profiles of the screened subjects, detection rates of gastric neoplasia and histopathology of the detected neoplasias were compared between groups according to the stage of Helicobacter pylori(H. pylori)-related chronic gastritis. RESULTS: Clinical profiles of subjects did not differ significantly between the two EGD groups, except that there were significantly more men in the transnasal EGD group. During the study period, 55 cases of gastric mucosal neoplasias were detected. Of these, 23 cases were detected by transnasal EGD and 32 cases by standard transoral EGD. The detection rate for gastric mucosal neoplasia in the transnasal EGD group was thus 1.66%, compared to 1.65% in the standard transoral EGD group, with no significant difference between the two groups. Detection rates using the two endoscopies were likewise comparable, regardless of H. pylori infection. However, detection rates when screening subjects without extensive chronic atrophic gastritis (CAG) were significantly higher with standard transoral EGD (0.70%) than with transnasal EGD (0.12%, P < 0.05). In particular, standard transoral EGD was far better for detecting neoplasia in subjects with H. pylori-related non-atrophic gastritis, with a detection rate of 3.11% compared to 0.53% using transnasal EGD (P < 0.05). In the screening of subjects with extensive CAG, no significant differences in detection of neoplasia were evident between the two endoscopies, although the mean size of detected cancers was significantly smaller and the percentage of early cancers was significantly higher with standard transoral EGD. CONCLUSION: These results strongly suggest that the diagnostic performance of transnasal endoscopy is suboptimal for cancer screening, particularly in subjects with H. pylori-related non-atrophic gastritis.

Prediction of sustained response to low-dose pegylated interferon alpha-2b plus ribavirin in patients with genotype 1b and high hepatitis C virus level using viral reduction within 2 weeks after therapy initiation.

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.

Steakhouse syndrome causing large esophageal ulcer and stenosis.

A 66-year-old man developed dysphagia during dinner and was evaluated 2 d later in our hospital because of persistent symptoms. Upper gastrointestinal endoscopy showed no impacted food, but advanced esophageal cancer was suspected based on the presence in the upper esophagus of a large irregular ulcerative lesion with a thick white coating and stenosis. Further imaging studies were performed to evaluate for metastases, revealing circumferential esophageal wall thickening and findings suggestive of lung and mediastinal lymph node metastases. However, dysphagia symptoms and the esophageal ulcer improved after hospital admission, and histopathological examination of the esophageal mucosa revealed only nonspecific inflammation. At the time of symptom onset, the patient had been eating stewed beef tendon (Gyusuji nikomi in Japanese) without chewing well. Esophageal ulceration due to steakhouse syndrome was therefore diagnosed. The lung lesion was a primary lung cancer that was surgically resected. Although rare, steakhouse syndrome can cause large esophageal ulceration and stenosis, so care must be taken to distinguish this from esophageal cancer.

Clinical features and risk factors of extrahepatic seeding after percutaneous radiofrequency ablation for hepatocellular carcinoma.

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.

Assessment of gastroesophageal reflux disease by serodiagnosis of Helicobacter pylori-related chronic gastritis stage.

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.

Altered cytokine levels and increased CD4+CD57+ T cells in the peripheral blood of hepatitis C virus-related hepatocellular carcinoma patients.

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+αßTCR+ 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+αßTCR+ cells (CD4+ T cells), but not that of CD4+CD57+ T cells to CD57+αßTCR+ 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.

Assessment of hepatocellular carcinomas using conventional magnetic resonance imaging correlated with histological differentiation and a serum marker of poor prognosis.

PURPOSE: To establish a method of assessing the malignant potential of hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.