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Genomic copy-number aberrations related to lymph-node metastasis of colon cancer.

Lymph-node metastasis is an important indicator in the diagnosis of colon cancer. In order to determine the genes involved in metastasis, genomic copy-number aberrations in the primary tumours and lymph-node metastases were analysed in 12 patients using comparative genomic hybridization. This method detects genomic copy-number changes at the chromosomal level and the identification of the regions of aberration on any chromosome. Copy-number gains at 6p12 and losses at 8p12 were observed in a greater number of the primary tumours than in the metastases. These aberrations appear to be involved in lymph-node metastasis of colon cancer, and may allow measurement of the risk of lymph-node metastasis from a given colon cancer.

Adenocarcinoma↗

Differentially expressed genes between primary cancer and paired lymph node metastases predict clinical outcome of node-positive breast cancer patients.

The axillary lymph node status remains the most valuable prognostic factor for breast cancer patients. However, approximately 20-30% of node-positive patients remain free of distant metastases within 15-30 years. It is important to develop molecular markers that are able to predict for the risk of distant metastasis and to develop patient-tailored therapy strategies. We hypothesize that the lymph node metastases may represent the most metastatic fraction of the primary cancers. Therefore, we sought to identify the differentially expressed genes by microarray between the primary tumors and their paired lymph node metastases samples collected from 26 patients. A set of 79 differentially expressed genes between primary cancers and metastasis samples was identified to correctly separate most of primary cancers from lymph node metastases. And decreased expression of matrix metalloproteinase 2, fibronectin, osteoblast specific factor 2, collagen type XI alpha 1 in lymph node metastases were further confirmed by real-time RT-PCR performed on 30 specimen pairs. This set of genes also classified 35 primary cancers into two groups with different prognosis: "high risk group" and "low risk group." Patients in "high risk group" had a 4.65-fold hazard ratio (95% CI 1.02-21.13, P = 0.047) to develop a distant metastasis within 43 months comparing with the "low risk group." This suggested that the gene signature consisting of 79 differentially expressed genes between primary cancers and lymph node metastases could also predict clinical outcome of node-positive patients, and that the molecular classification based on the gene signature could guide patient-tailored therapy.

Breast Neoplasms↗

Local administration of granulocyte/macrophage colony-stimulating factor increases the number and activation state of dendritic cells in the sentinel lymph node of early-stage melanoma.

The initial tumor-draining lymph node, the sentinel lymph node, not only constitutes the first expected site of micrometastasis but also the first point of contact between tumor-associated antigens and the adaptive immune system. A tumor-induced decrease in the frequency and activation state of sentinel lymph node dendritic cells will impair the generation of effective antitumor T-cell responses and increase the likelihood of metastatic spread. Here, we demonstrate that intradermal administration of granulocyte macrophage-colony stimulating factor around the excision site of stage I primary melanoma tumors increases the number and activation state of dendritic cells in the paracortical areas of the sentinel lymph node and enhances their binding to T cells. We conclude that local treatment of melanoma patients with granulocyte macrophage-colony stimulating factor, before surgery, conditions the sentinel lymph node microenvironment to enhance mature dendritic cell recruitment and hypothesize that this may be more conducive to the generation of T-cell-mediated antitumor immunity.

Adjuvants, Immunologic↗

Spontaneous contractions and stretch-evoked responses of isolated lymph nodes.

In this study the spontaneous activities of prescapular lymph nodes, which were isolated from calves, goats and sheep and mesenteric lymph nodes of guinea-pigs were recorded and analysed in the frequency domain. Stretch-evoked contractions of the mesenteric lymph nodes were also recorded and their frequency characteristics analysed. The preparations were placed in a Krebs solution which was kept at 37 degrees C and bubbled continuously with a mixture of 95% O2 and 5% CO2. The tension changes occurring in the lymph nodes were recorded. The patterns obtained were initially transformed into numerical values which were then used to obtain autocorrelation functions and power spectra, according to the time series analysis method. A passive stretch of 100 s duration was applied to the mesenteric lymph nodes and the responses were examined using the transient response-frequency characteristics method. It was observed that prescapular and mesenteric lymph nodes had spontaneous activities due to the contractions of the smooth muscles within the nodes. A frequency analysis of these contractions indicated that at least three contractile components were responsible for the contractions; these components contract within the frequency bands of 0.01-0.04 Hz, 0.05-0.07 Hz and 0.09-0.14 Hz respectively. It was also observed that the spontaneous activities could be regulated and synchronized by stretch. It is suggested that these contractions of the lymph nodes play an essential role in lymph propulsion within the nodes.

Animals↗

Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer.

BACKGROUND: Lateral lymph node metastases occur in some patients with low rectal cancer and may cause local recurrence after total mesorectal excision. The aims of this study were to identify risk factors for lateral node metastases in patients with pathological tumour (pT) stage 3 or pT4 low rectal adenocarcinoma, and to evaluate the prognostic significance of lateral node metastases. METHODS: A retrospective analysis was performed of the outcome of 237 patients with pT3 or pT4 low rectal adenocarcinoma who underwent R0 resection with systematic lateral node dissection. RESULTS: Lateral lymph node metastases were found in 41 patients (17.3 per cent). Increased risk of lateral lymph node metastases was associated with a distal tumour margin close to the anal margin, histological type other than well or moderately differentiated adenocarcinoma, and the presence of mesenteric lymph node metastases. Patients with lateral node metastases had a significantly shorter postoperative survival (5-year survival rate 42 versus 71.6 per cent; P < 0.001) and an increased risk of local recurrence (44 versus 11.7 per cent; P < 0.001) compared with those without lateral node metastases. CONCLUSION: Tumour site, histological type and the presence of mesenteric lymph node metastasis are factors predicting the risk of lateral node metastasis. The poor prognosis of patients with lateral lymph node metastases after systematic lateral dissection suggests the need for adjuvant therapy.

Adenocarcinoma↗

Appearance of killer (K) cells in the mesenteric lymph nodes in Crohn's disease.

The local lymph node in Crohn's disease contains killer (K) cells which are able to lyse antibody-coated heterologous target cells. K cells are not found in mesenteric lymph nodes from control patients not suffering from Crohn's disease, whereas they are regularly found in similar amounts in the peripheral blood of both control and patients with Crohn's disease. Even mesenteric lymph node cells from areas not macroscopically affected by inflammatory disease show increased K cell activity as compared to control lymph node lymphocytes, suggesting a generalized mesenteric lymph node involvement with regard to K activity in Crohn's disease.

Adult↗

Surgical lymph node biopsies in University of Ilorin Teaching Hospital, Ilorin, Nigeria.

BACKGROUND: To determine the diagnostic value of lymph-node biopsy, commonest causes of lymph node enlargement requiring biopsy and the usual nodes involved. METHODS: A retrospective study of 169 lymph node biopsies representing 97% of lymph node biopsies and 3.2% of total biopsies specimen received at Pathology Department of University of Ilorin Teaching Hospital Ilorin, Nigeria over a 5 year period was undertaken. RESULTS: Tuberculous lymphadenitis (38%) and metastatic nodal involvement (25%) were the commonest causes of lymph node enlargement. Generalised lymphadenopathy occurred in 105 (62%) patients while localised enlargement was seen in 64{38%) of cases. The commonest sites of localised lymphadenopathy were axillary (38%), cervical (32%), inguinal (8%), and submandibular (8%). While axillary lymph node enlargements were mostly associated with tumour metastasis, cervical node enlargements were mostly associated with tuberculosis. Supraclavicular lymphadenopathy has the highest risk of malignancy. CONCLUSION: The result shows that tuberculous lymphadenitis and metastatic nodal malignancies are the commonest causes of lymph node enlargement in our environment. Reasons for this include the often involvement of lymph nodes in tuberculous infections {as lymphadenitis constituted the most frequent form of extra pulmonary tuberculosis} and cancer's metastasis. With an effective and nationwide immunisation against tuberculosis, health education on HIV infection coupled with early screening and detection of malignancies in generals, we hope this trend will change in the future. Lymph node biopsy remains an important and valuable diagnostic tool in evaluation of lymph node enlargement as it allows for the architecture of the gland to be viewed thereby given an accurate and concise diagnosis with very minimal risk to the patient.

Adolescent↗

[Clinical study of metastasis of thoracic lymph node in resectable lung cancer].

OBJECTIVE: To study the metastatic pattern of thoracic lymph node in resectable lung cancer. METHODS: From January 1992 to July 1998, the lymph nodes in hilar(N1) and mediastinal(N2) were resected based on their distribution in 160 patiens with resectable lung cancer and were examined by pathology. Number, size and colour of lymph nodes in each regions were recorded. Each lymph node was examined by routine pathology and immunohistochemistry. Quantity of metastatic lymph node was reported according to their regions. RESULTS: 99 cases(61.9%) had thoracic lymph nodes metastasis and 73 cases (45.6%) had mediastinal lymph nodes metastasis. Of those, only N1 metastasis was 16.3%, from N1 to N2 metastasis was 32.5%, only N2 metastasis was 13.1%. The metastatic frequencies in 11, 10, 7, 5 and 4 regions around the hilar or root of lung were 30.0%, 27.5%, 16.9%, 28.8% and 20.0%, respectively. Those were higher than 9, 6, 3, 2 and 1 regions far from the root of lung. The metastatic rate of lymph node in 2.0 cm or greater, 1.0 cm or greater and less than 1.0 cm was 60.7%, 15.5% and 4.3%, respectively (P < 0.001). The smallest metastatic lymph node was only 0.2 cm x 0.2 cm. Statistical analysis revealed that metastatic rate of thoracic lymph nodes was not relevant to different area, size and course of tumors. CONCLUSIONS: The lymph nodes metastases of most cases were spreading from the near to the distant, from lower to upper, through the hilar to the mediastinal. Lymph nodes metastases occurred easier in SCLC than in NSCLC (P < 0.05). It must be depended on pathologic examination to confirm whether or not the tumor has metastasis to lymph node.

Female↗

[Clinical study of the sentinel lymph node of patients with laryngeal and hypopharyngeal carcinomas].

OBJECTIVE: To investigate the methods of detecting the sentinel lymph node of laryngeal and hypopharyngeal carcinomas and its predictive value in the cervical metastasis of the carcinoma. METHODS: In 29 patients who suffered from laryngeal or hypopharyngeal carcinoma with NO neck, the patent blue was injected into the surrounding tissue of the tumor during the operation to identify the sentinel lymph nodes. The sentinel lymph nodes were dyed blue. The frozen histopathology was done during the operation, the lymph nodes at the ipsilateral side of the neck were dissected completely, and the routine histopathology was done as the gold standard to study the predictive value of the sentinel lymph node in the metastasis of the cervical node. RESULTS: Of 29 patients, 28 patients' sentinel lymph nodes were detected successfully during operation. There was an average of 2.5 lymph nodes per side per patient. Most of the sentinel lymph nodes were in the level II and level III regions of the ipsilateral side of the neck, and there were bilateral sentinel nodes in patients suffered from superglottic carcinoma. Three patients' sentinel lymph nodes were found to be positive in the frozen inspection, and the routine histopathology confirmed the result. The micrometastasis rate was 10.7% (3/28). There were no metastatic lymph nodes found in patients who were negative for the sentinel lymph nodes during the operative frozen histopathology. The predicted value of the sentinel lymph nodes to the cervical lymph node metastasis was 100 per cent. CONCLUSION: There is a very important predicted value of sentinel lymph nodes in the cervical metastasis of patients suffered from laryngeal and hypopharyngeal carcinomas. It could reduce the neck dissection in patients with laryngeal and hypopharyngeal carcinomas.

Adult↗

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.

Adult↗

[The role of the body's defense against tumors by regional lymph nodes].

The role of bodily defense against tumor by regional lymph nodes was discussed in this study, especially focused on anti-tumor effect. Anti-tumor immune response was observed in regional lymph nodes in the tumor-bearing mouse. Advance of tumor or distance between lymph nodes and tumor effected the strength of the immune responses. In clinical study, anti-tumor immune response was observed similarly on draining lymph nodes of gastric cancer or colo-rectal cancer by measuring the PHA lymphocyte blastogenesis formation, the natural killer activity and the T-cell subpopulation. The response of regional lymph nodes was suppressed in early stage cases, while that of remote nodes was preserved comparatively. As is stated above, anti-tumor immune response was confirmed in draining lymph nodes. This suggested that at least for early gastric cancer without lymph node metastasis, surgical treatment with limited lymph node dissection should be considered in order to preserve bodily defense mechanism of regional lymph nodes.

Animals↗

Prediction of supraclavicular lymph node metastasis in breast carcinoma.

PURPOSE: Supraclavicular lymph node metastasis in breast cancer patients has a poor prognosis, and aggressive local treatment has usually resulted in severe morbidity. The purpose of this study was to select high-risk neck metastasis patients for prophylactic radiotherapy. METHODS: Between 1990 and 1998, 2658 consecutive invasive breast cancer patients underwent surgery and adjuvant therapy in the hospital. The median age was 47 years (range 22-92). The median follow-up period was 39 months. The following factors were analyzed: age, tumor size, tumor location, histologic type, histologic grade, estrogen and progesterone receptor status, DNA flow cytometry study results, number of positive axillary lymph nodes, use of chemotherapy, radiotherapy, and/or hormonal therapy, and level of involved axillary nodes. RESULTS: Of the 2658 patients, 113 (4.3%) developed supraclavicular lymph node metastasis during this period. Young age (< or =40 years), tumor size >3 cm, high histologic grade, angiolymphatic invasion, negative estrogen receptor status, synthetic phase fraction >4%, >4 positive nodes, and level II or III involved nodes were all significant for predicting neck metastasis in the univariate analysis. Three predictive factors were significant after multivariate analysis: high histologic grade, >4 positive nodes, and axillary level II or III involved nodes. In patients with axillary level I involved nodes and < or =4 positive nodes, the incidence was 4.4%. If axillary level III was involved, the rate of supraclavicular lymph node metastasis was 15.1%. CONCLUSION: The incidence of supraclavicular lymph node metastasis was higher in the groups with >4 positive nodes and in those with axillary level II or III involved nodes. Selective use of comprehensive radiotherapy for these high-risk patients will achieve good locoregional control.

Adult↗

Leiomyomatosis of mesenteric lymph nodes associated with duodenal adenocarcinoma.

Leiomyomatosis of lymph nodes is an extremely rare disease. Only a few cases have previously been reported in pelvic lymph nodes. They were related to a benign uterine leiomyoma, a metastasizing uterine leiomyoma, an endometrial adenocarcinoma, and an ovarian endometrioid carcinoma. We report on a case of leiomyomatosis of the mesenteric lymph nodes associated with a duodenal adenocarcinoma with no history of uterine leiomyoma or any gynecological malignancy. The patient, a 56-year-old woman, was found to have an adenocarcinoma of the duodenum. All mesenteric lymph nodes removed showed leiomyomatosis, which was verified by immunohistochemical study showing positive immunostaining for smooth muscle actin, desmin, and vimentin, but negative staining for HMB-45. It is necessary to make a differential diagnosis from other examples of spindle cell proliferation involving lymph nodes such as a hemorrhagic spindle cell tumor with amianthoid fibers (palisade myofibroblastoma), angiomyolipoma, lymphangiomyomatosis, inflammatory pseudotumor, and Kaposi's sarcoma.

Adenocarcinoma↗

Preoperative lymph-node staging in gastrointestinal cancer--correlation between size and tumor stage.

Our data suggest that lymph-node size is not a reliable indicator for lymph-node metastasis in gastric, esophageal, and colon cancer. Despite a significant difference in diameter of metastatic and non-metastatic nodes, the accurate evaluation of lymph-node metastasis in gastro-intestinal carcinoma cannot be determined by nodal size, because the majority of counted lymph nodes is ?5 mm and the frequency of small lymph-node metastases is high. Therefore imaging techniques using the size as criterion of nodal infiltration can not exactly assess the nodal status of patients with gastro-intestinal carcinomas. For rational lymphadenectomy, the value of sentinel node biopsy in gastro-intestinal cancer is now discussed. At the moment it is too early to apply sentinel node biopsy in order to reduce the extent of lymphadenectomy in these carcinomas [11]. Recent interest has focused on PET scanning in the detection of lymph-node metastases. PET represents a potentially ideal imaging modality for malignancy. It allows a quick and simultaneous assessment of both local and distant sites and, as a result of avid uptake of the glucose moiety, may potentially identify small tumor loads. There are only limited experience in detecting lymph-node metastases in gastro-intestinal carcinoma and the results of the published reports are controversially discussed [12, 13]. Our data demonstrate a high frequency of small lymph-node metastases in gastro-intestinal carcinoma and suggest that a careful histological search for small lymph-node metastases should be undertaken to avoid false-negative lymph-node staging. These results emphasize that a reliable pathological staging of gastro-intestinal cancer must be based on a standardized systematic lymphadenectomy because lymph-node sampling based on lymph-node size is not sufficient.

Gastrointestinal Neoplasms↗

Lymph node size in uterine cancer: A revisit.

To study whether lymph node size is a good predictor of lymph node metastasis in uterine cancer, we reviewed the pathologic sections of pelvic and para-aortic lymph node removed from uterine cancer patients who underwent surgical staging in our institution from January 1994 to December 2004. The long axis of each individual node was measured. Out of 4280 total nodes obtained (178 cases), 86 nodes (28 cases) were positive for metastatic cancer (2.0% of total nodes or 15.7% of cases). Among the positive nodes, 11 nodes (12.8%) had nodal long axis <5 mm, 34 nodes (39.5%) had long axis of 5-9 mm, and 32 (37.2%) and 9 nodes (10.5%) had long axes of 10-19 mm and >20 mm, respectively. More than half (52.3%) of these positive nodal long axes were less than 10 mm. At lymph node size of 10 mm that was the common point of reference for pathologic enlargement, the sensitivity, specificity, negative and positive predictive value of lymph node to predict metastatic cancer were 47.7%, 76.7%, 98.6%, and 4.0%, respectively. From these findings, we tended to conclude that lymph node size is not a good predictor of lymph node metastasis in uterine cancer.

Carcinoma↗

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↗

[Metastasis rates of lymph nodes and distribution in advanced gastric cancer and its clinical significance].

OBJECTIVE: To investigate the characteristics of lymph node metastases in advanced gastric cancer and its clinical significance. METHODS: From April 2002 to July 2003, we studied 91 patients with advanced gastric cancer who underwent radical gastrectomy and lymphadenectomy from which specimens were obtained during surgery. Then, collection of dissected lymph node, histopathological and immunohistological studies were performed to detect the lymph node metastasis rates and calculation. In addition, to analyze the relationship between lymph node metastasis rates and tumor diameters, TNM classification, Borrmann analysis, tumor localization and the extent of lymph node resection. RESULTS: Among 91 patients with advanced gastric cancer, lymph node metastases were found in 63 patients (69.2%) with a total collection of 3149 lymph nodes and an average of 34.6 lymph nodes collected per patient. Lymph node metastasis rate was lower in tumor < 3 cm than that in tumor >3 cm. About TNM classification, lymph node metastases in advanced gastric cancer among patients in stage IIIa and stage IV was 100%, with the lymph node metastasis rates varying from 30.3% to 58.4%, which were significantly higher than that among patients in stage I and II (P<0.001). About Borrmann classification, lymph nodes metastasis in advanced gastric cancer among patients in Borrmann type III (79.6%) was higher than other Borrmann types, while in Borrmann type IV with the highest lymph node metastasis rate of 35.3% (P<0.05). Patients undergone lymph node dissection D(3) had higher lymph node metastases among patients and higher lymph node metastasis rate (88.2%, 38.0%) than patients in the D(1) and D(2) (P<0.05). Among 91 patients, 17 patients was found with micrometastasis (18.7%) from which 183 lymph nodes was collected, but no statistically significant difference between tumor location and micrometastasis was found (P>0.05). For tumor localization, lymph node metastases in proximal gastric cancer were more shown in station 1, 2, 3, 5, 7, 8, 9, 12, 13 and 16, with the highest metastasis rate in station 8 (68.1%). Lymph node metastases in middle gastric cancer were more shown in station 1, 3, 7, 12, 13 and 16, with the highest metastasis rate in station 3 (47.6%). Lymph node metastases in distal gastric cancer were more shown in station 1, 2, 3, 5, 6, 12, 13, and 16, with the highest metastasis rate in station 16 (83.3%). CONCLUSION: Metastasis among patients and lymph node metastasis rates are significantly correlated with the severity of gastric malignancy and they may be valuable guideline to evaluate the extension of lymph nodes dissection in gastric cancer.

Adult↗

Frequency distribution of tissue mast cells and eosinophilic granulocytes in tumor-draining axillary and paracolic lymph nodes.

The frequency distribution of tissue mast cells and eosinophilic granulocytes in tumor-draining lymph nodes was evaluated. In total 483 axillary lymph nodes draining invasive ductal breast cancer and 162 paracolic lymph nodes draining infiltrating adenocarcinoma of the large bowel were analyzed. Significantly higher number of sinus mast cells were found in axillary lymph nodes as compared with the paracolic ones whereas eosinophilic granulocytes were more frequent in paracolic than in axillary lymph nodes. Concerning both cell systems no significant differences could be demonstrated when all lymph nodes from nodal-negative cases were compared with the lymph nodes from cases with regional lymph node metastases. Tumor-free axillary lymph nodes, however, showed a significantly higher mast cell content in the sinus and medulla than did lymph nodes bearing metastases. The number of eosinophilic granulocytes did not differ in either lymph node group.

Adenocarcinoma↗