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Experimental study on trans-nodal cancer chemotherapy for metastatic lymph nodes.

As complete dissection of metastatic lymph nodes in the upper mediastinum is impossible in conventional surgery for esophageal carcinoma, we devised a form of intraoperative local adjuvant cancer chemotherapy for metastatic lymph nodes of the mediastinum, via tracheal bifurcation lymph nodes located at the anatomical pivot in the upper mediastinal lymph flow. Emulsion type bleomycin (BLM) was injected into the bifurcation lymph nodes of mongrel dogs, and BLM was identified in the pulmotracheal lymph nodes within 20 minutes. When the cervicothoracic lymph nodes in the ipsilateral side were dissected beforehand, the BLM levels in the contralateral side doubled those seen in the controls. In rabbits with VX2 carcinoma, the level of BLM decreased in lymph nodes with metastasis, however, the spread was still evident even when about 75 per cent of the nodes were occupied with metastasis.

Animals↗

Lymphatic drainage of heart and lungs: comparison between pig and man.

In its anatomy and physiology the pig is comparable with humans and its organs can be considered for xenotransplantation. We have studied the lymphatic drainage of the heart and lungs in 15 pigs. A coloured mass was injected into the myocardium and/or beneath the visceral pleura. The first nodes coloured were directly injected again. No lymph node was observed inside the heart and lungs. The first lymph nodes coloured were the peritracheobronchial nodes. There was no node in front of the thoracic trachea (Barety's compartment in man). Left suprabronchial nodes were connected with the thoracic duct in the mediastinum. The lymphatics of the heart and lungs in the pig are similar to those of human. Phylogenesis explains "skipping" metastases and the significance of N1 disease in lung cancer, as well as chylothorax occurring after heart and lung surgery.

Animals↗

Filtered versus unfiltered technetium sulfur colloid in lymphatic mapping: a significant variable in a pig model.

BACKGROUND: Lymphatic mapping with sentinel node biopsy is becoming a standard diagnostic test for melanoma and is being extensively investigated for use with other soft tissue tumors. Both filtered and unfiltered technetium sulfur colloid (Tc 99) have been used for preoperative lymphoscintigraphy, as well as intraoperative lymphatic mapping, and it is not clear if one is preferable over the other. The purpose of this study was to compare these two preparations to determine whether the form of Tc 99 used affects the results of lymphatic mapping. METHODS: Mock skin sites were placed on each extremity of 12 domestic pigs totaling 48 skin sites. Twenty-four of the lesions were injected with unfiltered Tc 99; the remaining 24 were injected with Tc 99 passed over a 0.2-microm filter. Both preparations of Tc 99 were mixed with 1 mL of isosulfan blue before injection. Sentinel node dissection was performed using a gamma probe, with counts recorded over a 10-second period and timed to begin 5 minutes after injection. RESULTS: Sentinel nodes were identified in all 48 lymph node basins draining the mock sites and characterized as hot (10x background), blue, or both. Significantly more sentinel nodes were found in the filtered (105 total, X = 4.4/basin), than in the unfiltered group (total 53, X = 2.2/basin, P <.0001). The filtered group had both a higher number of nodes that were hot (35 vs. 6) and more nodes that were hot and blue (69 vs. 43). In addition, hot secondary level lymph nodes (iliac and deep cervical) were found in 11 of 24 of the basins (46%) in the filtered group compared to 1 of 24 (4%) in the unfiltered group (P <.003). There was no significant difference in injection site or residual basin counts between the two groups, but in vivo counts over the sentinel node sites were significantly lower in the unfiltered group (X = 2670+/-1829 vs. X = 6027+/-4333; P = .003). CONCLUSION: Use of filtered Tc 99 results in more sentinel nodes (both hot/blue and hot non-blue) and a higher proportion of secondary lymph nodes. These findings indicate that the Tc 99 preparation used is a significant variable in the results of lymphatic mapping. It is critical that future clinical studies document which preparation of Tc 99 was used. Only large clinical trials will be able to determine whether the additional nodes found with filtered Tc 99 increase the sensitivity of the technique or merely increase the number of nodes that must be removed unnecessarily.

Animals↗

Ketamine abolishes the tonic phase of the seizures evoked by sudden cooling of toad isolated spinal cords.

Spinal seizures evoked by sudden cooling (SSSC) were used to investigate the anticonvulsant activity of ketamine (KET) injected either intralymphatically (i.l., 5-40 mg/kg) or intrathecally (i.t., 0.5-1.0 mumol/20 microliters) using isolated spinal cord-hindleg preparation. KET inhibited the tonic phase and prolonged the clonic phase in a dose-dependent manner. The cionic phase was depressed or totally blocked at KET doses of 80-160 mg/kg, i.l. or 2 mumol/20 microliters, i.t. This depression was not prevented by i.t. administration of concanavalin A. The latency of onset of seizures was also increased by KET. KET abolishes the tonic-extensor phase of SSSC in which activation of N-methyl-D-aspartate-receptors may play a role.

Animals↗

Chronic lymphocytic leukemia: a proliferative or accumulative disorder?

In two untreated patients with progressive CLL, quantitative 14C autoradiography of lymph nodes and, subsequently, continuous infusion of [3H] thymidine over eight and nine days, respectively, were performed in order to analyse the lymph node cell kinetics. Simultaneously, the turnover of labelled lymphocytes in the peripheral blood was evaluated. From another CLL patient a regional lymph node was removed 6 h after an intralymphatic flash injection of [3H] thymidine and sectioned for autoradiographic study of the distribution of labelled cells within the lymph node tissue. While the durations of DNA synthesis were found to be normal, the labelling indices were reduced. The relative cell production rate was far lower than normal. Very small growth fractions were calculated, amounting to less than 1% in one patient, and to 2.4% in the other. The distribution of labelled cells in the lymph nodes was focal, which supports the finding of low growth fractions. According to the present data, CLL is a disorder in which a very small number of cells cycle at a roughly normal rate. A kinetic definition of accumulative and proliferative tumour growth is introduced. Tumour growth is termed accumulative if growth appears to result from a decreased relative cell loss rate rather than an increased relative cell production rate. According to this definition, the kinetics in CLL may be classified as accumulative. In absolute terms, however, the number of lymphoid cells produced per unit of time was found to be far higher in CLL than in the healthy state.

Aged↗

The bone marrow as a site of antibody production after a mucosal immunization.

To study the importance of the bone marrow in the production of specific antibodies after a mucosal immunization with cholera toxin, the IgG, IgA and IgM specific antibody forming cells were evaluated by ELISPOT in Peyer patches, mesenteric lymph node (MLN), spleen, blood and bone marrow (BM). When 50-day-old rats were immunized intra-Peyer patches, a similar number of IgG and IgA antitoxin antibody forming cells (AFC) were found in the BM, whereas in the other lymphoid tissues a higher number of IgG antitoxin AFC were found. In all sites the peak of AFC was obtained 2 weeks after immunization. The administration of CT to 35-week-old rats resulted in a stronger immune response in all lymphoid tissues studied, but the proportion of antitoxin AFC contributed by the BM had not changed. One oral dose of cholera toxin resulted in a low number of antitoxin AFC, whereas when two or three doses of CT were administered orally an increase in the number of AFC was observed in the BM, reaching similar or higher numbers of IgG and IgA AFC than in the spleen. In all cases the highest number of AFC/10(6) cells was observed in the MLN, whereas antitoxin AFC were not found in the blood. The total number of AFC recovered from each organ was calculated taken into account that the BM of one femur represents 9% of the total BM. So, it was found that the BM is an important site in the production of IgG antitoxin antibodies, being the main site in the IgA antitoxin antibody production.

Administration, Oral↗

Migration of dendritic cell based cancer vaccines: in vivo veritas?

Ex vivo generated cancer vaccines based on dendritic cells (DCs) are currently applied in the clinic. The migration of DCs from the tissues to the lymph nodes is tightly controlled and involves many different mediators and their receptors. A recent study demonstrated that the rate of migration of antigen-bearing DCs in situ from the skin to the lymph node is 100-fold higher than previously estimated. The migration of ex vivo generated DCs is rather inefficient but can be improved by pre-conditioning of the vaccine injection site with inflammatory cytokines. An alternative approach that is currently being explored is to target tumor antigens directly to DCs in situ, thereby exploiting the intricate migratory capacity of DCs in vivo. Recent advances have been made in understanding DC migration in the context of DC-based vaccines.

Animals↗

Dendritic-cell-based therapeutic vaccination against cancer.

Early clinical trials, in which over 1000 cancer patients received dendritic cell (DC) vaccines, tested different vaccine preparations, but they did not always induce sufficient acquired immunity or meet the expected level of tumor regressions. Current studies aim to improve the DC vaccine approach and capture the potential of these cells in order to gain access to lymphoid tissues and induce strong cell-mediated immunity. DC clinical trials are moving towards a more professional environment, in accordance with the latest quality standards. This explains the current need for innovative well designed trials with defined endpoints that induce robust anti-tumor immunity.

Animals↗

Radiation dose estimates for interstitial radiocolloid lymphoscintigraphy.

The spatial distribution of radioactivity in the injection site, and its rate of clearance, have been measured in patients undergoing various types of interstitial radiocolloid lymphoscintigraphy using 99mTc-antimony sulfide colloid. The clearance of radioactivity from the injection site, and the expansion with time of the localized radioactivity vary considerably for different sites of injection. Maximum absorbed dose estimates of 45.6 rads to the center of the injection site (rectus sheath) and 21 rads to individual lymph nodes have been calculated for patients undergoing internal mammary lymphoscintigraphy with 450 mu Ci injected radioactivity. Absorbed dose estimates for finger web, toe web, and perianal injection sites are also presented.

Antimony↗

Targeted lymph node immunization can protect cats from a mucosal challenge with feline immunodeficiency virus.

With the rapid spread of human immunodeficiency virus (HIV) infection worldwide it is clear that effective strategies for mucosal vaccination against lentiviruses are urgently required. The aim of the present study is to determine whether protective immune responses against a mucosal challenge by feline immunodeficiency virus (FIV) can be elicited by targeting the immunization to the medial iliac lymph nodes--the principal site of migration of cells from the genital and rectal mucosa. Cats were challenged with homologous FIV via the rectal route. Targeted lymph node immunization was found to be an effective route of immunization eliciting both humoral and proliferative responses to peptide-based and fixed cell vaccines. Vaccination with fixed virus infected cells elicited protection against a cell-free mucosal FIV challenge. In addition, some cats vaccinated with fixed uninfected cells also remained uninfected following a cell-associated FIV challenge.

Administration, Rectal↗