Clinical impact of micrometastasis of the lymph node in gastric cancer

Micrometastasis in regional lymph nodes has been observed immunohistochemically, but the biological and clinical roles of minute nodal invasion of carcinoma in gastric cancer remain unclear. We used the anti-cytokeratin (AE1/AE3) antibody to immunohistochemically detect nodal micrometastatic lesions that could not be identified by routine pathological examination. A total of 4203 lymph nodes were examined in 180 gastric cancer patients. Lymph node metastasis was found in 36 of the 180 patients by routine pathological evaluation. Immunohistochemically micrometastasis was detected in the lymph nodes of 19 node-negative patients. Micrometastasis was not detected in any of the mucosal gastric cancer patients who underwent lymph node dissection. Gastric cancer patients with more than six metastatic lymph nodes all had nodal micrometastasis. Patients with micrometastasis had a significantly poorer survival rate than those without micrometastasis (P < 0.05). Based on the present results the presence of lymph node micrometastasis may provide a more accurate indication for surgical outcome in gastric cancer patients at the same clinical stage.     

胃黏膜下层癌淋巴结转移临床病理因素分析

【摘要】 目的 研究胃黏膜下层癌淋巴结转移率及其影响因素。 方法 回顾性分析南京医科大学第一附属医院1998年1月至2007年12月手术证实的181例胃黏膜下层癌的临床病理资料,对病人年龄、性别、肿瘤组织学类型、形态学类型、大小、部位、浸润深度、脉管内癌栓等与淋巴结转移的关系进行单因素与多因素分析。 结果 胃黏膜下层癌淋巴结转移率为20.44%。影响胃黏膜下层癌淋巴结转移的因素主要有肿瘤组织学类型（分化型 vs 分化不良型,P =0.0352）、直径大小（＜2cm vs ≥2cm,P =0.0143）、部位（近端胃vs胃体vs远端胃,P =0.0254）及脉管内癌栓（无vs有,P =0.0323）。Logistic回归分析显示肿瘤组织学类型与大小为胃黏膜下层癌淋巴结转移的独立性危险因素。结论 胃黏膜下层癌淋巴结转移与肿瘤组织学类型、大小、部位及脉管内癌栓等因素有关。临床上应参考上述临床病理因素判断淋巴结转移风险,制定合适的治疗方案。     

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??Clinicopathological Characteristics Associated with Lymph Node Metastasis in Early Gastric Cancer with Submucosal Invasion SHEN Li-zong, HUANG Yi-ming, SUN Mao-cai, et al. Department of General Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China Corresponind author: SHEN Li-zong, E-mail: shenlz@163.com Abstract Objective To investigate the clinicopathological characteristics of early gastric cancer with submucoal invasion associated with lymph node metastasis. Methods The data from 181 patients surgically treated for early gastric cancer with submucosal invasion between 1998 and 2007 were reviewed retrospectively. The clinicopathological variables associated with lymph node metastasis were evaluated. Results Lymph node metastasis was observed in 20.44% of patients. The histological classification, tumor size, location in the stomach and presence of vascular or lymphatic invasion showed a positive correlation with the rate of lymph node metastasis by univariate analysis. Multivariate analyses revealed histological classification and tumor size to be significantly and independently related to lymph node metastasis. Conclusion Histological classification, tumor size, location in the stomach and presence of vascular or lymphatic invasion are risk factors for lymph node metastasis in early gastric cancer with submucoal invasion. Minimal invasive treatment, such as endoscopic submucosal dissection, may be possible in highly selective cancers.     

Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma

BACKGROUND: The aims of this study were to assess the incidence of micrometastases of lymph nodes in patients with early gastric cancer invading the submucosal layer and to investigate the correlation between nodal micrometastases and malignancy potential to determine whether micrometastases of lymph nodes have prognostic significance, by use of an anticytokeratin immunohistochemical technique. METHODS: A total of 2272 lymph nodes taken from 88 patients (25.8 per case) were assessed by immunohistochemical technique by use of monoclonal anti-human cytokeratin 8 antibodies. Clinicopathologic parameters and prognosis were compared between patients with and without micrometastases. RESULTS: The incidence of nodal involvement by tumor cells in 88 patients with submucosal gastric cancer increased from 19.3% (17 patients) by hematoxylin-eosin (H&E) staining to 31.8% (28 patients) by cytokeratin immunostaining. The rate of positive node in this study increased from 1.0% (23 of 2272 nodes) by H&E staining to 2.5% (57 of 2272 nodes) by immunostaining (P = .0002). No correlation was observed between the incidence of lymph node micrometastases and various clinicopathologic parameters, including tumor site and size, histological differentiation, Lauren classification, gross tumor type, vascular and lymphatic invasion, and perineural invasion. There was no difference in disease-free survival, estimated by the Kaplan-Meier life-table method, between the micrometastasis-negative and -positive groups (95% and 92.9%, respectively). Multivariate analyses showed that tumor size and diffuse subtype by the Lauren classification were significant factors for survival time (P = .0042 and .014, respectively). CONCLUSIONS: Immunohistochemical staining with an anticytokeratin antibody seems to be of little prognostic value in patients with submucosal gastric carcinoma. Thus, this immunostaining technique does not offer a significant benefit of different strategies for additional therapy or follow-up over conventional pathologic staging with H&E staining.     

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors). SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma. METHODS: A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors. CONCLUSIONS: Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.     

Appropriate lymph node dissection for early gastric cancer based on lymph node metastases

BACKGROUND: Lymph node dissection in patients with early gastric cancer is controversial because lymph node metastases are much less common than in advanced cancer. Therefore, routine extensive lymph node dissection with wide resection of the stomach may be excessive, and an appropriate lymph node dissection procedure in patients with early gastric cancer should be established. METHODS: Retrospectively, 588 consecutive patients with early gastric cancer were analyzed by univariate and multivariate analysis to predict lymph node metastases with clinicopathologic variables. The sites and rates of lymph node metastases for each tumor location were mapped. RESULTS: In early gastric cancer, depth of invasion was an independent predictive factor of lymph node metastases. In cancer confined to the mucosa, however, tumor diameter was the only predictive factor. In contrast, tumor diameter, macroscopic appearance, and histologic type were not predictive factors in early gastric cancers invading the submucosa. In mucosal cancer, metastasis to lymph nodes was confined to the paragastric lymph nodes on the same side of the stomach as the tumor. In submucosal cancer, the incidence of lymph node metastasis was 2% to 17% in group 1 and 1% to 3% in group 2 lymph nodes. CONCLUSIONS: In mucosal cancer, lymph node dissection is unnecessary for tumors measuring less than 30 mm, and limited lymph node dissection with local gastrectomy is appropriate when tumor diameters are 30 mm or greater. In submucosal cancer, gastrectomy with dissection of group 1 and some group 2 lymph nodes should be sufficient to remove all nodal metastases.     

早期黏膜下胃癌微转移和微浸润的临床意义

目的 探讨临床早期黏膜下胃癌的淋巴结微转移和原发灶微浸润的临床意义。方法 对79例早期黏膜下胃癌患者手术切除的1945个淋巴结及68例肿瘤原发灶分别进行连续超薄切片,并应用抗细胞角蛋白(CK)单克隆抗体(CAM5．2)进行免疫组化检测并结合临床病理学指标及患者预后进行综合分析研究。结果 常规HE染色时,淋巴结转移率为13％(10／79),而CK染色为34％(27／79)。早期黏膜下胃癌的微转移发生率为25％(17／69)。68例早期黏膜下胃癌患者中,微浸润的发生率为16％(11,／68)。淋巴结微转移分别多发于肿瘤直径大于2cm(43％),凹陷型(48％),淋巴管侵犯(73％)和深度黏膜下侵犯(53％)的肿瘤。微浸润多发于低分化癌(33％)和深度黏膜下侵犯(31％)的肿瘤。5年生存率在没有微转移的患者为100％,有微转移的患者为82％,有微浸润的患者为73％。结论 CK免疫组化检查在诊断微转移和微浸润上明显优于常规HE检查。淋巴结的微转移和原发灶的微浸润明显影响黏膜下胃癌患者预后。     

Clinical significance of lymph node micrometastasis in gallbladder carcinoma

BACKGROUND: This retrospective study was intended to define the clinical significance of lymph node micrometastasis in gallbladder carcinoma. METHODS: A total of 1136 regional lymph nodes taken from 63 consecutive patients undergoing radical resection were examined histologically. Micrometastasis was defined as a metastasis missed on routine histologic examination with hematoxylin-and-eosin but detected by immunohistochemical examination with an antibody against cytokeratins 8 and 18. RESULTS: None of 9 patients (0%) with pT1 disease and 19 of 54 patients (35%) with pT2-4 disease had nodal micrometastases. Univariate analysis identified nodal micrometastasis, type of radical resection, M classification, pT classification, perineural invasion, pTNM stage, timing of radical resection, lymphatic vessel invasion, and pN classification as significant variables. Multivariate analysis revealed that nodal micrometastasis (P =.0003) and type of radical resection (P=.0044) were independent prognostic factors. Nodal micrometastasis affected survival adversely, despite the absence (P=.0002) or presence (P <.0001) of overt nodal metastasis. Nodal micrometastasis correlated significantly with invasive characteristics: lymphatic vessel invasion, perineural invasion, and distant metastasis. CONCLUSIONS: Lymph node micrometastasis is the strongest independent predictor of worse survival regardless of the overt nodal status and may indicate aggressive tumor biology among patients undergoing curative resection for gallbladder carcinoma.     

Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer

BACKGROUND: It is important to clarify the clinicopathologic characteristics of micrometastasis in lymph nodes and microinvasion in primary lesions for the treatment options with regard to submucosal gastric cancer. METHODS: We examined 1945 lymph nodes and 68 primary tumors resected from 79 patients with submucosal gastric cancer. Two consecutive sections were prepared for simultaneous staining with ordinary hematoxylin and eosin and immunostaining with anticytokeratin antibody (CAM 5.2), respectively. RESULTS: The incidence of nodal involvement in 79 patients with submucosal gastric cancer increased from 13% (10/79 patients) by hematoxylin and eosin staining to 34% (27/79 patients) by cytokeratin immunostaining. Micrometastases in the lymph nodes were found in 17 of 69 patients (25%), with cancer-free nodes examined by hematoxylin and eosin. Microinvasion to the muscularis propria was found in 11 of 68 patients (16%) who were histologically diagnosed with submucosal gastric cancer. Survival analysis demonstrated a lesser 5-year survival in the patients with micrometastasis in lymph nodes (82%) and with microinvasion to muscularis propria (73%). A high incidence of nodal involvement was found in submucosal cancers of large size (> 2 cm; 43%), a depressed type (48%), lymphatic invasion (73%), and deeper submucosal invasion (submucosal 3, 53%). A higher incidence of microinvasion was found with the diffuse-type carcinoma (33%). CONCLUSIONS: Cytokeratin immunostaining is useful for detecting micrometastasis and microinvasion in submucosal gastric cancer. Tumor size, macroscopic type, lymphatic invasion, and the depth of submucosal invasion are strongly associated with lymph node involvement.     

Lymph Node Status in Patients with Submucosal Gastric Cancer

Background The aim of this study was to clarify the lymph node status in patients with submucosal gastric cancer.Methods Between April 1994 and December 1999, 615 patients with histologically proven submucosal gastric cancer who underwent curative resection were included in this study. The results of the surgery and predictive factors for lymph node metastasis were evaluated by univariate and multivariate analyses. The accuracy of the predictive factors was assessed in a second population of a further 186 patients.Results Lymph node metastasis was observed in 119 patients (19.3%). Multivariate analysis showed that pathologic tumor diameter (≥20 mm) and lymphatic invasion were independent predictive factors for lymph node metastasis. The incidence of lymph node metastasis without these 2 predictive factors was 1.8% (2 of 113), and it was 51.2% (85 of 166) with the 2 predictive factors, 9.5% (14 of 148) in tumors <20 mm in diameter, and 5.3% (22 of 414) in tumors without lymphatic invasion. Among patients with a tumor <20 mm in diameter, the incidence of lymph node metastasis was significantly reduced in those with a differentiated tumor: 4.2% (4 of 95). These results were almost identical to those observed in the second population.Conclusions Lymph node status can be accurately predicted on the basis of pathologic tumor diameter <20 mm, lymphatic invasion (absence), and histological type (differentiated) in patients with submucosal gastric cancer. Less extensive surgery for these patients might be reconsidered after confirmation of the reproducibility of the results of this study by an appropriately designed prospective clinical trial.     

进展期胃癌的淋巴结转移特点及其临床意义

目的探讨进展期胃癌的淋巴结转移特点及临床意义。方法对2002年4月至2003年7月期间进行胃癌根治淋巴结清扫手术的91例患者的手术切除标本进行解剖，收集切除的淋巴结，逐枚进行病理组织学和免疫组织化学检查，判断淋巴结是否转移并计算淋巴结转移率。分析淋巴结转移率与肿瘤大小、TNM分期、Borrmann分型、肿瘤部位和淋巴结清扫范围等方面的关系。结果91例胃癌患者中淋巴结转移阳性63例（69．2％）。共收获3149枚淋巴结，平均每例34．6枚。肿瘤直径小于3cm者淋巴结转移率较3cm以上者低（P〈0．05）。TNM分期中Ⅲa和Ⅳ期患者淋巴结转移率均为100％，其转移度在30．3％～58．4％之间，较Ⅰ、Ⅱ期者高（P〈0．001）；Borrmann分型中Ⅲ型病例的淋巴结转移率（79．6％）较其他型患者高，而Ⅳ型患者淋巴结转移度（35．3％）最高（P〈0．05）。施行D3淋巴结清扫手术患者的淋巴结转移率和转移度（88．2％、38．0％）均高于D1、D2术患者（P〈0．05）。17例（18．7％）患者常规病理检查发现有183枚淋巴结微转移，肿瘤各部位与淋巴结微转移的关系差异无统计学意义（P〉0．05）。近端胃癌淋巴结转移主要在第1、2、3、5、7、8、9、12、13和16组，以8组转移度为最高（68．1％）；中部胃癌淋巴结转移主要在第1、3、7、12、13和16组，其中最高转移度为第3组（47．6％）；远侧胃癌淋巴结转移主要见于1、2．3、5、6、12、13和16组，其中第16组转移度为最高（83．3％）。结论淋巴结转移率和转移度与胃癌的恶性程度密切相关，因此D3淋巴结清扫手术对某些进展期胃癌患者值得考虑使用。     

胃癌胰头后淋巴结清扫术指征的探讨

目的 分析胃癌患者胰头后淋巴结(第13组)微转移率及转移规律,探讨第13组淋巴结清扫术的指征.方法 通过实时定量免疫荧光PCR法(RQ-PCR)检测研究组44例行D2胃癌根治术+胰头后淋巴结清扫术的胃癌患者术中切除的第13组淋巴结中胃癌特异性标志物CK20 mRNA的表达情况,另选取49例同期行标准D2胃癌根治术的患者作为对照组,对比分析两组患者的生存情况.结果 研究组44例中共有11例发生第13组淋巴结微转移,微转移率为25%.微转移与患者年龄、性别、原发肿瘤部位、原发癌灶大小、Bormann分型、肿瘤浸润深度无关(P>0.05),但与原发肿瘤病理类型相关(P<0.01),黏液细胞癌、印戒细胞癌患者容易出现第13组淋巴结转移.6例肝十二指肠韧带淋巴结(第12组)和11例肠系膜上血管旁淋巴结(第14组)转移的患者中分别有2例(F=23.694,P<0.01)和4例(F=13.756,P<0.01)出现第13组淋巴结转移,与其他各组淋巴结相比差异有统计学意义.两组的中位随访时间分别为448 d和419 d,研究组中无1例出现术后第13组淋巴结转移所造成的梗阻性黄疸,对照组中发现1例,但两组患者肿瘤复发率之间相比差异无统计学意义(x2=0.426,P=0.514).结论 对于黏液细胞癌、印戒细胞癌患者,或术中发现第12组或第14组淋巴结肿大的患者,应该在标准D2根治术的基础上施行胰头后淋巴结清扫术.     

Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer

Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P<0.05, P<0.0001, and P<0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P<0.005 and P<0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P<0.0001 and P<0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM. Supported in Grant No. 17390373 part by grants-in-aid for scientific research from the Ministry of Education, Science, Sports and Culture, Japan. (Shoji Natsugoe, M.D., Ph.D.)     

胃癌组织中血管内皮生长因子C的表达与淋巴结微转移的关系

目的：检测胃癌患者血管内皮因子C（VEGF-C）蛋白及mRNA在胃癌组织中的表达情况,探讨其与胃癌淋巴结微转移的关系。方法应用免疫组织化学法及RT-PCR法检测80例胃癌组织、癌旁组织及正常组织中的VEGF-C蛋白及mRNA表达情况;免疫组化法检测淋巴结微转移情况,比较有无淋巴结微转移的VEGF-C蛋白和mRNA的表达差异,明确存在的关联性。结果VEGF-C蛋白及mRNA两者在胃癌组织中明显高于癌旁组织和正常组织（P＜0.05）。结论胃癌组织中的VEGF-C蛋白及mRNA与胃癌淋巴结微转移相关,基因检测优于蛋白,可作为评价胃癌患者是否存在淋巴结微转移的优选指标。     

Predictive factors for lymph node metastasis in early gastric cancer with submucosal invasion: analysis of a single institutional experience

OBJECTIVE: An accurate assessment of a potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the amount of invasive procedures used in cancer treatment is critical for improving the patient's quality of life. Therefore, this study analyzed the predictive risk factors for a lymph node metastasis in early gastric cancer with a submucosal invasion. METHODS: The data from 1043 patients surgically treated for early gastric cancer with submucosal invasion between 2002 and 2005 were reviewed retrospectively. The patients were divided into 3 layers according to their depth: SM1, SM2, and SM3. The clinicopathological variables predicting a lymph node metastasis were evaluated. RESULTS: A lymph node metastasis was observed in 19.4% of patients. The tumor size, histologic type, Lauren classification, tumor depth, and perineural invasion showed a positive correlation with the rate of lymph node metastasis and N category by univariate analysis. Multivariate analyses revealed the tumor size (>or=2 cm) and lymphatic involvement to be significantly and independently related to lymph node metastasis. The presence of lymphatic involvement was the strongest predictive factor for a lymph node metastasis, being observed in 43.8% of cases in which a lymph node metastasis had been revealed. No lymph node metastasis was observed in the 12 cases with no lymphatic involvement, SM1 invasion, and tumor size <1 cm. CONCLUSIONS: Lymphatic involvement and tumor size are independent risk factors for a lymph node metastasis in early gastric cancer with submucosal invasion. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible in highly selective submucosal cancers with no lymphatic involvement, SM1 invasion, and tumor size <1 cm.     

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with otherwise node-negative hilar cholangiocarcinoma

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has prognostic significance in patients with histologically node-negative (pN0) hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, no reports have addressed this issue with regard to hilar cholangiocarcinoma. METHODS: A total of 954 lymph nodes from surgical specimens of 45 patients with histologically node-negative hilar cholangiocarcinoma who underwent macroscopically curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were examined for relationships with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 11 (24.4%) of the 45 patients, being found in 13 (1.4%) of 954 lymph nodes examined. Of the 13 nodal micrometastases, 11 (84.6%) were found in the N2 regional lymph node group rather than N1. Clinicopathologic features showed no associations with lymph node micrometastases. Survival curves were essentially similar between patients with and without micrometastasis. In addition, the grade of micrometastasis showed no effect on survival. The Cox proportional hazard model identified microscopic venous invasion, microscopic resection margin status, and histologic differentiation as significant prognostic factors in patients with pN0 disease. CONCLUSIONS: Lymph node micrometastasis has no survival impact in patients with otherwise node-negative hilar cholangiocarcinoma. The authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostic evaluation.     

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.     

Impact of Lymph Node Micrometastasis in Patients with Pancreatic Head Cancer

Purpose The purpose of this study was to investigate the clinical significance of nodal micrometastasis in patients who underwent a curative operation for pancreatic cancer. Experimental Design Fifty-eight patients underwent a macroscopically curative resection with extended lymph node dissection for pancreatic cancer. The total number of resected lymph nodes was 1,058, and 944 histologically negative lymph nodes were subjected to immunohistochemical staining to detect occult micrometastases. Results Nodal micrometastases were detected immunohistochemically in 147 out of 944 resected histologically negative lymph nodes (15.6%). Forty-four of all 58 patients (75.9%) and 13 of the 23 histologically node-negative patients (56.5%) had nodal micrometastases. Nodal micrometastases existed in the N1 lymph node area most frequently, followed by the N2 and N3 lymph node areas. The distribution was similar to that of histologically metastatic lymph nodes. Ten out of 16 patients (62.5%) with histological N1, and 5 out of 16 patients (31.3%) with histological N2 had nodal micrometastases beyond the histological lymph node status. Three and 5-year survival rates of pN0 patients without lymph node nodal micrometastases were both 60.0%, while those with nodal micrometastases were 19.2% and 0%, respectively. There was statistically significant difference between the both groups (P = 0.041). Conclusions Nodal micrometastasis in pancreatic cancer existed in wider and more distant areas than histological lymph node status, and it was an unfavorable predictive factor, even in N0 patients.     

胃癌患者No.14v淋巴结转移或微转移与临床病理特征及预后关系研究

目的探讨胃癌患者No.14v淋巴结转移或微转移与临床病理特征及预后的关系。 方法回顾性分析2018年1月至2020年12月行胃癌D2+根治术（联合No.14v淋巴结清扫）的128例胃癌患者临床资料。数据应用软件SPSS 22.0进行处理,单因素分析等级计数资料行秩和检验,其他计数资料行χ²检验;多因素分析行Logistic回归分析;生存情况采用Kaplan-Meier法并行Log-Rank检验。P<0.05为差异有统计学意义。 结果128例胃癌患者中,病理学检查发现No.14v淋巴结转移者19例（14.8%）,No.14v淋巴结阴性者109例,免疫组织化学检查发现No.14v淋巴结微转移者5例（3.9%）,No.14v淋巴结的总转移率为18.8%。单、多因素分析结果显示,胃下部肿瘤、Borrmann分型Ⅲ-Ⅳ型、pN₃期、脉管浸润及No.6淋巴结转移是胃癌患者No.14v淋巴结转移或微转移的独立危险因素（P<0.05）。术后中位随访时间27个月,转移组与非转移组患者的累积总生存率（37.5% vs. 77.9%）及无病生存率（29.2% vs. 76.0%）比较,差异有统计学意义（Log-Rank χ²=16.142、28.691,P=0.000、0.000）。 结论胃癌患者No.14v淋巴结转移或微转移与胃下部肿瘤、Borrmann分型Ⅲ-Ⅳ型、pN₃期、脉管浸润、No.6淋巴结转移等临床病理特征密切相关,且伴有No.14v淋巴结转移或微转移的胃癌患者预后较差。     

Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer

Background There is no consensus as to the impact of lymph node micrometastasis on survival of patients with gastric cancer. The aim of this study was to clarify the prognostic significance of lymph node micrometastasis in patients with histologically node-negative gastric cancer Methods Lymph nodes (n=2039) from 64 patients with histologically node-negative gastric cancer (T2, T3) were evaluated for micrometastasis. Three serial 5-μm sections of the resected lymph nodes were prepared for immunohistochemical staining with the anti-cytokeratin antibody CAM 5.2. Results Micrometastasis was found in 73 of 2039 nodes (4%) and 20 of 64 patients (32%). The 5-year survival rate was significantly lower for patients with lymph node micrometastasis than for those without lymph node micrometastasis (66% vs. 95%,P<.01). The 5-year survival rate was significantly lower when there were four or more positive micrometastatic nodes (94% vs. 29%,P <.01) and when there were extragastric micrometastatic nodes (89% vs. 53%,P<.01). Conclusions Lymph node micrometastasis was associated with poor outcome in patients with histologically node-negative gastric cancer. The number and the level of lymph node micrometastases are useful prognostic markers for deciding treatment strategies for additional therapy and follow-up.