Pattern of Lymph Node Micrometastasis and Prognosis of Patients with Colorectal Cancer

Background: Studies of lymph node micrometastases in patients with colorectal cancer have ignored the prognostic significance of the number and level of lymph node micrometastases. The aim of this study was to clarify the prognostic significance of the status of lymph node micrometastases in histologically node-negative colorectal cancer.Methods: We used immunohistochemistry with anti-cytokeratin antibody CAM5.2 to examine 1013 lymph nodes in 42 patients (12 recurrent and 30 nonrecurrent) with histologically determined Dukes B colorectal cancer. Five serial 6-m sections were used for immunohistochemical staining. The frequency, tumor cell pattern, and number and level of lymph node micrometastases were compared between the recurrent and nonrecurrent groups.Results: Micrometastasis was confirmed in 16% (59/373) of lymph nodes in the recurrent group and 12% (77/640) of lymph nodes in the nonrecurrent group, and the frequency of lymph node micrometastases was 92% (11/12) in the recurrent group and 70% (21/30) in the nonrecurrent group. The tumor cell pattern in the metastatic lymph nodes was similar in the recurrent and nonrecurrent groups. Micrometastasis in four or more lymph nodes occurred more frequently in the recurrent group than in the nonrecurrent group (58% vs. 20%, P < .05), and micrometastasis to N2 or higher nodes occurred more frequently in the recurrent group than in the nonrecurrent group (92% vs. 47%, P < .01).Conclusions: The number and level of positive micrometastatic lymph nodes was significantly correlated with postoperative recurrence of histologically determined Dukes B colorectal cancer. This parameter is a useful prognostic indicator in histologically node-negative colorectal cancer and is helpful in planning adjuvant chemotherapy.     

结直肠癌患者淋巴结微转移与其免疫功能的关系

目的以细胞角蛋白20（CK20）mRNA为标志物检测结直肠癌患者淋巴结微转移情况,并探讨其与患者免疫功能的关系。方法对21例结直肠癌患者的281枚淋巴结,分别采用病理切片常规HE染色检测转移癌灶及逆转录聚合酶链反应（RT-PCR）法检测淋巴结CK20mRNA表达;采用流式细胞仪检测患者外周血CD4^＋、CD8^＋及NK细胞活性,ELISA法检测外周血IL-2、sIL-2R及IL-12水平。结果21例患者281枚淋巴结中,HE染色法检出有淋巴结转移者为2例16枚（5.7%,16/281）,RT-PCR法检出有淋巴结转移（CK20mRNA表达阳性）者10例140枚（49.8%,140/281）,2种方法在淋巴结转移检出率及检出阳性病例数方面差异均有统计学意义（P〈0.01）。11例淋巴结CK20mRNA表达阴性患者术前CD4^＋及NK细胞活性、CD4^＋/CD8^＋比值、IL-2及IL-12水平高于8例HE染色无法检出而CK20mRNA表达阳性（即存在微转移）患者（P〈0.05）,而前者术前CD8^＋细胞活性及sIL-2R水平低于后者（P〈0.05）;且CK20mRNA的表达与CD4^＋（r=-0.769）及NK（r=-0.532）细胞活性、CD4^＋/CD8^＋比值（r=-0.755）、IL-2（r=-0.834）及IL-12（r=-0.819）水平间均呈负相关（P〈0.05,P〈0.01）,与CD8^＋细胞活性（r=0.562）及sIL-2R水平（r=0.751）之间呈正相关（P〈0.01）。结论结直肠癌淋巴结微转移的发生与患者免疫功能低下关系密切。     

Distribution of Lymph Node Metastasis Including Micrometastasis in Gastric Cancer with Submucosal Invasion

Abstract The purpose of this retrospective study was to analyze the distribution of lymph node metastases, including micrometastases, according to the location of the gastric cancer with submucosal invasion. A total of 118 patients with submucosal gastric cancer were enrolled in this study. The distribution of lymph node metastases was examined according to tumor location. Immunohistochemical examination using anti-cytokeratin antibody was performed to examine nodal micrometastases in 118 patients. Lymph node metastasis was found in 19.5% (23/118) of the patients. Significant differences were found for tumor size and depth, lymphatic invasion, and venous invasion for patients with and without nodal metastasis. The distribution of lymph node metastasis for tumors at upper or middle portions of the stomach was mainly found along the left gastric artery. The distribution of lymph node metastasis for tumors in the lower and lesser curvature varied. Immunohistochemical analysis found that 15 of 23 patients with lymph node metastasis found by histologic examination had micrometastases. The presence of two or more lymph node micrometastases was found in these 15 patients, and they were distributed in another stations, including distant nodes. The incidence of micrometastasis was 24.2% (23/95) in pN0 patients. Lymph node micrometastases were confined to regional nodes near the primary tumor. When planning minimally invasive treatment for submucosal gastric cancer, it is important to understand the distribution of lymph node metastasis, including micrometastasis, according to tumor location.     

pT1～3N0期胃癌淋巴结微转移检测的临床意义

目的 研究淋巴结微转移及临床病理因素对pT1～3N0期胃癌患者术后5年无瘤生存率的影响.方法 纳入我院2000年1月至2004年12月期间pT1～3N0期胃癌患者行根治术者120例2 106枚淋巴结,每例患者淋巴结9～28枚,平均18枚,所有淋巴结经HE染色均为阴性.应用免疫组化染色法检测淋巴结中CK20表达,并分析胃癌患者的临床病理特征及胃癌淋巴结中CK20表达对5年无瘤生存率的影响.结果 经免疫组化染色,有9.07%(191/2 106)的淋巴结出现CK20阳性表达;有26.67%(32/120)患者的淋巴结中出现CK20阳性表达,其中11例(9.17%)为微转移,21例(17.50%)为孤立肿瘤细胞巢(ITC).术后随访24～121个月(平均66.35个月).淋巴结中CK20阴性表达、ITC和微转移的患者,5年无瘤生存率分别为87.4%、78.3%和40.9%.5年无瘤生存率在淋巴结CK20出现微转移者中明显低于CK20阴性表达者(P＝0.000)和以ITC为特征者(P＝0.046),而仅以ITC为特征者与CK20阴性表达者间比较,差异无统计学意义(P＝0.253).淋巴结中CK20阳性表达与胃癌患者的肿瘤直径(P＝0.011)、浸润胃壁深度(P＝0.043)和是否有淋巴管浸润(P＝0.002)有关.所有临床病理因素对5年无瘤生存率均无明显影响(P>0.05).11例胃癌患者被检测出微转移,应划分为pN1(Mi)期,本组重新分期率9.17%.而88例胃癌患者淋巴结CK20(-)和21例表达为ITC,分别被记为pN0(I-)和pN0(I+),不建议重新分期,仍为pN0期.结论 对于pT1～3N0期胃癌,若淋巴结中检测出微转移,其预后较差,术后5年无瘤生存率较低,建议术后应予以积极的辅助治疗.     

胃癌淋巴管生成、淋巴管浸润及淋巴结微转移的临床意义

目的探讨胃癌淋巴管生成、淋巴管浸润及淋巴结微转移的临床意义。方法免疫组化法检测68例胃癌原发灶中D2-40的表达及其中51例胃癌的791枚淋巴结中CK20和CKpan的表达，结合患者的l临床病理特征进行综合分析。结果胃癌HE染色淋巴管浸润（LVI-HE）和D240染色淋巴管浸润（LVI-IM）的阳性率分别为66．2％（45／68）和76．5％（52／68），差异无统计学意义（P=0．118）。LVI-IM阳性率与肿瘤浸润深度（P=0．044）、TNM分期（P=0．003）及存在淋巴结转移（P=0．000）有关。68例胃癌平均淋巴管密度（LVD）为（18．19&#177;7．44）个／HP.LVD升高与LVI-HE阳性（P=0．040）、LVI—IM阳性（P=0．001）、静脉浸润（P=0．037）、TNM分期较晚（P：0．020）及存在淋巴结转移（P=0．001）有关系。LVD值≥15个／HP者近期生存率较LVD值≤14个／HP者明显降低（P=0．032）。51例胃癌HE染色和CK（CK20或CKpan）染色检出淋巴结转移率分别为74．5％（38／51）和88．2％（45／51），791枚淋巴结的转移淋巴结检出率由HE染色的32．0％（253／791）提高到CK染色的41．5％（328／791），P〈0．001。CKpan的微转移检出率明显高于CK20（P=0．003）。微转移淋巴结数量与肿瘤大小（P=0．001）、LVIHE（P=0．040）、肿瘤浸润深度（P=0．018）及TNM分期（P=0．012）有关。微转移淋巴结的检出使淋巴结转移站别及TNM分期迁移：7例N0→N1，6例N1→N2，1例N2→N3；4例Ⅰb→Ⅱ，4例Ⅱ→Ⅲa，3例Ⅲa→Ⅲb，1例Ⅲb→Ⅳ。结论D2-40及CK检测在诊断淋巴管浸润和淋巴结微转移上优于HE检查。CK20和CKpan的联合检查有利于发现微转移淋巴结。肿瘤TNM分期越晚，越易发生淋巴结微转移。LVI-IM、LVD及淋巴结微转移三者都与胃癌淋巴结转移有关。LVD值较高者近期生存率较低。     

Revisiting the Concept of Lymph Node Metastases of Pancreatic Head Cancer: Number of Metastatic Lymph Nodes and Lymph Node Ratio According to N Stage

Background

Some suggest that metastatic lymph node ratio (LNR) may be prognostic of survival in patients with pancreatic cancer. However, this phenomenon was confused by inclusion of node-negative patients in the analysis. The present study was designed to evaluate the prognostic impact of metastatic LNR and the absolute number of metastatic LNs in patients resected for pancreatic cancer.

Methods

Data were collected from 398 patients who underwent curative surgery for pancreatic head cancer at Seoul National University Hospital. Long-term survival was analyzed according to LNR and absolute number of metastatic LNs.

Results

Of the patients, 227 (57.0 %) had LN metastasis. The mean numbers of total retrieved and metastatic LNs were 19.5 and 1.9, respectively, and the mean LNR was 0.11. Median overall survival (OS) of patients was significantly higher in N0 than in N1 patients after curative resection (25.4 vs. 14.8 months, p < 0.001). Median OS was significantly lower in patients with 1 than in those with 0 positive LNs (17.3 vs. 25.4 months, p = 0.001). Among N1 patients, those with 0 < LNR ≤ 0.2 had comparable prognosis than those with >0.2 LNR (median OS 17.2 vs. 12.8 months, p = 0.096), and the number of metastatic LNs did not correlate with median OS (p = 0.365).

Conclusions

The presence of a single positive metastatic LN was associated with significantly poorer OS in patients with pancreatic cancer. When LN metastasis was present, the number of metastatic LNs and LNR had limited prognostic relevance.     

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.     

S-Classification of Sentinel Lymph Node Predicts Axillary Nonsentinel Lymph Node Status in Patients with Breast Cancer

Background One-half of breast cancer patients with positive sentinel lymph node (SN) have no further metastases in the axillary lymph node basin. The aim of the present study was to identify patients with positive SN who are unlikely to have further metastases in the axillary lymph node basin, using a new classification of SN, namely the S-classification. Methods Specimens of positive SN were subjected to a pathological review according to the previously published S-classification. S-stages of positive SN were correlated with the status of further metastases in the axillary lymph node basin after axillary lymph node dissection (ALND). Results Of 117 patients who underwent sentinel lymph node biopsy, 36 (30.8%) had a positive SN and were subjected to level I and II ALND. The occurrence of positive nonsentinel nodes was significantly related to the S-stage of SN. No patient with stage SI had additional metastases in the nonsentinel lymph nodes, while 14.3% of patients with SII stage disease and 60.9 % of patients with SIII disease had other non-SN that were metastatic. Conclusion S-stages of positive SN are highly predictive for axillary nonsentinel node status. Especially patients with SI sentinel node metastases appear to be at low risk for further nonsentinel node metastases.     

Clinical Significance of Lymph Node Micrometastasis in Ampullary Carcinoma

Background This study aimed to clarify the clinical significance of lymph node micrometastasis in ampullary carcinoma. Materials and Methods Pancreaticoduodenectomy with regional lymphadenectomy was performed for 50 consecutive patients with ampullary carcinoma. A total of 1,283 regional lymph nodes (median, 25 per patient) were examined histologically for metastases. Overt metastasis was defined as metastasis detected during routine histologic examination with hematoxylin and eosin. Micrometastasis was defined as metastasis first detected by immunohistochemistry with an antibody against cytokeratins 7 and 8. The median follow-up period was 119 months after resection. Results Overt metastasis was positive in 90 lymph nodes from 27 patients. Micrometastasis was positive in 33 lymph nodes from 12 patients, all of whom also had overt nodal metastases. Patients with nodal micrometastasis had a larger number of lymph nodes with overt metastasis (median, 3.5) than those without (median, 0; P < 0.001). Overt metastasis to distant nodes (superior mesenteric nodes, para-aortic nodes) was more frequent (P = 0.001 and P = 0.038, respectively) in patients with nodal micrometastasis. Nodal micrometastasis was found to be a strong independent prognostic factor on univariate (P < 0.0001) and multivariate (relative risk, 5.085; P = 0.007) analyses. From among the 27 patients with overt nodal metastasis, the outcome after resection was significantly worse in the patients with nodal micrometastasis (median survival time of 11 months) than in those without (median survival time of 63 months; P = 0.0009). Conclusions Immunohistochemically detected lymph node micrometastasis indicates intensive lymphatic spread, and thus adversely affects the survival of patients with ampullary carcinoma.     

Low-Level Expression of Smad7 Correlates with Lymph Node Metastasis and Poor Prognosis in Patients with Pancreatic Cancer

Background  Whether Smad7 acts as a tumor proliferation promoting factor or as a metastatic suppressor in human pancreatic cancer remains unclear. This study aims to determine the prognostic value of Smad7 in patients with pancreatic adenocarcinoma. Methods  Surgical specimens obtained from 71 patients with pancreatic adenocarcinoma were immunohistochemically assessed for Smad7, Ki-67, MMP2, CD34, and Smad4 expression. The relationship between Smad7 expression and the clinicopathological characteristics of patients with pancreatic adenocarcinoma were also evaluated. Results  Fifty-one of 71 specimens (71.8%) were Smad7 positive and 20 specimens were Smad7 negative. Negative expression of Smad7 correlated with lymph node metastasis, liver metastasis after surgery, and a poor survival rate (P = 0.0004, 0.0044, and 0.0003, respectively). We also found an inverse correlation between the expression of Smad7 and MMP2 (P = 0.0189). Multivariate analysis revealed that Smad7 expression was an independent prognostic factor [hazard ratio (HR) 0.3902; 95% confidence interval (CI) 0.1839–0.8277; P = 0.0142]. Furthermore, in both Smad4-negative and Smad4-positive groups, survival of patients with Smad7-positive tumors was significantly better than those with Smad7-negative tumors (both P < 0.0001). Conclusions   We conclude that low-level expression of Smad7 in pancreatic cancer is significantly associated with lymph node metastasis, high MMP2 expression, and poor prognosis. Peng Wang and Jie Fan contributed equally to this work.     

The Impact of the Lymph Node Ratio is Greater than Traditional Lymph Node Status in Stage III Colorectal Cancer Patients

Background

The prognostic value of nodal status in colorectal cancer (CRC) patients may be influenced by the total number of lymph nodes (LNs) harvested. This study evaluates the impact of LN ratio (LNR) on CRC patients’ outcome.

Methods

A total of 612 stage III CRC patients who underwent curative-intent surgery between 2004 and 2008 were enrolled. The measured end point was postoperative disease-free survival (DFS) and overall survival (OS).

Results

The metastatic LN numbers were significantly higher in patients with more than 12 LN harvested (4.6 ± 5.81 vs. 2.7 ± 1.97, P < 0.001). The mean LNR was 22.9 ± 20 % (range = 2–100 %, median = 16.7 %). As the cutoff value of LNR was set above 17 %, the impact of the LNR on 5-year DFS became statistically significant. In univariate analysis, the 5-year DFS and OS for patients with high-LNR tumors was 54.4 and 57.3 %, respectively, significantly lower than those for patients with low-LNR tumors (72.8 and 76.4 %; P < 0.001). In multivariate analysis, the independent factors affecting the 5-year DFS and OS were tumor depth, carcinoembryonic antigen level, and LNR.

Conclusion

The LNR, set at the median value or 17 %, could be an independent prognostic factor for stage III CRC patients.     

Prognostic Impact of Para-aortic Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma

Background  

The aim of the present study was to clarify the prognostic impact of para-aortic lymph node metastasis in pancreatic ductal adenocarcinoma.     

Prognostic Implication of Para-aortic Lymph Node Metastasis in Resectable Pancreatic Cancer

BACKGROUND: The survival curve of patients who undergo surgical resection of pancreatic cancer displays a steep decline within 1 year and a relatively slow decline thereafter. The patients with a short survival time may have identifiable clinicopathologic factors that lead to rapid relapse. STUDY DESIGN: We analyzed clinicopathologic factors in 133 patients who underwent margin-negative pancreatoduodenectomy with extended radical lymphadenectomy for invasive ductal carcinoma of the pancreas to detect factors that could be responsible for the short survival. RESULTS: Tumor size, invasion of the anterior pancreatic capsule, retroperitoneal invasion, portal venous invasion, major arterial invasion, and metastasis to the para-aortic lymph nodes were variables associated with survival time in univariate analysis. Metastasis to the para-aortic lymph nodes was the single independent factor with a significant association with mortality in multivariate analysis. Some 84% of the patients who had positive para-aortic lymph nodes died within 1 year, versus 46% of the patients with negative nodes. CONCLUSIONS: Although tumors that involve the para-aortic lymph nodes may technically be resectable, the expected postoperative survival time for most patients is less than 1 year. If para-aortic nodal metastasis is detected, alternative treatment strategies should be considered.     

Accuracy of Lymph Node Staging in Pancreatic Cancer after Neoadjuvant Therapy

World Journal of Surgery -