Increased Monocyte Chemotactic Protein-1 Accompanying Pro-Inflammatory Processes are Associated with Progressive Hearing Impairment and Bilateral Disability of Meniere's Disease.

BACKGROUND: The progression of hearing impairment and the bilateral involvement of Meniere's disease (MD) may depend on the disease duration and aging. Recent studies reported that MD might involve dysfunction of the microvascular circulation damaged due to inflammatory changes. OBJECTIVES: The aim of this study was to determine that the progress of the MD's hearing impairment and bilateral disability may be associated with the pathogenesis of several pro-inflammatory processes. PATIENTS AND METHODS: We recruited 30 unilateral MD patients (56.8 ± 14.7 years old), 7 bilateral MD patients (65.3 ± 13.9 years old), and 17 age-matched control subjects (53.5 ± 14.4 years old, p > 0.05). We measured the plasma vascular endothelial growth factor (VEGF), plasma interleukin-6 (IL-6), plasma tumor-necrosis factor α (TNFα), and plasma monocyte chemotactic protein-1 (MCP-1). RESULTS: The bilateral MD group and the unilateral MD group had higher plasma MCP-1 (204.7 ± 41.0 pg/mL and 169.5 ± 32.0 pg/mL) than the control group (149.2 ± 30.7 pg/mL) (p < 0.05). There was no significant difference in plasma TNFα, IL-6, and VEGF among 3 groups (p > 0.05). There was a strong correlation between the plasma MCP-1 and age in MD patients (r = 0.58, p < 0.01); however, no significant correlation between the plasma MCP-1 and age was found in control subjects (p > 0.05). The plasma MCP-1 significantly correlated with the average hearing level of 500, 1,000, 2,000, and 4,000 Hz, and the maximum slow phase eye velocity in caloric test in the better side (p < 0.05). Also, the plasma MCP-1 showed significant positive correlations with the plasma IL-6 (r = 0.49, p < 0.01) and plasma TNFα (r = 0.32, p < 0.05) in MD group. CONCLUSIONS: Our results suggest that the increased plasma MCP-1 accompanying pro-inflammatory processes are associated with the progression of the hearing impairment and the bilateral disability of MD.

The clinical meaning of mucin phenotype and Epstein-Barr virus infection in gastric cancer.

BACKGROUND/AIMS: Differentiated type adenocarcinomas producing gastric type mucin are receiving much attention because of their degree of clinical malignancy. Most Epstein-Barr virus (EBV)-associated gastric cancers are undifferentiated type, and correlate with gastric type mucin. We analyzed the clinical meaning of mucin phenotypes and the detection of EBV in gastric cancers. METHODOLOGY: The objects of study were 120 consecutive gastric cancer lesions, resected endoscopically (EMR group, n=54) or surgically (surgery group, n=66). The mucin phenotypes were determined using immunostaining for human gastric mucin (HGM), MUC2, and CD10. Changes in histological type within the lesions were examined. The presence of EBV was determined using in situ hybridization for EBV-encoded small RNA 1 (EBER-1). RESULTS: The incomplete intestinal phenotype accounted for 83% of the EMR group, and the gastric phenotype for only 13%. None of the EMR group lesions had changes in the degree of differentiation, and there was no EBER-1-positive lesion. In the surgery group, the gastric phenotype accounted for 29%, significantly more than in the EMR group (p=0.0363). The incomplete intestinal phenotype accounted for 64% of surgically resected lesions. Changes in the degree of differentiation were significantly more common in the surgery group (16/66) than in the EMR group (0/54) (p=0.0001), tending to be more common in the gastric phenotype lesions. There were 3 EBER-1-positive lesions in the surgery group, accounting for 5%, and all were HGM positive. CONCLUSIONS: There appears to be little need to determine the mucin phenotype or EBV status of endoscopically resected lesions. In cases of gastric cancer where surgical resection is indicated, however, where the preoperative findings indicate a depth of invasion to SM or greater, and/or an undifferentiated lesion, then mucin phenotyping of biopsy specimens may be useful in predicting the predominant histological type of the tumor.

Mucin and differentiation in Epstein-Barr virus-associated gastric carcinoma.

BACKGROUND/AIMS: Epstein-Barr virus (EBV) is present in roughly 1 in 10 cases of gastric carcinoma, particularly in undifferentiated adenocarcinomas. To clarify the histological developmental processes in EBV-associated gastric carcinoma, we investigated the presence of EBV infection, changes in the degree of differentiation within lesions, and mucin phenotypes of gastric carcinomas. METHODOLOGY: We had already examined 124 gastric carcinomas using in situ hybridization for EBV-encoded small RNA1 (EBER-1) and 12 lesions were EBER-1-positive. From these lesions we selected 8 carcinomas positive for EBER-1, and then chose 16 EBER-1-negative carcinomas as controls. Hematoxylin and eosin (H&E) stained specimens were examined for changes in histological type within each lesion. Mucin phenotypes of the specimens were determined using human gastric mucin (HGM), MUC2 and CD10 immunostaining. RESULTS: Of the EBER-1-positive lesions, 50% exhibited the gastric type mucin phenotype, whereas only 19% of the EBER-1-negative lesions were of the gastric phenotype. Changes in the histological type were seen within 75% of the EBER-1-positive lesions and within 62.5% of the EBER-1-negative lesions. CONCLUSIONS: The gastric mucin phenotype tended to be more common in the EBV-associated gastric carcinomas. The influence of EBV infection on the change in the histological type within the lesion was considered to be slight.

Endoscopic findings potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.

BACKGROUND/AIMS: When a benign-malignant borderline lesion is diagnosed by the usual small gastric biopsy, there is sometimes difficulty in making a clinical decision. To clarify potentially useful findings to predict the existence of gastric cancer in borderline lesions diagnosed by forceps biopsy, we retrospectively analyzed endoscopic features. METHODOLOGY: We diagnosed 68 consecutive gastric benign-malignant borderline lesions (57 cases) by forceps biopsy and endoscopically resected them. The final diagnosis for 24 lesions (35.3%) was adenocarcinoma (adenocarcinoma group), and for 40 lesions (58.8%) was adenoma (adenoma group). Comparison with endoscopic findings for the groups was carried out using digitally filed endoscopic photos. RESULTS: We found six endoscopic findings (distal location, reddish surface color, lack of smoothness, lack of glossiness, focal roughness, and focal redness) having statistically significant relationships with adenocarcinoma at the final pathological diagnosis. In multivariate analysis, focal redness (p<0.01) and lack of glossiness (p<0.05) were found to have a significant relationship to gastric cancer. CONCLUSIONS: Endoscopic findings such as focal redness and lack of glossiness were potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.

Clinical impact of strip biopsy for early gastric cancer.

BACKGROUND: The impact of EMR (strip biopsy method) on the selection of subsequent treatment for early gastric cancer was analyzed retrospectively. METHODS: A total of 163 consecutive patients with gastric epithelial tumors (186 lesions) underwent strip biopsy. On the basis of pretherapeutic findings, the indications for strip biopsy were classified into 4 groups: benign-malignant borderline group (93 lesions), curative indication group (65), diagnostic indication group (22), and palliative indication group (6). The clinical impact of the strip biopsy result on the subsequent treatment strategy was assessed. RESULTS: Of the lesions in the benign-malignant borderline group, 36.6% were intramucosal cancer. In the curative indication group, the results of strip biopsy differed from the pretherapeutic findings for 7.7% of the lesions. Strip biopsy was effective treatment for all lesions in the benign-malignant borderline group and for 92.3% of those in the curative indication group. Strip biopsy avoided unnecessary surgery in 50% of patients in the diagnostic indication group and 16.7% of those in the palliative indication group. After the strip biopsy results were explained, 50% of the patients in the palliative indication group reversed their initial decision and opted for surgery. Strip biopsy results reversed the decision for surgery, which had been based on inaccurate pretherapeutic information, in 20% of cases of early gastric cancer. CONCLUSIONS: Strip biopsy has a major clinical impact, because it provides an accurate diagnosis, aids in the selection of an appropriate treatment strategy, and reduces unnecessary surgery.

Increased expression of matrix metalloproteinase-7 in invasive early gastric cancer.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7), a proteolytic enzyme, is suspected to play an important role in the progression of various cancers. To clarify the clinical importance of MMP-7, we retrospectively analyzed MMP-7 expression in gastric epithelial tumors. METHODS: We tested 201 lesions (from 172 patients) of surgically or endoscopically resected gastric epithelial tumors (gastric cancer, 158 lesions; gastric adenoma, 32 lesions; hyperplastic polyp, 11 lesions). MMP-7 expression was immunohistochemically examined. Sections with immunostaining signals in more than 30% of tumor cells were judged to show positive expression. RESULTS: MMP-7 was expressed in 33.3% (67/201) of all lesions. MMP-7-positive tumors were significantly more frequent in diffuse-type adenocarcinomas (62.2%; 28/45) compared with intestinal-type lesions (31.9%; 36/113; P < 0.001). Cancers invading the submucosa or deeper (60.5%; 46/76) were showed positivity significantly more frequently than mucosal cancers (22.0%; 18/82; P < 0.001). MMP-7-positive lesions increased with the progression of gastric epithelial tumors, including adenomas, mucosal cancers, and cancers invading the submucosal layer or deeper (P < 0.001). MMP-7 expression occurred significantly more often in lymphatic invasion-positive cancers (65.1%; 41/63) than in lymphatic invasion-negative cancers (24.2%; 23/95; P < 0.001). CONCLUSIONS: The MMP-7-positive rate increased with the progression of gastric epithelial tumors, such as adenoma, mucosal cancer, and cancer invading the submucosal layer or deeper. MMP-7 was significantly associated with aggressive pathological phenotypes of cancer. The detection of the MMP-7 protein may be useful in pretherapeutic diagnosis.

Clinical interpretation of the histological typing of gastric cancer using endoscopic forceps biopsy.

BACKGROUND/AIMS: Histological typing of gastric cancer is important for determining the treatment strategy and predicting the prognosis. We compared the histological types obtained by endoscopic forceps biopsy with the finally determined histological types of surgically resected specimens to investigate the reliability of histologically typing gastric cancer by biopsy. METHODOLOGY: Agreement between the biopsy typing and the final histological typing based on the predominant histology of the resected tumor was studied in 115 consecutive gastric cancers. RESULTS: The overall agreement rate of histological typing of gastric cancer was 75.7%. In patients with early gastric cancer, the agreement rate was a high 82.5% and the final histological type was usually predicted. In patients with advanced gastric cancer, the agreement rate was 72.0%, which was significantly lower than for early gastric cancer (p<0.05). The agreement rate for advanced differentiated cancer was also significantly lower than that for early cancer (63.6% vs. 90.0%) (p<0.05). CONCLUSIONS: The reliability of using histological typing by biopsy to set the indications for endoscopic treatment and for preoperative prediction of the prognosis is expected to be good for differentiated early gastric cancer, but it might not be adequate for advanced cancer or undifferentiated cancer.

Evaluation of epstein-barr virus DNA load in gastric mucosa with chronic atrophic gastritis using a real-time quantitative PCR assay.

PURPOSE: It is hypothesized that Epstein-Barr virus (EBV) has already infected the noncarcinomatous gastric mucosa before carcinogenesis of EBV-associated gastric carcinoma. However, the frequency and distribution of EBV infection in the gastric mucosa of chronic atrophic gastritis (CAG) are still unclear. To clarify these points, we evaluated the EBV DNA load in gastric mucosa with CAG. METHODS: We tested samples from 35 CAG cases. Paired biopsy specimens from five sites of the stomach were obtained according to the Updated Sydney System. One of each pair of specimens was subjected to areal-time quantitative polymerase chain reaction (Q-PCR) assay to detect EBV. Q-PCR was performed using the LightCycler System (Roche, Mannheim, Germany). The other was subjected to hematoxylin and eosin (H&E) and Giemsa staining. The histological degree of CAG was graded according to the Updated Sydney System. To evaluate the surface distribution of gastric mucosal atrophic changes of CAG, we modified the endoscopic classification of Kimura and Takemoto. RESULT: EBV DNA was detected in 65.7% (23 of 35 cases) of the gastric biopsy specimens of the cases examined. EBV DNA was detected most frequently (92.3%; 12 of 13 cases) in the cases with endoscopically moderate CAG (p < 0.01). There was a significant association between EBV detection and the presence of inflammatory cell infiltration and atrophy in the stomach with endoscopically moderate CAG. CONCLUSION: EBV mainly infects the gastric mucosa of patients with moderate CAG.

The pilot experience of immunotherapy-combined photodynamic therapy for advanced gastric cancer in elderly patients.

BACKGROUND: Therapeutic efficacy of endoscopic photodynamic therapy (PDT) for advanced gastric cancer is limited. Recent animal studies have clarified the very important role of host immune cells in PDT. We expected a potential cooperative effect of PDT and immunotherapy, and developed immunotherapycombined PDT (I-PDT) for advanced gastric cancer. METHODS AND MATERIALS: We applied I-PDT for two elderly patients with complicated advanced gastric cancer (92- and 89-yr-old males). Tumor bleeding prevented them from leading an ordinary home life. Initial simple PDT was not effective. Patients received over 109 activated T-lymphocyte-predominant autologous immune cells, mainly intravenously, 5x for one course. PDT was performed endoscopically on the day of the third infusion. RESULTS: Two or three courses of I-PDT safely stopped tumor bleeding, and the initial poor prognoses of a few months of survival seemed to be improved (patient 1, over 32 mo; patient 2, 14 mo). CONCLUSIONS: I-PDT was found to be a safe, feasible treatment that could improve symptoms resulting from advanced gastric cancer.