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Ranking of allergenic potency of rubber chemicals in a modified local lymph node assay.

A modified local lymph node assay (LLNA) with ex vivo tritium thymidine (3H-TdR) labeling of the proliferating lymph node cells was used for determination of the allergenic potency of chemicals used in the production of rubber for latex medical gloves. Fifteen chemicals known to induce contact hypersensitivity reactions in man, including various thiuram, carbamate, and benzothiazole compounds, and one amine were tested. The EC3 (effective concentration inducing a 3-fold increase in proliferation of lymph node cells [Stimulation Index, SI = 3]) was calculated with nonlinear regression analysis, including a bootstrap method for determination of the 5-95% confidence interval of the EC3 value. This procedure identified 14 out of the 15 chemicals tested as sensitizers, while for one chemical, ZDBC, no EC3 could be calculated due to low responses and a lack of a dose-response relationship in the data obtained. The ranking order of the chemicals with increasing EC3 values (and thus decreasing allergenic potency) was found to be in the following order: ZDEC < TMTD < TETD < ZPC < ZDMC < MBTS < PTD < TMTM < MBT < MBI < PTT < ZMBT < TBTD < DEA < ZDBC. Our results indicate that the chemicals of choice for use in the production of natural rubber latex products would be for the thiuram compounds, TBTD; for the carbamates, ZDBC; and for the benzothiazoles, ZMBT. However, one has to be aware that besides potency, the total amount of residual chemical present in the final product is also important for allergy induction.

Administration, Cutaneous↗

[Application of endoscopic ultrasonography in the diagnosis of mediastinal lymph node metastasis].

OBJECTIVES: To calculate the rate of detection for mediastinal lymph nodes and to set up a criteria for the diagnosis of metastatic mediastinal lymph nodes in lung neoplasm by means of endoscopic ultrasonography (EUS). METHODS: In 21 patients with lung cancer who underwent preoperative EUS on mediastinal lymph nodes, 103 lymph nodes detected by EUS were resected and confirmed pathologically all. The difference between benign and malignant lymph nodes was analysed statistically. RESULTS: The rates of metastatic lymph nodes detected by EUS were significantly higher than these of non-metastatic lymph nodes (chi(2) = 11.752, P = 0.01) in levels 5, 7, 8, and 9 of mediastinal lymph node staging map (Union Internationale Contre le Cancer, 1997). The mean long and short axis of metastatic lymph nodes were significantly longer than those of non-metastatic lymph nodes (short axis: t = 4.541, P = 0.000; long axis: t = 3.278, P = 0.002). Metastatic lymph nodes showed some characteristic ultrasonographic features, including short axis >/= 1.0 cm, long axis >/= 1.5 cm, and clear boundary. According to the equation P((1)) = 1/[1 + e(-(-2.963 + 2.041 X1 + 1.681 X2))], the lymph nodes were assumed to be malignant when P((1)) >/= 0.5. The accuracy, sensitivity, specificity of this methods were 72.8%, 72.7%, 72.9% respectively, and were superior to those of CT for the same nods in levels 5, 7, 8 and 9 (chi(2) = 6.812, P = 0.013). CONCLUSION: EUS is an effective method of diagnostic evaluation of mediastinal lymph nodes of lung cancer.

Adult↗

Prediction of drug allergenicity: possible use of the local lymph node assay.

The mouse local lymph node assay (LLNA) is currently used for the prospective identification of chemicals that have the potential to cause skin sensitization and allergic contact dermatitis. In this respect, the assay has been fully and formally evaluated and validated, and has been accepted recently as a stand-alone method for the identification of potential skin sensitizers. The assay involves topical application of test substance and the subsequent measurement of proliferative responses in the lymph nodes draining the site of exposure. The testing of new drug entities using a similar assay technique could offer a potential alternative for the identification of potential drug allergens. Currently, the popliteal lymph node assay (PLNA), or modifications of it, are used in research studies for the identification of drugs which have the potential to cause allergic or autoimmunogenic reactions. The PLNA involves subcutaneous application of test substance into the hind footpad, followed by the measurement of proliferative responses, or other parameters of immune activation, in the popliteal lymph nodes. However, these assays have not been validated systematically and the potential utility of a modified LLNA for use in the identification of such compounds is discussed.

Animals↗

The immunologically specific retention of recirculating long-lived lymphocytes in lymph nodes stimulated by xenogeneic erythrocytes.

The lymph nodes of mice actively or adoptively immunized to sheep RBC and/or chicken RBC selectively retain long-lived lymphocytes after challenge with the appropriate antigen. This retention is demonstrable within 8 hr of the time of stimulation, though it probably begins even before this, and it is essentially complete within the first 24 hr. A similar selective retention is seen in nodes regional to the injection of some nonimmunogenic substances such as turpentine, but not others such as colloidal carbon or syngeneic RBC. In animals adoptively immunized to sheep and chicken RBC simultaneously, there is a preferential accumulation of the labeled long-lived lymphocytes of donors immunized to sheep RBC in lymph nodes challenged with sheep RBC, and a preferential accumulation of lymphocytes (labeled with a different radioisotope) from donors immunized to chicken RBC in lymph nodes challenged with this antigen. This immunologically specific component is demonstrable whether the antigen is given before or after adoptive immunization, suggesting that the only labeled cells capable of specific localization in this system are those cells that normally remain in the recirculating pool. In the present experiments, 31 out of 31 sets of antigenically stimulated lymph nodes have shown radiochemical evidence of immunological specificity in the distribution of donor lymphocytes between them, while corresponding sets of nonstimulated lymph nodes have shown only small random variations in the distribution of donor cells. Two different mechanisms are postulated whereby antigenic stimulation can alter the traffic of recirculating long-lived lymphocytes through stimulated lymph nodes. One affects recirculating cells of a particular immunological specificity, while the other affects recirculating cells without regard to their immunological specificity.

Animals↗

Modern thoughts on lymph nodes in breast cancer.

Axillary lymph node status remains the single most useful prognostic parameter in breast cancer patients. As clinical examination, imaging techniques, and lymph node sampling methods cannot accurately assess the axillary node involvement, a complete axillary dissection should always be performed. Moreover, this technique provides an excellent treatment modality for regional disease, abolishing the need for radiotherapy to the axilla. The status of the internal mammary lymph nodes is of less importance in the management of the breast cancer patient.

Axilla↗

Anatomy and nomenclature of murine lymph nodes: Descriptive study and nomenclatory standardization in BALB/cAnNCrl mice.

Murine lymph nodes are intensively studied but often assigned incorrectly in scientific papers. In BALB/cAnNCrl mice, we characterized a total of 22 different lymph nodes. Peripheral nodes were situated in the head and neck region (mandibular, accessory mandibular, superficial parotid, cranial deep cervical nodes), and at the forelimb (proper axillary, accessory axillary nodes) and hindlimb (subiliac, sciatic, popliteal nodes). Intrathoracic lymph nodes included the cranial mediastinal, tracheobronchal and caudal mediastinal nodes. Abdominal lymph nodes were associated with the gastrointestinal tract (gastric, pancreaticoduodenal, jejunal, colic, caudal mesenteric nodes) or were located along the major intra-abdominal blood vessels (renal, lumbar aortic, lateral iliac, medial iliac and external iliac nodes). Comparative and nomenclative aspects of murine lymph nodes are discussed. The position of the lymph nodes of BALB/cAnNCrl mice is summarized and illustrated in an anatomical chart containing proposals for both an official nomenclature according to the Nomina Anatomica Veterinaria and English terms.

Animals↗

Targeting colloidal particulates to thoracic lymph nodes.

BACKGROUND: Thoracic lymphatics and lymph nodes can be affected by cancer and other diseases. Micro- or nanoparticulates are used as carriers for therapeutic agents. We investigated the lymphatic distribution after intrapleural administration of three different particulates. METHODS: Various micro- and nanoparticles of charcoal, polystyrene and poly(lactide-co-glycolide) were administered into the pleural space of rats to study the lymphatic distribution of particles from the pleural cavity to the thoracic lymph nodes. Experimental animal models included healthy rats, rats following pneumonectomy and rats bearing orthotopic lung cancer to mimic relevant clinical scenarios and pathophysiology. Macroscopic examination, light microscopy, fluorescence microscopy complemented by transmission electron microscopy analysis of the lymphatic tissue allowed precise mapping and detection of the particulates in the thoracic lymphatic system. RESULTS: We found that (1) the particles studied are cleared by the regional thoracic lymphatic system when placed in the pleural space; (2) the lymphatic uptake occurred as early as 3h after injection and is primarily through the parietal pleura; (3) the transport of particles to regional lymph nodes was consistently found in all three animal models; (4) particles of 0.7-2 microm in size give the best lymphatic distribution. CONCLUSIONS: Regional thoracic lymphatics and lymph nodes can be accessed by colloidal particles injected into the pleural space.

Animals↗

Judging the therapeutic value of lymph node dissections for melanoma.

BACKGROUND: The management of the regional lymph nodes remains controversial for early-stage melanoma and for those patients with lymph node metastases; American Joint Committee on Cancer stage III. This study examines the importance of quality of the surgical resection measured by the extent of lymph node dissection (quartile of the total number of lymph nodes removed) to determine if this factor is an important prognostic factor for survival. STUDY DESIGN: We reviewed our computer-assisted database of more than 8,700 melanoma patients prospectively collected from 1971 through the present to identify patients who underwent lymph node dissection for stage III melanoma. We included only patients who had their nodal dissections performed at our institute. Patients who underwent sentinel lymph node dissection were excluded. These patients were then analyzed as a group and by individual lymphatic basins: cervical, axillary, and inguinal basins. Univariate and multivariate analyses were used to examine the model that included tumor burden, thickness of the primary melanoma, gender, age, clinical status of the lymph nodes (palpable versus not palpable), and the primary site. The survival and recurrence rates were analyzed using the Cox proportional hazards model. RESULTS: Five hundred forty-eight patients underwent regional lymph node dissections. Of these patients, 214 underwent axillary dissections, 181 inguinal dissections, and 153 cervical dissections. The extent of the nodal dissections was based on the quartile of nodes excised, ranging from 1 to 98 (mean +/- SD = 25.8 +/- 15.8). Patients were stratified by tumor burden and quartile of number of lymph nodes removed. The overall 5-year survival of patients with four or more lymph nodes having tumor and the highest quartile of lymph nodes removed was 44% and was 23% for the lowest quartile of total lymph nodes excised (p = 0.05). By univariate analysis, tumor burden (p = 0.0001), quartile of total lymph nodes removed (p = 0.043), and primary site (p = 0.047) were statistically significant for predicting overall survival. Gender, clinical status of the nodes, primary tumor thickness, age, and dissected basin were not significant (p > 0.05). By multivariate analysis only the tumor burden (p = 0.0001) and quartile of lymph nodes resected (p = 0.044) were statistically significant. CONCLUSIONS: The extent of lymph node dissection for melanoma when analyzed by quartiles is an independent factor in overall survival. This factor appears to be more important with increasing tumor burden in the lymphatic basin. The extent of lymph node dissection should be considered as a prognostic factor in the design of clinical trials that involve stage III melanoma.

Female↗

[Kinetics of T- and B-lymphocytes in the lymph nodes of human fetuses].

Investigations of the lymph nodes embryogenesis had mainly an anatomo-histological character. At the present time a new approach is necessary: elucidation of main immunological characteristics of lymphoid elements, occupying lymph nodes already at early stages of ontogenesis. The aim of the investigation was to study marker composition of lymphocytes, occupying the lymph nodes of various regional groups, that are in anatomical and functional connection with the thymus, Waldeyer-Pirogov lympho-epithelial pharyngeal ring, appendix and Peyer's patches. The anterior, mediastinal, ileocecal and deep cervical lymph nodes have been studied in 23 human fetuses 17-28-week-old. Immunological and morphological peculiarities of development have been followed in the groups of the lymph nodes mentioned. According to the expression of superficial markers the character of heterogeneity in T- and B-cell systems and their kinetics during embryogenesis has been stated to be characteristic for each regional group. In all lymph nodes the number of T-lymphocytes predominate, their greatest content is noted in the ileocecal lymph nodes. The B-lymphatic system in the lymph nodes is presented poorly with its predominance among immunoglobulin-positive lymphocytes of Ig M(+)-cells.

B-Lymphocytes↗

Lymphoid subpopulation changes in regional lymph nodes in squamous head and neck cancer.

Lymph nodes from 10 normal patients and regional lymph nodes (RLN) from 19 patients with squamous cancer of the head and neck were evaluated as to their lymphoid subpopulations. In comparison to normal lymph nodes, RLN from cancer patients demonstrated a marked increase in the proportion of cells with membrane immunoglobulin, the receptor for the third component of complement, and the receptor for the Fc portion of immunoglobulin G. The increased Fc receptor cells were not Fc-bearing thymus-derived lymphocytes, inasmuch as they separated with the non-sheep erythrocyte-lymphocyte rosette-forming population. The overall thymus-derived lymphocyte percentage in RLN was proportionally decreased. A transition from the normal lymph node composition to the altered lymphocyte profile seen in RLN was demonstrated on moving from distal lymph nodes to RLN within the lymphatic drainage of a tumor. Lymph nodes involved with tumor also showed the pattern of bursa equivalent cell population increases.

Adult↗

[Lymph node dissection for T1 esophageal cancer].

Proper mucosal cancer of esophagus of esophageal has no lymph node metastasis, and lymph node metastasis occurs when the tumor invades to muscularis mucosa. Submucosal cancer of esophagus has lymph node metastasis in the rate of 44.4% (40/90). The incidence and number of metastatic lymph node increase with the depth of invasion. Lymph node metastasis of esophageal cancer spreads widely to cervix, mediastinum and abdomen. It's same in submucosal cancer and first metastasis occurs also appears at everywhere from cervix to abdomen. There are high rate of lymph node metastasis in 101L, 105, 106rR, 106rL, 108, 110, 1, 2, 3, 7 lymph nodes. The cancer in upper thoracic esophagus has high rate of lymph node metastasis in cervix and upper mediastinum and lymph node metastasis of lower thoracic esophageal cancer is liable to appear in lower mediastinum and abdomen. Then the cancer in middle thoracic esophagus should be performed the lymph node dissection in cervix, mediastinum and abdomen, especially 101, 102m, 104, 105, 106r, 106t, 107, 108, 110, 1, 2, 3, 7 lymph nodes. On the other hand, cancers limited to proper mucosal layer should be treated with endoscopic mucosal resection. And its same as in the greater part of cancers invaded to muscularis mucosa and shallow layer of esophageal submucosa. The 5 year survival rate of T1 cancers of esophagus is 85.6%, which were performed surgical treatment.

Endoscopy↗

Management of sentinel lymph nodes in malignant skin tumors using dynamic lymphoscintigraphy and the single-photon-emission computed tomography/computed tomography combined system.

BACKGROUND: The differentiation of true sentinel lymph nodes from nonsentinel lymph nodes is difficult in cases of multiple radiolabeled or dyed lymph nodes. METHODS: We examined the locations of sentinel lymph nodes in melanoma and other malignant skin tumors by using dynamic lymphoscintigraphy and the single-photon-emission computed tomography/computed tomography (SPECT/CT) combined system. RESULTS: Sentinel lymph nodes were detected in 45 of the 53 patients examined using only the ordinary blue dye method (85%), and were detected in all 35 patients examined using the SPECT/CT method (100%). Twenty of the 35 patients mentioned above had one sentinel lymph node. Multiple sentinel lymph nodes were demonstrated in the head and neck areas using the SPECT/CT method. Significant differences (P=0.0015) in the numbers of sentinel lymph nodes were found between the blue dye method only and the SPECT/CT method in the neck area. Popliteal sentinel lymph nodes were recognized in three patients, and cubital sentinel lymph nodes were recognized in two patients. Two patients had plural regional lymph nodes: one had popliteal and groin sentinel lymph nodes, while the other had cubital and axillary sentinel lymph nodes. The probe counts of the popliteus and cubitus were significantly lower (P=0.0241) than the counts in the groin, axilla, and neck areas. Micrometastatic sentinel lymph nodes were recognized in four patients, and two patients had metastases in both sentinel and nonsentinel lymph nodes. CONCLUSIONS: Dynamic lymphoscintigraphy was useful when we were concerned about cubital and popliteal lymph nodes. The SPECT/CT combined system was useful in recognizing the anatomical location of sentinel lymph nodes before biopsy. The detection rate of sentinel lymph nodes using the SPECT/CT method was always better than that with the blue dye method (P=0.0197).

Adult↗

[Study of the pelvic lymph nodes in urology].

The lymph nodes of genito-urinary cancers are discussed and the topography of the pelvic lymph nodes is described. The various staging methods are described including imaging modality, examination by operative biopsy, showing the specificity, sensitivity and accuracy of these methods. According to the author, these two methods complement each other.

Humans↗

MR-axillography oriented surgical sampling for assessment of nodal status in the selection of patients with breast cancer for axillary lymph nodes dissection.

BACKGROUND: We have reported that magnetic resonance axillography (MR-axillography) is the best method for assessing lymph node size and representing the relation of the lymph node to normal anatomy. METHODS: The four largest nodes on MR-axillography were sampled in 62 consecutive patients with breast cancer undergoing axillary clearance. Axillary clearance yielded a mean of 17.0 (range 5-28) nodes. RESULTS: A method of preliminary sampling of four nodes in the axilla oriented by MR-axillography was assessed in all cases, 22 of whom were histologically node positive. Based on the sampled nodes, lymph node metastases were detected in 20 of 22 (91%) of the node-positive patients. Based on the sampled nodes, of the 19 patients with macrometastatic nodes, lymph node metastases were detected in all 19 (100%), but only in 1 of the 3 (33%) patients with only one micrometastatic node. CONCLUSIONS: This experience indicates that sampling the four largest nodes by MR-axillography orientation accurately identifies patients with macrometaststic nodes. This result may be comparable to that of surgical sampling performed by the most skilled surgeons.

Adult↗

Laparoscopic retroperitoneal lymph node dissection.

PURPOSE: Retroperitoneal lymph node dissection is the most sensitive and specific diagnostic modality for detecting occult lymph node metastases in clinical stage I testicular tumor. In stage II disease, residual tumors after chemotherapy have to be removed surgically. To reduce the morbidity of these procedures we have replaced open surgery by laparoscopy. PATIENTS AND METHODS: Between August 1992 and December 1999 125 patients underwent laparoscopic RPLND (stage I: 76 pts., stage II: 49 pts.) RESULTS: Laparoscopic RPLND could be completed as planned in all but two patients in whom bleeding required conversion to open surgery. Once the learning curve had been overcome, mean operative time decreased significantly from 476 to 219 min for stage I and averaged 226 min in stage IIB disease. Only minor postoperative complications occurred such as asymptomatic lymphoceles (7 pts.) and chylous ascites (6 pts.). Mean post-op hospital stay was 3.3 and 3.5 days, respectively (stages I and II). Mean followup is currently 46 months for stage I and 35 months for stage II tumors. Over this period a single retroperitoneal recurrence was observed (stage I), which, however, was not due to surgical failure, but to false negative histologic findings. All other patients have remained free of relapse. CONCLUSIONS: Laparoscopic RPLND is a demanding procedure with a long and steep learning curve. It has proved feasible also after chemotherapy. The diagnostic accuracy of laparoscopic RPLND was as good as that of the open procedure, while the morbidity is significantly lower. Tumor control was not compromised by the laparoscopic approach.

Adolescent↗

The sentinel lymph node in colorectal cancer - of clinical value?

Lymph node involvement is an important prognostic factor in colorectal cancer. Sentinel node status has a significant impact on the management of breast cancer and melanoma. A 'sentinel lymph node' (SLN) is defined as the first regional lymph node to receive lymph flow from the primary tumour site. An electronic literature search was performed for all articles using key words: sentinel + lymph node + colorectal + cancer. The review indicated that the sentinel node model may help understanding different aspects of tumour biology in colorectal cancer. It will provide important information about variations in lymphatic pathways and skip metastases. It may alter the management if sentinel lymph node can be assessed preoperatively with radioisotope techniques by identifying patients with micrometastases who may benefit from adjuvant therapy. Although the sentinel lymph node concept has only recently been applied to colorectal cancer, it has a great potential for management.

Journal Article↗

[The role of the histopathological analysis of sentinel lymph nodes in breast cancer. Preliminary findings].

Axillary lymph node status is the single most powerful prognostic marker for breast cancer. Histopathological assessment of lymph nodes has become the gold standard, although conventional histological work-up may miss 10-20% of node-positive cases, potentially resulting in undertreatment and poorer survival of these patients. Identification and detailed histological assessment of sentinel lymph nodes may improve the error rate of conventional methods. We performed the first 30 lymphatic mappings using patent blue vital staining at our department of Surgery in the second semester of 1997. The success rate of identifying 1 or 2 sentinel nodes was 73.3% (22 cases). Axillary dissection and either breast conserving surgery of mastectomy were performed on all patients. Sentinel lymph nodes were serially sectioned and also investigated by immunohistochemistry using primary antibodies to cytokeratin and epithelial membrane antigen. This correctly predicted the qualitative axillary nodal status gained from all the nodes in 21 cases (95.5%). The only false negative sentinel node was associated with a micrometastatis in a non-sentinel lymph node. From the predictive cases 10 (47.6%) had positive nodes, and half of these had metastases only in the sentinel node. To our knowledge, we are the first in Hungary to report preliminary results from a lymphatic mapping study for breast cancer. It seems evident that assessment of sentinel lymph nodes increases the sensitivity of the less reliable conventional histopathological work-up, and this provides a more accurate staging when performed in conjunction with axillary dissection. On the other hand negativity of the sentinel lymph node may question the need for the clearance procedure.

Axilla↗

Prognostic significance of the carcinoma area in the thickest part of the lymph node.

BACKGROUND/AIMS: The carcinoma volume in each metastatic lymph node varies widely. Our aim was to define the meaning of carcinoma volume in lymph nodes as a prognostic factor. METHODOLOGY: One hundred and five patients with preoperatively untreated esophageal carcinoma who underwent surgery were enrolled as subjects. In the present study, the carcinoma area within lymph nodes at their thickest level was substituted for carcinoma volume in lymph nodes for measurement and analysis. A total of 3,703 lymph nodes were isolated and the area of the carcinoma in the thickest part of the lymph node (CALN) was measured. Univariate and multivariate analysis of prognostic significance were made for the factors age, sex, cancer location, cell differentiation, pT, conventional classification of lymph nodes for surgical dissection (n), number of metastatic lymph nodes (MLN number), and CALN. RESULTS: In all 105 cases, n was the best prognostic factor and CALN was more useful than MLN number. In the cases in which absolute curative resection was successful, CALN was the best prognostic factor. CONCLUSIONS: The carcinoma area in the thickest part of the lymph node is a meaningful prognostic factor.

Adult↗