EGFR基因单核苷酸多态性与胃癌的相关性

目的探讨表皮生长因子受体（EGFR）rs 28384375C／T单核苷酸多态性在胃癌发生、发展中的作用。方法采用PCR．限制性片断长度多态性（PCR-RFLP）法对61例胃癌患者（胃癌组）和20例健康查体正常者（对照组）的EGFR基因单核苷酸多态性进行检测,并分析其与幽门螺杆菌（HP）感染的相关性。结果①EGFR位点：胃癌组EGFR基因型频率分别为C／T26．22％、T／T73．78％;对照组分别为C／T5．00％、T／T95．00％,两组均未发现C／C基因型;P=0．0316;②C、T等位基因频率：胃癌组分别为13．11％、86．89％,对照组分别为2．50％、97．50％,P=0．0443;③胃癌组两种基因型者HP感染检出率无统计学意义;④EGFRC／T多态性与胃癌淋巴结转移、远处转移、TNM分期和组织分化程度相关（P〈0．05）;与患者性别、年龄、胃癌发生部位、浸润深度、原发肿瘤侵犯范围和组织类型无相关性。结论EGFR单核苷酸多态性可促进胃癌的发生发展;与HP感染无明显相关性。     

Relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer

AIM: To elucidate the relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer. METHODS: Routine autopsy was carried out in the randomly selected 102 patients (among them 100 patients died of various diseases, and 2 patients died of non-diseased reasons), their superficial lymph nodes locating in bilateral necks (include supraclavicle), axilla, inguina, thorax, and abdomen were sampled. Haematoxylin-Eosin staining was performed on 10 % formalin-fixed and paraffin-embedded lymph node tissue sections (5 um). The histological patterns of the lymph sinuses containing blood were observed under light microscope. The expression of CD31, a marker for endothelial cell, was detected both in blood and non-blood containing lymph node sinuses with the method of immunohistochemistry. RESULTS: Among the 1 322 lymph nodes sampled from the autopsies of 100 diseased cases, lymph node sinuses containing blood were found in 809 lymph nodes sampled from 91 cases, but couldn't be seen in the lymph nodes sampled from the non-diseased cases. According to histology, we divided the blood containing lymph node sinuses into five categories: vascular-opening sinus, blood-deficient sinus, erythrophago-sinus, blood-abundant sinus, vascular-formative sinus. Immunohistochemical findings showed that the expression of CD31 was strongly positive in vascular-formative sinuses and some vascular-opening sinuses while it was faint in blood-deficient sinuses, erythrophago-sinuses and some vascular-opening sinuses. It was almost negative in blood-abundant sinus and non-blood containing sinus. CONCLUSION: In the state of disease, the phenomenon of blood present in the lymph sinus is not uncommon. Blood could possibly enter into the lymph sinuses through the lymphaticovenous communications between the veins and the sinuses in the node. Lymph circulation and the blood circulation could communicate with each other in the lymph node sinuses. The skipping and distal lymphatic metastasis of gastric cancer may have some connection with the blood containing lymph node sinuses.     

胃癌淋巴结转移规律及其清扫范围探讨

目的　探讨胃癌淋巴结转移规律及其清扫范围。方法　对188例接受手术治疗的胃癌患者,于术中用美蓝-胃癌单克隆抗体(MAb)3H11标记淋巴结,并对染色淋巴结进行清扫,术后统计切除标本的淋巴结转移情况及病理特征。结果 188例胃癌患者的淋巴结转移率为62.8％(118／188)。胃上1／3(U区)、中1／3(M区)、下1／3(L区)及全胃癌患者的淋巴结转移率分别为61.9％、60.0％、57.5％及95.0％。早、中、晚期胃癌患者淋巴结转移率依次呈递增趋势,P<0.05。浸润型(Ⅲ、Ⅳ型)转移率(76.1％)明显高于局限型(Ⅰ、Ⅱ型)(44.3％),P<0.05。肿瘤直径≤4cm、-7cm和≥8cm者的淋巴结转移率依次增加,差异有显著性,P均<0.01。结论 胃癌淋巴结转移率较高。尤其晚期、浸润型及直径>4cm的胃癌,其淋巴结转移率更高,术中应按胃癌的临床病理分期、部位、大小及Borrman分型,选择淋巴结清扫范围。如果根据术中美蓝-MAb3H11标记结果确定淋巴清扫范围将更准确可靠。     

Clinical significance of lymph node metastasis in gastric cancer

Gastric cancer,one of the most common malignancies in the world,frequently reveals lymph node,peritoneum,and liver metastases.Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection,which results in poor prognosis.Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer.Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials,it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year followup study.Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide,but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis.It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer.Besides,the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer.     

单核苷酸多态性与血吸虫病相关性研究进展

单核苷酸多态性具有丰富的动态性和相对稳定的遗传性,近年来被认为是新一代遗传标志物,并可以通过探索表达基因与疾病之间的关系,在疾病存在的情况下寻找有关基因。国内外多项研究表明,血吸虫虫卵肉芽肿的形成与人类白细胞抗原（HLA）?Ⅱ类相关抗原有密切联系。通过检测基因各等位点,进而鉴定与血吸虫病易感性及与病程相关的基因或单倍型。对检测到的候选基因进行分析可为血吸虫病治疗和预防提供新的技术手段,有利于临床上评估易感性、进行早期诊断或预防性治疗。     

Association between neutrophil-lymphocyte ratio and lymph node metastasis in gastric cancer: A meta-analysis

Introduction and Aim:The prognostic role of neutrophil to lymphocyte ratio (NLR) has been explored extensively in the literature. The aim of this meta-analysis was to evaluate the link between NLR and lymph node metastasis in gastric cancer. A method for increasing specificity and sensitivity of pre-treatment staging has implications on treatment algorithms and survival.Search Strategy:The relevant databases were searched as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. After selection, 12 full text articles that met the inclusion criteria were included for quantitative analysis. 2 × 2 squares were generated using lymph node positive/negative, and NLR high/low data. The effect size for each study was calculated using the DerSimonian–Laird random effects model. P values were calculated using the chi-square method. Finally publication bias was evaluated. All statistics were calculated using R Studio.Results:Meta-analysis showed a 1.90 times (odds ratio, with 95% CI 1.52–2.38) increase in risk of positive lymph node status with high neutrophil to lymphocyte ratio. This has significant implications for cancer screening and staging, as NLR is a highly reproducible, cost-effective, and widely available prognostic factor for gastric cancer patients. Additionally, high or low NLR values may have implications for management pathways. Patients with lymph node metastasis can be offered neoadjuvant chemotherapy, avoiding salvage therapy in the form of adjuvant chemoradiotherapy, which is poorly tolerated.Conclusion:This meta-analysis shows an association between NLR and positive lymph node status in gastric cancer patients with implications for staging, as well as preoperative personalisation of therapy.     

Solitary lymph node metastasis of gastric cancer as a basis for sentinel lymph node biopsy

BACKGROUND/AIMS: In order to examine the biology of sentinel lymph node of stomach cancer, we investigated solitary lymph node metastases that were hypothesized to represent sentinel lymph node. METHODOLOGY: In the 4,620 primary gastric cancers between 1964 and 1997, 1271 cases with a localized tumor were selected and the localization of the solitary metastases in relation to the primary tumors were studied. RESULTS: Of the 130 tumors with a single basin metastasis, only 71% of the tumors in the upper third, 75% of the middle and 80% of the lower involved the node basins in the close vicinity. In the anterior wall and the greater curvature the rates of adjacent metastasis were more than 90%, while in the posterior wall and the lesser curvature they were 76% and 43%, respectively. Metastases of the remaining cases were found at more distant basins. CONCLUSIONS: In stomach cancer sensitivity of sentinel lymph node biopsy would be very low by the exploration of the adjacent basin especially for the lesions in the lesser curvature and posterior wall.     

Clinical characteristics of hepatoduodenal lymph node metastasis in gastric cancer

AIM: To assess the clinical features of hepatoduodenal lymph node(HDLN) metastasis and to clarify the optimal indication of HDLN dissection.METHODS: We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy,including HDLN dissection,for gastric cancer between 1999 and 2012. Of these,26 patients(9.4%) had HDLN metastasis. First,we investigated the clinicopathological characteristics,their perioperative clinical outcomes,such as postoperative complications,and prognostic outcomes between patients with and without HDLN metastasis. Second,we detected the prognostic factors,particularly in patients with HDLN metastasis. Third,we assessed the therapeutic value of HDLN dissection to determine its optimal indication.RESULTS: The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location(the middle or lower stomach [P = 0.005,OR = 5.88(95%CI: 1.61-38.1)] and p T category [T3 or T4,P = 0.017,OR = 4.45(95%CI: 1.28-21.3)] were independent risk factors for HDLNmetastasis. Cox proportional hazard analysis identified p N3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021,HR = 5.17(95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection,HDLN metastasis was a prognostic indicator in p N3 gastric cancer(P 0.0001),but not p N1-2(P = 0.602). Furthermore,the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0,respectively.CONCLUSION: We suggest that HDLN dissection should be indicated for p N1 or p N2 gastric cancers located at the middle or lower stomach.     

Prognosis of patients with gastric cancer and solitary lymph node metastasis

AIM:To investigate the relationship of solitary lymph node metastasis(SLNM)and age with patient survival in gastric cancer(GC).METHODS:The medical records databases of China’s Beijing Cancer Hospital at the Peking University School of Oncology and Shanghai Tenth People’s Hospital affiliated to Tongji University were searched retrospectively to identify patients with histologically proven GC and SLNM who underwent surgical resection between October 2003 and December 2012.Patients with distant metastasis or gastric stump carcinoma following resection for benign disease were excluded from the analysis.In total,936 patients with GC+SLNM were selected for analysis and the recorded parameters of clinicopathological disease and follow-up(range:13-2925 d)were collected.The Kaplan-Meier method was used to stratify patients by age(≤50 years-old,n=198;50-64 years-old,n=321;≥65 years-old,n=446)and by metastatic lymph node ratio[MLR<0.04(1/25),n=180;0.04-0.06(1/25-1/15),n=687;≥0.06(1/15),n=98]for 5-year survival analysis.The significance of intergroup differences between the survival curves was assessed by a log-rank test. RESULTS:The 5-year survival rate of the entire GC+SLNM patient population was 49.9%.Stratification analysis showed significant differences in survival time(post-operative days)according to age:≤50 yearsold:950.7±79.0 vs 50-64 years-old:1697.8±65.9 vs≥65 years-old:1996.2±57.6,all P<0.05.In addition,younger age(≤50 years-old)correlated significantly with mean survival time(r=0.367,P<0.001).Stratification analysis also indicated an inverse relationship between increasing MLR and shorter survival time:<0.04:52.8%and 0.04-0.06:51.1%vs≥0.06:40.5%,P<0.05.The patients with the shortest survival times and rates were younger and had a high MLR(≥0.06):≤50 years-old:496.4±133.0 and 0.0%vs 50-65 years-old:1180.9±201.8 and 21.4%vs≥65 years-old:1538.4±72.4 and 37.3%,all P<0.05.The same significant trend in shorter survival times and rates for younger patients was seen with     

胃癌组织中血管内皮生长因子C表达及与淋巴结转移关系

目的探讨胃癌组织中血管内皮生长因子C(VEGFC)的表达及与肿瘤淋巴结转移的关系。方法取30例胃癌患者手术切除的新鲜标本和距癌灶5cm以外的胃组织各1块,采用半定量RTPCR法和免疫组化染色法检测胃癌组织及癌旁正常组织的VEGFC表达,图像分析仪检测VEGFC的免疫组化阳性指数(positiveindex,PI)。结果胃癌细胞呈高水平表达VEGFC,癌旁正常组织则未见表达。在胃癌组织中,有淋巴结转移(PI=1.345±0.079)、淋巴管浸润(PI=1.315±0.037)患者的VEGFC表达水平分别较无转移(PI=1.156±0.045)及无浸润者(PI=1.154±0.043)增高(P<0.05)。高分化胃癌患者的VEGFCmRNA[VEGFC/βactin比值(Ar)=0.846±0.042]和VEGFC表达(PI=1.372±0.023)均分别高于中低分化胃癌者(Ar=0.663±0.007,P<0.01和PI=1.126±0.078,P<0.05)。结论VEGFC阳性表达的胃癌患者可能更易发生淋巴结转移。     

Identification of proteins associated with lymph node metastasis of gastric cancer

Purpose

The aim of this study was to identify proteins associated with gastric cancer lymph node metastasis and explore the clinicopathological significance of these proteins.

Methods

Gastric cancer tissues were obtained from 24 patients with high or low lymph node metastatic potential. Total cellular proteins were separated by two-dimensional gel electrophoresis (2-DE), analyzed by MALDI/TOF–TOF MS, and identified by a database search. Expression of 14-3-3β and profilin-1 was then immunohistochemically verified in paraffin-embedded gastric cancer tissues from 128 patients and analyzed by multivariate logistic regression models, Kaplan–Meier curves, and Cox proportional hazard models.

Results

A total of 26 differentially expressed proteins were identified, 20 of which were overexpressed and 6 of which were underexpressed. 14-3-3β and profilin-1 were upregulated in gastric cancer tissues with and without lymph node metastasis, respectively. Expression of 14-3-3β protein was associated, but profilin-1 expression was inversely associated with gastric cancer lymph node metastasis. Multivariate analysis showed that overexpression of 14-3-3β and reduced expression of profilin-1 were independent risk factors for gastric cancer lymph node metastasis, while 14-3-3β overexpression was an independent prognostic factor for gastric cancer patients.

Conclusions

The current study identified 26 differentially expressed proteins. Further studies showed that both 14-3-3β and profilin-1 protein may be useful biomarkers for prediction of gastric cancer lymph node metastasis and that expression of 14-3-3β was a prognostic marker for gastric cancer patients.     

The clinicopathological analysis of lymph node metastasis of gastric cancer]

One hundred-twenty-one cases of curative resection for gastric cancer with lymph node metastasis were analyzed to determine the prognostic value of the nodal stage (n), number of metastatic lymph nodes, maximum diameter of metastatic lymph nodes, micrometastasis of lymph nodes, histological type of lymph node metastasis, extranodular invasion and infiltration into lymphatic vessels around metastatic lymph nodes. In patients with a higher nodal stage the survival rate was lower and the nodal stage was a good prognostic indicator. Inpatients who had 7 or more metastatic lymph nodes or in whom the maximum diameter of the metastatic lymph nodes was over 15 mm or who had not only micrometastasis of lymph nodes, the survival rate was lower. These results suggest that quantitative analysis of metastatic lymph nodes is necessary. In patients who had nudifferentiated type metastatic lesions of lymph nodes, the survival rate was lower than in those with the differentiated type and the difference was larger than for the primary lesion. In patients who had extranodular invasion or infiltration into lymphatic vessels around metastatic lymph nodes, the survival rate was decreased. These results suggest that histopathological analysis of metastatic lymph nodes is necessary.     

胃癌淋巴结转移相关分子研究

淋巴结转移是评价胃癌预后及治疗策略的重要因素。然而,胃癌术前确诊是否存在淋巴结转移非常困难。为此,此文总结近年来国外相关文献,综述胃癌淋巴结转移相关分子学水平的研究,即阐述与胃癌淋巴结转移密切相关的蛋白分子,以探索胃癌淋巴结转移新的诊断方法,为临床胃癌治疗提供新的靶点。     

Indications for pylorus-preserving gastrectomy for gastric cancer based on lymph node metastasis

BACKGROUND/AIMS: It is necessary to study the relation between lymph node metastasis in the suprapyloric or lesser curvature regions and clinicopathologic findings in order to determine the indications for pylorus-preserving gastrectomy. METHODOLOGY: We reviewed all pertinent data from the cases of 109 patients with gastric cancer located mainly in the middle third of the stomach focusing particularly on status of lymph node metastasis and clinicopathologic findings. All patients had been treated by conventional gastrectomy with regional lymph node dissection (D2 or D3). RESULTS: Lymph node metastases were found in the lesser curvature or suprapyloric regions in 18 patients. Primary tumors were located in the lesser curvature side in 15 of these 18 patients and in the greater curvature side in only 3. Primary tumors in the greater curvature side with involvement in the lesser curvature or suprapyloric lymph nodes were greater than 4.0 cm in diameter, whereas primary tumors in the lesser curvature side with such metastasis were greater than 1.3 cm. CONCLUSIONS: Indications for pylorus-preserving gastrectomy with preserving of the pyloric branch of the vagal nerve perhaps can be expanded to middle stomach cancer located in the greater curvature side that is less than 4.0 cm in diameter.     

Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer

Background and Aims:  Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry.
Methods:  A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[–] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, β-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(−) groups.
Results:  Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and β-catenin was associated with the histopathological type of cancer, but not with LN status.
Conclusion:  Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.     

Solitary AFP- and PIVKA-II-producing hepatoid gastric cancer with giant lymph node metastasis

A 61-year-old man was admitted to our hospital because of abdominal pain and an abdominal mass. The patient had anemia and elevated serum alpha-fetoprotein (AFP) (9630ng/mL) and PIVKA-II (91mAU/mL) levels. Roentgenographic examination revealed an extra-gastric tumor in the upper abdomen, and gastroscopy revealed Bormann type 2 gastric cancer in the lower portion of the stomach. The preoperative diagnosis was synchronous gastric cancer and hepatocellular carcinoma (HCC), and surgery was performed. The extra-gastric tumor appeared to be an extra-hepatically growing HCC because the tumor was fed by vessels ramifying from the umbilical portion of the liver. Distal gastrectomy with resection of the extra-gastric tumor was performed, and histological examination of the resected specimen revealed that the gastric cancer was an AFP-producing hepatoid gastric adenocarcinoma and that the extra-gastric tumor was a lymph node metastasis. AFP-producing hepatoid gastric adenocarcinoma tends to metastasize to the regional lymph nodes and form a giant tumor. A giant tumor in the upper abdomen associated with gastric cancer may therefore be a clinical manifestation of AFP-producing hepatoid gastric adenocarcinoma.