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.     

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.     

Most Important Lymph Node Information in Gastric Cancer: Multivariate Prognostic Study

Background: In gastric cancer, the level and number of lymph node metastases is useful for predicting survival, and there are several staging systems for lymph node metastasis. The aim of this study was to compare the several lymph node classifications and to clarify the most important lymph node information associated with prognosis using multivariate analysis.Methods: A total of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and extended lymph node dissection (D2, D3) were studied. The level of lymph node metastasis was categorized simply as Level I nodes (perigastric, No.1–6), Level II nodes (intermediate, No.7–9), and Level III nodes (distant, No.10–16), irrespective of the tumor location. The Level II nodes included lymph nodes along the left gastric artery, common hepatic artery, and celiac trunk.Results: Overall 5-year survival rate was 51%. Univariate analysis showed that 5-year survival rate was significantly influenced by the level of positive nodes (P < .01), total number of positive nodes (P < .01), number of positive Level I nodes (P < .01), and number of positive Level II nodes (P < .01), in addition to the tumor location (P < .05), tumor size (P < .05), gross type (P < .01), and depth of wall invasion (P < .01). Of these, independent prognostic factors associated with 5-year survival rate were the number of positive Level II nodes (0–1 vs. 2) (62% vs. 19%, P < .01) and the depth of wall invasion (within vs. beyond muscularis) (79% vs. 43%, P < .01).Conclusions: Among several staging systems for lymph node metastases, the number of positive Level II nodes provided the most powerful prognostic information in patients with node-positive gastric cancer. When there were two or more metastases in the Level II nodes, prognosis was poor even after D2 or D3 gastrectomy.     

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.     

常规检查淋巴结阴性No.7组胃癌患者的淋巴结微转移研究

目的探讨常规病理检查无淋巴结转移的胃癌淋巴结微转移的特点,并分析微转移与各种临床病理因素的关系.方法应用淋巴结组织连续切片和端粒酶 RT-PCR ELISA方法检测 46例胃癌患者常规病理检查无淋巴结转移的 No.7组淋巴结 138个,并结合胃癌患者的临床病理资料进行统计学分析.结果本组 13例(28.3%) 32枚淋巴结(23.2%)经连续切片检出有微转移;而端粒酶阳性表达为 20例(43.5%) 49枚淋巴结(35.5%).端粒酶 RT-PCR ELISA检测敏感性为 100%,特异性为 84%,阳性预测值为 65%,阴性预测值为 100%,诊断准确率为 88%.淋巴结微转移与患者年龄、性别、原发肿瘤部位、组织学类型和转移淋巴结分型无关(P >0.05),但与原发肿瘤大体类型、大小及是否浸透浆膜有关(P< 0.05).结论对常规病理检查无淋巴结转移的胃癌患者,为客观评价胃癌临床病理分期及其预后,有必要监测其微转移,端粒酶 RT-PCR ELISA方法可以作为传统组织学检查方法的补充.     

Prognostic Implications of Pathological Lymph Node Status After Preoperative Chemotherapy for Operable T3N0M0 Breast Cancer

Background: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo.Methods: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years.Results: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P 5 .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P 5 .01) and diseasespecific survival (P 5 .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4–9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4–9 positive nodes (17 vs. 48%, P 5 .04).Conclusions: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.     

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.     

Size of Residual Lymph Node Metastasis After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients Is Prognostic

Background The prognostic significance of micrometastasis after neoadjuvant chemotherapy for locally advanced breast cancer is unknown. We examined the residual lymph node metastasis size in patients after treatment with neoadjuvant chemotherapy to determine the relevance of metastasis size on outcome. Methods Stage II/III breast cancer patients treated with neoadjuvant chemotherapy at our institution from 1991 to 2002 were included. We examined the relationship of postneoadjuvant chemotherapy lymph node metastasis size and number with distant disease-free survival (DDFS) and overall survival (OS). Results In 122 patients with a median follow-up of 5.4 years, we found not only that patients with an increasing number of residual positive nodes had progressively worse DDFS and OS (P < .0001 for both) compared with patients with negative nodes, but also that the size of the largest lymph node metastasis was associated with worse DDFS and OS (P < .0001 for both) in both univariate and multivariate analysis. Compared with negative nodes, even lymph node micrometastasis (<2 mm) was associated with worsened DDFS and OS (adjusted P = .02 and P = .005, respectively). Conclusions Residual micrometastatic disease in the axillary lymph nodes after neoadjuvant chemotherapy is predictive of worse prognosis than negative nodes. In this study, the lymph node metastasis size and the number of involved lymph nodes were independent powerful predictors of DDFS and OS.     

Extended lymphadenectomy is associated with a survival benefit for node-negative gastric cancer

The purpose of this study was to determine whether extended lymph node (D2) dissection is associated with a survival benefit for patients with histologically node-negative gastric cancer at a single institution in the United States. Review of the prospective gastric database at Memorial Sloan-Kettering Cancer Center from July 1985 to August 1995 identified 774 patients who had undergone curative gastric resection. Of these, 247 patients (32 %) were identified with histologically negative lymph nodes by hematoxylin-eosin staining. Data are expressed as median (range). Overall survival was compared by log-rank test. The overall 5-year survival rate for the entire cohort was 79%. The extent of lymph node dissection did not predict survival over the entire cohort. However, when stratified for tumor (T) stage, D2 dissection offered a survival advantage for T3 tumors. The 5-year survival rate for patients with T3 tumors undergoing a D2 dissection (n = 15) was 54% compared to 39% for those undergoing a DI dissection (n = 53, P < 0.05). D2 dissection is associated with improved survival in advanced T stage, node-negative gastric cancer. With adequate staging, results of gastric resection for adenocarcinoma in Western countries begin to approximate those seen in Japan. Excision of N2 lymph nodes may also remove microscopic metastatic disease, contributing to the survival benefit. Supported by the Lillian Wells Foundation. Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997.     

Outcome of Histologically Node-negative Esophageal Squamous Cell Carcinoma

The outcome of node-negative esophageal carcinoma and the prognostic significance of lymph node micrometastasis remain unknown. The aim of this retrospective study was to clarify these two points. A series of 98 patients who underwent curative operation for histologically node-negative (pN0 in TNM classification) esophageal carcinoma were enrolled in the study. We reviewed the cause of death of these patients. The survival curves were calculated and compared after stratifications according to clinicopathologic parameters. Lymph node micrometastasis in the patients with recurrences was examined using immunohistochemical staining of cytokeratin. Their ages ranged from 45 to 83 years (mean 64.3 years). There were 83 men and 15 women. Altogether, 54 patients were still alive, and 44 had died. A total of 9 patients died from recurrence of their esophageal carcinoma, 33 died from other causes (pneumonia 11, extraesophageal carcinoma 7, and so on), and 2 died from unknown causes. Eight patients had locoregional recurrences, and two patients had distant recurrences. The overall survival rate for the 98 patients was 58.2%. The survival for patients with pT2 or pT3 tumors was significantly worse than for those with pTis or pT1 tumors (p = 0.02, log-rank test). Other clinicopathologic factors did not affect the prognosis. Immunohistochemical study found no lymph node micrometastasis in 365 lymph nodes resected from the patients with recurrences. Only the depth of tumor invasion affected the outcome of patients with node-negative esophageal carcinoma. Altogether, 75% of patients died of other causes without recurrence, with the two main causes of death being pulmonary complications and extraesophageal carcinoma in these patients. Lymph node micrometastasis was not associated with recurrence in this series.     

Survival benefit of extended D2 lymphadenectomy in gastric cancer with involvement of second level lymph nodes: a longitudinal multicenter study

Background The survival benefit of extended lymphadenectomy in the surgical treatment of gastric cancer is still being debated. The aim of this longitudinal multicenter study was to evaluate long-term survival in a group of patients with involvement of second level lymph nodes, which would not have been removed in the case of a limited lymphadenectomy. Results were compared with those in patients with involvement of first level lymph nodes. Methods Between 1991 and 1997, 451 patients with primary gastric cancer underwent curative resection with extended lymphadenectomy at three surgical departments in Italy according to the rules of the Japanese Research Society for Gastric Cancer. Results In 451 cases treated by extended lymphadenectomy, morbidity and mortality rates were 17.1% and 2%, respectively. In 126 patients (27.9%) (group A), metastases were found in lymph node stations 7 to 12; 109 patients (24.2%) had metastases confined to the first level (group B). Lymph node stations 7 and 8 showed the highest incidence of metastases in the second level (17.1% and 12.4%, respectively). A significant difference in 5-year survival was observed between group A and group B (32% vs. 54%;P=.0005). This difference disappeared when cases were stratified according to the number of positive lymph nodes. By multivariate analysis, only the number of positive lymph nodes (relative risk, 1.8;P<.0001) and the depth of invasion (relative risk. 2.1;P<.0001), but not the level of involved nodes, showed to be independent predictors of poor prognosis. Conclusions Japanese-type extended lymphadenectomy yields low morbidity and mortality rates if performed in specialized centers. This procedure could provide a good probability of long-term survival, even for patients with involvement of regional lymph nodes.     

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。     

Solitary Lymph Node Metastasis in Gastric Cancer

The feasibility and diagnostic reliability of sentinel node (SN) biopsy for gastric cancer are still controversial. We studied the clinicopathological features and localization of solitary lymph node metastasis (SLM) in gastric cancer to provide useful information for use of the SN concept in gastric cancer. From 2000 to 2004, 3,267 patients with gastric cancer underwent D2 radical gastrectomy. The clinicopathological features of 195 patients with histologically proven SLM and the distribution of metastasized nodes were assessed. The incidence of SLM was 6.0% in all cases. Compared with the node-negative patients, significant differences were observed in age, tumor size, depth of invasion, and surgical type. The cumulative 5-year survival rate of patients with SLM was 80.5%, which was significantly lower than 90.2% for node-negative patients (P < 0.001). Of patients with SLM, 82.6% had it in the perigastric node area (N1), and the other 17.4% patients had skip metastasis in the N2-N3 nodes. Perigastric nodes were the most common first sites of drainage from the tumor, making them the main targets of the operative SN mapping procedure. Due to the higher than expected incidence of skip metastasis in gastric cancer, D2 lymphadenectomy should be performed until the reliability of SN navigation surgery is validated in multicenter prospective clinical trials.     

Immunohistochemistry analysis of micrometastasis in pretreatment lymph nodes from patients with esophageal cancer

BACKGROUND: With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. METHODS: Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. RESULTS: 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. CONCLUSIONS: Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.     

Outcome of histologically node-negative esophageal squamous cell carcinoma

The outcome of node-negative esophageal carcinoma and the prognostic significance of lymph node micrometastasis remain unknown. The aim of this retrospective study was to clarify these two points. A series of 98 patients who underwent curative operation for histologically node-negative (pN0 in TNM classification) esophageal carcinoma were enrolled in the study. We reviewed the cause of death of these patients. The survival curves were calculated and compared after stratifications according to clinicopathologic parameters. Lymph node micrometastasis in the patients with recurrences was examined using immunohistochemical staining of cytokeratin. Their ages ranged from 45 to 83 years (mean 64.3 years). There were 83 men and 15 women. Altogether, 54 patients were still alive, and 44 had died. A total of 9 patients died from recurrence of their esophageal carcinoma, 33 died from other causes (pneumonia 11, extraesophageal carcinoma 7, and so on), and 2 died from unknown causes. Eight patients had locoregional recurrences, and two patients had distant recurrences. The overall survival rate for the 98 patients was 58.2%. The survival for patients with pT2 or pT3 tumors was significantly worse than for those with pTis or pT1 tumors (p = 0.02, log-rank test). Other clinicopathologic factors did not affect the prognosis. Immunohistochemical study found no lymph node micrometastasis in 365 lymph nodes resected from the patients with recurrences. Only the depth of tumor invasion affected the outcome of patients with node-negative esophageal carcinoma. Altogether, 75% of patients died of other causes without recurrence, with the two main causes of death being pulmonary complications and extraesophageal carcinoma in these patients. Lymph node micrometastasis was not associated with recurrence in this series.     

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.     

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.     

The impact of lymph node yield on Duke’s B and C colorectal cancer survival

Aim The number of positive lymph nodes retrieved following colorectal cancer (CRC) resection impacts on the staging and further treatment of the disease. We compared 5‐year survival by lymph node yield for Duke’s B and C patients to assess the impact on prognosis. Method A retrospective methodology was employed to review patients who underwent operative resection for Duke’s B or C CRC between 1999 and 2003. Results A total of 351 patients were included in our analyses. Lymph node yield, N‐stage and extramural vascular invasion were independent predictors of overall 5‐year survival. A significant difference in 5‐year survival by lymph node yield was seen among Duke’s B patients (< 9 nodes vs≥ 9 nodes, 45.2%vs 68.4%; P = 0.0043) and Duke’s C patients (< 10 nodes vs≥ 10 nodes, 25.6%vs 48.8%; P = 0.0099). There was a significant reduction in the relative risk of 2.8% in mortality for each additional node sampled in Duke’s B and C patients (RR 0.972, 95% confidence interval 0.949–0.994, P = 0.0102). Duke’s B patients who had < 9 lymph node yield and no neoadjuvant/adjuvant treatment had a similar survival to all Duke’s C patients (47.8%vs 41.7%, P = 0.5136). Conclusion Lymph node yield independently predicts for survival in patients with Duke’s B and C CRC. Duke’s B patients with < 9 lymph node yield have no better survival than patients with Duke’s C disease. Therefore, prospective randomized studies are required to examine if inadequate lymph node yield could be one of the deciding factors in offering adjuvant therapy among Duke’s B cancer patients.     

Lymph node micrometastases in early gastric cancer and their impact on prognosis

Abstract While the presence of lymph node metastases in early gastric cancer (EGC) is the most significant prognostic factor, the relevance of lymph node micrometastases remains uncertain. The authors studied 5400 lymph nodes dissected from 300 patients treated surgically for EGC between 1976 and 1999, all of whom were histologically pN0. Micrometastases were defined as single or small clusters of neoplastic cells identifiable only by immunohistochemical methods. Lymph node micrometastases were observed in 30 of the 300 patients (10%). No significant correlation was observed between micrometastases and other clinicopathological characteristics. Analysis of overall survival showed no significant difference between positive or negative micrometastasis groups. The results of our study show that the presence of lymph node micrometastases in EGC does not influence patient prognosis. Electronic Publication     

Adenocarcinoma of the Duodenum: Importance of Accurate Lymph Node Staging and Similarity in Outcome to Gastric Cancer

Background: This study examined prognostic discrimination by lymph node staging for duodenal adenocarcinoma and compared the nodal stage–specific survival with that associated with gastric antral adenocarcinoma.Method: Prospectively maintained databases from 1983 to 2000 were reviewed to identify 137 patients with duodenal adenocarcinoma and 545 patients with gastric antral adenocarcinoma at a single institution.Results: R0 resection was performed for 72 patients with duodenal cancer. At least 15 lymph nodes were retrieved in 34 cases (47%). Lymph node metastasis (pN⁺) was detected in 31 patients (43%). With median follow-up of 36 months, the pN category was an independently significant prognostic factor (pN0, 5-year disease-specific survival of 83%, vs. pN⁺, 56%; P = .03). The survival difference between pN0 and pN⁺ was pronounced in patients with 15 nodes (100% vs. 47%, respectively; P = .01) but was lost in those with <15 nodes (75% vs. 64%; P = .5). For gastric antrum cancer, 331 patients had R0 resection, and 15 nodes were retrieved in 256 cases (77%). Lymph node metastasis was detected in 157 cases (47%). For patients with 15 nodes, 5-year survival with pN0 (87%) or pN⁺ (44%) was not significantly different from the corresponding categories for duodenal adenocarcinoma.Conclusion: For duodenal adenocarcinoma, examination of 15 regional lymph nodes improved prognostic discrimination by the pN category. With accurate nodal staging, pN0 was associated with excellent prognosis. With pN⁺, prognosis was similar to that for gastric antral adenocarcinoma.