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目的 探讨早期胃癌的淋巴结转移规律及其对预后的影响。方法 对161例有癌病人术后进行长期随访，对24例伴有淋巴结转移的早期胃癌与137例无淋巴结转移的早期胃癌的临床病理特征及3、5年生存率进行比较。结果 早期胃癌的淋巴结转移与肿瘤大小、浸润深度及淋巴、静脉侵犯有关，伴有淋巴结转移的早期胃癌3、5年生存率分别为82.8%和80.5%，明显低于无淋巴结转移者，后者分别为96.1%和92.4%。结论 术前或术中正确评估早期胃癌的淋巴结转移状态是选择合理的治疗方案和改善预后的重要条件。     

Lymph node metastasis in early gastric cancer

From 1969 through 1984, 304 case of early gastric cancer (EGC) were resected. Nodal status was studied in 272 cases in which lymph node dissection was performed. The lymph nodes were negative for metastasis in 90% of the cases. In 7%, metastasis was noted in the Group 1 lymph nodes alone and in 3%, as far as the Group 2 nodes. But in no case were the Group 3 involved. The 10-year survival rate was poorer in patients with positive nodes than in those with negative nodes (52.8% vs. 94.1%). Cancer recurred more often in patients who had no lymph node dissection than in those with node dissection (9.4% vs. 1.5%). Lymph node metastasis was more frequent in the following EGC types: macroscopically combined type, over 5 cm, and with submucosal invasion. Dissection as far as the Group 2 nodes should be routinely performed even in EGC, especially in cases with the above-mentioned characteristics.     

Lymph node metastasis of early gastric cancer and lymph node dissection

Five hundred and four cases of early gastric cancer and their status of lymph node metastases were analyzed. The patients were classified into 4 groups by age; Group A: Younger than 50 years, Group B: 50-59, Group C: 60-69 and Group D: Over 70 years. The tumors were divided into 2 histologic groups, differentiated type and undifferentiated type. The results are as follows. 1. The incidence of lymph node metastasis was 2.4% in mucosal cancer and 17.1% in submucosal cancer. 2. The incidence of lymph node metastasis in Group D was remarkably lower compared to that in other younger groups. 3. No lymph node metastasis was found in mucosal cancer of differentiated type. 4. Positive node was usually found in the regional nodes near the tumor and in the nodes adjacent to the left gastric artery. 5. Extended lymph node dissection is not necessary for the patient over 70 years and for mucosal cancer of differentiated type.     

淋巴结转移对无浆膜浸润胃癌患者预后的影响

目的 探讨淋巴结转移对无浆膜浸润胃癌预后的影响.方法 回顾性分析1994年1月至2005年12月间大连医科大学附属第一医院普通外科行D2或D2以上胃癌根治术、且具有完整随访资料的616例无浆膜浸润胃癌患者的临床资料;并选取同期接受相同术式的有浆膜浸润的162例胃癌患者为对照组.结果 无浆膜浸润胃癌患者的5年生存率为77.9％,明显高于浆膜浸润组的37.3％（P＜0.01）.不同浸润深度患者5年生存率分别为T１a（M）95.6％,T1b（SM） 92.5％,T2（MP）73.5％,T3（SS） 62.7％,T4（SE、SI） 37.3％.按日本第13版《胃癌处理规约》,N0、N1（第1站）、N2（第2站）和N3（第3站）无浆膜浸润胃癌患者的5年生存率分别为91.5％、75.3％、54.8％和14.7％,差异有统计学意义（P＜0.01）;按第7版TNM分期,N0、N1（1～2枚）、N2（3～6枚）、N3a（7～15枚）和N3b（15枚以上）无浆膜浸润胃癌患者的5年生存率分别为91.5％、83.6％、59.8％、17.2％和11.8％,差异亦有统计学意义（P＜0.01）.淋巴结转移是无浆膜浸润胃癌患者预后的独立预后因素（P＜0.0l）.结论 无论是按转移淋巴结的范围还是数量进行评价,淋巴结转移均能对无浆膜浸润胃癌患者的预后作出较好的预测.     

早期胃癌淋巴结转移的研究

目的研究早期胃癌（early gastric cancer，EGC）淋巴结转移的规律。方法回顾性分析2001年6月-2005年7月手术治疗101例EGC的临床病理资料。结果16例（16％）伴有淋巴结转移的EGC均为胃下部癌。黏膜下癌淋巴结转移率为28％，黏膜癌为7％（P〈0．05）。微小胃癌未见淋巴结转移，小胃癌淋巴结转移率为5％。直径1．1～2．0cm及〉2．0cm胃癌的淋巴结转移率分别为15％及28％（P〈0．05）。高分化EGC未见淋巴结转移，中分化及低分化的淋巴结转移率分别为17％及20％。黏膜癌仅累及N1淋巴结，而黏膜下癌则可转移至N2。结论EGC淋巴结转移主要与肿瘤浸润深度、病灶大小有关。应根据淋巴结转移的风险合理选择EGC术式。     

胃癌淋巴结微转移与E-钙黏附素表达的关系

目的检测E-钙黏附素(E-cadherin)在胃癌组织中的表达及探讨其与淋巴结微转移的关系.方法对30例胃癌共850枚淋巴结采用细胞角蛋白-20(Cytokerarin-20,CK-20)逆转录聚合酶链反应(RT-PCR)扩增检测微转移,采用免疫组织化学染色检测该30例胃癌组织中E-cadherin的表达情况.结果46.7%(14/30)的胃癌组织E-Cadherin表达阴性;E-Cadherin表达阴性与Lau-ren分型、淋巴结转移密切相关(P＜0.05),与分化程度及淋巴管侵犯明显相关(P＜0.001),但与性别、年龄、肿瘤位置、直径及浸润深度无关(P＞0.05).14例检测出淋巴结微转移的癌组织中10例(71.4%)E-Cadherin表达阴性,而16例未检测出淋巴结微转移的癌组织中仅有4例(25%)E-Cad-herin表达阴性,P=0.026.结论E-cadherin表达减弱或消失参与了胃癌淋巴结微转移的发生.     

Lymph node micrometastases do not predict relapse in stage II colon cancer

Background: Over one third of patients with stage II colonic adenocarcinoma experience tumor recurrence. Because effective adjuvant therapy is now available, it is important to identify subsets of patients at higher risk for relapse who may benefit from early treatment. Immunohistochemistry has been used to detect microscopic metastases in histologically uninvolved mesenteric lymph nodes, but the prognostic significance of minimal nodal involvement has not been established. Methods: Hematoxylin and eosin (H&E)-stained recuts of 900 mesenteric lymph nodes from 55 patients (range, 2–47; mean, 16.4 nodes per case) with resected pT3 or pT4, N0, M0 (TNM stage II) colonic adenocarcinomas were re-examined for the presence of metastases and then stained immunohistochemically for keratin using the AE1:AE3 antibody. Twenty-seven patients did not experience recurrence of tumor within 5 years following resection (no evidence of disease [NED]); 28 patients relapsed during the same time frame. Lymph nodes from 10 patients having colonic resections for nonneoplastic disorders also were stained as controls. Keratin-positive cells and cell clusters were quantified in the lymph nodes, and comparisons were made between patients with and without tumor relapse. Results: In the relapse group, four patients had positive nodes already identified on the H&E-stained recuts and had to be excluded from further analysis. Sixteen additional patients had keratin-positive cells; thus, 16 of 24 (67%) had micrometastases. In the NED group, one patient had a positive node on H&E staining and 22 additional patients had keratin-positive cells, so 22 of 26 (84%) patients had micrometastases. In the patients who had micrometastases, there was a mean of 3.5 and 4.6 positive nodes in the relapse and NED groups, respectively, and a mean of 11.3 and 12.4 keratin-positive cells or clusters in the relapse and NED groups, respectively. No keratin-positive cells were found in the 1 to 21 (mean, 9.1) nodes per case studied in the control patients. Conclusions: Micrometastases to histologically uninvolved mesenteric lymph nodes commonly are detected in patients with pT3 or pT4 colonic adenocarcinomas on recuts stained immunohistochemically for keratin. Nodal micrometastases detected by immunohistochemical staining are not useful for identifying stage II patients at higher risk for relapse. Presented at the annual meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.     

Sentinel node micrometastases have high proliferative potential in gastric cancer

BACKGROUND: The 6th edition of the TNM classification has recently defined "sentinel nodes (SN)," "micrometastasis," and "isolated tumor cells (ITC)." The present study examines the frequency and proliferative activity of such metastases with focus on the SNs of gastric cancer. METHODS: We enrolled 133 patients with cT1-2 tumors (cT1: 104, cT2: 29) and mapped SNs. Lymph node metastases were examined by routine histology and by immunohistochemistry with anti-cytokeratin. We used the Ki-67 antibody to detect the primary tumor and lymph node metastases to evaluate proliferative activity. RESULTS: The number of patients with SNs metastases and metastatic SNs was 19 and 52, respectively. The frequencies of macrometastasis, micrometastasis, and ITC were 48%, 25%, and 27%, respectively. Ki-67 expression in the tumor closely correlated with lymphatic invasion (P = 0.0001), venous invasion (P < 0.0001), and lymph node metastasis (P < 0.0001). Cells in 96% of macrometastases, 92% of micrometastases, and 29% of ITCs were Ki-67 positive. CONCLUSIONS: We showed that micrometastasis and some ITCs in SNs had proliferative activity. We suggest that micrometastasis and ITCs should be removed, especially during SN navigation surgery, until their clinical significance is clarified.     

淋巴结微转移及相关蛋白检测在大肠癌患者Dukes分期、治疗和预后中的意义

目的 探讨淋巴结微转移（LNMM）和nm23-H1、基质金属蛋白酶9（MMP9）、金属蛋白酶2组织抑制因子（TIMP2）蛋白检测及其相关性在大肠癌患者Dukes分期、治疗和预后中的意义。方法 应用免疫组化SABC法检测30例DukesB期大肠癌淋巴结细胞角蛋白20（CK20）和癌组织nm23-H1、MMP9、TIMP2蛋白表达,另对同期30例DukesC和D期大肠癌患者检测nm23-H1、MMP9和TIMP2;随访、记录患者的临床病理参数和生存资料,分析其相关性。结果 （1）26．7％DukesB期大肠癌患者、7．8％DukesB期大肠癌淋巴结存在CK20阳性。（2）DukesB期大肠癌nm23-H1、MMP9表达与DukesC和D期差异显著（P〈0．05）;nm23-H,表达下降和（或）MMP9表达增强与LNMM相关（P〈0．05）,两者预测大肠癌LNMM敏感性和特异性分别为62．5％和81．8％、75．0％和69．8％,联合检测特异性则达90．9％;而TIMP2与Dukes分期、LNMM无关。（3）DukesB期LNMM（＋）患者癌复发转移率明显高于同期LNMM（-）组（P〈0．05）,而生存率则降低（P〈0．05）;nm23-H1（-）LNMM（＋）、MMP9（＋）LNMM（＋）患者生存期明显短于nm23-H1（＋）LNMM（-）、MMPq（＋）LNMM（-）组（P〈0．05）。结论 CK20免疫组化可检出大肠癌LNMM;DukesB期大肠癌nm23-H1、MMP9表达与LNMM相关,且表达异常LNMM患者预后差;联合检测淋巴结CK20和癌组织rim23-H1、MMP9表达,对大肠癌Dukes分期、术后辅助化疗和预后判断有重要意义。     

Lymph node metastasis as a significant prognostic factor in early gastric cancer: Analysis of 1,136 early gastric cancers

Background: Gastric cancer is the most frquent cancer and the leading cause of death from cancer in Korea. Early gastric cancer has been defined as a gastric carcinoma confined to mucosa or submucosa, regardless of lymph node status, and has an excellent prognosis with a >90% 5-year survival rate. From 1974 to 1992, we encountered 7,606 cases of gastric cancer and performed 6,928 gastric resections. Among them, 1,136 cases were early gastric cancer (14.9% of all gastric cancer cases and 16.4% of resected gastric cancer cases). Methods: A retrospective analysis of 1,136 cases of early gastric cancer was performed to evaluate the prognostic significance of clinicopathologic features (sex, age, tumor location, gross type, histologic type, depth of invasion, status of lymph node metastasis, resection type). Lymph node metastasis was classified into three groups: N(n=0) for no lymph node metastasis; N(n=1–3) for one to three lymph node metastases; and N(n>3) for more than three lymph node metastases. All patients received radical total or subtotal gastrectomy with lymph node dissection. Results: In univariate and multivariate analysis of these nine factors, the only statistically significant prognostic factor was regional lymph node metastasis (p<0.001). The others had no statistically significant association with prognosis. Lymph node metastasis was present in 178 cases (15.7%). The factors associated with the lymph node metastasis were depth of invasion and gross type [protruding type (e.g., types I, IIa)]. One hundred twenty-five of these patients had one to three lymph node metastases, and 53 cases had more than three lymph node metastases. The difference in 5-year survival rates among these groups was statistically significant: 94.5% for N(n=0), 88.3% for N(n=1–3), and 77.3% for N(n>3). Conclusion: We propose that for early gastric cancer, lymph node dissection is necessary in addition to gastric resection, at least in patients with a high risk of lymph node metastasis.     

Lymph node metastasis from early gastric cancer: endoscopic resection of tumour.

The clinicopathological features of 748 solitary early gastric cancers were examined with regard to lymph node metastasis. Among several factors, only depth of invasion and tumour size correlated significantly with node involvement. Tumours which satisfy the following criteria may not metastasize to lymph nodes: (1) confined to the mucosa; (2) less than 1.5 cm in diameter; (3) macroscopically elevated; (4) macroscopically depressed, without intramural ulcers or ulcer scars (endoscopically, no fold convergence); and (5) histologically differentiated. With a recently developed endoscopic technique small gastric tumours can safely be resected. The cut margin and depth of tumour invasion can be verified histologically in the specimen. If an endoscopically removed tumour satisfies the above criteria, further surgical intervention may be optional as the outcome of endoscopic resection is comparable to that of radical surgery in the absence of node involvement.     

胃下部癌常规病理阴性第11P组淋巴结微转移的研究

目的 检测胃下部癌患者常规病理阴性第11P组淋巴结微转移的情况,分析淋巴结微转移与临床病理因素的关系.方法 应用连续切片法和端粒酶重复扩增-ELISA方法 检测43例胃下部癌常规病理阴性的43枚第11P组淋巴结,结合临床病理资料进行统计学分析. 结果 本组43例胃下部癌患者常规病理阴性第11P组淋巴结经连续切片法检出有4例4枚淋巴结发生微转移,微转移发生率为9%;应用端粒酶重复扩增-ELISA法检测微转移发生率为44%,其中包括应用连续切片法检测出有微转移的4枚淋巴结.端粒酶重复扩增-ELISA法微转移检出率明显高于连续切片法(x 2 =13.07,P<0.05).胃下部癌第11P组淋巴结微转移与原发肿瘤大小(x 2 =8.488,P<0.05)、浸润深度(x 2 =6.473,P<0.05)及临床分期(x 2 =12.022,P<0.05)有关,与患者年龄、性别、大体分型、组织分化程度尤关.结论 胃下部癌常规病理阴性第11P组淋巴结中存在较高的微转移发生率,其微转移发生率与原发肿瘤大小、浸润深度及临床分期有关.     

Angiogenic factors and their relation to stage, lymph-node micrometastases and prognosis in patients operated on for gastric cancer

The aim of the present study was to investigate the expression of a number of angiogenic factors such as VEGF, VEGF-C, TGF-alpha and apoptosis in an attempt to relate these biological markers to TNM staging, lymph-node status and prognosis. Angiogenic factors and apoptosis were studied immunohistochemically in 72 gastric cancer cases. The search for micrometastases was performed with an immunohistochemical technique in 20 NO cases. Apoptosis determination was assessed with the TUNEL assay. The chi2 test according to Pearson was used for statistical analysis. The apoptotic index was related to both stage and prognosis: high expression cases showed an earlier stage (p < 0.02) and a better prognosis (p < 0.05). The determination of high neovessel density was related to poorer 5-year survival (p < 0.05). Only the expression of VEGF-C correlated inversely with prognosis (p < 0.05). The presence of micrometastases was unrelated to any of the biological markers studied. Our results partly confirm those reported in the literature. The present study revealed a number of biological markers that may be helpful for identifying particular subgroups of patients. More investigation with similar techniques in large prospective series is needed as a support to clinical practice.     

胃癌淋巴结微转移的研究进展

早期胃癌患者的预后相对较好,然而仍有少数淋巴结转移阴性的早期胃癌患者死于术后肿瘤复发或远处转移,有学者提出淋巴结微转移是这类患者复发与转移的潜在原因。相比于宏观淋巴结转移,淋巴结微转移的检测更为困难,其对胃癌预后的临床意义仍存在争议。笔者就胃癌淋巴结微转移的研究进展作一综述。

     

中下段直肠癌预后与淋巴结微转移的关系

目的 观察淋巴结微转移对中下段直肠癌预后的影响.方法 应用CK-20免疫组织化学技术对56例中下段直肠癌患者共计661枚淋巴结检测微转移.结果 20例(35.7%)67枚(10.1%)淋巴结检出微转移.20例检出淋巴结微转移者中10例TNM分期提高:Ⅰ→ⅢA 3例,Ⅰ→ⅢC 2例,ⅡA→ⅢB 3例,ⅢA→ⅢC 2例.Kaplan-Meier生存分析显示,淋巴结微转移阳性患者半数生存期为(36.90±3.37)个月(95%置信区间:30.29～43.51个月),明显短于淋巴结微转移阴性者的(48.72±2.25)个月(95%置信区间:44.30～53.14个月),两者差异有统计学意义(P＜0.05).结论 中下段直肠癌淋巴结微转移检测有助于更准确地进行临床病理分期.淋巴结微转移阳性者预后较差.     

中下段直肠癌淋巴结微转移的临床研究

目的探讨淋巴结微转移与中下段直肠癌生物学行为的关系,以及淋巴结微转移对淋巴结分期的影响。方法应用CK-20免疫组化技术对56例中下段直肠癌共计661枚淋巴结微转移进行检测。结果20例(36%)67枚(10%)淋巴结检出微转移。肿瘤直径≥5 cm的中下段直肠癌淋巴结微转移检出率为61%(11/18),而肿瘤直径<5 cm的淋巴结微转移检出率仅为24%(9/38) (x~2=7.452,P=0.006)。高分化和中分化直肠癌淋巴结微转移检出率分别为1/5和24%(9/37),明显低于低分化直肠癌的71%(10/14)(x~2=10.406,P=0.005)。Ⅰ期、Ⅱ期和Ⅲ期中下段直肠癌淋巴结微转移检出率分别为0、23%(5/22)和52%(15/29)(x~2=7.361,P=0.022)。中下段直肠癌淋巴结微转移检出率与性别、年龄、肿瘤浸润肠壁周径、Ming分型以及浸润深度无关(x~2=1.701,P= 0.192;x~2=0.271,P=0.602;x~2=1.748,P=0.626;x~2=0.278,P=0.870;x~2=1.840,P=0.399)。20例检出淋巴结微转移者中10例TNM分期提高:Ⅰ→ⅢA 3例,Ⅰ→ⅢC 2例,ⅡA→ⅢB 3例,ⅢA→ⅢC 2例。结论CK免疫组化技术可以显著提高中下段直肠癌淋巴结转移的检出率,有助于更准确地进行临床病理分期。淋巴结微转移与肿瘤直径、肿瘤分化程度和分期密切相关。     

Lymph node micrometastases is a poor prognostic factor for patients in pN0 gastric cancer: a meta-analysis of observational studies

Background

There is no consensus as to the impact of lymph node micrometastases (LNMM) on survival of patients with gastric cancer. The aim of this analysis was to investigate the prognostic significance of LNMM in patients with histologic node-negative gastric cancer.

Methods

We searched relevant studies from PubMed, Embase, and the Cochrane Library (1966–2013.5), used software STATA 12.0 to pool the outcomes of each study. Mantel-Haenszel and Inverse Variance methods were used in a fixed effect model and a random effect model, respectively. The hazard ratios (HR) and odds risk (OR) at their 95% confidence intervals (CIs) were used as measures to investigate the prognostic importance of LNMM, by searching for a correlation between the clinical pathologic features and LNMM.

Results

Our analysis of 18 eligible studies revealed that patients with LNMM had an increased likelihood of having a worse 5-y survival rate (HR 2.81; 95% CI：1.96–4.02). Subgroup analyses showed a more significant result for patients in pT1-2N0 (HR 3.52; 95% CI 1.88–6.62). The analyses also revealed that (OR 1.32; 95% CI 1.17–1.48), lymphatic invasion (OR 2.21; 95% CI 1.42–3.44) and venous invasion (OR 1.41; 95% CI 1.08–1.85) were associated with the occurrence of LNMM.

Conclusions

There is a positive correlation between LNMM and an unfavorable surgical outcome in gastric cancer. Undifferentiated histologic findings, lymphatic invasion, and venous invasion are high risk factors for the occurrence of LNMM.     

远端胃癌患者肝动脉周围淋巴结微转移的研究

目的 探讨远端胃癌患者正常肝动脉及异常肝动脉周围淋巴结的微转移及清扫的必要性,为胃癌D2根治术中合理地选择淋巴清扫范围提供依据。方法 选择广西医科大学第一附属医院胃肠外科2008年6月至2010年6月间由同一手术者进行远端胃癌D2根治术的60例胃癌患者,对正常肝动脉及源自肠系膜上动脉异常肝动脉周围淋巴脂肪组织行重组人细胞角蛋白20(CK20)和CEA微转移免疫组化检查,从而判断正常及异常肝动脉周围是否有淋巴结转移的发生。结果 本组经CK20和CEA微转移免疫组化测定,正常肝动脉周围淋巴结转移率为27％,患者年龄、肿瘤大小、Borrmann分型、TNM分期均为转移的影响因素。存在源自肠系膜上动脉异常肝动脉的患者共7例,变异率为12％,其中走行于胰腺前方的1例,胰腺后方的6例,胰前、后型异常血管周围淋巴组织中未发现淋巴结转移。结论 CK20和CEA免疫组化检查是检测淋巴结微转移良好的指标;对于年龄≥60岁、肿瘤＞3 cm、BorrmannⅢ～Ⅳ型的远端胃癌患者,走行正常的肝动脉周围淋巴结转移率甚高,术者应重视对此处淋巴结的清扫;发自肠系膜上动脉的异常肝动脉周围淋巴结转移率则很低。