Epstein-Barr virus detection in endoscopic submucosal dissection-proven early gastric cancer with mixed-type histology.

BACKGROUNDS: Early gastric cancer (EGC) with mixed-type histology is a significant risk factor for additional surgery after endoscopic submucosal dissection (ESD). On the other hand, Epstein-Barr virus-associated gastric cancer (EBVaGC) with mixed-type histology is a favorable risk factor with regard to lymph node metastasis. METHODS: We performed EBV detection in 13 ESD-proven lesions in 13 cases of early gastric cancer with mixed-type histology using EBV-encoded small RNA1 in situ hybridization (EBER1 ISH). RESULTS: EBVaGC was diagnosed in only one (7.7%) of the tested lesions. That EBVaGC patient underwent surgery and there was no residual lesion and no lymph metastasis. EBVaGC is not frequent in EGC with mixed-type histology. CONCLUSIONS: EBV testing of gastric biopsy specimens seems not to be useful to predict the mixed-type histology results of ESD. However, EBV testing for ESD specimens of EGC with mixed-type histology is expected to be useful for avoiding excessive additional surgery.

Endoscopic and pathologic motifs for the clinical diagnosis of Epstein-Barr virus-associated gastric cancer.

Objectives: Based on the recent therapeutic trends for gastric cancer (GC), the clinical impact of the diagnosis of Epstein-Barr virus (EBV)-associated GC (EBVaGC) appears to be important. We retrospectively analyzed endoscopic and pathologic motifs of GC lesions to narrow the number of candidates for EBV testing. Methods: We performed EBV tests for 32 upper gastrointestinal lesions of 32 patients in the clinical setting. These tests were ordered by endoscopists or by pathologists without an endoscopist's order. EBV-encoded small RNA1 (EBER1) in situ hybridization was used for the EBV tests. The endoscopic motif for the EBV test was the location in the upper part of the stomach or remnant stomach, mainly the depressed type with a submucosal tumor-like protrusion of the lesion. The pathologic motif was carcinoma with lymphoid stroma (CLS) or CLS-like histology of the lesion. We retrospectively analyzed the results of EBV tests for the endoscopic and pathologic motifs. Results: The final pathological diagnoses of the 32 subjects were 26 GCs including CLS, gastric endocrine cell carcinoma, gastric hepatoid carcinoma, gastric T-cell lymphoma, gastritis of the remnant stomach, esophageal adenocarcinoma, and esophageal squamous cell carcinoma. When nontypical lesions were excluded, the EBER1-positive rate was 42.3% (11/26) in GCs. Of the 14 GC lesions ordered examined by endoscopists, three (21.4%) were EBVaGC. Eight of the 12 (66.7%) GCs ordered examined by pathologists were EBVaGC. Conclusions: The pathologic motif is expected to be useful and the endoscopic motif may be helpful for EBVaGC diagnosis.

Clinical impact of tumor invasion depth staging of esophageal squamous cell carcinoma using endoscopic ultrasonography.

BACKGROUND/AIMS: To demonstrate how EUS tumor staging has a practical effect on deciding the treatment strategy for esophageal carcinoma, we retrospectively evaluated the clinical impact of thin-probe EUS staging. METHODOLOGY: The results of EUS performed 54 times were classified according to clinical impact into three grades (none, supportive, and important) and analyzed to assess their impact on the treatment strategy on individual occasions. RESULTS: EUS was important in determining treatment strategy for 23 of 39 lesions (59.0%) in the EUS-superficial group and supportive for 16 lesions (41.0%). The clinical impact of EUS for 15 lesions in the EUS-deep group was graded important for 8 lesions (53.3%), supportive for 6 lesions (40.0%) and none for one lesion (6.7%). CONCLUSIONS: Thin-probe EUS is expected to have some clinical impact on the determination of treatment strategies for squamous cell carcinoma of the esophagus.

Epstein-Barr Virus-associated Early Gastric Cancer Treated with Endoscopic Submucosal Dissection: A Possible Candidate for Extended Criteria of Endoscopic Submucosal Dissection.

A 73-year-old man visited our hospital for the treatment of an early gastric cancer (GC) lesion. We performed en bloc resection using endoscopic submucosal dissection (ESD) for his GC lesion. The present GC lesion was Epstein-Barr virus (EBV)-associated poorly differentiated-type adenocarcinoma invading into the submucosal layer. Recently, accumulating data has shown that the risk of lymph node metastasis from early EBV GC without local lymphovascular infiltration is low. The present patient has been in good health for over three years since ESD. Some cases of early EBV GC with invasion into the submucosal layer may be candidates for further extension of the ESD criteria.

Effect of a late evening snack on outpatients with liver cirrhosis.

AIMS: We have reported that one-week administration of a late evening snack (LES) improved not only malnutrition but also glucose intolerance in hospitalized patients with liver cirrhosis. Thus, we investigated whether long-term LES administration to outpatients for 3 months could reproduce the results obtained from hospitalized patients, especially improved glucose intolerance. If this treatment aggravated glucose intolerance, we tried to find any marker predicting this aggravation before the treatment. METHODS: Outpatients were prescribed one pack of oral supplementation of a branched-chain amino acid (BCAA)-enriched nutrient, Aminoleban EN (210 kCal) as a LES without dietician supervision. Both before LES administration and after 3 months, glucose tolerance and liver function were examined using a 75 g oral glucose tolerance test (OGTT), biochemical parameters in blood and the relationship between glucose tolerance (area under the curve (AUC)) and the following serum markers. RESULTS: Branched-chain amino acid/tyrosine ratio (BTR), the number of red blood cells (RBC), and hematocrit (Ht) significantly increased, with significant reduction of blood NH(3) level in patients with a blood glucose level less than 200 mg/dL 2 h after 75 g OGTT. However, the increase of AUC was seen after 3 months of LES administration in patients who had blood glucose higher than 200 mg/dL 2 h after 75 g OGTT. AUC weakly correlated positively with serum 7S collagen and negatively with choline esterase (ChE) and albumin (Alb). CONCLUSION: 75 g OGTT is a useful marker to predict the worst outcome and avoid the adverse effect of LES treatment in liver cirrhosis patients if performed without adequate nutrient conduct by a dietician.

Hepatocellular carcinoma with nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) was originally believed to be a benign disease. However, it has been recently revealed that NASH could lead to irreversible liver disease in some patients. We report an unusual case of hepatocellular carcinoma (HCC) in a 76-year-old man with NASH. He had no history of alcohol consumption, drug use, or blood transfusion. He was negative for all serological viral markers and autoantibodies. In addition, he was obese (body mass index [BMI], 30.75 kg/m(2)) and had type 2 diabetes mellitus. A liver biopsy specimen showed moderate steatosis with necroinflammatory changes, ballooning degeneration, Mallory bodies, pericellular fibrosis, and evidence of nodular regeneration. He was diagnosed with NASH with cirrhosis. Simultaneously, a liver tumor, measuring 19 mm in diameter, was detected in segment 6. A tumor biopsy specimen revealed well-differentiated HCC, and imaging modalities confirmed the characteristics of HCC. To our knowledge, ten patients who had HCC with NASH were reported. In all patients with NASH and HCC, cirrhosis was present. Patients with NASH and cirrhosis may progress to HCC, and regular screening, based on tumor markers and imaging modalities, is needed to detect HCC in patients with NASH and cirrhosis.

Th1 down-regulation at the single-lymphocyte level in HCV-related liver cirrhosis and the effect of TGF-beta on Th1 response: possible implications for the development of hepatoma.

Patients with hepatitis C virus (HCV) related-liver cirrhosis (LC) often develop hepatoma. The type 1 helper T cell (Th1) response presents an antitumor effect. We evaluated the Th1 response in patients with HCV-related LC at the single-cell level and examined the influence of transforming growth factor (TGF)-beta, an immunosuppressive cytokine, on the Th1 response. We determined the ratios of Th1-type cytokine (IFN-gamma, IL-2)-producing cells to CD3-positive cells in 14 patients (LC group) and in 16 normal controls using flow cytometry and measured serum TGF-beta(1) and TGF-beta(2) levels by ELISA. We then incubated, peripheral blood mononuclear cells from seven healthy volunteers with recombinant TGF-beta(1) or TGF-beta(2) for 48 h, and determined the ratio of IFN-gamma producing cells to CD3-positive cells. The IFN-gamma ratio was significantly lower in the LC group (29.7+/-0.3 vs. 44.2+/-15.0%, P<0.01). The serum TGF-beta(2) level was significantly increased in the LC group (601+/-232 vs. 329+/-118 pg/ml, P<0.001). TGF-beta(2) significantly suppressed IFN-gamma production at the single-cell level (10.0+/-4.3 vs. 7.3+/-2.0%, P<0.05). These findings indicated that the enhanced down-regulation of Th1 by TGF-beta(2) in patients with HCV-related LC might be effective against hepatoma.

Antioxidant, N-acetyl-L-cysteine inhibits the expression of the collagen alpha2 (I) promoter in the activated human hepatic stellate cell line in the absence as well as the presence of transforming growth factor-beta.

Although recent studies suggest the inhibitory property of N-acetyl-L-cysteine (NAC) on activation of hepatic stellate cell (HSC), the effects on once-activated HSCs are not well clarified. We investigated the influences of NAC on human-derived once-activated HSC line, LI90 with a focus on the collagen alpha2 (I) (COL1A2) promoter expression. Plasmid containing whole length of COL1A2 promoter linked to firefly luciferase gene and its various 5'-deletions were transiently transfected to LI90. The luciferase activity was determined with or without 10 mM of NAC in the absence or presence of 1 ng/ml of transforming growth factor (TGF)-beta. The effects of NAC on generation of intracellular reactive oxygen species (ROS) in LI90 were also analyzed. As a result, NAC significantly (P<0.05) suppressed the COL1A2 promoter expression in the absence or presence of TGF-beta. The expression was much more inhibited when used the deletion containing only AP-1/NF-kappaB binding sites than that including only three SP-1 binding sites. The ROS production was also comparably inhibited by NAC in both condition. These results indicated NAC suppressed, through its anti-oxidative action, the COL1A2 promoter expression in once-activated HSCs in the absence or presence of TGF-beta at least partly by affecting the signal transduction cascade encompassing AP-1/NF-kappaB activation.

Ultraslim endoscopy with flexible spectral imaging color enhancement for upper gastrointestinal neoplasms.

AIM: To conduct a preliminary study on the effect of flexible spectral imaging color enhancement (FICE) used in combination with ultraslim endoscopy by focusing on the enhanced contrast between tumor and non-tumor lesions. METHODS: We examined 50 lesions of 40 patients with epithelial tumors of the upper gastrointestinal tract before endoscopic submucosal dissection using ultraslim endoscopy with conventional natural color imaging and with FICE imaging. We retrospectively investigated the effect of the use of FICE on endoscopic diagnosis in comparison with normal light. RESULTS: Visibility of the epithelial tumors of the upper gastrointestinal tract with FICE was superior to normal light in 54% of the observations and comparable to normal light in 46% of the observations. There was no lesion for which visibility with FICE was inferior to that with normal light. FICE visualized 69.6% of hyperemic lesions and 58.8% of discolored lesions better than conventional endoscopy with natural color imaging. FICE significantly improved the visibility of lesions with hyperemia or discoloration compared with normocolored lesions. CONCLUSION: This study suggests that the use of FICE would improve the ability of ultraslim endoscopy to detect epithelial tumors of the upper gastrointestinal tract.

Stenosis of gastric body as a rare complication after endoscopic submucosal dissection for multiple gastric epithelial tumors.

We experienced a rare case of stenosis of the gastric body, a wider tract, that occurred after multiple, wide endoscopic resection five times for four lesions of early gastric cancer and gastric adenomas. We report this case as a sentinel experience of endoscopic submucosal dissection of the stomach.