Effectiveness and safety of splenectomy for gastric carcinoma： A meta-analysis

AIM: To evaluate the impact of splenectomy on long-term survival, postoperative morbidity and mortality of patients with gastric cancer by performing a meta-analysis.METHODS: A search of electronic databases to identify randomized controlled trials in The Cochrane Library trials register, Medline, CBMdisc (Chinese Biomedical Database) and J-STAGE, etc was performed. Data was extracted from the studies by 2 independent reviewers. Outcome measures were survival, postoperative morbidity and mortality and operation-related events. The meta-analyses were performed by RevMan 4.3.RESULTS: Three studies comprising 466 patients were available for analysis, with 231 patients treated by gastrectomy plus splenectomy. Splenectomy could not increase the 5-year overall survival rate [RR = 1.17, 95% confidence interval (CI) 0.97-1.41]. The postoperative morbidity (RR = 1.76, 95% CI 0.82-3.80) or mortality (RR = 1.58, 95% CI 0.45-5.50) did not suggest any significant differences between the 2 groups. No significant differences were noted in terms of number of harvested lymph nodes, operation time, length of hospital stay and reoperation rate. Subgroup analyses showed splenectomy did not increase the survival rate for proximal and whole gastric cancer. No obvious differences were observed between the 2 groups when stratified by stage. Sensitivity analyses indicated no significant differences regarding the survival rates (P > 0.05).CONCLUSION: Splenectomy did not show a beneficial effect on survival rates compared to splenic preservation. Routinely performing splenectomy should not be recommended.     

Nuclear factor kappa B： A marker of chemotherapy for human stage Ⅳ gastric carcinoma

AIM： To detect the nuclear factor kappa B （NF-κB） condition in human stage IV gastric carcinoma patients and to explore the correlation between NF-κB activation and survival of these patients after chemotherapy. METHODS： Expression of NF-κB-p65 was determined by immunohistochemical analysis. Activity of NF-κB DNA-binding in carcinoma tissue was detected by electrophoretic mobility shift assay. Kaplan-Meier survival analysis was performed to show the relation between NF-κB and progression-free survival （PFS） or overall survival （OS） of the patients. RESULTS： The positive expression rate of NF-κB-p65 in 60 gastric cancer tissue samples was 76.7% （46160）. The expression of NF-κB-p65 was reduced in adjacent carcinoma and normal tissue samples. Electrophoretic mobility shift assay （EMSA） analysis showed a strong activation of NF-κB in cancer tissue samples. A survival difference was found in NF-κB-p65 positive and negative patients. NF-κB-p65 expression was negative in cancer tissue samples （n = 14）. PFS was 191.40 ± 59.88 d and 152.93 ±16.99 d, respectively, in patients with positive NF-κB-p65 expression （n = 46） （P = 0.4028）. The survival time of patients with negative and positive NF-κB-p65 expression was 425.16 ±61.61 d and 418.85 ±42.98 d, respectively （P = 0.7303）. Kaplan-Meier analysis showed no significant difference in PFS or OS. The 46 patient tissue which positive NF-κB-p65 expression was found in the tissue samples from the 46 patients whose PFS and OS were 564.89 ± 75.94 d and s 352.37 ±41.32 d, respectively （P = 0.0165）. CONCLUSION： NF-κB is activated in gastric carcinoma tissue, which is related to the OS after chemotherapy.     

Neuroendocrine gastric carcinoma expressing somatostatin： A highly malignant, rare tumor

Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.     

Extremely well-differentiated adenocarcinoma of the stomach： Clinicopathological and immunohistochemical features

AIM: Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma (EWDA), is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS: Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected. RESULT: Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions (mean follow-up period, 56 mo). All 9 cases of EWDA could be classified into gastric phenotype (5 lesions) and intestinal phenotype (4 lesions). The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cells and their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION: Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.     

Differences in proximal （cardia） versus distal （antral） gastric carcinogenesis via retinoblastoma pathway

AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb) tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences. METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour. RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional) decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections) to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections. CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis. It may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.     

大肠癌及大肠息肉中端粒酶、PTEN的表达及意义

目的探讨端粒酶和PTEN在大肠癌及大肠息肉中的表达与病理特征的关系及临床意义。 方法应用免疫组织化学(S-P)法检测68例大肠息肉、25例息肉旁正常组织、15例结直肠癌癌灶组织、9例癌旁组织中端粒酶和PTEN蛋白的表达。 结果端粒酶在大肠癌组织中的阳性率(80.00%)显著高于癌旁组织(22.22%)、大肠息肉组织(19.12%)和息肉旁组织(0.00%)。PTEN在大肠癌组织中的阳性率(20.00%)显著低于癌旁组织(77.78%)、大肠息肉组织(54.41%)和正常大肠黏膜组织(80.00%)。在大肠癌及大肠息肉中,端粒酶和PTEN均成负相关(r＝－0.516;r＝－0.261)。端粒酶与息肉大小(r＝0.262)关系密切。端粒酶和PTEN的表达与大肠癌是否有淋巴结转移关系密切(r＝0.560;r＝－0.707)。 结论PTEN在大肠癌中的表达缺失,在腺瘤性息肉表现出缺失倾向,端粒酶和PTEN在大肠癌、大肠息肉中的表达呈负相关。两者的变化可能与结直肠肿瘤的恶性程度和疾病进展有关系。     

Epstein-Barr virus-associated gastric carcinoma： Evidence of age-dependence among a Mexican population

AIM: To investigate features of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) among a Mexican population. METHODS: Cases of primary gastric adenocarcinoma were retrieved from the files of the Departments of Pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutricion in Mexico City. The anatomic site of the gastric neoplasia was identified, and carcinomas were histologically classified as intestinal and diffuse types and subclassified as proposed by the Japanese Research Society for Gastric Cancer. EBV-encoded small non-polyadenylated RNA-1 (EBER-1) in situ hybridization was conducted to determine the presence of EBV in neoplastic cells. RESULTS: We studied 330 consecutive, non-selected, primary gastric carcinomas. Among these, there were 173 male and 157 female patients (male/female ratio 1.1/1). EBER-1 was detected in 24 (7.3%) cases (male/female ratio: 1.2/1). The mean age for the entire group was 58.1 years (range: 20-88 years), whereas the mean age for patients harboring EBER-1-positive gastric carcinomas was 65.3 years (range: 50-84 years). Age and histological type showed statistically significant differences, when EBER-1-positive and -negative gastric carcinomas were compared. EBER-1 was detected in hyperplastic- and dysplastic-gastric mucosa surrounding two EBER-1-negative carcinomas, respectively. CONCLUSION: Among Latin-American countries, Mexico has the lowest frequency of EBVaGC. Indeed, the Mexican population >50 years of age was selectively affected. Ethnic variations are responsible for the epidemiologic behavior of EBVaGC among the worldwide population.     

Spiral CT in gastric carcinoma： Comparison with barium study, fiberoptic gastroscopy and histopathology

AIM: To evaluate spiral computed tomography (CT) including virtual gastroscopy for diagnosis of gastric carcinoma in comparison with upper gastrointestinal series (UGI), fiberoptic gastroscopy (FG) and histopathology. METHODS: Sixty patients with histologically proven gastric carcinoma (54 advanced and 6 early) were included in this study. The results of spiral CT were compared with those of UGI and FG. Two observers blindly evaluated images of spiral CT and UGI and video recording of FG with consensus in terms of diagnostic confidence with a five-point scale. Sensitivities of lesion detection, Borrmann‘‘s classification of spiral CT, UGI and FG, as well as the accuracy of TNM staging of spiral CT were determined by comparing them to surgical and histological findings. RESULTS: The lesion detection rate was 98 % (5g/60), 95 % (57/60) and 98 % (59/60) for spiral CT, UGI and FG, respectively. There were no statistical differences in the detection sensitivity among the three techniques (P>0.05).For the sensitivity in Borrmann‘‘s classification, spiral CT was higher than that of UGI (P=0.025) and similar to that of FG (P>0.05). The accuracy of spiral CT in staging the gastric carcinoma was 76.7 %. Six cases of early gastric carcinoma were all detected by spiral CT as well as FG. CONCLUSION: Spiral CT is equivalent to UGI and FG in the detection of gastric carcinoma, and superior to UGI but similar to FG in the Borrmann‘‘s classification of advanced gastric carcinoma. Spiral CT is more valuable than FG in the staging of gastric carcinoma.     

-765G＞C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

INTRODUCTION Gastric adenocarcinoma mortality rates have been decreasing in Europe[1], although, in Portugal it still remains one of the leading causes of cancer-related deaths (third in men and fourth in women). Portugal has one of the highest mortality …     

Clinicopathologic characteristics of gastric carcinoma in elderly patients： A comparison with young patients

AIM: To examine the clinicopathologic features of elderly patients with gastric carcinoma and to investigate the relationship between prognosis and age. METHODS: We reviewed the hospital records of 2 014 patients with gastric carcinoma retrospectively to compare the clinicopathologic findings in elderly (age＞70 years) and young (age＜36 years) patients during the period from 1986 to 2000 in a tertiary referral center in Gwangju, Korea. Overall survival was the main outcome measure. RESULTS: Of the 2 014 patients, 194 (9.6%) were in the elderly group and 137 (6.8%) were in the young group. The elderly and young patients had similar distributions with respect to depth of invasion, nodal involvement, hepatic metastasis, peritoneal dissemination, tumor stage at the initial diagnosis, and type of surgery. Synchronous multiple carcinomas were found in 14/194 (7.2%) of the elderly group and 4/137 (2.9%) of the young group (P＜0.05). Using the Borrmann classification, type Ⅳ was more frequent in the young patients than in the elderly patients (P＜0.05). Significantly more elderly patients had a well or moderately differentiated histology, and more young patients had a poorly differentiated histology and signet ring cell carcinoma (P＜0.001). The 5-year survival rates of elderly and young patients did not differ statistically (52.8% vs 46.5%, P=0.5290). Multivariate analysis showed that the histologic type, nodal involvement and operative curability were significant prognostic factors, and age itself was not an independent prognostic factor of survival for elderly gastric carcinoma patients. CONCLUSION: Elderly patients with gastric carcinoma do not have a worse prognosis than young patients. The important prognostic factor is whether the patients undergo a curative resection.     

High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma.

The natural history of gastric epithelial dysplasia and its relation to gastric cancer are ill defined. A consecutive series of 40 patients with an initial diagnosis of gastric epithelial dysplasia based on examination of endoscopic biopsies has been reviewed to determine the clinical outcome and to evaluate a two tier histological grading system as a predictor of the risk of cancer. On review, only 20 of the 40 patients were considered to have true dysplasia: seven patients had low grade dysplasia and 13 had high grade dysplasia. Of the 13 patients with high grade dysplasia, 11 (85%) were found to have gastric cancer within 15 months. Of the 10 patients with high grade dysplasia who underwent gastrectomy, six were found to have early gastric cancer, three had cancer invading into the muscularis propria, and none had lymph node metastases. High grade dysplasia is thus a marker of gastric cancer. Moreover, the cancers associated with high grade dysplasia are usually pathologically favourable and curable. The finding, by an experienced pathologist, of high grade dysplasia in two separate sets of endoscopic biopsies is therefore an indication for radical surgical treatment, provided that the patient's age and general condition permit such an approach.     

CDw75 is a significant histopathological marker for gastric carcinoma

AIM: To study the expression of CDw75 in patients with gastric carcinoma and to correlate CDw75 expression with progression of the tumor. METHODS: Immunohistochemical method was used to examine the expression of CDw75 in 72 cases of the gastric carcinoma and adjacent normal gastric mucosa, and the percentage of the cells positively stained with CDw75 was calculated using a computer-aided microscopic image analysis system. RESULTS: CDw75 was not expressed in normal gastric mucosa but detected in 37 of the 72 neoplastic gastric lesions. The expression of CDw75 was associated with the tumor progression as indicated by its close correlation with the depth of the tumor infiltration (chi(2)=18.415, P<0.01), TNM stage (chi(2)=10.419, P<0.05) and lymph node metastasis (chi(2)=6.675, P<0.01). The overall survival rate of the patients with positive CDw75 expression (32.4%) was significantly lower than that of the patients without CDw75 expression (71.4%) (P<0.01). There was no significant correlation between the expression of CDw75 and the sex and age and histological type of patients (P>0.05). CONCLUSION: These findings suggest that the expression of CDw75 is a significant histopathological marker for more advanced stage of gastric carcinoma and indicates a poor prognosis for the patients.     

Maspin expression and its clinicopathological significance in tumorigenesis and progression of gastric cancer

AIM:To investigate maspin expression in tumorigenesis and progression of gastric cancer and to explore its relevant molecular mechanisms.METHODS:Formalin-fixed and paraffin-embedded tissues from normal mucosa (n=182), dysplasia (n=69), cancer (n=l13) of the stomach were studied for maspin expression by immunohistochemistry. Microvessel density (MVD) in gastric cancer was labeled using anti-CD34 antibody. Maspin expression was compared with clinical parameters and MVD of tumors. Caspase-3 expression was also detected in gastric carcinoma by immunohistochemistry. The relationship between Caspase-3 and maspin expression was concerned as well.RESULTS:The positive rates of maspin expression were 79.8% (145/182), 75.4%(52/69) and 50.4%(57/113) in normal mucosa, dysplasia and cancer of the stomach,respectively.Cancer less frequently expressed maspin than normal mucosa and dysplasia (P&lt;0.05).Maspin expression showed a significantly negative association with invasive depth, metastasis, Lauren‘s and Nakamura‘s classification (P&lt;0.05),but not with tumor size, Borrmann‘s classification,growth pattern or TNIVl staging (P&gt;0.05). The positive rate of Caspase-3 was significantly lower in gastric cancer than in normal gastric mucosa (P&lt;0.05,32.7% vs 50.4%). It was noteworthy that maspin expression was negatively correlated with MVD, but positively correlated with expression of Caspase-3 in gastric cancer (P&lt;0.05).CONCLUSION:Down-regulated maspin expression is a late molecular event in gastric carcinogenesis. Reduced expression of maspin contributes to progression of gastric cancer probably by inhibiting cell adhesion, enhandng cell mobility,decreasing cell apoptosis and facilitating angiogenesis.Additionally altered expression of maspin underlies the molecular mechanism of differentiation of gastric cancer and supports the different histogenetic pathways of intestinal and diffuse gastric cancers. Maspin expression can be considered as an effective and objective marker to reveal biological behaviors of gastric cancer.     

抑癌基因PTEN在胃癌中的表达及临床意义

目的探讨胃癌组织中PTEN基因表达与胃癌临床病理的关系及其对预后的判断价值。方法应用免疫组化SP技术和图像分析技术,研究PTEN在胃癌和正常胃黏膜组织中的表达情况及阳性表达面积、强阳性表达面积,分析与病理参数的关系,并采用Kaplan-Meier生存曲线分析不同表达水平对术后生存率的影响。结果发现胃癌组织PTEN表达阳性率、阳性面积、强阳性面积均明显低于正常胃黏膜组织（P〈0.01）。胃癌组织PTEN表达与胃癌组织分化程度、浸润深度、淋巴转移、肿瘤分期明显相关,术后3、5 a生存率低表达者明显低于高表达者（P均〈0.05）。结论PTEN基因表达低下或丢失与胃癌发生、浸润、转移有关,可作为预测术后生存率的指标。     

p73、PTEN 在胃癌中的表达

目的 检测肿瘤相关基因p73、肿瘤抑制基因PTEN（phosphatase and tensin homolog deleted on chromosometen）在胃癌组织中的表达，并研究其临床病理意义。方法 采用逆转录聚合酶链式反应（RT-PCR）法检测p73、PTEN在40例胃癌中的表达。结果 ①PTNM（pathological tumor-node-metastasis）分期Ⅰ、Ⅱ期胃癌与对照组正常胃黏膜组织间p73、PTEN的表达均有非常显著性差异（P〈0．01）；PTNM分期Ⅲ、Ⅳ期和Ⅰ、Ⅱ期胃癌p73、PTEN的表达均有非常显著性差异（P〈0．05）；②p73在高、中分化胃腺癌组与低分化腺癌组阳性率表达无显著性差异（P〉0．05）；而PTEN在高、中分化腺癌和低分化腺癌阳性率表达差异具有显著性（P〈0．05）。③p73、PTEN在有淋巴结转移组和无淋巴结转移组检出阳性率差异具有显著性（P〈0．05）。结论 p73、PTEN的表达与胃癌临床病理特征和生物学行为存在密切关系，p73、PTEN基因是胃癌细胞增生活跃的重要影响因素。     

Soluble E-cadherin is a valid prognostic marker in gastric carcinoma

BACKGROUND: Gastric cancer remains a major cause of cancer mortality globally but no good prognostic tumour marker is available. Soluble fragment of E-cadherin protein has been reported to increase in the sera of patients with cancer and recently was found to be elevated in 67% of patients with gastric cancer. AIMS: To investigate if serum soluble E-cadherin is a valid prognostic marker in gastric cancer. METHODS: Concentrations of soluble E-cadherin from 116 patients with histologically confirmed gastric adenocarcinoma and 40 healthy subjects were measured using an immunoenzymometric method with a commercially available sandwich ELISA kit based on monoclonal antibodies. RESULTS: The logarithm of the means of soluble E-cadherin concentration was significantly higher in patients with gastric cancers (mean 3.85 (SD 0.28)) than in healthy subjects (3.71 (0.18)) (p=0.001), and in palliative/conservatively treated cancers (3.91 (0.35)) than in operable cancers (3.78 (0.19)) (p=0.015). The logarithm of the concentrations correlated with tumour size (p=0.032) and carcinoembryonic antigen concentrations (p=0.001). The cut off value calculated from discriminant analysis on operability and inoperability/palliative treatment was 7025 ng/ml. Soluble E-cadherin concentrations higher than this cut off value predicted tumour (T4) depth invasion (p=0.020, confidence interval (CI) 1.008-1.668) and palliative/conservative treatment (p=0.023, CI 1.038-2.514). In contrast, the relative risks for lymph node (N2) metastasis, distant metastasis, and stage III/IV disease were 1.41, 1.33, and 1.55 respectively, despite not reaching statistical significance. CONCLUSION: Serum soluble E-cadherin is a potential valid prognostic marker for gastric cancer. A high concentration predicts palliative/conservative treatment and T4 invasion.