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Identification and importance of lymphocyte subpopulations in the regional lymph nodes of breast cancer patients.

To determine whether the presence of metastatic cancer cells in lymph nodes is accompanied by changes in lymphocyte subpopulations identified in tissue sections, the authors studied metastatic and nonmetastatic lymph nodes from eight patients with breast cancer and lymph nodes of three control patients. In all metastatic lymph nodes, T cells were seen in close contact with infiltrating cancer cells; B cells tended to accumulate focally, apart from cancer cell nests. In both metastatic and nonmetastatic lymph nodes from breast cancer patients, the fractional areas occupied by the T4 (helper) and T8 (suppressor/cytotoxic) lymphocytes were comparable. The B-cell fractional area was significantly (p less than 0.01) greater in nonmetastatic than in metastatic nodes. The fractional area occupied by the T8 lymphocytes in the breast cancer patients was significantly (p less than 0.01) greater than in the normal lymph nodes, but no difference was noted in the fractional area occupied by the T4 cells. These findings indicate that all lymph nodes in breast cancer patients are characteristically increased in suppressor/cytotoxic lymphocytes, and the presence of metastatic cancer cells in the nodes is manifested by a depletion of B lymphocytes.

Antibodies, Monoclonal↗

Comparison of antigen presentation by lymph node cells from protein and peptide-primed mice.

Lymph node cells from mice primed with peptides from the allergens Der p I and Der p II (the group I and II allergens of Dermatophagoides pteronyssinus) were unable to recall responses to the protein antigen when cultured in vitro despite being able to mount large responses to the peptides. The T cells could however recall responses to the protein when spleen-adherent cells were added into culture. Treating the spleen accessory cells with the monoclonal antibody (mAb) 33D1 and complement largely abrogated the protein response of peptide-primed T cells which indicates that dendritic cells were mainly responsible for the antigen-presenting function. If mice were primed with two injections of peptide the lymph node cells obtained could respond to both protein and peptides in vitro without the need for exogenous accessory cells. Using either negative depletion with the J11D mAb or positive purification, it was found that the presentation of protein antigen to lymph node T cells primed with either protein or peptide was limited to antigen-specific B cells. Peptide antigens could however be presented by both B and non-B populations. In one case the peptide 105-129 from Der p II which contains a T-cell epitope could not be shown to induce T-cell responses in the lymph node unless presentation was mediated by spleen-adherent or B-specific cells. These results are important for peptide-based immunomodulation and in interpreting results obtained from lymph node cultures.

Allergens↗

Relationship of sentinel and axillary level I-II lymph nodes to tangential fields used in breast irradiation.

PURPOSE: To evaluate the volume of nodal irradiation associated with breast-conserving therapy, we defined the anatomic relationship of sentinel lymph nodes and axillary level I and II lymph nodes in patients receiving tangential breast irradiation. METHODS AND MATERIALS: A retrospective analysis of 65 simulation fields in women with breast cancer treated with sentinel lymph node surgery and 39 women in whom radiopaque clips demarcated the extent of axillary lymph node dissection was performed. We measured the relationship of the surgical clips to the anatomic landmarks and calculated the percentage of prescribed dose delivered to the sentinel lymph node region. RESULTS: A cranial field edge 2.0 cm below the humeral head the sentinel lymph node region was included or at the field edge in 95% of the cases and the entire extent of axillary I and II dissection in 43% of the axillary dissection cases. In the remaining 57%, this field border encompassed an average of 80% of cranial/caudal extent of axillary level I and II dissection. In 98.5% of the cases, all sentinel lymph nodes were anterior to the deep field edge and 71% were anterior to the chest wall-interface, whereas 61% of the axillary dissection cohort had extension deep to the chest wall-lung interface. If the deep field edge had been set 2 cm below the chest wall-lung interface, the entire axillary dissection would have been included in 82% of the cases, and the entire sentinel lymph node would have been covered with a 0.5-cm margin. The median dose to the sentinel lymph node region was 98% of the prescribed dose. CONCLUSIONS: By extending the cranial border to 2 cm below the humeral head and 2 cm deep to the chest wall-lung interface, the radiotherapy fields used to treat the breast can include the sentinel lymph node region and most of axillary levels I and II.

Axilla↗

The biologic features of intramucosal gastric carcinoma with lymph node metastasis.

This review concentrates on the clinicopathologic studies and molecular biologic studies of intramucosal gastric carcinomas (IMGCs) with lymph node metastasis that have been published to date. There have been several reports in which IMGCs with lymph node metastasis were compared with IMGCs without lymph node metastasis from the view of clinicopathologic features. However, there have been a few reports in which IMGCs with lymph node metastasis were compared with IMGCs without lymph node metastasis from the view of molecular biologic features. In general, IMGCs with lymph node metastasis have been commonly reported to be large lesions, poorly differentiated adenocarcinoma, and associated with peptic ulcer, in comparison with IMGCs without lymph node metastasis. Regarding genetic studies or molecular biologic studies, only DNA distribution pattern, proliferative cell nuclear antigen and the monoclonal antibody Ki-67, or matrix metalloproteinases 2 and 9 have been investigated in IMGCs with lymph node metastasis. The malignant potential of the carcinoma cells cannot been evaluated by a clinicopathologic study with the use of hematoxylin and eosin staining. It may be unavoidable that minimal operation is widely accepted for the treatment of IMGCs. It may be more essential to establish the staging by both clinicopathologic and molecular biologic examinations to rule out the presence of IMGCs with lymph node metastasis.

Adenocarcinoma↗

B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization.

Dendritic cell (DC) migration from the periphery to lymph nodes is regulated by the pattern of genes expressed by DCs themselves and by signals within the surrounding peripheral environment. Here, we report that DC mobilization can also be regulated by signals initiated within the downstream lymph nodes, particularly when lymph nodes enlarge as a consequence of immunization. Lymph node B lymphocytes orchestrate expansion of the lymphatic network within the immunized lymph node. This expanded network in turn supports increased DC migration from the periphery. These results reveal unique relationships between B cells, lymphatic vessels, and migratory DCs. Knowledge that DC migration from the periphery is augmented by B cell-dependent signals reveals new potential strategies to increase DC migration during vaccination.

Animals↗

Real-time endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes.

STUDY OBJECTIVES: Although various techniques are available for obtaining pathology specimens from the mediastinal lymph nodes, including conventional bronchoscopic transbronchial needle aspiration (TBNA), transesophageal ultrasonography-guided needle aspiration, and mediastinoscopy, there are limitations to these techniques, which include low yield, poor access, need for general anesthesia, or complications. To overcome these problems, we undertook the current study to evaluate the clinical utility of the newly developed ultrasound puncture bronchoscope to visualize and perform real-time TBNA of the mediastinal and hilar lymph nodes under direct endobronchial ultrasonography (EBUS) guidance. DESIGN: Prospective patient enrollment. SETTING: University teaching hospital. PATIENTS: From March 2002 to September 2003, 70 patients were included in the study. INTERVENTIONS: The new convex probe (CP) EBUS is integrated with a convex scanning probe on its tip with a separate working channel, thus permitting real-time EBUS-guided TBNA. The indications for CP-EBUS were the diagnosis of mediastinal and/or hilar lymphadenopathy for known or suspected malignancy. Lymph nodes and the surrounding vessels were first visualized with CP-EBUS using the Doppler mode. The dimensions of the lymph nodes were recorded, followed by real-time TBNA under direct EBUS guidance. Final diagnosis was based on cytology, surgical results, and/or clinical follow-up. RESULTS: All lymph nodes that were detected on the chest CT scan could be visualized using CP-EBUS. In 70 patients, CP-EBUS-guided TBNA was performed to obtain samples from mediastinal lymph nodes (58 nodes) and hilar lymph nodes (12 nodes). The sensitivity, specificity, and accuracy of CP-EBUS-guided TBNA in distinguishing benign from malignant lymph nodes were 95.7%, 100%, and 97.1%, respectively. The procedure was uneventful, and there were no complications. CONCLUSIONS: Real-time CP-EBUS-guided TBNA of mediastinal and hilar lymph nodes is a novel approach that is safe and has a good diagnostic yield. This new ultrasound puncture bronchoscope has an excellent potential for assisting in safe and accurate diagnostic interventional bronchoscopy.

Adult↗

Immunomorphologic lymph node changes in rats bearing experimental breast tumors.

In this paper regional lymph nodes draining tumors and also nonregional lymph nodes have been studied at the light- and electron-microscopic levels. These nodes were obtained from rats bearing long-evolving autochthonous breast cancers. They were compared with a control group of the same age. A morphometric quantitative analysis was done to evaluate immunologically competent cell populations. In the experimental group there were no differences between regional and distal lymph nodes in the tumor challenge. However, when the experimental group was compared with the control group, differences appeared. The changes involved were diminution of the paracortical area with stimulation of plasma cells in the medullary cords. Ultrastructurally, in lymph nodes of the experimental group there were lymphoblasts in the paracortex and germinal centers, suggesting active lymphopoiesis. In addition, many plasma cells showed morphologic evidence of involution or other alterations. It is suggested that regional and distal lymph nodes have similar morphologic behavior when the tumor grows for a long period of time, a finding that contributes to our knowledge of the systemic implications of the lymphatic system.

Animals↗

CT of interpectoral lymph nodes.

The presence of lymph nodes between the pectoralis major and minor muscles (Rotter's nodes) has been noted in the anatomic and surgical literature. We analyzed the appearance of the interpectoral space and nodes on chest CT scans of 25 patients without known chest wall abnormalities or causes for lymphadenopathy. In some of these cases small structures were detected in the interpectoral fat that could be either vessels or nodes. In addition we studied chest CT scans in six patients with interpectoral adenopathy due to metastases from breast cancer. The nodes were oval soft-tissue densities ranging from 1.5 X 1 cm to 3.5 X 3 cm in diameter.

Breast Neoplasms↗

[Flow cytometric analysis of DNA content of urinary bladder cancers--study on primary tumors and metastasized lymph nodes].

PURPOSE: This study was designed to evaluate DNA ploidy patterns and metastatic patterns between primary tumors and metastatic lymph nodes in bladder tumor patients with lymph node metastases. METHODS: Flow cytometry (FCM) was used to study the DNA ploidy. The DNA ploidy patterns in 16 lymph node metastases in relation to the degree of ploidy in the primary bladder tumor were evaluated in 63 patients who underwent total cystectomy. RESULTS: The primary tumor that had metastasized was G3 tumor in grade and over pT2 in stage in many cases. Thirty-nine diploid tumors had given raise to lymph node metastases in only 5 cases (13%), whereas 11 cases (46%) of aneuploid tumors had metastasized (p < 0.01). With regard to ploidy patterns between primary tumors and the corresponding lymph node metastases, four patterns were noted, namely D-->D (5 cases), D + A-->D (4), A-->A (5) and A-->D (2) (D: DNA diploid, A: DNA aneuploid). The DNA index between the primary tumors and the corresponding lymph node metastases was the same in all but 2 cases (14/16.88%). In cases with lymph node metastases, the prognosis was very poor whether or not the DNA ploidy of the primary tumors or the metastatic tumors was DNA aneuploid. CONCLUSION: These data suggest that a malignant cell on the primary tumor metastasized to the lymph node in many cases.

Aged↗

Omission of mediastinal lymph node dissection in lung cancer: its techniques and diagnostic procedures.

To reduce or omit a mediastinal lymph node dissection in the patients with clinical stage I non-small cell lung cancer (NSCLC), several authors examined the prevalence of metastatic sites of lymph nodes. Because lymphatic drainage usually heads for the upper mediastinum in upper lobe cancer and for the lower mediastinum in lower lobe cancer, upper and lower mediastinal lymph node dissection could be reduced in lung cancers of lower lobe and upper lobe. By using sentinel node (SN) navigation surgery, it is possible to omit mediastinal lymph node dissection. Radiological findings are also useful to determine reduction of mediastinal lymph node dissection. In clinical stage Ia adenocarcinomas that show ground glass opacity (GGO) findings on computed tomography (CT) or negative for fluorodeoxyglucose accumulation on positron emission tomography (PET), mediastinal lymph node dissection can be omitted, because these types of adenocarcinomas rarely metastasize to the lymph nodes. By using these procedures, mediastinal lymph node dissection can be reduced or omitted with little risk of local recurrence.

Carcinoma, Non-Small-Cell Lung↗

Ultrasonographic evaluation of neck and supraclavicular lymph nodes metastasized from lung cancer.

The significance of ultrasonography in the evaluation of metastasized neck and supraclavicular lymph nodes from lung cancer was analyzed. By ultrasonography, the lymph nodes could be visualized clearly as low-echogenic round areas, and the size could be precisely measured in three dimensions. It was also possible to diagnose whether or not the lymph node adhered to the surrounding tissues and to determine the relationship and the connection of supraclavicular lymph node and upper mediastinal lymph node. The therapeutic effect related to the size of the lymph node was evaluable by ultrasonography. Therefore, the ultrasonographic approach to the neck and supraclavicular lymph nodes metastasized from lung cancer is considered to be useful for clinical use.

Clavicle↗

Lymphography and computed tomography in lymph node metastases from malignant melanoma.

Contrast lymphography and regional computed tomography (CT) were performed prior to lymph node dissection in 49 patients with clinical suggestion of lymph node metastases from malignant melanoma. The overall specificity and sensitivity for lymphography was 62% and 70%, respectively, and for CT 83% and 70%, respectively. There was 67% concordance of the radiologic reports. The combined modality sensitivity and specificity were 79% and 84%, respectively. Clinical lymph node examination was poor in accurately diagnosing lymph node involvement with melanoma (42% true positive, 58% false positive). Lymphography produced too many false negative and false positive reports to be of value in detecting lymph node metastases on its own. CT was slightly superior to lymphography in correctly predicting the lymph node status of the upper extremity. The present clinical and radiologic techniques would seem to be inadequate for detecting lymph node metastases in malignant melanoma.

Humans↗

[Lymph node excision in cancer of the stomach].

Lymph node involvement is the major prognostic factor in gastric carcinoma. The benefit of extended regional lymph node dissection D2 is still controversial. For Japanese, these dissection can improve significantly long-term survival, while in western countries discussion is still open. Rationale for extensive lymphadenectomy in Japan is based on the results of many studies about lymph node (number involved, number resected per station, ratio, location, grouping, radical clearance ...). However, these studies are not controlled studies. Four prospective randomized controlled studies comparing D2 to D1 in the curative treatment of gastric cancer were performed during the 10 last years. Currently, all have failed to demonstrate any improvement on survival after D2. But in the two last studies, final survival results are pending for two years. On the other hand, mortality and morbidity of D2 are significantly higher, particularly because of anastomotic leakage, and distal pancreatectomy and/or splenectomy. Benefit of D2 dissection in general practice of curative gastric cancer surgery is not proved. A middle position, as a D "1.5" dissection, avoiding distal pancreatectomy, might be suggested. Final survival results could counterbalance the negative effects of D2 on morbidity and mortality, and would question present data.

Anastomosis, Surgical↗

Elective inguinal lymph node irradiation for pelvic carcinomas. The University of Florida experience.

BACKGROUND: There is little published information pertaining to elective inguinal lymph node irradiation for carcinomas originating in the pelvis that place the inguinal lymph nodes at risk. METHODS: Between October 1964 and October 1988, 164 patients with primary carcinomas originating in the pelvis that placed the inguinal lymph nodes at risk for subclinical disease received elective inguinal lymph node irradiation at the University of Florida. All patients had a minimum follow-up of 2 years from the start of radiation therapy. Primary sites included the penis, urethra, vulva, anal canal, distal rectum (within 4 cm of the verge), and the cervix or vagina when the tumor involved the distal one-third of the vagina. In 148 patients, both groins were clinically negative; in 16 patients, one groin was positive and the other negative by clinical examination. Treatment techniques were individualized according to the primary site. Tumor doses to the inguinal lymph nodes varied, although more than 70% of patients received 4500-5000 cGy (range, 2650-6780 cGy) over 5 weeks (range, 2-7 weeks) at 180-200 cGy per fraction. Patients were excluded from the analysis of disease control in the inguinal area if they died less than 2 years from treatment with the inguinal lymph nodes continuously disease free or if they experienced recurrence at the primary site with the inguinal lymph nodes clinically negative at the time of recurrence. RESULTS: The inguinal lymph node control rate was 96% (101 of 105). No patient in whom recurrent disease developed in the inguinal lymph nodes underwent salvage therapy. CONCLUSIONS: Elective irradiation of the inguinal lymph nodes is highly effective in controlling subclinical disease from carcinomas originating in the pelvis and can be accomplished with minimal acute or long-term complications.

Adult↗

Clinical significance of sentinel lymph node involvement in malignant melanoma.

In the period 1997-2002, sentinel lymph node (SLN) surgery was performed on 179 primary skin melanoma patients, one to two months after the removal of the primary. Staining with patent blue was combined with an isotope technique. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph node was followed, preferably within 2-3 weeks, by regional block dissection. In these cases interferon-a2 in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26/177 patients (14.7%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p<0.00001). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007 respectively). Comparison of the tumor thickness and positive SLN by discriminance analysis, yielded 81.7% and 79.9%, respectively for correct classification rates. Based on our study and data from the literature, we suggest SLN-positivity as equally strong poor prognosis factor for skin melanoma as the tumor thickness.

Biomarkers, Tumor↗

Electrical impedance scanning-application of this new technique for lymph node evaluation in children.

BACKGROUND: Precise assessment of lymph nodes is crucial to the choice of therapy and prediction of outcome in cases of malignancy. Electrical impedance scanning (EIS) is being experimentally investigated for potential use as a diagnostic tool for differentiation of malignant lesions. Malignancies show different electrical properties with changes in conductivity and capacitance that can be analysed by EIS. Using a TransScan TS-2000 (TransScan Medical, Migdal Ha'Emek, Israel, distributed by Siemens-Elema AB, Solna, Sweden), EIS has been used in various studies for the identification of breast cancer as well as for characterisation of superficial lesions. OBJECTIVE: To evaluate the reliability of EIS for classifying lymph nodes in a pediatric population with sonographically suspicious lesions and to prove its accuracy. MATERIALS AND METHODS: The study population consisted of 77 children (42 boys, 35 girls) aged 1.1-17.1 years. All EIS results were compared to either histopathological findings or long-term follow-up investigations. RESULTS: Sensitivity for malignancies using EIS was 75% and specificity was 87%. The negative predictive value was 93% and the positive predictive value was 60%. CONCLUSIONS: This study suggests the potential usefulness of EIS as an additional imaging modality for the differentiation of lymph-node diseases in children. The histopathological spectrum of malignant lymph node transformation in children compared to studies in adults, and the characteristic meltdown in inflammatory or granulomatous transformed nodes, pose challenges to differentiation based on sonographic evaluation, and also to EIS classification.

Adolescent↗

Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging.

BACKGROUND: The use of computed tomography in mediastinal staging of lung cancer relies on the premiss that malignant lymph nodes are larger than benign ones. This hypothesis was tested by linking node size and presence or absence of malignancy and looking at factors possibly influencing the size of benign nodes. METHODS: All accessible mediastinal lymph nodes were taken from 56 consecutive patients with lung cancer who underwent thoracotomy. Nodes were measured and histologically examined. Resected cancer bearing lung from 44 of these patients was assessed for degree of acute and chronic inflammation. RESULTS: Lymph node size was not significantly related to the presence of metastatic disease, 58% of malignant and 43% of benign lymph nodes measuring over 15 mm. Similarly, there was no statistically significant relation between size of lymph nodes and the likelihood of malignancy, 20% of lymph nodes of 10 mm or more but also 15% of those less than 10 mm being malignant. Thresholds of 15 and 20 mm showed similar results. The maximum size of benign lymph nodes was significantly greater in those patients with histological evidence of acute pulmonary inflammation than in those without. CONCLUSIONS: The study shows that in patients with lung cancer (1) malignant mediastinal lymph nodes are not larger than benign nodes; (2) small mediastinal lymph nodes are not infrequently malignant; and (3) benign adenopathy is more common in patients with acute pulmonary inflammation.

Adenocarcinoma↗

The distribution of large dividing lymph node cells in syngeneic recipient rats after intravenous injection.

The distribution of large dividing lymph node or thoracic duct lymph cells, labeled in vitro with (3)H-thymidine, was studied in syngeneic recipient rats after intravenous injection. In most experiments the donor rats had been immunized with Bacillus pertussis 4 days earlier, but in some instances cells from nonimmunized donors were used. In smears, the labeled donor cells had the appearance of large lymphocytes or large pyroninophilic cells. By electronmicroscopy, the majority of labeled donor cells were seen to have only scanty endoplasmic reticulum. It was found that the labeled cells rapidly "homed" to lymphoid tissue and recirculated in the recipient, in a fashion resembling that of small lymphocytes. However, the distribution of labeled cells was found to depend upon the source of the donor cells. Cells from mesenteric lymph nodes or thoracic duct lymph showed a marked preferential accumulation in lymphoid tissue within or adjacent to the intestine, whereas cells from peripheral nodes accumulated preferentially in peripheral lymph nodes. Cells from any of these sources showed an equal tendency to accumulate in the white pulp of the spleen. Suspensions of small lymphocytes, labeled in vitro with (3)H-uridine, did not display a similar tendency to localize preferentially in lymphoid tissue in certain regions. It was also found that large dividing lymph node cells from donors immunized with an antigen (2,4-dinitrophenyl-bovine gamma globulin (DNP-BGG) or B. pertussis) showed a greater tendency to accumulate in a recipient lymph node containing that antigen than in the contralateral node. It was not determined whether the selective accumulation of large dividing lymphoid cells from different sources in lymphoid tissue of different regions in recipients was due to an antigen recognition mechansim or was the result of two different populations of cells with different "homing" mechanisms.

Animals↗