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[Cytokinetics of lymph nodes in lymph nodes in lymphatic system diseases (author's transl)].

Untreated malignant lymphatic system diseases are characterized by a preponderance of cell new formation (proliferation) against the destruction of lymphatic cells. If the lymph nodes are enlarged during these diseases, then cell new formation occurs largely or mostly in these lymph nodes. The proliferating cells of the lymph node are bigger than small lyphocytes and have, in general, a mean diameter of the nucleus of 10 mu and more. In normal lymph nodes they belong morphologically to the big lymphocytes, immunoblasts and plasmoblasts. In pathological lymph nodes they have to be looked for among the bigger cells of the disease-specific cell population. Whereas in healthy lymph nodes and in chronic lymphatic leukemia only about 1% of lymph node cells was found to proliferate, they amount on the average to 5% in lymphomas of lymphogranulomatosis and mostly to 30--50% in the lympho-reticulosarcoma (lymphoblast and immunoblast sarcoma, corresponding to large-cell, poorly differentiated lymphomas). The proliferating cells often appear as foci in the lymphomas. The generation times of the proliferating cells both in normal and pathological lymph nodes are about 24 hrs. or slightly longer. In lymphatic proliferation, apart from plasma cells big and smallymphocytes are produced in the normal lymph node; in CLL, big and small lymphocytes, in lymphogranulomatosis, big and small lymphocytes and Hodgkin-cells, and in poorly differentiated lymphomas, the corresponding lymphoma cells are produced. The clinicist is at the beginning of drawing conclusions from prevalent kinetic disturbances.

Cell Division

Killer cell (K) activity in human normal lymph node, regional tumour lymph node and inflammatory lymph node.

Human normal lymph nodes, irrespective of their anatomical site of origin, have a low K cell activity, which may not be detected except with the appropriate target cell and at high lymphocyte to target cell ratios (100:1). This very low killer cell activity is also found in all the homolateral axillary nodes of patients with clinical stage I and II carcinoma of the breast and in the regional draining nodes of a variety of solid tumours, whether small and localized or large and with extensive spread. In all cases proximity to the tumour and obious hyperplastic changes in the nodes have no modifying effect. This pattern of minimal reactivity is similarly found with tonsillar lymphocytes and with nodes draining inflammatory foci. The Fc and C3 receptors on surface membranes are dectected with ease, and pretreatment of lymphocytes by incubation, washing and enzymatic treatment fail to alter their reactivity, thus excluding effector cell inhibition by immune complexes. The killer cell activity of lymphocytes from the blood of breast tumor patients is similar to the activity of lymphocytes from healthy controls.

Binding Sites

T and B lymphocyte populations in human normal lymph node, regional tumour lymph node and inflammatory lymph node.

We have determined the T and B lymphocyte subpopulations in normal human lymph nodes. The lymphocyte profile was the same irrespective of the anatomical distribution and was similar to that found in peripheral blood with identical T and B cell values but with a lower Fc and a higher C3-receptor-bearing lymphocyte subpopulation. This pattern showed a marked change in the regional nodes of patients with mammary carcinoma and nodes draining a variety of other solid tumours, with a fall in T and pronounced elevation of B, Fc and C3 cells but with a persistence of C3 predominance. The lymphocyte profile found in tonsils and nodes draining inflammatory foci was a similar but further exaggeration of the tumour node pattern, with reversal of T and B cell ratios. The T and B lymphocyte percentages in the peripheral blood of patients with clinically localized breast cancer are identical to those of the healthy controls. Different Fc/C3 subsets exist in peripheral blood and lymphoid structures and probably represent a differential functional heterogeneity. Proximity of tumour to the draining node modified this profile.

B-Lymphocytes

A three-dimensional reconstruction of metastatic adenocarcinoma in lymph node.

Lymph nodes are a common site of metastatic cancer. The ability to view the three-dimensional configuration of complex biological structures, rendered in solid model form, might help to further elucidate the pathophysiology of metastatic disease. This paper presents a method for three-dimensional reconstruction from serial sections of a lymph node containing metastatic adenocarcinoma. The reconstruction and subsequent animation were carried out using the P3D graphics software (developed at the Pittsburgh Supercomputing Center) and rendered by the Dore high-speed renderer on an Ardent Titan graphics workstation. As different views of the model were produced, they were recorded a frame at a time on U-matic video tape. A three-dimensional solid-modeled object portrays metastatic, neoplastic elements within a lymph node.

Adenocarcinoma

Cyclophosphamide-dependent lymph node modification in lymph node metastasis of MM48 tumor cells in syngeneic mice.

We investigated the role of immunosuppressive activity induced in the regional lymph nodes (RLN, popliteal lymph nodes) in the establishment of lymph node metastasis by cyclophosphamide (CY) administration. The CY treatment led to the elimination of suppressive activity with the appearance of positive immune responses, and the inhibition of lymph node metastasis of MM48 tumor cells. In CY-treated mice, the removal of RLN together with the primary tumor lowered the survival rate compared with the mice in which the RLN remained intact. During 4 days after primary tumor resection, the proliferation of tumor cells in the RLN was significantly decreased in CY-treated mice. These results suggested that the induction of suppressive activity in the lymph node is closely associated with the establishment of lymph node metastasis.

Animals

[The magnetic resonance tomographic differential diagnosis between reactively enlarged lymph nodes and cervical lymph node metastases].

A prospective study was carried out involving 27 patients to determine whether MRT can distinguish between lymph node metastases and reactive lymph node enlargement. The results of MRT were compared with the pathological findings. Using T1 and T2 weighted sequences and proton density sequences it was not possible to differentiate between reactively enlarged lymph nodes and lymph node metastases. Following the administration of Gd-DTPA the observation of central hypo-intensity with marginal hyper-intensity is a reliable sign of a lymph node metastasis. Using the criterion of length greater than 10 mm for lymph node metastases results in a specificity of 32% and sensitivity of 75%. The use of the sonographic maximal/cross measurement quotient > 2 in the axial/coronary/sagittal dimension improves specificity and sensitivity to 94%.

Contrast Media

[Endoscopic-radiological demonstration of the gastrointestinal lymph nodes and lymph vessels].

Using an intragastric contrast medium (Lipiodol) the paragastric lymph nodes of 23 patients were lymphangiographed prior to laparotomy. The patients suffered from gastric or duodenal ulcers (15 cases), postresectional ulcers (3 cases), or gastric carcinoma (5 cases). The surgically resected material was examined by radiological and histological techniques. The following results were obtained: 1. After application of the contrast medium the paragastric lymph nodes could firstly be seen 5 hours later and even after 7 days and more. 2. The radiographs presented typical storage phenomena with granular or clod-like structures as an equivalent of the inflammatory lymph node alterations. Histologically a marked sinus catarrh with lipid laden reticulum cells and multinuclear giant cells of the foreign body types was observed. 3. In gastric carcinoma characteristic storage defects up to complete destruction of the lymph nodes were found as a roentgenological equivalent of lymph nodes metastases. In addition there were occasionally abnormal courses of the lymphatic vessels with variations in diameter and bizarre storage formations. 4. The described method provides a helpful tool in the diagnosis of gastric lesions. No side effects have been observed.

Adolescent

[Analysis of lymph node status and lymph node morphology in cervix cancer operated by the Wertheim-Meigs-Okabayashi method].

We evaluated in the histologic labor, of the Department of Obstetrics and Gynaecology of the Tübingen University 133 specimens of cervical carcinomas stages I and II operated on according to Wertheim-Meigs-Okabayashi. Topic of this analysis is lymph node status, concomitant alterations and lymphangiosis carcinomatosa. On the average 22.1 lymph nodes (1-58) have been removed. 12.8 per cent of cervical carcinomas had metastases, on the average 3 ones. 78.6 per cent of the metastases were localized in nondilymphatici interiliaci, 14.3 per cent in nodi iliaci communes. 5-year survival with metastases was 70.6 per cent, without 90.5 per cent. Over all a lymphangiosis carcinomatosa in 20.3 per cent was detectable. In 59.9 per cent of the lymph node metastases additionally a lymphangiosis carcinomatosa was present, on the contrary only 9.9 per cent of tumour-free ones. 5-year survival with lymphangiosis carcinomatosa was 70.4 per cent and 92.4 per cent without. Regressive changes, mostly as vacat fat, were observed in like the same percentage both in tumour positive and tumourfree lymph nodes.

Adenocarcinoma

[Reactive enlargement of cervical lymph nodes and cervical lymph node metastases: sonography (M/Q quotient) and computed tomography].

Ranking of sonographic maximum/transverse diameter quotients was compared with the ranking of CT in respect of identification and exclusion of cervical lymph node metastases. Both sonography and CT are distinguished by a high degree of sensitivity in the imaging of cervical lymph node metastases. Sonography, with the assistance of the maximum/transverse diameter quotient, can differentiate between benign enlarged and non-enlarged lymph nodes on the one hand and cervical lymph node metastases on the other, with a safety of 95 per cent. CT can yield definite information regarding the tumour status only after contrast medium administration under the criteria of central hypodensity and peripheral marginal enhancement. CT is much less specific than the sonographic M/T quotient (66% vs 95%). Accuracy of sonography (94%) is clearly superior to that of CT (79%).

Adult

Type-oriented therapy for gastric cancer effective for lymph node metastasis: management of lymph node metastasis using activated carbon particles adsorbing an anticancer agent.

Activated carbon particles are taken selectively up by lymphatics when injected into the tissues and visualize regional lymph nodes colored black. Furthermore, carbon particles adsorb a large amount of the anticancer agent mitomycin C (MMC) on their surface and release the drug reversibly. Using these properties of activated carbon particles, we have applied it for lymph node dissection and chemotherapy of lymph node metastasis. After injection of carbon particles, regional lymph nodes of the stomach were found to be black; blackened lymph nodes extending widely from perigastric to para-aortic nodes were identified from other structures. Four hundred and twenty-four patients with gastric cancer were treated with this method for lymph node metastasis during 1984-1988. Involved nodes were generally colored in high incidence, about 70% of involved ones except for highly positive nodes, which was the same as noninvolved nodes. In highly positive nodes, the colored incidence was decreased to about 48%. The cumulative 5-year survival rate of the patients treated with this series was 74.6%, which was significantly higher than the figures without this method.

Carbon

Extraperitoneal endoscopic pelvic lymph node dissection vs. laparoscopic lymph node dissection in the staging of prostatic and bladder carcinoma.

Eighteen patients undergoing laparoscopic pelvic lymphadenectomy were compared with eighteen patients undergoing lymph node dissection performed via a totally extraperitoneal approach called extraperitoneal endoscopic pelvic lymph node dissection. Operative time, nodal yield, and hospital stays were essentially the same in both groups. However, the laparoscopic approach had a greater incidence of morbidity, leading the authors to adopt a totally extra-peritoneal endoscopic approach to pelvic lymph node dissection. Advantages of using an extraperitoneal approach are presented.

Aged

[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

[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

[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

[Study of para-aortic lymph node metastasis of gastric cancer subjected to superextensive lymph node dissection].

Para-aortic lymph nodes (n4), were dissected out to the technical extreme (superextensive lymph node dissection) from 129 gastric cancer cases, and were subjected to the histological study for metastasis. Following observations led us to the conclusions in reference to the significance of n4 node dissections on curability of surgery. 1) Among 25 cases with n4(+) metastasis n3 was free [n3(-)] in 11 cases (44.0%). 2) ps(+) cancer presented high rate of n4(+) (31.5%). 3) n4(+) occurred irrespective of the location of the cancer, with particularly high rate of occurrence among CMA and cancers. 4) The rate of the metastasized lymph nodes to the total number of the n4 lymph nodes, was found low (34.9%) in cases with n3(-), and high (90.1%) with n3(+). 5) The cumulative survival rate of the cases with n4(+) was found significantly high with n3(-), as compared to n3(+) cases. The lymphatic drainage from the stomach seems more direct and/or more abundant to the n4 than to the n3 nodes. Such observation coincides with our experience that the n4 nodes are involved in metastasis in earlier timing and in higher incidence than n3 nodes. These results warn the present evaluation of curability in which the n4 node dissection is not performed. It is our opinion that the thorough dissection extended to the n4 nodes (superextensive lymph node dissection) is warranted, particularly in order to improve the curability of n3(-)-n4(+) cases.

Aorta, Abdominal

[Contrast retention in retroperitoneal lymph nodes after lymphography; the effect of lymph node abnormalities, radiotherapy and contrast quantity].

The rate of contrast loss from retroperitoneal lymph nodes after lymphography was studied radiologically over a prolonged period in 302 patients. It varied remarkably, even in normal persons who were not receiving any treatment. Lymph nodes empty more quickly if only a small quantity of contrast has been used. Irradiation accelerates contrast transport, not only in the irradiated, but also in the neighbouring, group of nodes. This effect is dose dependent. There is evidence that pathological lymph nodes empty more quickly than normal ones.

Adult

[Correlation of lymph node size and metastatic involvement of lymph nodes in bronchial cancer].

For preoperative staging in lung cancer mediastinoscopy is in competition with X-ray, tomography, and computer-tomography (CT). Many authors certify a high sensitivity and specificity to CT in staging lung cancer preoperatively by measuring the diameter of the hilar and mediastinal lymph nodes. In this study we measured the diameter of 162 lymph nodes from 83 patients postoperatively. In view of staging we found no sufficient correlation between the diameter of the lymph nodes and their infiltration by cancer cells. Even 35.7% of the nodes with a diameter of more than 2 cm were not infiltrated. The data support the opinion that CT alone is not sufficient for preoperative staging in lung cancer.

Adenocarcinoma