Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer.

BACKGROUND: This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). MATERIALS AND METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above. RESULTS: Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio [HR] = 12.193, 95% confidence interval [95% CI] 1.039-143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917-25.525, P = 0.063). CONCLUSION: The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.

Where has the tumor gone? The characteristics of cases of negative pathologic diagnosis after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Discrepancies can occur between the histopathological findings from forceps biopsy and endoscopic mucosal resection (EMR), and occasionally in embarrassing cases tumorous tissue is not found at EMR. The aim of the present study was to evaluate the clinical, endoscopic, and histological features of gastric tumors in patients with pathololgically negative findings at EMR. PATIENTS AND METHODS: We retrospectively reviewed data from all patients with gastric tumor treated with EMR or endoscopic submucosal dissection (ESD) between August 1999 and April 2007 at our institution, and enrolled into the study patients with no tumor tissue found at mucosal resection. Their biopsy and EMR specimen slides were reviewed by a single pathologist. Patient characteristics, including demographic and clinical features, and the endoscopic appearance of mucosal lesions were evaluated. RESULTS: Out of 633 patients treated with EMR or ESD, 20 patients (3.2 %) were included. The mean +/- SD maximal dimension of the mucosal lesions was 6.40 +/- 2.19 mm (range 3 - 10). Mean number of forceps biopsy fragments was 3.80 +/- 1.96 and mean sampling ratio was 2.08 +/- 1.07 mm/fragment. Before resection, histological findings from forceps biopsy were: 13 low grade dysplasias (65.0 %), 2 high grade dysplasias (10.0 %), and 5 intramucosal carcinomas (25.0 %). CONCLUSIONS: In the case of pathologically negative findings at EMR, tumors might have been small enough to have been removed by the previous forceps biopsy. However, the possibility of sampling error or of a different location should be considered. Furthermore, appropriate communication between endoscopists and pathologists is essential.

Hyperglycaemia, hypercholesterolaemia and the risk for developing gastric dysplasia.

BACKGROUND/GOALS: Gastric dysplasia is believed to be the penultimate stage of gastric carcinogenesis. Few studies have evaluated whether there is a relationship between such risk factors and gastric dysplasia. This case-control study was conducted to investigate the associations between obesity, serum glucose, lipids and gastric dysplasia. STUDY: Endoscopic findings and pathology specimens were reviewed from 1 July 1997 to 31 December 2006 in the Health Promotion Center. One hundred thirty patients have the dysplasia in the stomach during screening endoscopy. The same number of controls was evaluated and matched to the gastric dysplasia group for age and gender. RESULT: The univariate analysis showed that the dysplasia risk was slightly increased among persons with a higher low-density lipoprotein, lower high-density lipoprotein, impaired fasting glucose and higher total cholesterol. However, a higher body mass index and higher triglyceride level were not associated with the diagnosis of gastric dysplasia. In the multivariate-adjusted model, a higher low-density lipoprotein cholesterol and glucose were strongly associated with an increased risk of dysplasia compared to the controls. However, the body mass index, triglyceride and total cholesterol were not associated with the risk for dysplasia. CONCLUSION: Hyperglycaemia and low-density lipoprotein cholesterol appear to be associated with the risk for gastric dysplasia. Further epidemiologic studies including a large cohort of patients with gastric dysplasia and adenocarcinoma are needed to clarify the association of low-density lipoprotein cholesterol, serum glucose and gastric carcinogenesis.

Factors related to lymph node metastasis and the feasibility of endoscopic mucosal resection for treating poorly differentiated adenocarcinoma of the stomach.

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is currently not accepted as an alternative treatment to surgery in early gastric cancer (EGC) of the undifferentiated histologic type. The present retrospective analysis examined the correlation of various histologic factors with the presence of lymph node metastasis (LNM). PATIENTS AND METHODS: A retrospective analysis on 234 patients with poorly differentiated EGC who underwent radical gastrectomy with D2 lymph node dissection was undertaken. Several clinicopathologic factors were investigated to identify predictive factors for LNM: age, sex, type of operation, tumor location, tumor size, gross type, ulceration, lymphatic invasion, and depth of invasion. RESULTS: Of the 234 lesions with poorly differentiated EGC, half (n = 116) already showed submucosal invasion in the resection specimen; 25.9 % of those (30/116) were limited to the upper third (SM1). Of the lesions confined to the mucosa, LNM was found in 3.4 % (4/118). With minor submucosal infiltration (SM1), the LNM rate was lower (0/30) in our patient population. Only with SM2/3 infiltration did the LNM rate sharply rise to around 30 %. The cut-off for submucosal infiltration depth was 500 microm (0/32 LNM), above which LNM rates were substantial (31.2 %; 24/77). There was limited correlation between the SM1-3 classification and actual measurement of submucosal infiltration depth. In a multivariate analysis, tumor size ( P = 0.033), depth of invasion ( P = 0.004), and lymphatic invasion ( P < 0.001) were associated with LNM. CONCLUSION: Poorly differentiated EGC confined to the mucosa or with minimal submucosal infiltration (

Vascular endothelial growth factor gene polymorphisms associated with prognosis for patients with gastric cancer.

BACKGROUND: The present study analyzed vascular endothelial growth factor (VEGF) gene polymorphisms and their impact on the prognosis for patients with gastric cancer. PATIENTS AND METHODS: Five hundred and three consecutive patients with surgically resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and four VEGF (-460T > C, -116G > A, +405G > C, and +936C > T) gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The survival analysis showed no association of three VEGF gene polymorphisms with the prognosis. For the +936C > T polymorphism, the T/T genotype, however, had a worse overall survival (OS) compared with the C/C genotype (P = 0.037). The -460 T/C or C/C genotype was a poor prognostic factor in patients with stage 0 or I gastric cancer (OS: hazard ratio (HR) = 3.96, disease-free survival (DFS): HR = 4.87). In the haplotype analysis, the CACC haplotype was associated with a significantly worse survival when compared with the TGGC haplotype (OS: HR = 1.72, DFS: HR = 1.73). CONCLUSIONS: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with gastric cancer. Consequently, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome.

Perforating disorder caused by salt-water application and its experimental induction.

BACKGROUND: Perforating disorders are uncommon diseases characterized by transepidermal elimination histopathologically and include reactive perforating collagenosis, elastosis perforans serpiginosa, Kyrle's disease and perforating folliculitis. In addition, perforating disorders can develop in patients with diabetes mellitus, renal failure and even by accidental exposure of calcium salts. METHODS: We report two cases of perforating disorder caused by chemical burn with commercially available salt-water application for self-treatment of chronic dermatitis or pruritus. RESULTS: The commercially used salt water for making bean curd was analyzed and it consisted of calcium and other salts without harmful heavy metals. We induced a similar phenomenon by experimental application of commercial salt water on guinea pigs. CONCLUSION: Bean curd is used as a food commonly in the Far-East, allowing a greater chance of exposure to salt water accidentally or occupationally. Bean curd is becoming more popular even in Western countries. To confirm causation, we induced a similar phenomenon in guinea pigs by experimental application of commercial salt water.

A case of Dowling-Degos disease suggesting an evolutional sequence.

We report a 47-year-old woman who presented with asymptomatic reticulate hyperpigmentations on the neck, lateral face, axillae, trunk, inguinal areas, and dorsa of both hands and feet. We thought it was an unusual case in the spectrum between the pole of Dowling-Degos disease (DDD) and that of reticulate acropigmentation of Kitamura (RAK). Another interesting point was that the biopsied specimens from the abdomen, neck, and axillary lesions showed somewhat different histopathologic features from typical DDD, suggesting an evolutional sequence. From these findings we suggest that a lichenoid inflammation may be responsible for the typical maculo-papular lesions of DDD.