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PubMed2003

Immune changes in lymph nodes after skin grafting. I. Effects of bacterial antigens.

Transplantation of skin brings about response of the regional lymph nodes. Lymph node cells (B and T lymphocytes, dendritic cells, imigrating monocytes, high endothelial venous cells) respond to three types of antigens: allogeneic, bacterial and self-antigens. Allogeneic reaction is induced by contact of antigen presenting cells (APC) with donor antigens. Bacteria penetrate rejecting graft epidermis and travel along lymphatics to the nearest lymph node. Rejecting graft debris is phagocytized by macrophages and dendritic cells and transported to lymph nodes. These different type antigens induce different reaction of node cells. In this review we present data from literature and own studies on the effect of bacteria normally residing on skin surface on lymph node after penetration of epidermis. Further reviews will be dealing with the response of lymph nodes to allo- and autoantigens.

Animals↗
PubMed1984

[Morphological correlates of anti-tumor immunity. IV. Mastocytes in regional lymph nodes].

Mastocytes of regional lymph nodes were studied in three groups of oncological patients suffering from cancer of stomach, breast or lung. Lymph nodes in all three groups showed varied numbers of mastocytes; top figures were found in stomach cancer. There was a convincing relation of lymph node mastocyte number neither to lymphatic tissue reaction (predominant lymphocytes, predominant germinal centres, lymphocyte depletion, sinus histiocytosis, unstimulated lymph node) nor to frequency of secondaries nor to patient survival rate.

Breast Neoplasms↗
PubMed1997

Laparoscopic pelvic lymph node dissection for prostate cancer: comparison of the extended and modified techniques.

PURPOSE: We compared the results of extended (obturator, hypogastric, common and external iliac nodes) to modified (obturator and hypogastric nodes only) laparoscopic pelvic lymph node dissection in patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 189 patients with stage T1 to T3 prostate cancer underwent modified (150) or extended (39) laparoscopic pelvic lymph node dissection for pelvic nodal assessment before definitive treatment. RESULTS: Twice as many lymph nodes were removed via extended than modified laparoscopic pelvic lymph node dissection (mean 17:8 versus 9.3). The overall positivity rate was 23 of 189 lymph nodes (12.2%), including 14 of 150 (7.3%) for modified and 9 of 39 (23.1%) for extended dissection (p = 0.02). Two patients (22%) who underwent extended dissection had positive lymph nodes in the external iliac area. Patients who presented with the high risk features of prostate specific antigen (PSA) greater than 20 ng./ml., Gleason score 7 or greater, or stage T2b disease or greater had a 26.5% (p = 0.0002), 22% (p = 0.0006) or 16.4% (p = 0.003) likelihood of positive lymph nodes, respectively. For extended versus modified laparoscopic pelvic lymph node dissection node positivity in high risk patients was 27% versus 18.8% (p = 0.4), 30 versus 26.4% (p = 0.8) and 25.4 versus 14.6% (p = 0.17) for Gleason score 7 or greater, PSA greater than 20 ng./ml. and disease stage T2b to T3a, respectively. Patients who underwent the extended procedure had a higher complication rate (35.9 versus 2%, p < 0.0001). No laparotomy was required. CONCLUSIONS: Despite yielding a 2-fold higher node count and higher node positivity rate, extended laparoscopic pelvic lymph node dissection offers no advantage over modified laparoscopic pelvic lymph node dissection for diagnosing positive lymph nodes when results are analyzed by prognostic factors. The extended procedure is associated with a much higher complication rate. In patients with the high risk features of PSA greater than 20 ng./ml., Gleason score 7 or greater and stage T2b to T3a disease modified laparoscopic pelvic lymph node dissection can be performed safely and effectively to help identify those who may benefit most from curative therapy.

Aged↗
PubMed2006

Nuclear localization of nuclear factor-kappaB p65 in primary prostate tumors is highly predictive of pelvic lymph node metastases.

PURPOSE: Lymph node invasion (LNI) is associated with increased risk of prostate cancer progression. Unfortunately, pelvic lymph node dissections are fraught with a high rate of false-negative findings, emphasizing the need for highly accurate markers of LNI. Because nuclear factor-kappaB (NF-kappaB) is a candidate marker of prostate cancer progression, we tested the association between nuclear localization of NF-kappaB in radical prostatectomy specimens and the presence of LNI. EXPERIMENTAL DESIGN: NF-kappaB expression in radical prostatectomy specimens was assessed with a monoclonal NF-kappaB p65 antibody, in 20 patients with LNI and in 31 controls with no LNI and no biochemical relapse 5 years after radical prostatectomy. Univariate and multivariate logistic regression models were used. The accuracy of multivariate predictions with and without NF-kappaB was quantified with the area under the receiver operating characteristics curve and 200 bootstrap resamples were used to reduce overfit bias. RESULTS: Univariate regression models showed a 7% increase in the odds of observing LNI for each 1% increase in NF-kappaB nuclear staining (odds ratio, 1.07; P = 0.003). In multivariate models, each 1% increase in NF-kappaB was associated with an 8% increase in the odds of LNI (odds ratio, 1.08; P = 0.03) and its statistical significance was only surpassed by the presence of seminal vesicle invasion (P = 0.003). Addition of NF-kappaB to all other predictors increased the accuracy of LNI prediction by 2.3% (from 84.8% to 87.1%; P < 0.001). CONCLUSION: This is the first study that shows that the extent of nuclear localization of NF-kappaB in primary prostate tumors is highly accurately capable of predicting the probability of locoregional spread of prostate cancer.

Aged↗
PubMedDate not supplied

Sentinel node mapping identifies vaccine-draining lymph nodes with tumor-specific immunological activity.

BACKGROUND: Adoptive immunotherapy (AIT) with 4T07-IL2 vaccine-draining lymph node (DLN) cells induced regression of established 4T07 mammary carcinomas, but contralateral non-DLN were inactive. These experiments were performed to determine whether mapping with isosulfan blue (IB), as described for identification of sentinel nodes, would identify vaccine-DLN with antitumor activity. METHODS: Ten days after vaccination with 4T07-IL-2, .1 ml of 1% IB was injected into the vaccination site (footpads or flanks). After 3 minutes, mice were euthanized, and the blue-stained nodes were collected. With flank vaccination, IB identified both an inguinal and an axillary node. We also collected DLNs blindly in mice not receiving IB dye. DLN cell suspensions were then activated with bryostatin 1, ionomycin, and IL-2, expanded in culture, and adoptively transferred to mice bearing established 4T07 flank tumors. RESULTS: Complete tumor regression occurred in nearly all mice treated with popliteal or inguinal DLNs collected with or without IB. IB-stained axillary DLNs cured 100% of tumor-bearing mice, whereas none of the mice treated with blindly collected axillary DLNs were cured. CONCLUSION: We have shown that IB identifies immunologically active DLNs, does not interfere with expansion of lymphocytes in vitro, and, more importantly, has no detrimental effect on the ability of lymphocytes to induce tumor regression in vivo. For axillary DLNs, use of IB mapping identified immunologically active lymph nodes that could not otherwise be found.

Animals↗
PubMed2001

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Chi-Square Distribution↗
PubMed1992

Locally increased metastatic efficiency as a reason for preferential metastasis of solid tumors to lymph nodes.

Metastases from solid tumors to lymph nodes do not portend as poor a prognosis as metastases to other sites. The authors wished to determine whether specific subpopulations of cells metastasized to lymph nodes and whether they have different properties than cells metastatic to visceral sites. Repetitive selection for "spontaneous" metastases of a B16 melanoma to either lung or lymph node increased the incidence of lymph node metastases. Cells derived from pulmonary and lymph node metastases were assayed for their ability to adhere to cryostat sections of lung and lymph node and respond to target organ-conditioned media in serum-free conditions. Both cell types were four times more adherent to lymph node than lung, and consistently attached to the hilar and subcapsular sinuses. Attachment of cells derived from pulmonary metastases to either tissue was threefold greater than that of cells derived from nodal metastases. Lung-conditioned media stimulated proliferation of both cell types, and transiently induced differentiated morphology in cells derived from lymph node metastases, but not in cells from pulmonary metastases. Neither effect was found in lymph-node-conditioned medium. These results suggest that cells metastasize to lymph nodes preferentially not because of a specific predilection for lymph node, but because it is an easy site to colonize. Adhesive interactions in the lymph node rather than trophic ones appear to account for this effect. Cells metastatic to lymph node may be less "malignant" than cells metastatic to visceral sites because less has been required for them to succeed as a metastatic focus.

Animals↗
PubMed1996

[Lymph node dissections in malignant melanoma].

Elective lymph node dissection and its potential as a staging procedure, the prognosis of established lymph node metastases and the sentinel lymph node identification procedure are the most important aspects of lymph node dissection in malignant melanoma. It is widely accepted that subgroups of patients benefit from elective lymph node dissection. The question of which parameters identify the relevant patients properly is still under discussion. pT-categories are the most important prognostic factor; however, localisation and type of tumour and the sex of the patients are additional parameters influencing patient selection. Recently, the first studies have identified subgroups of nodal positive patients who would profit from adjuvant chemo-/immunotherapy. Therefore, lymph node dissection as a staging procedure has to be discussed in the future. Identification of the sentinel lymph node is receiving increasing attention because of its potential influence on the reassessment of elective lymph node dissection. However, this method needs further evaluation. If lymph node metastases have occurred, the prognosis of malignant melanoma decreases by 20%-50%, depending on the extent of metastasis in the individual case. The relevant topics and results are discussed on the basis of data of the Surgical Department of the University Hospital of Erlangen-Nuremberg.

Female↗
PubMed1998

Expression of CD44 variant 6 and lymphatic invasion: importance to lymph node metastasis in gastric cancer.

Lymph node metastasis is a critical prognostic factor for gastric cancer. In the present investigation we examined clinicopathologic factors influencing the metastatic processes to the lymph mode and their prognostic importance. A randomly selected group of 98 patients with adenocarcinomas of the stomach who underwent gastrectomy plus systematic lymph node dissection at Osaka Police Hospital from 1991 to 1996 were analyzed. Altogether 37 (38%) cancers were positive for CD44 variant 6 (v6) staining, 31 (32%) were intermediately stained, and 30 (30%) were negative. CD44-v6 expression correlated well with lymph node metastasis. Expression of CD44-v6 and lymphatic invasion were independent risk factors for metastatic lymph nodes. Among the patients with CD44-v6-positive and lymphatic invasion-positive cancers, 88% had lymph node metastasis, whereas only 13% of patients negative for both factors had lymph node metastasis. Although CD44-v6 expression and lymphatic invasion have been reported to be risk factors for recurrence and a poor prognosis, in this investigation these factors were found not to be significant for hematogenous and lymphatic recurrences or overall survival rates. Thus expression of CD44-v6 and lymphatic invasion may regulate lymph node metastases from gastric cancer.

Adenocarcinoma↗
PubMed2001

[Sentinel lymph node excision. Treatment method of the N0 neck in patients with oral and oropharyngeal carcinoma].

BACKGROUND: The clinically non-metastatic neck is an unsolved problem in the treatment of oral and oropharyngeal squamous cell carcinomas. A rational procedure is looked for which is neither exaggerated nor neglects the needed safety. PATIENTS AND METHODS: 15 patients with primary squamous cell carcinomas of the oral cavity and the oropharynx, staging T1-4N0M0 were examined. After peritumoral intramucodermal injection of tc99m-labeled colloidal albumin the lymphoscintigraphy using gamma-camera imaging prior and hand-held gamma-probe during operation were used for identification of the nodes. Selective sentinel lymph node exstirpation was followed by radical tumor resection. RESULTS: In all cases (n = 41) lymph nodes could be detected, 40 of them were sentinel lymph nodes, distributed to all neck levels, in 5 cases bilateral drainage. 92.5% of sentinel lymph nodes could be actually removed. All but 1 (97.5%) were true-negative. In the positive case modified radical neck dissection harvested another affected node. CONCLUSIONS: Methodically seen, the sentinel procedure works well and might lead to reduced post-surgical morbidity in about 50% of patients with oral cancer. To date, the procedure should be confined to studies with special requirements to diagnostics and subsequent treatment.

Adult↗
PubMed2005

Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis.

Dissemination to draining lymph nodes is a frequent first step in prostate cancer metastasis. Although tumors metastasize to lymph nodes via the lymphatics, the importance of lymphangiogenesis in mediating the process remains controversial. Here, we inhibit intratumoral lymphangiogenesis in s.c. and surgical orthotopic implantation mouse models of human prostate cancer using several strategies. Stable expression of small interfering RNAs (siRNA) targeted against human vascular endothelial growth factor-C (VEGF-C) in PC-3 cells reduced intratumoral lymphatics by 99% in s.c. tumors, indicating that tumor-secreted VEGF-C is necessary for lymphangiogenesis. Expression of siRNAs against human VEGF-A somewhat reduced tumor lymphangiogenesis. Secretion of a soluble VEGF receptor-3/Flt4 fusion protein by PC-3 cells reduced intratumoral lymphatics by 100% in s.c. tumors. Combination of soluble Flt4 and VEGF-C siRNA yielded >92% reduction of intratumoral lymphatics in orthotopic prostate tumors. However, metastasis to lymph nodes was not significantly affected regardless of intratumoral lymphatic vessel density. The abundance of marginal lymphatics at the tumor-stromal interface was unchanged in orthotopic tumors whose intratumoral lymphatics were inhibited, suggesting that these marginal vessels could be sufficient for lymph node metastasis. Hematogenous metastasis (blood tumor burden, lung metastasis) correlated with degree of lymph node invasion. We also analyzed the lymphatics in spontaneous transgenic adenocarcinomas of the mouse prostate which metastasize to lymph nodes. Progression from well-differentiated prostate intraepithelial neoplasia to metastatic, undifferentiated adenocarcinoma was accompanied by loss of lymphatics. These results suggest that tumor-secreted VEGF-C and, to a lesser extent, VEGF-A, are important for inducing prostate cancer intratumoral lymphangiogenesis but are unnecessary for lymph node metastasis.

Adenocarcinoma↗
PubMed1990

[Clinico-pathologic evaluation of retroperitoneal lymph node metastasis in ovarian carcinoma].

Retroperitoneal lymph node dissection was performed in 18 cases of ovarian carcinoma. Of 18 patients, 8 (44.4%) patients had lymph node metastasis. It was found that 50.0% of patients with stage III and 100% of patients with stage IV had lymph node metastasis. Serous cystadenocarcinoma and poorly differentiated carcinoma were demonstrated to be the risk factors in lymph node metastasis. Lymph node metastasis was found to be significantly correlated with the volume of ascites, peritoneal cytology, or peritoneal dissemination. Patients without peritoneal dissemination or positive peritoneal cytology had no lymph node metastasis. Patients with bilateral ovarian tumors tended to have a higher incidence of lymph node metastasis than those with a unilateral ovarian tumor. The incidence of para-aortic lymph node metastasis was found to be higher than that of pelvic or inguinal lymph node metastasis. We concluded that in the clinical stage, serous cystadenocarcinoma, poorly differentiated epithelial carcinoma, ascites, peritoneal cytology, peritoneal dissemination and bilateral ovarian tumors were assumed to affect the incidence of retroperitoneal lymph node metastasis of ovarian carcinoma. It was suspected that the lymphatic spread of ovarian carcinoma had two routes: via ascites and peritoneal dissemination.

Ascitic Fluid↗
PubMed1975

T and B cell populations in blood and lymph node in lymphoproliferative disease.

Lymph node and peripheral blood lymphocytes were studied simultaneously for surface markers of T and B cells in 22 patients with lymphoproliferative diseases and 8 patients with non-neoplastic lymphadenopathy. This resulted in the classification of the malignancy from involved lymph nodes into 4 groups. Six patients had B cell lymphomata with normal or strong immunofluorescent staining for surface membrane immunoglobulin; 8 patients had B cell chronic lymphocytic leukaemia with pale staining for surface membrane immunoglobulin; 5 patients had T cell lymphomata and 3 patients were not definitely classifiable. In 6 out of 8 patients with B cell CLL, histopathology of lymph nodes showed infiltration with well differentiated lymphocytes and in all T cell lymphomata, the infiltrating cells were poorly differentiated. By the use of these markers, malignant lymphocytes were identified in the circulation in only 3 out of 6 patients with B cell lymphoma, in all patients with B cell CLL but in none of those with T cell lymphoma or unclassifiable lymphoma. Therefore a more conclusive characterization of the malignant lymphocyte in lymphoproliferative diseases must include an examination of involved lymph nodes.

B-Lymphocytes↗