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PubMed2005

Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles.

Signaling by G protein-coupled receptors coupled to Galpha(i) assists in triggering lymphocyte movement into and out of lymph nodes. Here, we show that modulating the signaling output from these receptors dramatically alters B cell trafficking. Intravital microscopy of adoptively transferred B cells from wild-type and Rgs1-/- mice revealed that Rgs1-/- B cells stick better to lymph node high endothelial venules, home better to lymph nodes, and move more rapidly within lymph node follicles than do wild-type B cells. In contrast, B cells from Gnai2-/- mice enter lymph nodes poorly and move more slowly than do wild-type B cells. The Gnai2-/- mice often lack multiple peripheral lymph nodes, and their B cells respond poorly to chemokines, indicating that Galpha(i1) and Galpha(i3) poorly compensate for the loss of Galpha(i2). These results demonstrate opposing roles for Rgs1 and Gnai2 in B cell trafficking into and within lymph nodes.

Animals↗
PubMed1996

[Differential diagnosis of cervical lymph node enlargements: ultrasound and histomorphology of reactive lymph nodes].

The purpose of this study was to investigate the morphology of reactive lymph nodes of the neck in ultrasound and its histological implications. By revealing a characteristic sonomorphology of reactive lymph nodes we would like to contribute to the differential diagnosis of cervical lymph node enlargements. In 81 patients the morphology and the longitudinal/ transverse axis ratio (L/T ratio) of 257 reactively enlarged lymph nodes were examined. Besides 6 false-positive cases the L/T ratio turned out to be a reliable instrument in detecting reactive lymph nodes. Concerning the nodal texture, 89 lymph nodes (34.6%) appeared homogenously. Those lymph nodes which demonstrated a more complex nodal texture could be assigned to three sonomorphological groups: In 134 lymph nodes (52.1%) a centrally located echogenoic line ("central echogenoic line', CEL) was observed. Its maximal diameter was defined to be maximally up to one third of the lymph node width. In the histological examination this CEL could be identified as a widened hilus with an increased fibrosis. An echogenoic nodal area measuring between one third up to one half of the lymph node width demonstrated histologically a fatty replacement of the hilar tissue. This "echogenoic hilus reflex' occurred in 28 lymph nodes (10.9%). A nearly complete lipomatous atrophy of the lymph node parenchyma was found in 6 lymph nodes (2.4%) demonstrating a "central echogenicity' with just a small peripheral, less echogenoic border corresponding to the remaining parenchyma.

Adult↗
PubMed2003

Prognostic significance of axillary node and infraclavicular lymph node status after mastectomy.

AIMS: The American Joint Committee on Cancer staging system for breast carcinomas has been revised. According to this revised staging system, metastasis to infraclavicular lymph nodes and number of positive axillary nodes have prognostic significance and a new stage, stage IIIC, has been introduced. The aim of this study is to investigate the association of positive axillary nodes by level and number with survival and stage migration between the old and the new stages in a large series of mastectomy patients. METHODS: Data from 1277 consecutive breast cancer patients treated by mastectomy were studied, retrospectively. Prognostic value of number of positive axillary nodes and entirely invasion of apex axillary nodes were analysed. Survival curves were generated by Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazard model. RESULTS: Five-year survival rates for metastasis to axillary level III and for stage IIIC breast cancer were 35.4 and 38.2%, respectively. Metastases to apex axillary nodes, 4-9 and 10 or more positive lymph nodes were found to be adverse and independent prognostic factors for survival in lymph node positive patients. CONCLUSION: Invasion of infraclavicular nodes and 4-9 and > or =10 positive axillary lymph nodes were independent predictors for survival in node positive breast carcinomas in this series. Patients with the new stage IIIC had the worst survival among breast cancer patients.

Adult↗
PubMed2001

Sentinel lymph-node biopsy compared to axillary lymph-node dissection for axillary staging in breast cancer patients.

AIMS: The purpose of this study was to evaluate the feasibility of sentinel lymph-node biopsy in breast cancer patients at our institution and to compare the results of sentinel node (SN) biopsy to standard axillary lymph-node dissection (ALND). METHODS: In a retrospective study the percentage of lymph-node positive patients and the number of micrometastases in 165 breast cancer patients following SN biopsy was compared to 195 patients who underwent ALND of level I and II without SN biopsy. The SN was identified using a combination of vital blue dye and a radiolabelled colloid. RESULTS: Patients and tumour characteristics were comparable between both groups. SN biopsy found no significant difference in the number of node positive T1 cancer patients (SN group: 31/108 (28.7%) -- ALND group: 21/92 (22.8%)) and T2 tumours (SN group: 27/57 (47.4%) -- ALND group: 49/103 (47.6%)) between both groups. Micrometastases were more frequently found in the SN group when compared to the ALND group (six of 70 positive nodes) (P=0.04). CONCLUSION: SN biopsy may be as accurate as standard axillary lymph-node dissection for the evaluation of the axillary lymph-node status in breast cancer patients.

Adult↗
PubMed2005

Dynamic MR lymphangiography and carbon dye for sentinel lymph node detection: a solution for sentinel lymph node biopsy in mucosal head and neck cancer.

BACKGROUND: The practical application of sentinel lymph node biopsy in squamous cell carcinoma of the head and neck is restricted by the time sensitivity of blue dye and lack of spatial resolution and nonspecific node enhancement with radiocolloid. This study evaluates the use of magnetic resonance (MR) lymphangiography and carbon dye labeling to circumvent these limitations. METHODS: Gadomer/carbon dye mixture was injected into the tongue and stifle of adult swine (n = 4). MR lymphatic mapping was followed by intraoperative mapping with isosulfan blue dye. Sentinel lymph node biopsy and completion node dissection were performed 60 minutes after injection in four nodal basins and at 7 days after injection in eight. RESULTS: The technique was successful in all 12 nodal basins. The sentinel lymph nodes were stained black at the time of the immediate and delayed dissections. CONCLUSIONS: MR lymphangiography provides temporal and anatomic localization of the sentinel lymph node with a single investigation. Carbon dye is a sensitive and persistent visual marker of MRI-targeted sentinel lymph nodes.

Animals↗
PubMed2004

Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique: implications for patients with breast cancer.

OBJECTIVE: To assess our long-term complications from complete axillary lymph node dissection (AXLND) in patients with breast cancer. SUMMARY BACKGROUND DATA: Complete AXLND as part of the surgical therapy for breast cancer has come under increased scrutiny due the use of the sentinel lymph node (SLN) biopsy technique to assess the status of the axillary nodes. As the enthusiasm for the SLN technique has increased, our impression has been that the perceived complication rate from AXLND has increased dramatically while the negative aspects of the SLN technique have been underemphasized. METHODS: Female patients seen in routine follow-up over a 1-year period were eligible for our retrospective study of the long-term complications from AXLND if they were a minimum of 1 year out from all primary therapy; ie, surgery, radiation, and/or chemotherapy. All patients had previously undergone either a modified radical mastectomy (MRM) or a segmental mastectomy with axillary dissection and postoperative radiation (SegAx/XRT). All patients had a Level I-III dissection. Objective measurements, including upper and lower arm circumferences and body mass index (BMI), were obtained, and a subjective evaluation from the patients was conducted. RESULTS: Ninety-four patients were eligible for our study; 44 had undergone MRM, and 50 had undergone SegAx/XRT. The average number of nodes removed was 25.6 (standard deviation, 8). Thirty-three percent of the patients had positive nodal disease, 95% of the patients had an upper arm circumference within 2 cm of the unaffected side, and 93.3% had a lower arm circumference within 2 cm of the unaffected side. Subjectively, 90.4% of the patients had either no or minimal arm swelling, and 96.8% of the patients had "good" or "excellent" overall arm function. The most common long-term symptom was numbness involving the upper, inner aspect of the affected arm (25.5%). CONCLUSIONS: Our data indicate that a complete AXLND can be performed with minimal long-term morbidity. The lower the morbidity of AXLND, the less acceptable are the unique complications of the SLN technique.

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↗
PubMed1989

An index for estimating the probability of lymph node metastasis in rectal cancers. Lymph node metastasis and the histopathology of actively invasive regions of cancer.

We examined resected specimens from 40 cases of advanced rectal cancer to determine the extent of microtubular cancer nests and undifferentiated cancer cells (budding). We investigated the relationship between this budding and lymphatic invasion (ly), venous invasion (v), and lymph node metastasis (n), respectively. Moreover, we examined the relationship between ly, budding, and n in the preoperative biopsy specimens of 112 patients, including those of the 40 cases mentioned above. The degree of budding, which was abundant in the actively invasive region, showed a strong correlation with the degree of ly and the existence of n in the resected specimens. Also, budding was recognized in a relatively large portion of the biopsy specimens (52 of 112 [46.4%]) and lymph node metastasis was found in 41 of 52 specimens (78.8%). In 57 specimens, neither ly nor budding was found, and 16 of these specimens (28.1%) had positive lymph nodes. These results implied that the degree of budding in the actively invasive region can be a great help in predicting the presence of n. The presence or absence of budding in preoperative biopsy specimens also can be an important factor (along with the degree of differentiation and ly) in estimating the probability of n.

Adult↗
PubMed1992

[Experimental study of lymph node metastasis in thoracic esophageal carcinoma--regarding lymph node metastasis and changes in lymphatic flow by ultrafine charcoal in rabbit esophageal carcinoma model].

Esophageal carcinoma models were created by transplanting VX2 cells to rabbit esophagus endoscopically. By injecting finely divided activated charcoal into normal rabbit esophagus and tumor sites of esophageal carcinoma model, lymph flow was observed directly. Existence of lymph node metastasis was studied in detailed pathology. In 30 rabbits with upper esophageal carcinoma, lymph node metastasis was seen in 77%. Metastasis to bilateral intrathoracic paratracheal lymph node was seen in 50%, and also concentration of lymphatic flows from tumor site was seen. However, there were no metastasis and no lymph flow to abdominal lymph nodes. While, metastasis to cervical lymph nodes showed around 13%. Esophageal lymphatic flows were also seen reaching the cervical area along the esophagus. In 40 models with mid lower esophageal carcinoma, lymph node metastasis were seen in 88%. Metastasis to right and left thoracic paratracheal lymph nodes was 75% and 53%, respectively, and 25% of metastasis went to cardia lymph nodes. The lymph flows were going up and down around these lymph nodes, and reaching to lymph nodes at upper highest mediastinum or left gastric artery. The metastatic rate to the cervical lymph nodes was about 5%. There were no significant differences in lymphatic metastasis between right and left mediastinum. These findings suggest the necessity of radical dissection for both sides of the mediastinum.

Animals↗
PubMed1990

[Immunohistochemical analysis of T-lymphocyte subsets on the sarcoid lymph nodes using the computerized analytic system for the light microscopic figures: the relation to the histological maturation stages of the lymph nodes].

Lymph nodes obtained from 19 patients with sarcoidosis were classified into four groups according to their histological maturation stages, which were the early stage, the former mature stage, the late mature stage and the healing stage. Immunohistochemical analysis of CD4 positive cells and CD8 positive cells were performed using monoclonal antibodies to these lymph nodes. Then the number of the positive cells per square millimeters of a granuloma was estimated using a computerized analytic system for light microscopic figures. The number of CD4-positive cells per square millimeter of a granuloma was almost constant from the early stage to the mature stage, but inclined to decrease in the healing stage; on the other hand, the number of CD8-positive cells per square millimeter of granuloma decreased extremely in the mature stage, compared with the early stage and the healing stage. Moreover the CD4/CD8-positive cell ratio in granulomas, calculated from these data, was elevated in the mature stage, compared with the early and the healing stages. From the above results, the CD4/CD8-positive cell ratio in a granuloma was demonstrated to be a valuable index for evaluating the histological activity of the granuloma of sarcoid lymph nodes. Furthermore, the decrease of CD8-positive cells in mature stage granuloma was considered to be related to the maturation of the epithelioid cell granulomas in sarcoidosis.

Computers↗
PubMed1999

Lymph node tumor volumes in patients undergoing sentinel lymph node biopsy for cutaneous melanoma.

BACKGROUND: Regional lymph node tumor volumes in patients undergoing sentinel lymph node (SN) biopsy (SNB) for treatment of cutaneous melanoma have not been described. The objectives of this study were to describe the lymph node tumor volumes typically seen in this population and to correlate tumor volumes with tumor thickness and positive SN characteristics. METHODS: Review of a consecutive series of patients with clinically localized cutaneous melanoma who underwent SNB of nonpalpable regional lymph node basins followed by complete lymphadenectomy (LND) was performed. Multiple lymph node sections from positive SNs and nonsentinel nodes (NSNs) in LND specimens were examined microscopically. Individual tumor deposit diameters were measured using an ocular micrometer. Aggregate tumor volumes were calculated for SN and LND specimens. Tumor volumes and SN and LND positivity rates were correlated with tumor thickness, the number of positive SNs, and the presence of multiple SN tumor deposits. RESULTS: SNB procedures were performed for 149 melanomas in 189 regional nodal basins. The mean tumor depth was 2.48 mm. The mean number of SNs/basin was 2.1. Thirty-two of 149 SNB procedures (21.5%) revealed a total of 34 nodal basins with at least one positive SN. The median tumor volume in positive SNs was 4.7 mm3 (range, 0.1-3618 mm3; mean, 209 mm3). The median aggregate tumor volume in positive LND specimens was 4.9 mm3 (range, 0.1-3618 mm3; mean, 224 mm3). Six basins (17.6%) contained at least one positive NSN. The regional node aggregate tumor volume correlated weakly with tumor thickness (Pearson's correlation coefficient = .302, P = .0934). NSN positivity was not predicted by tumor thickness, American Joint Committee on Cancer tumor stage, number of positive SNs, or number of metastatic deposits within SNs. CONCLUSIONS: Most melanoma-positive SNs contain minute tumor volumes. Tumor thickness and patterns of SN metastases may not be predictive of tumor burden or the presence of positive NSNs.

Biopsy↗
PubMed2002

Extraction and analysis of carcinoembryonic antigen in lymph nodes: a new approach to the diagnosis of lymph node metastasis of colorectal cancer.

PURPOSE: To detect lymph node metastasis of colorectal cancer, we extracted protein from lymph nodes and determined the concentration of carcinoembryonic antigen. METHODS: In Experiment 1, a total of 237 lymph nodes from 23 colorectal cancer patients were examined histologically after immersion in 200 microl of saline for 2 hours. Concentrations of protein and carcinoembryonic antigen in each saline sample were determined by protein assay and immunoradiometric assay, respectively. Each value of carcinoembryonic antigen in the saline was divided by extracted protein, and the carcinoembryonic antigen levels in lymph nodes were represented as nanograms per milligram of protein. In Experiment 2, 63 lymph nodes from 8 colorectal cancer patients were cut into 2 pieces and immersed in 1 ml of saline for 15 minutes, and they were subjected to reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen and histologic examination, respectively, after measurement of the carcinoembryonic antigen concentration in the extract. RESULTS: From 236 of 237 lymph nodes in Experiment 1, an average of 3,249.4 microg/ml protein was successfully extracted. Histologic examination revealed that 33 of 236 lymph nodes had colorectal cancer metastases, with a significantly higher concentration of carcinoembryonic antigen on average (655.5 ng/mg protein) than in the 203 lymph nodes without metastasis (18.2 ng/mg protein; P < 0.0001). In Experiment 2, 19 of 63 lymph nodes examined were positive for metastasis in both reverse transcriptase-polymerase chain reaction and histology and showed a significantly higher carcinoembryonic antigen concentration on average (1,003.9 ng/mg protein) than the 42 lymph nodes that demonstrated no metastasis by either method (18.0 ng/mg protein; P < 0.0001). The remaining two lymph nodes, which were positive by reverse transcriptase-polymerase chain reaction but negative by histology, showed high carcinoembryonic antigen concentrations of 514.7 and 61,970.5 ng/mg protein, respectively. CONCLUSION: This simple method of protein extraction and determination of carcinoembryonic antigen concentration in lymph nodes may provide an alternative tool for the diagnosis of colorectal cancer metastasis.

Carcinoembryonic Antigen↗
PubMed1999

An experimental study of surgical treatment for lymphedema in rats: A modified Kinmonth procedure and autologous lymph node capsule-venous anastomosis with lymph node transfer.

This study was carried out in order to determine the effect of various surgical procedures on lymphedema in a rat model. In 26 adult male Sprague-Dawley rats, randomly divided into four groups, surgical lymphedema was created in the left hind limbs.: The control group had no drainage, Group 1 had a conventional Kinmonth operation, Group 2 had a modified Kinmonth operation using the greater omentum and Group 3 had autologous lymph node capsule-venous anastomosis with lymph node transfer. Circumference measurement was performed to calculate percent difference and circumferential reduction rate. In Groups 2 and 3, patent blue violet was injected to identify lymphatics. In all groups, hematoxylin-eosin (H-E) and 5'-nucleotidase stainning were done to evaluate lymphatics histopathologically. The percent difference and the circumferential reduction rate respectively showed the smallest and largest values in Group 2. A significant difference was found between the control group and Group 2 (p < 0.05). Lymphatic vessels were shown by patent blue violet injection in Groups 2 and 3. H-E and 5'-nucleotidase staining revealed patency of lymphatics. A modified Kinmonth procedure using the greater omentum was the most effective procedure for early lymphedema in a rat model and autologous lymph node capsule-venous anastomosis with lymph node transfer was effective for lymph draining in certain conditions, so it may assist in elucidating surgical treatment of lymphedema.

Anastomosis, Surgical↗