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PubMed1993

Histologic study on the metastatic process in the experimental model of lymph node metastasis.

The process of lymph node metastasis was studied in an experimental model that was successfully established in our laboratory. The model O-1N carcinoma was transplanted to the buccal pouch of 60 hamsters, and seven or eight hamsters were killed every week from 1 to 8 weeks for histologic examination. At 3 weeks, neoplastic invasion of vascular spaces was demonstrated, and early stage lymph node metastases were seen in five of seven animals. At 5 weeks, lymph node metastases were more advanced, and lung metastasis occurred in one animal. At 8 weeks, lymph node metastases were seen in all eight animals and lung metastases were seen in two of them. Tumor cells initially seen as clusters in afferent lymphatic vessels and in the peripheral sinuses gradually spread to the medulla, replaced the entire lymph node, and extended into adjacent extranodal tissue. The process of metastasis closely resembled that seen in human oral carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Lymph node metastasis along the recurrent nerve chain is an indication for cervical lymph node dissection in thoracic esophageal cancer.

This study examined whether recurrent nerve chain node metastasis serves as an indicative factor for cervical lymph node dissection in thoracic esophageal cancer. The association of recurrent nerve chain lymph node metastasis and cervical node metastasis was analyzed for 91 patients with thoracic esophageal cancer who had undergone three-field lymph node dissection. In patients with upper thoracic esophageal cancer, the incidence of cervical lymph node metastasis was similar regardless of recurrent nerve chain node metastasis. On the other hand, in patients with middle or lower esophageal cancer, the incidence was significantly higher in recurrent nerve-positive (16/31, 51.6%) than in recurrent nerve-negative (5/43, 11.6%) patients. The prognosis of patients with recurrent nerve chain node metastasis was significantly better in the three-field dissection group than in the two-field dissection group, while in patients with no recurrent nerve chain node metastasis, survival was similar between the two groups. In conclusion, cervical lymphadenectomy can be omitted for recurrent nerve chain node-negative patients with middle and lower thoracic esophageal cancer.

Abdomen↗

PubMed1994

[Pelvic lymph node metastasis in endometrial cancer].

Various factors associated with pelvic lymph node metastasis were analysed in 393 cases with stage I endometrial cancer treated with extended total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The results are as follows. 1. The positive rates for lymph node metastasis and the relapse rate in 393 cases were 8.4% and 12.5%, respectively. 2. Myometrial invasion, tumor size, vessel permeation, cervical involvement, peritoneal cytology and adnexal metastasis were significant factors for lymph node metastasis. 3. Internal iliac nodes were the most common metastatic sites for cases with a single node metastasis, whereas external iliac nodes were the most common in all cases with lymph node metastasis. 4. The relapse rate for cases with single node metastasis was 40%, while the relapse rate for cases with three or more metastatic lymph nodes was 70%. 5. The relapse rate for 33 cases with lymph node metastasis was 54.5% and all of the relapse cases showed distant recurrence, whereas the relapse rate for 360 cases without lymph node metastasis was only 8.6%. It is therefore considered that pelvic lymphadenectomy is important in detecting high-risk patients and to reduce the relapse rate. Cytotoxic chemotherapy seems to be more adequate as adjuvant therapy for cases with lymph node metastasis.

Adult↗

PubMed2003

Preoperative evaluation of lymph node metastasis in esophageal cancer.

Lymph node metastasis (LMN) in esophageal cancer occurs from the superficial cancer and spreads wildly from the neck to the abdomen. Hence precise determination of LMN is essential when adequate treatments are employed. There are several reports about ultrasonic features of malignant lymph nodes (LNs), and in summary, reports of endoscopic ultrasonography (EUS) findings of malignant LNs showed they were more than 5-10 mm in diameter, with a distinct border, hypoechoic internal echo and round shape. Sensitivity, specificity and accuracies for the diagnosis of malignant LNs by EUS were 49-99%, 33-99% and 71-96%. The rates widely varied, because the accuracy of EUS's ability to determine malignancy were based on the evaluation of various echo features of LNs, and were dependent on the judgement of subjective observers. Therefore histological analysis is necessary for adequate treatments. Endoscopic ultrasonography guided fine-needle aspiration cytology (EUS-FNA) has been performed for the diagnosis of malignant LNs since 10 years. Results of those reports were sensitivity 81-97%, specificity 83-100% and accuracy 83-97%. EUS-FNA staging was better than EUS staging. Also clinically obvious complications by EUS-FNA have not been reported. Therefore published evidence showed that EUS-FNA is safe and useful for confirmation of malignant LNs.

Biopsy, Needle↗

PubMed2007

Lymphatic vessel density at the site of deepest penetration as a predictor of lymph node metastasis in submucosal colorectal cancer.

PURPOSE: Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (x200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. RESULTS: Lesions with high lymphatic vessel density (> or =9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. CONCLUSIONS: Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer.

Colorectal Neoplasms↗

PubMed2003

Enhancement of lymph node metastasis and distant metastasis of thyroid carcinoma.

BACKGROUND: The mechanisms of local and distant metastases are imperfectly understood. The goal of the current study was to add to the body of knowledge regarding local and distant metastases of thyroid malignancies. METHODS: The authors performed multivariate analysis of 573 patients who underwent surgery between November 1994 and May 2002 for follicular (FTC; n = 100), papillary (PTC; n = 236), or medullary thyroid carcinoma (MTC; n = 237) at a university hospital. RESULTS: In multivariate analysis, extrathyroidal extension consistently evolved as the key risk factor for both lymph node metastasis and distant metastasis. This correlation was most pronounced in MTC and least pronounced in FTC. The risk of lymph node metastasis also increased with reoperative status in patients with MTC and with primary tumor diameter in patients with MTC (tumor diameter > 10 mm) and patients with PTC (tumor diameter > 20 mm). In the PTC group, lymph node metastasis was more common among patients younger than age 45. In the MTC group, extrathyroidal growth and distant metastasis were associated exclusively with lymph node metastasis. Lymph node metastasis was the only secondary risk factor for distant metastasis. In the analysis of risk factors for distant metastasis in the FTC and PTC groups, no interaction was found between extrathyroidal growth and lymph node metastasis. This finding suggests that extrathyroidal growth and lymph node metastasis of FTC and PTC, and presumably also MTC, represent separate mechanisms and routes of distant metastasis. CONCLUSIONS: Screening for both local residual disease and distant metastases should be intensified in the high-risk population of patients whose primary tumors exhibit large diameters, extrathyroidal growth, or lymph node metastasis.

Adenocarcinoma, Follicular↗

PubMed1995

[Renal cell carcinoma with regional lymph node metastasis].

A follow up study of 20 cases of renal cell carcinoma with regional lymph node metastasis at the department of urology in Niigata Cancer Center Hospital from 1979 to 1993 is presented. During this period, we treated 249 patients with renal cell carcinoma with or without lymph node metastasis. Lymph node metastasis could be estimated in 188 out of 249 patients. Histologically, lymph node metastasis was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and 5-year survival rates of 20 patients with lymph node metastasis were 45.0% and 16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases had distant metastasis. Three of the 9 patients with distant metastasis had no recurrence. Two of these 3 patients are still alive after 10 years and 3 years and 1 patient died because of acute heart failure. These 3 patients had pN1 metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant metastasis had more than a two-year survival. However, 3 patients died due to renal cell carcinoma although primary and metastatic regions were resected and IFN with chemotherapy were given. Only one patient is still alive without recurrence after 3 years. This case detected as right renal cell carcinoma with pN2 metastasis and bilateral pulmonary metastasis was treated with radical nephrectomy with regional lymph node dissection and administered Methotrexate, VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2000

ICAM-1 (intercellular adhesion molecule-1) gene transfection inhibits lymph node metastasis by human gastric cancer cells.

Lymph node metastasis is one of the prognostic factors in gastric cancer. We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression on cancer cells is associated with lymph node metastasis using a gastric cancer cell. In this study, we transfected ICAM-1 gene into a gastric cancer cell line, 2MLN, and analyzed the effect on lymph node metastasis in vitro and in vivo. A significantly greater amount of peripheral blood mononuclear cells (PBMC) adhered to ICAM-1 transfected 2MLN cells, 2MLN / ICAM cells, than to 2MLN / Vector cells. The lysis of 2MLN / ICAM cells by PBMC was significantly increased compared with that of 2MLN / Vector cells. The tumor growth rate of 2MLN / ICAM cells was significantly decreased in vivo. Lymph node metastases caused by 2MLN / ICAM cells were recognized as being fewer in number and smaller, while many lymph node metastases were caused by 2MLN cells. Histologic findings showed that leukocytes were heavily infiltrated in both the 2MLN / ICAM tumors and metastatic lesions, while only a few leukocytes were observed in the lesions associated with 2MLN cells. The above findings indicate that ICAM-1 gene transduction could prove to be an effective gene therapy for lymph node metastasis of gastric cancer.

Animals↗

PubMed1996

[An analysis of pelvic and para-aortic lymph node metastasis in ovarian carcinoma by systematic retroperitoneal lymph node dissection].

We performed a systematic retroperitoneal lymph node dissection (RPLND) on 137 patients with primary ovarian carcinoma, of whom 97 had undergone RPLND during the primary surgery before chemotherapy and 40 had undergone RPLND during the secondary cytoreductive surgery after preoperative chemotherapy. The tentative staging of the ovarian carcinoma used in this study was determined according to the FIGO criteria without considering the pathologic findings of retroperitoneal lymph nodes. Nodal metastasis was seen in 21.9% (30/137) of them. Thirteen had positive pelvic lymph nodes (PLN) but no positive para-aortic nodes (PAN). Eleven had both positive PLN and positive PAN. Six had positive PAN but no positive PLN. The PAN was the most frequent site of metastasis (17/137). Next were the common iliac, obturator, and lateral group of deep inguinal nodes. Solitary metastasis in the patients who had undergone RPLND during the primary surgery was seen in a PAN and a common iliac node. Among 24 patients with PLN metastasis, there was a significant (p < 0.05) difference in the number of positive PLN between the patients with PAN metastasis (5.27 +/- 3.00) and the patients without PAN metastasis (2.62 +/- 1.66). These results indicate that the PAN and common iliac nodes are the most important site of nodal metastasis in ovarian carcinoma. The metastasis to PLN such as obturator node and internal iliac node seems to occur independently of the PAN metastasis, and the PAN metastasis occurs not only through the direct route but also as a consequence of extension of PLN metastases. Systematic retroperitoneal lymph node exploration therefore seems to be necessary to clarify the lymph node status.

Aorta↗

PubMed1998

Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma.

The distribution of lymph node metastasis and the clinicopathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces.

Adenocarcinoma, Clear Cell↗

PubMed2000

Membrane-type 1 matrix metalloproteinase enhances lymph node metastasis of gastric cancer.

The mechanisms of the lymph node metastasis remain unclear. We demonstrate the role of MT1-MMP on the lymph node metastasis using in vivo experimental model of lymph node metastasis by orthotopic implantation of MT1-MMP transfected gastric cancer cell line in the stomach of nude rats. TMK-1 cell line without expression of MT1-MMP was transfected with the pcDNA3 plasmid containing a 3.4-kb MT1-MMP cDNA fragment by calcium phosphate method, and the transfected cell line was designated as TMK-MT. Western blot and RT-PCR analyses showed the specific bands corresponding to MT1-MMP in the TMK-MT cells. By gelatin zymography, the activated form (62-kDa) of MMP-2 was identified in the medium of TMK-MT cell line, but was not detected in TMK-1 cells. Six weeks after orthotopic implantation of TMK-1 and TMK-MT xenografts of nude mouse-subcutaneus tumor into the stomach of nude rats, gastric tumors were found in all the animals. Histologically, the lymphatic invasion was found in the submucosa of the TMK-MT gastric tumors. Lymph node metastasis was not detected in nude rats bearing TMK-1 gastric tumor (0/8). In contrast, lymph node metastasis was detected in five out of 8 rats, bearing TMK-MT gastric tumor. MT1-MMP immunoreactivity was found on the cell membrane and cytoplasm of TMK-MT cells not only in the lymph node metastasis but also in the stomach tumor. These results suggest that MT1-MMP overexpression induced by transfection of its gene may promote lymph node metastasis of transformed cells.

Animals↗

PubMed2002

Enhanced production of matrix metalloproteinase-2 in human head and neck carcinomas is correlated with lymph node metastasis.

Matrix metalloproteinase (MMP)-2 and -9 degrade type IV collagen, which is one of the major components of the basement membrane in normal tissue and expressed in the surroundings of the cancer nest in squamous cell carcinoma. The degeneration of type IV collagen is an essential step in the metastasis to lymph nodes and distant organs. In this study, we examined MMP-2 and -9 levels of cancer tissue and serum obtained from patients with head and neck squamous cell carcinoma (HNSCC) in order to evaluate the relationship between the clinicopathologic features and MMPs. We examined the production of MMP-2 and -9 in cancer tissue homogenates of 73 patients who had HNSCC and the serum MMP levels of 16 patients with HNSCC and 8 healthy volunteers. We also studied the localization of MMP-2 in the carcinoma using an immunohistochemical approach. The concentrations of MMP-2 and -9 in the tissue homogenates and serum were measured by means of a sandwich enzyme immunoassay using a monoclonal antibody. Immunohistochemical analyses were performed with monoclonal antibody to MMP-2. The concentration of MMP-2 in the tumor tissue homogenates was unrelated to tumor size, but that in patients with lymph node metastases was significantly higher than in those without lymph node metastases. The concentration of MMP-9 was unrelated to lymph node metastasis and tumor size. The levels of both MMP-2 and -9 in serum were unrelated to lymph node metastasis. Immunohistochemistry indicated that MMP-2 was mainly expressed in cancer cells. Because MMP-2 degrades type IV collagen, the level of MMP-2 in carcinomas may be a useful indicator of the degree of invasion and metastasis.

Biomarkers, Tumor↗

PubMed1997

[Reasonable lymph node dissection for T2 or T3 midthoracic esophageal cancer with cervical lymph-node metastasis].

In order to determine the reasonable lymph node dissection for T2 or T3 midthoracic esophageal cancer with cervical lymph node metastasis, a retrospective study was carried out on 106 patients receiving resection between 1983 and 1996. Metastasis to cervical lymph node was obtained in 27.4% (29/106) of patients with T2 or T3 midthoracic esophageal cancer. Within 29 patients, metastasis in cervical node only, in two fields and in three fields occupied 17.2%, 41.4% and 41.4%, respectively. And according to the histologic examination of dissected lymph nodes, metastatic sites spreaded from neck to perigastric region. Five-year survival rate of 23 patients receiving curative operation was 33.0%, and that of 13 patients excluding 3-field metastasis was 51.9%. But the main sites of nodal recurrence were cervical or superior mediastinal nodes along the bilateral recurrent laryngeal nerves, and the rate of nodal recurrence was 47.8%. These results of actual state of lymph node metastasis and prognostic benefit of aggressive dissection suggest that 3-field lymph node dissection is mandatory for T2 or T3 midthoracic esophageal cancer with cervical lymph node metastasis. And we should endeavor to upgrade the precise dissection in order to decrease the nodal recurrence.

Esophageal Neoplasms↗

PubMed1991

[DNA ploidy in submucosal cancer of the stomach and its relationship to lymph node metastasis].

The relationship between DNA ploidy and lymph node metastasis was determined in 40 cases of gastric cancer confined to the submucosa (with lymph node metastasis 20 cases and without 20 cases). The DNA ploidy patterns were classified as follows: Type D, Type A1 and Type A2. Of the 20 cases with lymph node metastasis, 1 was Type D, 7 were Type A1 and 12 were Type A2. The likelihood of lymph node metastasis was 12.5% (1/8) for Type D, 43.8% (7/16) for Type A1 and 75.0% (12/16) for Type A2. It is concluded that although gastric cancer confined to the submucosa is classified as early one, analysis of DNA content places such tumors with lymph node metastasis into the advanced cancer category.

DNA, Neoplasm↗

PubMedDate not supplied

A nude mouse model of massive liver and lymph node metastasis of human colon cancer.

Liver and lymph nodes metastasis are the main causes of treatment failure for advanced colon cancer. However, currently-available animal models of human colon cancer do not demonstrate sufficient metastasis to represent highly malignant colon cancer that extensively metastasizes to these sites. A liver metastasis from a patient with highly malignant, poorly differentiated adenocarcinoma of the colon was established in nude mice by surgical orthotopic implantation to the mouse colon. The human origin of the tumor growing in nude mice was confirmed by in situ hybridization of human DNA. After 20 passages from the first implantation, massive liver and lymph nodes metastasis, occurred in 100% of the transplanted animals. Lymph nodes metastasis were found at the sites of lymph node drainage of the liver: celiac, portal and mediastinal lymph nodes. However no mesenteric and retroperitoneal nodes or lung tissue metastases were observed. Our data suggest that the mediastinal, celiac and hepatic lymph nodes metastases are derived form the liver metastasis, confirming the concept of metastasis of metastases or "remetastasis" of colon cancer.

Adenocarcinoma↗

PubMed1987

Tumor size in endometrial cancer: a prognostic factor for lymph node metastasis.

The association of tumor size and lymph node metastasis in endometrial cancer clinically confined to the uterus was evaluated in 91 patients. Other factors possibly associated with lymph node metastasis were also analyzed. Tumor size was independently associated with lymph node metastasis when analyzed by multivariate analysis (P = .022). Patients with tumors less than or equal to 2 cm in diameter had only a 5.7% incidence of lymphatic metastases. When tumors exceeded 2 cm in diameter or involved the entire endometrial surface, metastases occurred in 21.7 and 40.0% of patients, respectively. Measuring tumor size at surgery, or possibly preoperatively by hysteroscopy, will help predict which patients are at increased risk for lymph node metastasis. There were no lymph node metastases in patients with tumors less than or equal to 2 cm in diameter and invasion of less than half of the myometrium. For these patients, extended surgical staging with pelvic and aortic lymph node biopsies may not be indicated.

Female↗

PubMed2005

Right- and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis.

Accurate preoperative prediction of lymph node metastasis and degree of tumor invasion would facilitate an appropriate decision of the extent of surgical resection of cancers to reduce unnecessary complication or to minimize the risk of recurrence in patients. We analyzed gene expression profiles characteristic of the invasiveness of colorectal carcinoma in a total of 89 cases, using a cDNA array and pattern classification algorithms. We set binary classes for a panel of clinicopathologic parameters, each of which was divided at different levels for categories (discrete) or values (continuous). We searched an optimal combination of genes to discriminate the classes by using of a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P < or = 0.05). We used a sequential forward feature selection which additively searched a combination of genes, giving a minimal leave-one-out classification error rate of a k-nearest neighbor classifier. In the process of gene preselection, we found a remarkable difference in the expression pattern of genes according to the anatomical location of cancers. The difference was most prominent when the classes were set for cecum, ascending colon, transverse colon, and descending colon (CATD) versus sigmoid colon and rectum (SR). By stratifying these two locations, we were able to extract gene expression profiles characteristic of the classes of the presence versus absence of lymph node metastasis, lymphatic invasion, vascular invasion and degree of mural invasion, and pathological stages, with an accuracy of more than 90%. These results suggest that colorectal cancers harbor distinct molecular pathophysiological statuses according to their right-to-left locations, of which stratification is important for pattern classification of cDNA array data.

Adult↗

PubMed1991

[Study of para-aortic lymph node metastasis for advanced gastric cancer on consecutive lymph node slices].

Para-aortic lymph nodes (No. 16) from 21 patients with advanced gastric cancer who underwent extensive lymph node dissection, were sliced consecutively at intervals of 50 mu to study minute metastasis of No. 16 lymph nodes. Twenty-six of 30 metastatic lymph nodes had minute involvement, in which carcinoma cells were detected in marginal sinus of lymph node, microscopically. The rate of the metastases to No. 16 lymph nodes was 19% among N0-3 cases by conventional method (not consecutive slices). On the contrary, the percentage of metastasis to No. 16 lymph nodes by consecutive slices was 33% among N0-3 cases. Therefore, No. 16 nodes are involved in metastasis at high rate at operation and the extensive lymph node dissection including No. 16 nodes (R4) will be recommended to prevent lymph node recurrence caused by such a minute metastasis.

Aorta↗