The local lymph node assay (LLNA).

PubMed

Rovida, Costanza; Ryan, Cindy; Cinelli, Serena; Basketter, David; Dearman, Rebecca; Kimber, Ian

2012-02-01

The murine local lymph node assay (LLNA) is a widely accepted method for assessing the skin sensitization potential of chemicals. Compared with other in vivo methods in guinea pig, the LLNA offers important advantages with respect to animal welfare, including a requirement for reduced animal numbers as well as reduced pain and trauma. In addition to hazard identification, the LLNA is used for determining the relative skin sensitizing potency of contact allergens as a pivotal contribution to the risk assessment process. The LLNA is the only in vivo method that has been subjected to a formal validation process. The original LLNA protocol is based on measurement of the proliferative activity of draining lymph node cells (LNC), as determined by incorporation of radiolabeled thymidine. Several variants to the original LLNA have been developed to eliminate the use of radioactive materials. One such alternative is considered here: the LLNA:BrdU-ELISA method, which uses 5-bromo-2-deoxyuridine (BrdU) in place of radiolabeled thymidine to measure LNC proliferation in draining nodes. © 2012 by John Wiley & Sons, Inc.

Comparison of flow cytometry and immunohistochemistry in non-radioisotopic murine lymph node assay using bromodeoxyuridine.

PubMed

Jung, Kyoung-Mi; Bae, Il-Hong; Kim, Bae-Hwan; Kim, Wang-Ki; Chung, Jin-Ho; Park, Young-Ho; Lim, Kyung-Min

2010-02-01

Non-radioisotopic local lymph node assay (LLNA) employing 5-bromo-2'-deoxyuridine (BrdU) with flow cytometry (FACS) or immunohistochemistry (IHC) is gaining attention due to a regulatory issue of using radioisotope, (3)H-thymidine, in vivo in traditional LLNA. In this study, to compare the performance of these non-radioisotopic endpoints, 7 chemicals with known sensitizing potencies were examined in LLNA. Mice were topically treated with chemicals or vehicle on both ears for 3 days. After intraperitoneal injection of BrdU, bilateral lymph nodes were isolated separately and undergone respectively, FACS or IHC to determine BrdU incorporated lymph node cells (LNCs). Weight and histology of treated ears were also examined to evaluate chemical-induced edema and irritation. Both FACS and IHC could successively identify the skin sensitizers from non-sensitizers. Comparison of FACS and IHC with traditional LLNA revealed that FACS has a higher sensitivity although both assays produced comparable sensitivity and performance to traditional LLNA. In conclusion, non-radioisotopic LLNA using FACS and IHC can successfully detect sensitizers with a good correlation to traditional LLNA. Notably, FACS showed almost equivalent sensitivity and accuracy to traditional LLNA. 2009 Elsevier Ireland Ltd. All rights reserved.

[Improvement of local lymph node assay for cosmetics safety evaluation].

PubMed

Liu, Zhen; Liu, Junping; Wang, Fei; Xu, Guifeng; Hou, Juan; Wan, Xuying; Zhang, Tianbao

2009-09-01

To improve the local lymph node assay (LLNA) as an alternative method to detect chemicals for both sensitization and irritation. The following chemicals: one negative control: 4-Aminobenzoic Acid, three sensitizers: 2,4-dinitrochlorobenzene (DNCB), Hexyl cinnamic aldehyde (HCA), 2-Aminophenol (2-APC) and two irritations: potassium hydroxide (KOH), sodium lauryl sulphate (SLS) were selected. According to the normal LLNA, groups of female Balb/c mice were treated with test solutions. The thickness of each ear was measured and each auricle was weighed. On the sixth day, the bilateral draining auricular lymph nodes were excised and weighed. The single cell suspensions were prepared, the lymphocyte were counted and the proliferations of lymph cells were detected by cell counting kit-8 (CCK-8). Significant increase in ear thickness and weight were found in groups of KOH, SLS and DNCB (above 0.5%) (P < 0.05), which could be considered as irritants, whereas irritation were not found in 2-APC and HCA. In the allergic test, three sensitizers showed positive, but different sensitivity were found among each index. HCA, DNCB and 2-APC could all obviously augment the weight of lymph node and the lymphocyte count in different groups (P < 0.05). Conspicuous proliferation of lymphocyte were found in DNCB (all group), HCA (above the middle dose) and 2-APC (high dose) by CCK-8. The reformed LLNA using auricle thickness and weighing as observed markers for irritation, and using lymph nodes weighing and proliferation of lymphocyte as observed markers for sensitization, could evaluate both sensitization and irritation at the same time.

Effects of strain differences and vehicles on results of local lymph node assays.

PubMed

Anzai, Takayuki; Ullmann, Ludwig G; Hayashi, Daisuke; Satoh, Tetsuo; Kumazawa, Takeshi; Sato, Keizo

2010-01-01

The Local Lymph Node Assay (LLNA) is now regarded as the worldwide standard. The analysis of accumulated LLNA data reveals that the animal strains and vehicles employed are likely to affect LLNA results. Here we show that an obvious strain difference in the local lymph node response was observed between DMSO-treated CBA/CaOlaHsd and CBA/CaHsdRcc mice. We also show that a vehicle difference in the response was observed when CBA/CaHsdRcc mice were exposed to 6 vehicles; 4:1 v/v acetone/olive oil (AOO), ethanol/water (70% EtOH), N,N-dimethylformamide (DMF), 2-butanone (BN), propylene glycol (PG), and dimethylsulfoxide (DMSO). The dpm/LN level was lowest in the 70% EtOH group and highest in the DMSO group. When alpha-hexylcinnamaldehyde (HCA) was used as a sensitizer for the LLNA, HCA was a weak sensitizer when AOO or DMSO was used as a vehicle, but a moderate sensitizer when the other 4 vehicles were used. This study showed that there are vehicle differences in the local lymph node response (dpm/LN level) in the LLNA and that the sensitization potency of HCA may be classified in different categories when using different vehicles. This suggests that careful consideration should be exercised in selecting a vehicle for the LLNA. A further comprehensive study will be needed to investigate why vehicle differences are observed in the LLNA.

Qualitative and quantitative evaluation of a local lymph node assay based on ex vivo interleukin-2 production.

PubMed

Azam, Philippe; Peiffer, Jean-Luc; Ourlin, Jean-Claude; Bonnet, Pierre-Antoine; Tissier, Marie-Hélène; Vian, Laurence; Fabre, Isabelle

2005-01-15

The local lymph node assay (LLNA) is a regular method for the detection of sensitizing chemicals in mice which measures the incorporation of tritiated thymidine in lymph node cells. We have evaluated an alternative to this method based on the interleukin-2 (IL-2) production of lymph node cells. At the mRNA level, no change in the IL-2 gene expression level was detected by real-time PCR analysis. At the protein level, various experimental conditions were checked in order to improve the irritant versus sensitizer discrimination with a restricted set of prototypic compounds. In particular, the use of phytohemagglutinin A (PHA) in an ex vivo cell culture step showed an improvement of both signal and discrimination. In these optimised conditions, a panel of irritants and potency-graded sensitizers was used to assess the performance of the modified method. IFN-gamma production was used as a positive control. For each compound, a dose-response was performed and stimulation indexes (SI) were determined. Effective concentrations (EC) for each sensitizers were then extracted and compared to the literature data of the regular LLNA. The IL-2-based LLNA showed similar performances at both qualitative and quantitative levels compared to regular LLNA.

Use of an ex vivo local lymph node assay to assess contact hypersensitivity potential.

PubMed

Piccotti, Joseph R; Kawabata, Thomas T

2008-07-01

The local lymph node assay (LLNA) is used to assess the contact hypersensitivity potential of compounds. In the standard assay, mice are treated topically with test compound to the dorsum of both ears on Days 1-3. The induction of a hypersensitivity response is assessed on Day 6 by injecting [(3)H]-thymidine into a tail vein and measuring thymidine incorporation into DNA of lymph node cells draining the ears. The ex vivo LLNA is conducted similarly except lymphocyte proliferation is assessed after in vitro incubation of lymph node cells with [(3)H]-thymidine, which significantly reduces the amount of radioactive waste. The current study tested the use of this approach for hazard assessment of contact hypersensitivity and to estimate allergenic potency. Female BALB/c mice were treated on Days 1-3 with two nonsensitizers (4' -methoxyacetophenone, diethyl phthalate), three weak sensitizers (hydroxycitronellal, eugenol, citral), one weak-to-moderate sensitizer (hexylcinnamic aldehyde), two moderate sensitizers (isoeugenol, phenyl benzoate), and one strong sensitizer (dinitrochlorobenzene). On Day 6, isolated lymph node cells were incubated overnight with [(3)H]-thymidine and thymidine incorporation was measured by liquid scintillation spectrophotometry. The ex vivo LLNA accurately distinguished the contact sensitizers from the nonsensitizing chemicals, and correctly ranked the relative potency of the compounds tested. The EC3 values, i.e., the effective concentration of test substance needed to induce a stimulation index of 3, were as follows: 4' -methoxyacetophenone (> 50%), diethyl phthalate (> 50%), hydroxycitronellal (20.4%), eugenol (13.6%), citral (8.9%), isoeugenol (3.8%), hexylcinnamic aldehyde (2.7%), phenyl benzoate (2%), and dinitrochlorobenzene (0.02%). In addition, low inter-animal and inter-experiment variability was seen with 25% hexyl-cinnamic aldehyde (assay positive control). The results of the ex vivo LLNA in the current study were consistent with published reports using the standard LLNA and provided further evidence that supports the use of this alternative approach to assess the skin sensitization potential of test compounds.

B220 analysis with the local lymph node assay: proposal for a more flexible prediction model.

PubMed

Betts, Catherine J; Dearman, Rebecca J; Kimber, Ian; Ryan, Cindy A; Gerberick, G Frank; Lalko, Jon; Api, Anne Marie

2007-01-01

The mouse local lymph node assay (LLNA) has been developed and validated for the identification of chemicals that have the potential to induce skin sensitisation. In common with other predictive test methods the accuracy of the LLNA is not absolute and experience has revealed that a few chemicals, including for instance a minority of skin irritants, may elicit false-positive reactions in the assay. To improve further the performance of the LLNA, and to eliminate or reduce false-positives, there has been interest in an adjunct method in which the ability of chemicals to cause increases in the frequency of B220(+) lymphocytes in skin-draining lymph nodes is measured. Previous studies suggest that the use of B220 analyses aligned with the standard LLNA may serve to distinguish further between contact allergens and skin irritants. In the original predictive model, chemicals were regarded as being skin sensitisers if they were able to induce a 1.25-fold or greater increase in the percentage of B220(+) cells within lymph nodes compared with concurrent vehicle controls. Although this first prediction model has proven useful, in the light of more recent experience, and specifically as a consequence of some variability observed in the frequency of B220(+) lymphocytes in nodes taken from vehicle control-treated animals, it is timely now to reconsider and refine the model. As a result a new prediction model is proposed in which reliance on the use of absolute thresholds is reduced, and in which small changes in control values can be better accommodated. (c) 2007 John Wiley & Sons, Ltd.

Gene expression profiles in auricle skin as a possible additional endpoint for determination of sensitizers: A multi-endpoint evaluation of the local lymph node assay.

PubMed

Tsuchiyama, Hiromi; Maeda, Akihisa; Nakajima, Mayumi; Kitsukawa, Mika; Takahashi, Kei; Miyoshi, Tomoya; Mutsuga, Mayu; Asaoka, Yoshiji; Miyamoto, Yohei; Oshida, Keiyu

2017-10-05

The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H 3 -methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-γ, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results suggest that multi-endpoint analysis in the LLNA leads to a better determination of the sensitizing potential of test substances. We also show that the gene expression of CXCL1 and/or CXCL2, which is involved in elicitation of contact hypersensitivity (CHS), can be a possible additional endpoint for discrimination of sensitizing compounds in LLNA. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of breast cancer metastasis in sentinel lymph nodes using intra-operative real time GeneSearch BLN Assay in the operating room: results of the Cardiff study.

PubMed

Mansel, Robert E; Goyal, Amit; Douglas-Jones, Anthony; Woods, Victoria; Goyal, Sumit; Monypenny, Ian; Sweetland, Helen; Newcombe, Robert G; Jasani, Bharat

2009-06-01

Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of approximately 2 mm alternating node slabs and 3 additional sections cut at approximately 150 microm interval from each face of the node slab. 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI 86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was performed in a median time of 32 min (range 26-69 min). Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch BLN Assay.

Development and utilization of an ex vivo bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers.

PubMed

Williams, W C; Copeland, C; Boykin, E; Quell, S J; Lehmann, D M

2015-01-01

The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [(3) H]methyl thymidine. A more recent non-isotopic variation of the assay utilizes bromodeoxyuridine (BrdU) incorporation in vivo. To further improve the utility of this assay, we developed an ex vivo BrdU labeling procedure eliminating the need for in vivo injections. The results of this assay correctly identified a strong sensitizer (i.e., trimellitic anhydride) as well as weak/moderate sensitizers (i.e., eugenol, cinnamaldehyde and hexylcinnaminic aldehyde). As anticipated, neither non-sensitizers isopropanol and lactic acid nor the false negative chemical nickel II sulfate hexahydrate induced a positive threshold response in the assay. The results of this assay are in close agreement with those of the in vivo LLNA:BrdU-enzyme-linked immunosorbent assay labeling procedure. We also used the ex vivo BrdU LLNA procedure to evaluate ammonium hexachloroplatinate, ammonium tetrachloroplatinate and cis-diamminedichloroplatinum(II) and the assay correctly identified them as sensitizers based on the calculation of EC2 values. We conclude that this ex vivo BrdU labeling method offers predictive capacity comparable to previously established LLNA protocols while eliminating animal injections and the use of radioisotope. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Local lymph node assay (LLNA): comparison of different protocols by testing skin-sensitizing epoxy resin system components.

PubMed

Gamer, Armin O; Nies, Eberhard; Vohr, Hans-Werner

2008-12-01

Thirteen epoxy resin system components were tested in the LLNA with regard to their sensitizing potency. Lymph node stimulation was quantified not only by measuring the incorporation of [3H]-thymidine into the ear lymph nodes but also the counts of cells recovered from these organs. Equivalent figures were obtained with both endpoints used for the evaluation of lymph node cell proliferation if the reference stimulation indices were adjusted. When dissolved in acetone, all test substances showed skin-sensitizing potential, mainly on the boundary between "strong" and "moderate" according to common potency evaluation schemes. Replacing acetone with acetone/olive oil (4:1) as a vehicle for four selected test items, resulted in considerably lower estimated concentrations for sensitization induction. The challenges in comparing the results obtained by different LLNA variations are discussed.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round.

PubMed

Ehling, G; Hecht, M; Heusener, A; Huesler, J; Gamer, A O; van Loveren, H; Maurer, Th; Riecke, K; Ullmann, L; Ulrich, P; Vandebriel, R; Vohr, H-W

2005-08-15

The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC(3) values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme.

The regulatory use of the Local Lymph Node Assay for the notification of new chemicals in Europe.

PubMed

Angers-Loustau, Alexandre; Tosti, Luca; Casati, Silvia

2011-08-01

The regulatory use of the Local Lymph Node Assay (LLNA) for new chemicals registration was monitored by screening the New Chemicals Database (NCD), which was managed by the former European Chemicals Bureau (ECB) at the European Commission Joint Research Centre (JRC). The NCD centralised information for chemicals notified after 1981, where toxicological information has been generated predominantly according to approved test methods. The database was searched to extract notifications for which the information for skin sensitisation labelling was based on results derived with the LLNA. The details of these records were extracted and pooled, and evaluated with regard to the extent of use of the LLNA over time, as well as for analysing the information retrieved on critical aspects of the procedure e.g. strain and amount of animals used, lymph node processing, solvent and doses selected, stimulation indices, and for assessing their level of compliance to the OECD Test Guideline 429. In addition the accuracy of the reduced LLNA when applied to new chemicals was investigated. Copyright © 2011 Elsevier Inc. All rights reserved.

Utilization of the ex vivo LLNA: BrdU-ELISA to distinguish the sensitizers from irritants in respect of 3 end points-lymphocyte proliferation, ear swelling, and cytokine profiles.

PubMed

Arancioglu, Seren; Ulker, Ozge Cemiloglu; Karakaya, Asuman

2015-01-01

Dermal exposure to chemicals may result in allergic or irritant contact dermatitis. In this study, we performed ex vivo local lymph node assay: bromodeoxyuridine-enzyme-linked immunosorbent assay (LLNA: BrdU-ELISA) to compare the differences between irritation and sensitization potency of some chemicals in terms of the 3 end points: lymphocyte proliferation, cytokine profiles (interleukin 2 [IL-2], interferon-γ (IFN-γ), IL-4, IL-5, IL-1, and tumor necrosis factor α [TNF-α]), and ear swelling. Different concentrations of the following well-known sensitizers and irritant chemicals were applied to mice: dinitrochlorobenzene, eugenol, isoeugenol, sodium lauryl sulfate (SLS), and croton oil. According to the lymph node results; the auricular lymph node weights and lymph node cell counts increased after application of both sensitizers and irritants in high concentrations. On the other hand, according to lymph node cell proliferation results, there was a 3-fold increase in proliferation of lymph node cells (stimulation index) for sensitizer chemicals and SLS in the applied concentrations; however, there was not a 3-fold increase for croton oil and negative control. The SLS gave a false-positive response. Cytokine analysis demonstrated that 4 cytokines including IL-2, IFN-γ, IL-4, and IL-5 were released in lymph node cell cultures, with a clear dose trend for sensitizers whereas only TNF-α was released in response to irritants. Taken together, our results suggest that the ex vivo LLNA: BrdU-ELISA method can be useful for discriminating irritants and allergens. © The Author(s) 2015.

Cross-reactivity between methylisothiazolinone, octylisothiazolinone and benzisothiazolinone using a modified local lymph node assay.

PubMed

Schwensen, J F; Menné Bonefeld, C; Zachariae, C; Agerbeck, C; Petersen, T H; Geisler, C; Bollmann, U E; Bester, K; Johansen, J D

2017-01-01

In the light of the exceptionally high rates of contact allergy to the preservative methylisothiazolinone (MI), information about cross-reactivity between MI, octylisothiazolinone (OIT) and benzisothiazolinone (BIT) is needed. To study cross-reactivity between MI and OIT, and between MI and BIT. Immune responses to MI, OIT and BIT were studied in vehicle and MI-sensitized female CBA mice by a modified local lymph node assay. The inflammatory response was measured by ear thickness, cell proliferation of CD4 + and CD8 + T cells, and CD19 + B cells in the auricular draining lymph nodes. MI induced significant, strong, concentration-dependent immune responses in the draining lymph nodes following a sensitization phase of three consecutive days. Groups of MI-sensitized mice were challenged on day 23 with 0·4% MI, 0·7% OIT and 1·9% BIT - concentrations corresponding to their individual EC3 values. No statistically significant difference in proliferation of CD4 + and CD8 + T cells was observed between mice challenged with MI compared with mice challenged with BIT and OIT. The data indicate cross-reactivity between MI, OIT and BIT, when the potency of the chemical was taken into account in choice of challenge concentration. This means that MI-sensitized individuals may react to OIT and BIT if exposed to sufficient concentrations. © 2016 British Association of Dermatologists.

Performance standard-based validation study for local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method.

PubMed

Ahn, Ilyoung; Kim, Tae-Sung; Jung, Eun-Sun; Yi, Jung-Sun; Jang, Won-Hee; Jung, Kyoung-Mi; Park, Miyoung; Jung, Mi-Sook; Jeon, Eun-Young; Yeo, Kyeong-Uk; Jo, Ji-Hoon; Park, Jung-Eun; Kim, Chang-Yul; Park, Yeong-Chul; Seong, Won-Keun; Lee, Ai-Young; Chun, Young Jin; Jeong, Tae Cheon; Jeung, Eui Bae; Lim, Kyung-Min; Bae, SeungJin; Sohn, Soojung; Heo, Yong

2016-10-01

Local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) is a modified non-radioisotopic technique with the additional advantages of accommodating multiple endpoints with the introduction of FCM, and refinement and reduction of animal use by using a sophisticated prescreening scheme. Reliability and accuracy of the LLNA: BrdU-FCM was determined according to OECD Test Guideline (TG) No. 429 (Skin Sensitization: Local Lymph Node Assay) performance standards (PS), with the participation of four laboratories. Transferability was demonstrated through successfully producing stimulation index (SI) values for 25% hexyl cinnamic aldehyde (HCA) consistently greater than 3, a predetermined threshold, by all participating laboratories. Within- and between-laboratory reproducibility was shown using HCA and 2,4-dinitrochlorobenzene, in which EC2.7 values (the estimated concentrations eliciting an SI of 2.7, the threshold for LLNA: BrdU-FCM) fell consistently within the acceptance ranges, 0.025-0.1% and 5-20%, respectively. Predictive capacity was tested using the final protocol version 1.3 for the 18 reference chemicals listed in OECD TG 429, of which results showed 84.6% sensitivity, 100% specificity, and 88.9% accuracy compared with the original LLNA. The data presented are considered to meet the performance criteria for the PS, and its predictive capacity was also sufficiently validated. Copyright © 2016 Elsevier Inc. All rights reserved.

Experience with local lymph node assay performance standards using standard radioactivity and nonradioactive cell count measurements.

PubMed

Basketter, David; Kolle, Susanne N; Schrage, Arnhild; Honarvar, Naveed; Gamer, Armin O; van Ravenzwaay, Bennard; Landsiedel, Robert

2012-08-01

The local lymph node assay (LLNA) is the preferred test for identification of skin-sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. To facilitate acceptance of nonradioactive variants, validation authorities have published harmonized minimum performance standards (PS) that the alternative endpoint assay must meet. In the present work, these standards were applied to a variant of the LLNA based on lymph node cell counts (LNCC) run in parallel as a control with the standard LLNA with radioactivity measurements, with threshold concentrations (EC3) being determined for the sensitizers. Of the 22 PS chemicals tested in this study, 21 yielded the same results from standard radioactivity and cell count measurements; only 2-mercaptobenzothiazole was positive by LLNA but negative by LNCC. Of the 16 PS positives, 15 were positive by LLNA and 14 by LNCC; methylmethacrylate was not identified as sensitizer by either of the measurements. Two of the six PS negatives tested negative in our study by both LLNA and LNCC. Of the four PS negatives which were positive in our study, chlorobenzene and methyl salicylate were tested at higher concentrations than the published PS, whereas the corresponding concentrations resulted in consistent negative results. Methylmethacrylate and nickel chloride tested positive within the concentration range used for the published PS. The results indicate cell counts and radioactive measurements are in good accordance within the same LLNA using the 22 PS test substances. Comparisons with the published PS results may, however, require balanced analysis rather than a simple checklist approach. Copyright © 2011 John Wiley & Sons, Ltd.

Localization of antigen-specific lymphocytes following lymph node challenge.

PubMed Central

Liu, H; Splitter, G A

1986-01-01

The effect of subcutaneous injections of Brucella abortus strain 19 antigen on the specific localization of autologous lymphocytes in the regional nodes of calves was analysed by fluorescent labelling and flow cytometry. Both in vitro and in vivo FITC labelling of lymphocytes indicated the preferential migration of lymphocytes from a previously challenged lymph node to a recently challenged lymph node. However, lymphocytes from a lymph node challenged with B. abortus failed to localize preferentially in a lymph node challenged with a control antigen, Listeria monocytogenes. Lymph node cells, enriched for T lymphocytes and isolated from primary stimulated or secondary challenged B. abortus lymph nodes, could proliferate when cultured with autologous antigen-pulsed macrophages. The kinetics of [3H]thymidine incorporation in lymphocytes from secondarily challenged lymph nodes occurred earlier and to a greater extent when compared with lymphocytes from primary challenged lymph nodes. Our data show that the accumulation of B. abortus-specific lymphocytes in secondarily challenged lymph nodes is increased by the presence of the specific antigen. Images Figure 4 PMID:2426183

Investigation of allergenicity of some cosmetic mixtures by using ex vivo local lymph node assay-BrdU endpoints.

PubMed

Ulker, Ozge Cemiloglu; Kaymak, Yesim; Karakaya, Asuman

2014-01-01

Balsam of Peru and fragrance mix are commonly used in cosmetic products. Allergy to fragrance is the most common cause of cosmetic contact dermatitis. In the present study, ex vivo local lymph node assay-5-bromo-2'-deoxyuridine (LLNA-BrdU) was used to evaluate the dermal sensitization potential of these cosmetic mixtures. The stimulation index values and estimated concentration (EC3) values were calculated and the potency classification was found for each mixture. At the same time, in order to measure the irritant effect without having to use additional animals, a combination of ex vivo LLNA-BrdU and the irritancy assay was conducted. Th1 [interleukin (IL)-2, interferon-γ] and Th2 cytokine (IL-4, IL-5) releases from lymph node cell culture were investigated as non-radioactive endpoints. According to the results of ex vivo LLNA-BrdU assays, EC3 values were found to be 3.09% (moderate) for balsam of Peru and 4.44% (moderate) for fragrance mix. Cytokine analysis results indicate that both Th1 and Th2 cytokines are involved in the regulation of murine contact allergy and can be considered as useful endpoints. In conclusion, according to our results, fragrance mix and balsam of Peru can be considered as moderate sensitizers; however, in high concentrations, both of them have irritation properties. The cytokines investigated can be considered as the endpoints of the ex vivo LLNA-BrdU assay. © 2014 S. Karger AG, Basel.

New approach to predict photoallergic potentials of chemicals based on murine local lymph node assay.

PubMed

Maeda, Yosuke; Hirosaki, Haruka; Yamanaka, Hidenori; Takeyoshi, Masahiro

2018-05-23

Photoallergic dermatitis, caused by pharmaceuticals and other consumer products, is a very important issue in human health. However, S10 guidelines of the International Conference on Harmonization do not recommend the existing prediction methods for photoallergy because of their low predictability in human cases. We applied local lymph node assay (LLNA), a reliable, quantitative skin sensitization prediction test, to develop a new photoallergy prediction method. This method involves a three-step approach: (1) ultraviolet (UV) absorption analysis; (2) determination of no observed adverse effect level for skin phototoxicity based on LLNA; and (3) photoallergy evaluation based on LLNA. Photoallergic potential of chemicals was evaluated by comparing lymph node cell proliferation among groups treated with chemicals with minimal effect levels of skin sensitization and skin phototoxicity under UV irradiation (UV+) or non-UV irradiation (UV-). A case showing significant difference (P < .05) in lymph node cell proliferation rates between UV- and UV+ groups was considered positive for photoallergic reaction. After testing 13 chemicals, seven human photoallergens tested positive and the other six, with no evidence of causing photoallergic dermatitis or UV absorption, tested negative. Among these chemicals, both doxycycline hydrochloride and minocycline hydrochloride were tetracycline antibiotics with different photoallergic properties, and the new method clearly distinguished between the photoallergic properties of these chemicals. These findings suggested high predictability of our method; therefore, it is promising and effective in predicting human photoallergens. Copyright © 2018 John Wiley & Sons, Ltd.

Study of the sensitising potential of various textile dyes using a biphasic murine local lymph node assay.

PubMed

Ahuja, V; Platzek, T; Fink, H; Sonnenburg, A; Stahlmann, R

2010-09-01

Disperse dyes, which are suitable for dyeing synthetic fibres, are responsible for the great majority of allergic contact dermatitis (ACD) cases to textile dyes. The aim of the present study was to investigate the sensitising potential of various disperse dyes using a biphasic protocol of the local lymph node assay (LLNA). Briefly, mice were shaved over a surface of approximately 2 cm(2) on their backs and treated using a "sensitisation-challenge protocol". The shaved surface was treated once daily on days 1-3 with 50 microl of the test solution. Animals remained untreated on days 4-14. On days 15-17, mice were treated with 25 microl of the test solution on the dorsum of both ears. Mice were killed on day 19 with deep CO(2) anaesthesia, the lymph nodes prepared and various end points, such as ear thickness, ear punch weight, lymph node weight, lymph node cell count and the proportion of various lymphocyte subpopulations, were determined by flow cytometry. The results were compared to control group treated with the vehicle alone. Our results showed that almost all of the tested textile dyes caused a significant increase in lymph node cell count and lymph node weight. We also observed an increase in ear thickness and ear punch weight in most of the concentrations tested for various textile dyes. We observed a decrease in CD4+ and CD8+ cells and an increase in CD19+, CD45+ and CD45+/1A+ cells in most of the cases, which is characteristic for allergens. The CD4+/CD69+ cells increased in only few experiments mainly with Disperse Blue 124 and Disperse Blue 106. Based on our results, the disperse dyes could be arranged in four groups on the basis of their sensitising potency in the following decreasing order (in parenthesis: lowest concentration causing a significant increase in lymph node cell number): group 1, strong: Disperse Blue 124 and Disperse Blue 106 (0.003%); group 2, moderate: Disperse Red 1 and Disperse Blue 1 (3%); group 3, weak: Disperse Orange 37 and Disperse Blue 35 (10%); and group 4, very weak: Disperse yellow 3 and Disperse Orange 3 (increase at 30% or no increase at 30%). In conclusion, our study shows that the biphasic LLNA protocol was proficient enough to study the sensitisation potential of tested textile dyes and provides data allowing to discriminate them according to their potency.

Sentinel lymph node scintigraphy in cutaneous melanoma using a planar calibration phantom filled with Tc-99m pertechnetate solution for body contouring.

PubMed

Peştean, Claudiu; Bărbuş, Elena; Piciu, Andra; Larg, Maria Iulia; Sabo, Alexandrina; Moisescu-Goia, Cristina; Piciu, Doina

2016-01-01

Melanoma is a disease that has an increasing incidence worldwide. Sentinel lymph node scintigraphy is a diagnostic tool that offers important information regarding the localization of the sentinel lymph nodes offering important input data to establish a pertinent and personalized therapeutic strategy. The golden standard in body contouring for sentinel lymph node scintigraphy is to use a planar flood source of Cobalt-57 (Co-57) placed behind the patients, against the gamma camera. The purpose of the study was to determine the performance of the procedure using a flood calibration planar phantom filled with aqueous solution of Technetion-99m (Tc-99m) in comparison with the published data in literature where the gold standard was used. The study was conducted in the Department of Nuclear Medicine of Oncology Institute "Prof. Dr. Ion Chiricuţă" Cluj-Napoca in 95 patients, 31 males and 64 females. The localization of the lesions was grouped by anatomical regions as follows: 23 on lower limbs, 17 on upper limbs, 45 on thorax and 10 on abdomen. The calibration flood phantom containing aqueous solution of Tc-99m pertechnetate was used as planar source to visualize the body contour of the patients for a proper anatomic localization of detected sentinel lymph nodes. The radiopharmaceutical uptake in sentinel lymph nodes has been recorded in serial images following peritumoral injection of 1 ml solution of Tc-99m albumin nanocolloids with an activity of 1 mCi (37 MBq). The used protocol consisted in early acquired planar images within 15 minutes post-injection and delayed images at 2-3 hours and when necessary, additional images at 6-7 hours. The acquisition matrix used was 128×128 pixels for an acquisition time of 5 - 7 minutes. The skin projection of the sentinel lymph nodes was marked on the skin and surgical removal of detected sentinel lymph nodes was performed the next day using a gamma probe for detection and measurements. The sentinel lymph nodes were detected in 92 cases and confirmed with the gamma probe during the surgical procedure. The localization of the lymph nodes was as follows: for the tumors localized on lower limb 23 lymph nodes were localized in inguinal region, for the tumors localized on upper limb, 17 lymph nodes were localized in axilla, for the tumors localized on the thorax, 40 lymph nodes were localized in axilla and 3 were localized in the inguinal region; for the tumors localized on the abdomen, 1 lymph node was localized in axilla and 8 lymph nodes was localized in inguinal region. Regarding the negative sentinel lymph node cases, 2 cases were registered for primarily lesions localized on thorax and 1 for a lesion localized on abdomen. According to histology, 26 cases revealed lymphatic metastatic invasion. Dose rates measured at 1m from the calibrator phantom had an average value of 3.46 μSv/h (SD 0.19) and at 1.4m, the value was 2.57 μSv/h (SD 0.22). Dose rates measured at the same distances from the Co-57 planar flood source had a average values of 32.5μSv/h (SD 0.11) respectively 24.1 μSv/h (SD 0.14). The planar calibration flood phantom is an effective tool for body contouring in sentinel lymph node scintigraphy and offers accurate anatomical information to efficiently localize the detected sentinel lymph nodes in melanoma, being for the first time used and mentioned as a pertinent alternative in our department.

The respiratory allergen glutaraldehyde in the local lymph node assay: sensitization by skin exposure, but not by inhalation.

PubMed

van Triel, Jos J; van Bree, Bianca W J; Roberts, David W; Muijser, Hans; Duistermaat, Evert; Woutersen, Ruud A; Kuper, C Frieke

2011-01-11

Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen glutaraldehyde (GA) was tested. BALB/c mice were exposed by inhalation to 6 or 18ppm GA (respiratory LLNA), both generated as a vapor and as an aerosol. Other groups received 0.25% or 2.5% GA on the skin of the ears (skin LLNA). Lymphocyte proliferation and cytokine production were measured in the draining lymph nodes. GA was positive in the skin LLNA and its cytokine profile (IL-4/IFN-γ) skewed towards a Th2-type immune response with increasing dose. Inhalation exposure did not result in increased lymphocyte proliferation or increased cytokine levels, despite comparable tissue damage (irritation) in the skin and respiratory tract. We hypothesize that the highly reactive and hydrophilic GA oligomerizes in the protein-rich mucous layer of the respiratory tract, which impedes sensitization but still facilitates local irritation. Within the context of risk assessment in respiratory allergy, our results stress the importance of prevention of skin--besides inhalation-- exposure to aldehydes like GA. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The respiratory local lymph node assay as a tool to study respiratory sensitizers.

PubMed

Arts, Josje H E; de Jong, Wim H; van Triel, Jos J; Schijf, Marcel A; de Klerk, Arja; van Loveren, Henk; Kuper, C Frieke

2008-12-01

The local lymph node assay (LLNA) is used to test the potential of low molecular weight (LMW) compounds to induce sensitization via the skin. In the present study, a respiratory LLNA was developed. Male BALB/c mice were exposed head/nose-only during three consecutive days for 45, 90, 180, or 360 min/day to various LMW allergens. Ear application (skin LLNA) was used as a positive control. Negative controls were exposed to the vehicle. Three days after the last exposure, proliferation was determined in the draining mandibular lymph nodes, and the respiratory tract was examined microscopically. Upon inhalation, the allergens trimellitic anhydride, phthalic anhydride, hexamethylene diisocyanate, toluene diisocyanate, isophorone diisocyanate (IPDI), dinitrochlorobenzene, and oxazolone were positive and showed stimulation indices (SIs) up to 11, whereas trimeric IPDI, formaldehyde, and methyl salicylate were negative (viz. SI < 3). All compounds, except trimeric IPDI, induced histopathological lesions predominantly in the upper respiratory tract. Exposure by inhalation is a realistic approach to test respiratory allergens. However, based on the local toxicity, the dose that can be applied is (generally) much lower than can be achieved by skin application. It is concluded that strong LMW allergens, regardless their immunological nature, besides the skin can also sensitize the body via the respiratory tract. In addition, the contact allergens were as potent as the respiratory allergens, although the potency ranking differed from that in a skin LLNA.

Effect of early pregnancy on the expression of progesterone receptor and progesterone-induced blocking factor in ovine lymph node.

PubMed

Yang, Ling; Zang, Shengqin; Bai, Ying; Yao, Xiaolei; Zhang, Leying

2017-04-15

Lymph nodes are the sites where the immune reaction or suppression takes place. Progesterone (P4) exerts an essential effect of the immunomodulation on the maternal uterus during early pregnancy in ruminants. At present study, the inguinal lymph nodes were obtained at day 16 of non-pregnancy, days 13, 16 and 25 of pregnancy (n = 3 for each group) in ewes, and RT-PCR assay, western blot and immunohistochemistry analysis were used to analyze to the effect of early pregnancy on the expression of P4 receptor (PGR) and progesterone-induced blocking factor (PIBF) in the lymph nodes. Our results showed that the PGR and PIBF mRNA were up-regulated in the lymph nodes in pregnant ewes, and the PGR isoform (60 kDa) and the PIBF variant (75 kDa) were expressed constantly in the lymph nodes. However, there was no expression of the PGR isoform (40 kDa) and the PIBF variant (48 kDa) at day 16 of the estrous cycle. The immunohistochemistry results confirmed that the PGR and PIBF proteins were limited to the subcapsular sinus and trabeculae in the cortex, medullary sinuses, and were localized in the cytoplasm of the specific cells. This paper reports for the first time that early pregnancy exerts its effect on the specific cells in the lymph nodes through P4, which results in the up-regulated expression of the PGR mRNA and 40 kDa isoform, the PIBF mRNA and 48 kDa variant, and is involved in the immunoregulation of the lymph nodes through a cytosolic pathway in ewes. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay.

PubMed

Dearman, Rebecca J; Betts, Catherine J; Farr, Craig; McLaughlin, James; Berdasco, Nancy; Wiench, Karin; Kimber, Ian

2007-10-01

There are currently available no systematic experimental data on the skin sensitizing properties of acrylates that are of relevance in occupational settings. Limited information from previous guinea-pig tests or from the local lymph node assay (LLNA) is available; however, these data are incomplete and somewhat contradictory. For those reasons, we have examined in the LLNA 4 acrylates: butyl acrylate (BA), ethyl acrylate (EA), methyl acrylate (MA), and ethylhexyl acrylate (EHA). The LLNA data indicated that all 4 compounds have some potential to cause skin sensitization. In addition, the relative potencies of these acrylates were measured by derivation from LLNA dose-response analyses of EC3 values (the effective concentration of chemical required to induce a threefold increase in proliferation of draining lymph node cells compared with control values). On the basis of 1 scheme for the categorization of skin sensitization potency, BA, EA, and MA were each classified as weak sensitizers. Using the same scheme, EHA was considered a moderate sensitizer. However, it must be emphasized that the EC3 value for this chemical of 9.7% is on the borderline between moderate (<10%) and weak (>10%) categories. Thus, the judicious view is that all 4 chemicals possess relatively weak skin sensitizing potential.

The use of ethanol:diethylphthalate as a vehicle for the local lymph node assay.

PubMed

Betts, Catherine J; Beresford, L; Dearman, R J; Lalko, J; Api, A P; Kimber, I

2007-02-01

The murine local lymph node assay (LLNA) is used for the prospective identification of contact allergens. This method is not only accepted as a stand-alone test for the identification of contact allergenic hazard but also used increasingly for the measurement of the relative potency of skin-sensitizing chemicals as an integral component of the risk assessment process. During the development and validation phases of the method, a list of standard vehicles for use in the LLNA was identified, among them being the vehicle most commonly used acetone/olive oil (4:1, AOO). We have now explored the performance in the LLNA of a non-standard vehicle, ethanol:diethyl phthalate (1:3, EtOH:DEP), that is used frequently to evaluate dermal effects of fragrance materials in both human and experimental studies. Current investigations have demonstrated that EtOH:DEP induces similar levels of background proliferative responses in lymph nodes comparable with the standard vehicle AOO. Moreover, expected levels of activity are observed when EtOH:DEP is used to deliver a known contact allergen in the LLNA. The conclusion drawn is that EtOH:DEP provides a suitable vehicle for use in the LLNA and that the approach described provides a basis for future evaluation of novel vehicles.

The local lymph node assay and the assessment of relative potency: status of validation.

PubMed

Basketter, David A; Gerberick, Frank; Kimber, Ian

2007-08-01

For the prediction of skin sensitization potential, the local lymph node assay (LLNA) is a fully validated alternative to guinea-pig tests. More recently, information from LLNA dose-response analyses has been used to assess the relative potency of skin sensitizing chemicals. These data are then deployed for risk assessment and risk management. In this commentary, the utility and validity of these relative potency measurements are reviewed. It is concluded that the LLNA does provide a valuable assessment of relative sensitizing potency in the form of the estimated concentration of a chemical required to produce a threefold stimulation of draining lymph node cell proliferation compared with concurrent controls (EC3 value) and that all reasonable validation requirements have been addressed successfully. EC3 measurements are reproducible in both intra- and interlaboratory evaluations and are stable over time. It has been shown also, by several independent groups, that EC3 values correlate closely with data on relative human skin sensitization potency. Consequently, the recommendation made here is that LLNA EC3 measurements should now be regarded as a validated method for the determination of the relative potency of skin sensitizing chemicals, a conclusion that has already been reached by a number of independent expert groups.

Age-related changes in localization of injected radiolabelled lymphocytes in the lymph nodes of antigen-stimulated mice.

PubMed Central

Inchley, C J; Micklem, H S; Barrett, J; Hunter, J; Minty, C

1976-01-01

The localization of i.v. injected syngeneic lymph node cells, radiolabelled with 51Cr or 75Se-L-selenomethionine, was studied in male CBA/H mice aged between 3 and 30 months. The following results were obtained. (1) Localization of cells from young adult donors was greater in the s.c. lymph nodes of old than of young recipients, the main increase being between 15 and 17 months of age. Increases in lymph node weight and DNA-synthesis were also seen at this time; but the rise in cell localization was significant even when calculated per unit of tissue weight. Splenic localization either declined slightly with age or, like the liver, showed no significant change. (2) Local antigenic stimulation by a single injection of sheep erythrocytes into one front footpad, 24 hr before lymph node cell injection, resulted in increased localization in the regional lymph nodes of 3-17 month old, but rarely of 24-30 month old mice. (3) No consistent differences in localization were observed between lymph node cells from 4-month and 25-month old donors. Both age-related and antigen-related increases in cell localization were at least partly attributable to an enhanced rate of entry of lymphocytes from the blood to the lymph nodes. Although the changes underlying the decline in antigen-related localization of cells in old recipients have still to be clarified, it is probable that the defective immune responses of old mice result partly from this decline. PMID:991459

Extraperitoneal lymph node dissection in locally advanced cervical cancer; the prognostic factors associated with survival

PubMed Central

Köse, Mehmet Faruk; Kiseli, Mine; Kimyon, Günsu; Öcalan, Reyhan; Yenen, Müfit Cemal; Tulunay, Gökhan; Turan, Ahmet Taner; Üreyen, Işın; Boran, Nurettin

2017-01-01

Objective: Surgical staging was recently recommended for the decision of treatment in locally advanced cervical cancer. We aimed to investigate clinical outcomes as well as factors associated with overall survival (OS) in patients with locally advanced cervical cancer who had undergone extraperitoneal lymph node dissection and were managed according to their lymph node status. Material and Methods: The medical records of 233 women with stage IIb-IVa cervical cancer who were clinically staged and underwent extraperitoneal lymph node dissection were retrospectively reviewed. Paraaortic lymph node status determined the appropriate radiotherapeutic treatment field. Surgery-related complications and clinical outcomes were evaluated. Results: The median age of the patients was 52 years (range, 26-88 years) and the median follow-up time was 28.4 months (range, 3-141 months). Thirty-one patients had laparoscopic extraperitoneal lymph node dissection and 202 patients underwent laparotomy. The number of paraaortic lymph nodes extracted was similar for both techniques. Sixty-two (27%) of the 233 patients had paraaortic lymph node metastases. The 3-year and 5-year OS rates were 55.1% and 46.5%, respectively. The stage of disease, number of metastatic paraaortic lymph nodes, tumor type, and paraaortic lymph node status were associated with OS. In multivariate Cox regression analyses, tumor type, stage, and presence of paraaortic lymph node metastases were the independent prognostic factors of OS. Conclusion: Paraaortic lymph node metastasis is the most important prognostic factor affecting survival. Surgery would give hints about the prognosis and treatment planning of the patient. PMID:28400350

Scientific Impact Recognition Award. Sentinel node staging for breast cancer: intraoperative molecular pathology overcomes conventional histologic sampling errors.

PubMed

Blumencranz, Peter; Whitworth, Pat W; Deck, Kenneth; Rosenberg, Anne; Reintgen, Douglas; Beitsch, Peter; Chagpar, Anees; Julian, Thomas; Saha, Sukamal; Mamounas, Eleftherios; Giuliano, Armando; Simmons, Rache

2007-10-01

When sentinel node dissection reveals breast cancer metastasis, completion axillary lymph node dissection is ideally performed during the same operation. Intraoperative histologic techniques have low and variable sensitivity. A new intraoperative molecular assay (GeneSearch BLN Assay; Veridex, LLC, Warren, NJ) was evaluated to determine its efficiency in identifying significant sentinel lymph node metastases (>.2 mm). Positive or negative BLN Assay results generated from fresh 2-mm node slabs were compared with results from conventional histologic evaluation of adjacent fixed tissue slabs. In a prospective study of 416 patients at 11 clinical sites, the assay detected 98% of metastases >2 mm and 88% of metastasis greater >.2 mm, results superior to frozen section. Micrometastases were less frequently detected (57%) and assay positive results in nodes found negative by histology were rare (4%). The BLN Assay is properly calibrated for use as a stand alone intraoperative molecular test.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: first round.

PubMed

Ehling, G; Hecht, M; Heusener, A; Huesler, J; Gamer, A O; van Loveren, H; Maurer, Th; Riecke, K; Ullmann, L; Ulrich, P; Vandebriel, R; Vohr, H-W

2005-08-15

The new OECD guideline 429 (skin sensitization: local lymph node assay) is based upon a protocol, which utilises the incorporation of radioactivity into DNA as a measure for cell proliferation in vivo. The guideline also enables the use of alternative endpoints in order to assess draining lymph node (LN) cell proliferation. Here we describe the first round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in seven laboratories. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products, Swissmedic. Statistical analyses of all data were performed by an independent centre at the University of Bern, Department of Statistics. Ear-draining, LN weight and cell count were used to assess proliferation instead of radioactive labeling of lymph node cells. In addition, the acute inflammatory skin reaction was measured by ear swelling and weight of circular biopsies of the ears to identify skin irritating properties of the test items. Hexylcinnamaldehyde (HCA) and three blinded test items were applied to female, 8--10 weeks old NMRI and BALB/c mice. Results were sent via the independent study coordinator to the statistician. The results of this first round showed that the alternative endpoints of the LLNA are sensitive and robust parameters. The use of ear weights added an important parameter assessing the skin irritation potential, which supports the differentiation of pure irritative from contact allergenic potential. There were absolute no discrepancies between the categorisation of the three test substances A--C determined by each single participating laboratories. The results highlighted also that many parameters do have an impact on the strength of the responses. Therefore, such parameters have to be taken into consideration for the categorisation of compounds due to their relative sensitizing potencies.

Proposing alerts for pre and pro-haptens (QSAR2016)

EPA Science Inventory

Predictive testing to identify and characterise substances for their skin sensitisation potential has historically been based on animal tests such as the Local Lymph Node Assay (LLNA). In recent years, regulations in the cosmetics and chemicals sectors has provided a strong impe...

Automatic abdominal lymph node detection method based on local intensity structure analysis from 3D x-ray CT images

NASA Astrophysics Data System (ADS)

Nakamura, Yoshihiko; Nimura, Yukitaka; Kitasaka, Takayuki; Mizuno, Shinji; Furukawa, Kazuhiro; Goto, Hidemi; Fujiwara, Michitaka; Misawa, Kazunari; Ito, Masaaki; Nawano, Shigeru; Mori, Kensaku

2013-03-01

This paper presents an automated method of abdominal lymph node detection to aid the preoperative diagnosis of abdominal cancer surgery. In abdominal cancer surgery, surgeons must resect not only tumors and metastases but also lymph nodes that might have a metastasis. This procedure is called lymphadenectomy or lymph node dissection. Insufficient lymphadenectomy carries a high risk for relapse. However, excessive resection decreases a patient's quality of life. Therefore, it is important to identify the location and the structure of lymph nodes to make a suitable surgical plan. The proposed method consists of candidate lymph node detection and false positive reduction. Candidate lymph nodes are detected using a multi-scale blob-like enhancement filter based on local intensity structure analysis. To reduce false positives, the proposed method uses a classifier based on support vector machine with the texture and shape information. The experimental results reveal that it detects 70.5% of the lymph nodes with 13.0 false positives per case.

Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous melanoma.

PubMed

Korn, Jason M; Tellez-Diaz, Alejandra; Bartz-Kurycki, Marisa; Gastman, Brian

2014-04-01

Sentinel lymph node biopsy is the standard of care for intermediate-depth and high-risk thin melanomas. Recently, indocyanine green and near-infrared imaging have been used to aid in sentinel node biopsy. The present study aimed to determine the feasibility of sentinel lymph node biopsy with indocyanine green SPY Elite navigation and to critically evaluate the technique compared with the standard modalities. A retrospective review of 90 consecutive cutaneous melanoma patients who underwent sentinel lymph node biopsy was performed. Two cohorts were formed: group A, which had sentinel lymph node biopsy performed with blue dye and radioisotope; and group B, which had sentinel lymph node biopsy performed with radioisotope and indocyanine green SPY Elite navigation. The cohorts were compared to assess for differences in localization rates, sensitivity and specificity of sentinel node identification, and length of surgery. The sentinel lymph node localization rate was 79.4 percent using the blue dye method, 98.0 percent using the indocyanine green fluorescence method, and 97.8 percent using the radioisotope/handheld gamma probe method. Indocyanine green fluorescence detected more sentinel lymph nodes than the vital dye method alone (p = 0.020). A trend toward a reduction in length of surgery was noted in the SPY Elite cohort. Sentinel lymph node mapping and localization in cutaneous melanoma with the indocyanine green SPY Elite navigation system is technically feasible and may offer several advantages over current modalities, including higher sensitivity and specificity, decreased number of lymph nodes sampled, decreased operative time, and potentially lower false-negative rates. Diagnostic, II.

[Feasibility analysis of sentinel lymph node biopsy in patients with breast cancer after local lumpectomy].

PubMed

Wang, J; Wang, X; Wang, W Y; Liu, J Q; Xing, Z Y; Wang, X

2016-07-01

To explore the feasibility, safety and clinical application value of sentinel lymph node biopsy(SLNB)in patients with breast cancer after local lumpectomy. Clinical data of 195 patients who previously received local lumpectomy from January 2005 to April 2015 were retrospectively analyzed. All the patients with pathologic stage T1-2N0M0 (T1-2N0M0) breast cancer underwent SLNB. Methylene blue, carbon nanoparticles suspension, technetium-99m-labeled dextran, or in combination were used in the SLNB. The interval from lumpectomy to SLNB was 1-91 days(mean, 18.3 days)and the maximum diameter of tumors before first operation was 0.2-4.5 cm (mean, 1.8 cm). The sentinel lymph node was successfully found in all the cases and the detection rate was 100%. 42 patients received axillary lymph node dissection (ALND), 19 patients had pathologically positive sentinel lymph node, with an accuracy rate of 97.6%, sensitivity of 95.0%, false negative rate of 5.0%, and specificity of 100%, and the false positive rate was 0. Logistic regression analysis suggested that the age of patients was significantly associated with sentinel lymph node metastasis after local lumpectomy. For early breast cancer and after breast tumor biopsy, the influence of local lumpectomy on detection rate and accuracy of sentinel lymph node is not significant. Sentinel lymph node biopsy with appropriately chosen tracing technique may still provide a high detection rate and accuracy.

THE MURINE LOCAL LYMPH NODE ASSAY: AN ALTERNATIVE TEST METHOD FOR THE EVALUATION OF THE POTENTIAL FOR CHEMICALS TO ELICIT ALLERGIC CONTACT DERMATITIS

EPA Science Inventory

ABSTRACT
The process that a new toxicology test method must undergo to attain acceptance and regulatory implementation may seem daunting. As the first test method to undergo Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) review, the local...

Local lymph node assay: how testing laboratories apply OECD TG 429 for REACH purposes.

PubMed

Rovida, Costanza

2011-01-01

The Local Lymph Node Assay (LLNA) is the official method for assessing the allergic contact dermatitis potential of chemicals for the purposes of REACH regulation. The LLNA went through a validation process that allowed the delineation of a robust protocol for performing new tests. The OECD accepted this method in 2002 and published OECD TG 429. The European Chemical Agency (ECHA) recently published data that were submitted in the registration dossiers of chemicals. This database was analysed to determine how testing laboratories apply OECD TG 429. This analysis comes after a detailed analysis of four full study reports that were also prepared for REACH purposes. Although the majority of the tests are fully compliant with OECD TG 429, some showed major deviations, and a number of others used more animals than necessary. This suggests that in vivo tests need to be planned more carefully and consciously to obtain meaningful results with the minimum animal number necessary.

A multiplex real-time PCR assay, based on invA and pagC genes, for the detection and quantification of Salmonella enterica from cattle lymph nodes.

PubMed

Bai, Jianfa; Trinetta, Valentina; Shi, Xiaorong; Noll, Lance W; Magossi, Gabriela; Zheng, Wanglong; Porter, Elizabeth P; Cernicchiaro, Natalia; Renter, David G; Nagaraja, Tiruvoor G

2018-05-01

Cattle lymph nodes can harbor Salmonella and potentially contaminate beef products. We have developed and validated a new real-time PCR (qPCR) assay for the detection and quantification of Salmonella enterica in cattle lymph nodes. The assay targets both the invA and pagC genes, the most conserved molecular targets in Salmonella enterica. An 18S rRNA gene assay that amplifies from cattle and other animal species was also included as an internal control. Available DNA sequences for invA, pagC and 18S rRNA genes were used for primer and probe selections. Three Salmonella serotypes, S. Typhimurium, S. Anatum, and S. Montevideo, were used to assess the assay's analytical sensitivity. Correlation coefficients of standard curves generated for each target and for all three serotypes were >99% and qPCR amplification efficiencies were between 93% and 110%. Assay sensitivity was also determined using standard curve data generated from Salmonella-negative cattle lymph nodes spiked with 10-fold dilutions of the three Salmonella serotypes. Assay specificity was determined using Salmonella culture method, and qPCR testing on 36 Salmonella strains representing 33 serotypes, 38 Salmonella strains of unknown serotypes, 252 E. coli strains representing 40 serogroups, and 31 other bacterial strains representing 18 different species. A collection of 647 cattle lymph node samples from steers procured from the Midwest region of the US were tested by the qPCR, and compared to culture-method of detection. Salmonella prevalence by qPCR for pre-enriched and enriched lymph nodes was 19.8% (128/647) and 94.9% (614/647), respectively. A majority of qPCR positive pre-enriched samples (105/128) were at concentrations between 10 4 and 10 5  CFU/mL. Culture method detected Salmonella in 7.7% (50/647) and 80.7% (522/647) of pre- and post-enriched samples, respectively; 96.0% (48/50) of pre-enriched and 99.4% (519/522) of post-enriched culture-positive samples were also positive by qPCR. More samples tested positive by qPCR than by culture method, indicating that the real-time PCR assay was more sensitive. Our data indicate that this triplex qPCR can be used to accurately detect and quantify Salmonella enterica strains from cattle lymph node samples. The assay may serve as a useful tool to monitor the prevalence of Salmonella in beef production systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

PubMed Central

2013-01-01

Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy. PMID:23618132

The predictive factors for lymph node metastasis in early gastric cancer: A clinical study.

PubMed

Wang, Yinzhong

2015-01-01

To detect the clinicopathological factors associated with lymph node metastases in early gastric cancer. We retrospectively evaluated the distribution of metastatic nodes in 198 patients with early gastric cancer treated in our hospital between May 2008 and January 2015, the clinicopathological factors including age, gender, tumor location, tumor size, macroscopic type, depth of invasion, histological type and venous invasion were studied, and the relationship between various parameters and lymph node metastases was analyzed. In this study, one hundred and ninety-eight patients with early gastric cancer were included, and lymph node metastasis was detected in 28 patients. Univariate analysis revealed a close relationship between tumor size, depth of invasion, histological type, venous invasion, local ulceration and lymph node metastases. Multivariate analysis revealed that the five factors were independent risk factors for lymph node metastases. The clinicopathological parameters including tumor size, depth of invasion, local ulceration, histological type and venous invasion are closely correlated with lymph node metastases, should be paid high attention in early gastric cancer patients.

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 3. Apparent discrepancies between LLNA and GPMT sensitisation potential: False positives or differences in sensitivity?

PubMed

Roberts, David W; Schultz, Terry W; Api, Anne Marie

2016-10-01

The Local Lymph Node Assay (LLNA) is the gold standard regulatory toxicology test for skin sensitisation along with the guinea pig maximisation test (GPMT). Compared with the GPMT, LLNA uses fewer animals, it is quantitative, and it gives a numerical prediction of potency. However several concerns have been raised with this assay, mainly related to false positives and false negatives. Over the years, many authors, including the developers of the assay, have presented cases where there have been discrepancies between the GMPT and LLNA results. Several theories have been put forward for these discrepancies, the main one being the "over-sensitivity" of the GPMT. This paper analyses the data from a systematic study, published in three papers from 2008 to 2011, covering several classes of chemicals, in particular unsaturated fatty acids, sugar surfactants and ethoxylated alcohols, with many cases of chemicals testing positive in the LLNA being negative in the GPMT. Based on consideration of reaction chemistry and structural alerts, it is concluded that these discrepancies are not LLNA false positives, but can be rationalised in terms of the different protocols of the assays. Copyright © 2016 Elsevier Inc. All rights reserved.

Can currently available non-animal methods detect pre and pro-haptens? (QSAR2016)

EPA Science Inventory

Predictive testing to identify and characterise substances for their skin sensitisation potential has historically been based on animal tests such as the Local Lymph Node Assay (LLNA). In recent years, regulations in the cosmetics and chemicals sectors has provided a strong impe...

Thoracic lymph node station recognition on CT images based on automatic anatomy recognition with an optimal parent strategy

NASA Astrophysics Data System (ADS)

Xu, Guoping; Udupa, Jayaram K.; Tong, Yubing; Cao, Hanqiang; Odhner, Dewey; Torigian, Drew A.; Wu, Xingyu

2018-03-01

Currently, there are many papers that have been published on the detection and segmentation of lymph nodes from medical images. However, it is still a challenging problem owing to low contrast with surrounding soft tissues and the variations of lymph node size and shape on computed tomography (CT) images. This is particularly very difficult on low-dose CT of PET/CT acquisitions. In this study, we utilize our previous automatic anatomy recognition (AAR) framework to recognize the thoracic-lymph node stations defined by the International Association for the Study of Lung Cancer (IASLC) lymph node map. The lymph node stations themselves are viewed as anatomic objects and are localized by using a one-shot method in the AAR framework. Two strategies have been taken in this paper for integration into AAR framework. The first is to combine some lymph node stations into composite lymph node stations according to their geometrical nearness. The other is to find the optimal parent (organ or union of organs) as an anchor for each lymph node station based on the recognition error and thereby find an overall optimal hierarchy to arrange anchor organs and lymph node stations. Based on 28 contrast-enhanced thoracic CT image data sets for model building, 12 independent data sets for testing, our results show that thoracic lymph node stations can be localized within 2-3 voxels compared to the ground truth.

20170921 - An evaluation of selected (Q)SARs/expert systems for the Prediction of Skin Sensitization Potential (ASCCT)

EPA Science Inventory

Predictive testing to characterize substances for their skin sensitization potential has historically been based on animal models such as the Local Lymph Node Assay (LLNA) and the Guinea Pig Maximization Test (GPMT). In recent years, EU regulations have provided a strong incentiv...

Sentinel lymph node biopsy from the vantage point of an oncologic surgeon.

PubMed

Wilson, Lori L

2009-01-01

Sentinel lymph node biopsy has greatly influenced the surgical management of clinically localized primary melanoma. Lymphatic mapping and sentinel lymph node biopsy have been used for the selective management of the draining regional lymph node basin of primary cutaneous melanoma. Oncologic surgeons have adopted this procedure to selectively identify occult nodal status in melanoma patients who are at a higher risk of regional metastasis. The current standard of treatment of tumor-positive sentinel lymph node metastasis is immediate completion lymphadenectomy, but considerable debate surrounds the utility of this procedure. This contribution reviews development, technical aspects, selective management of the lymph node basin, and sentinel lymph node biopsy techniques.

The murine local lymph node assay: regulatory and potency considerations under REACH.

PubMed

McGarry, Helen F

2007-09-05

From June 2007, new chemicals legislation on the registration, evaluation, authorization and restriction of chemicals (REACH) will come into force across the European Union. This will require the submission of data on human health effects of chemicals, including chemical safety assessments which will require measurements of potency. For skin sensitization hazard identification, REACH states that the first-choice in vivo assay is the local lymph node assay (LLNA). This test has also been the UK competent authority's preferred test for skin sensitization since 2002, and has now replaced guinea pig tests in dossiers submitted to it under the Notification of New Substances Regulations. Advantages of the LLNA over guinea pig tests include improvements in animal welfare, a more scientific approach to hazard identification, and the inclusion of a dose-response element in the endpoint, which enables an estimation of potency. However, notifiers to the UK competent authority have sometimes been reluctant to use the assay because of concerns over false-positive reactions. Across Europe, these concerns have been heightened in the lead-up to the introduction of REACH, since the use of in vivo alternatives to the LLNA will require scientific justification. This review will address some of these concerns from a regulatory perspective.

Investigation of the sensitising and cross-sensitising potential of textile dyes and beta-lactam antibiotics using a biphasic mice local lymph node assay.

PubMed

Ahuja, Varun; Schreiber, Clemens; Platzek, Thomas; Stahlmann, Ralf

2009-07-01

We used a modified protocol of the murine local lymph node assay (LLNA) to study the cross-sensitising potential of (a) textile dye disperse yellow 3 and its metabolite 2-amino-p-cresol, (b) two antibiotics, penicillin G and cefotiam. The test substances were applied in a biphasic manner, i.e. first on the shaved skin of the back followed by application on the dorsal side of the ears after 2 weeks. The end-points analysed included thickness and weight of an ear-biopsy, weight and cell number of the draining lymph node, and lymphocyte cell surface markers analysed by flow-cytometry. Disperse yellow 3 and its metabolite significantly altered the various end-points at both the tested concentrations (0.5 and 1%), thus demonstrating the sensitising potential of the two substances. The cross-sensitisation study showed significant modulation in the tested variables in the treated group as compared to the control, signifying cross-sensitisation potential of the two substances. Penicillin G and cefotiam showed significant changes in various end-points, pointing towards their sensitising potential. However, even at 50% concentration of the beta-lactams no significant change in any end-point indicating absence of cross-reactivity of the antibiotics was noticed. We conclude that a biphasic, modified protocol of the LLNA is a suitable approach to test for a cross-reactivity potential of two related compounds.

Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rash, Dominique L.; Lee, Yongsook C.; Kashefi, Amir

Purpose: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. Methods and Materials: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response,more » assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. Results: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. Conclusions: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.« less

Nanoparticle Transport from Mouse Vagina to Adjacent Lymph Nodes

PubMed Central

Ballou, Byron; Andreko, Susan K.; Osuna-Highley, Elvira; McRaven, Michael; Catalone, Tina; Bruchez, Marcel P.; Hope, Thomas J.; Labib, Mohamed E.

2012-01-01

To test the feasibility of localized intravaginal therapy directed to neighboring lymph nodes, the transport of quantum dots across the vaginal wall was investigated. Quantum dots instilled into the mouse vagina were transported across the vaginal mucosa into draining lymph nodes, but not into distant nodes. Most of the particles were transported to the lumbar nodes; far fewer were transported to the inguinal nodes. A low level of transport was evident at 4 hr after intravaginal instillation, and transport peaked at about 36 hr after instillation. Transport was greatly enhanced by prior vaginal instillation of Nonoxynol-9. Hundreds of micrograms of nanoparticles/kg tissue (ppb) were found in the lumbar lymph nodes at 36 hr post-instillation. Our results imply that targeted transport of microbicides or immunogens from the vagina to local lymph organs is feasible. They also offer an in vivo model for assessing the toxicity of compounds intended for intravaginal use. PMID:23284844

Contact sensitizing potential of pyrogallol and 5-amino-o-cresol in female BALB/c Mice

PubMed Central

Guo, T.L.; Germolec, D.R.; Zhang, Ling X.; Auttachoat, W.; Smith, M.J.; White, K.L.

2013-01-01

Hair dye components such as pyrogallol and cresol have been shown previously to promote allergic reactions such as rashes, dermal inflammation, irritation and dermatitis. The objective of this study was to determine the contact sensitization potential of pyrogallol (PYR) and 5-amino-o-cresol (AOC) when applied dermally to female BALB/c mice. Measurement of the contact hypersensitivity response was initially accomplished using the local lymph node assay. For PYR, significant increases in the proliferation of lymph node cells were observed at concentrations of 0.5% (w/v) and higher. For AOC, borderline increases, albeit significant, in auricular lymph node cell proliferation were observed at 5% and 10%. Results from the irritancy assay suggested that PYR, but not AOC, was an irritant. To further delineate whether PYR was primarily an irritant or a contact sensitizer, the mouse ear swelling test (MEST) was conducted. A significant increase in mouse ear thickness was observed at 72 hr following challenge with 0.5% PYR in mice that had been sensitized with 5% PYR. In contrast, no effects were observed in the MEST in mice sensitized and challenged with the highest achievable concentration of AOC (10%). Additional studies examining lymph node subpopulations and CD86 (B7.2) expression by B cells further support the indication that PYR was a sensitizer in BALB/c mice. The results demonstrate that PYR is both a sensitizer and an irritant in female BALB/c mice. However, the contact sensitization potential of AOC is minimal in this strain of mouse. PMID:24172597

Local lymph node assay (LLNA) for detection of sensitization capacity of chemicals.

PubMed

Gerberick, G Frank; Ryan, Cindy A; Dearman, Rebecca J; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is a murine model developed to evaluate the skin sensitization potential of chemicals. The LLNA is an alternative approach to traditional guinea pig methods and in comparison provides important animal welfare benefits. The assay relies on measurement of events induced during the induction phase of skin sensitization, specifically lymphocyte proliferation in the draining lymph nodes which is a hallmark of a skin sensitization response. Since its introduction the LLNA has been the subject of extensive evaluation on a national and international scale, and has been successfully validated and incorporated worldwide into regulatory guidelines. Experience gained in recent years has demonstrated that adherence to published procedures and guidelines for the LLNA (e.g., with respect to dose and vehicle selection) is critical for the successful conduct and eventual interpretation of the data. In addition to providing a robust method for skin sensitization hazard identification, the LLNA has proven very useful in assessing the skin sensitizing potency of test chemicals, and this has provided invaluable information to risk assessors. The primary method to make comparisons of the relative potency of chemical sensitizers is to use linear interpolation to estimate the concentration of chemical required to induce a stimulation index of three relative to concurrent vehicle-treated controls (EC3). In certain situations where there are available less than optimal dose response data a log-linear extrapolation method can be used to estimate an EC3 value which can reduce significantly the need for repeat testing of chemicals. The LLNA, when conducted according to published guidelines, provides a robust method for skin sensitization testing that not only provides reliable hazard identification information but also data necessary for effective risk assessment and risk management.

Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.

PubMed

Roberts, Megan C; Miller, Dave P; Shak, Steven; Petkov, Valentina I

2017-06-01

The Oncotype DX ® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001). Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

Investigations of immunotoxicity and allergic potential induced by topical application of triclosan in mice

PubMed Central

Anderson, Stacey E.; Meade, B. Jean; Long, Carrie M.; Lukomska, Ewa; Marshall, Nikki B.

2016-01-01

Triclosan is an antimicrobial chemical commonly used occupationally and by the general public. Using select immune function assays, the purpose of these studies was to evaluate the immunotoxicity of triclosan following dermal exposure using a murine model. Triclosan was not identified to be a sensitizer in the murine local lymph node assay (LLNA) when tested at concentrations ranging from 0.75–3.0%. Following a 28-day exposure, triclosan produced a significant increase in liver weight at concentrations of ≥ 1.5%. Exposure to the high dose (3.0%) also produced a significant increase in spleen weights and number of platelets. The absolute number of B-cells, T-cells, dendritic cells and NK cells were significantly increased in the skin draining lymph node, but not the spleen. An increase in the frequency of dendritic cells was also observed in the lymph node following exposure to 3.0% triclosan. The IgM antibody response to sheep red blood cells (SRBC) was significantly increased at 0.75% – but not at the higher concentrations – in the spleen and serum. These results demonstrate that dermal exposure to triclosan induces stimulation of the immune system in a murine model and raise concerns about potential human exposure. PMID:25812624

76 FR 45254 - Report and Recommendations on the Usefulness and Limitations of the Murine Local Lymph Node Assay...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-28

... Contact Dermatitis in Humans AGENCY: Division of the National Toxicology Program (DNTP), National... categorizing the potency of substances with the potential to cause allergic contact dermatitis (ACD) as strong... Contact Dermatitis in Humans (NIH Publication No. 11-7709), describes ICCVAM's recommendations for using...

Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience.

PubMed

Betts, Catherine J; Dearman, Rebecca J; Heylings, Jon R; Kimber, Ian; Basketter, David A

2006-09-01

There is compelling evidence that contact allergens differ substantially (by 4 or 5 orders of magnitude) with respect to their inherent skin-sensitizing potency. Relative potency can now be measured effectively using the mouse local lymph node assay (LLNA) and such data form the basis of risk assessment and risk management strategies. Such determinations also facilitate distinctions being drawn between the prevalence of skin sensitization to a particular contact allergen and inherent potency. The distinction is important because chemicals that are implicated as common causes of contact allergy are not necessarily potent sensitizers. One example is provided by nickel that is undoubtedly a common cause of allergic contact dermatitis, but is a comparatively weak sensitizer in predictive tests. In an attempt to explore other examples of contact allergens where there may exist a discrepancy between prevalence and potency, we describe here analyses conducted with methyl methacrylate (MMA). Results of LLNA studies have been interpreted in the context of historical clinical data on occupational allergic contact dermatitis associated with exposure to MMA.

Results with OECD recommended positive control sensitizers in the maximization, Buehler and local lymph node assays.

PubMed

Basketter, D A; Selbie, E; Scholes, E W; Lees, D; Kimber, I; Botham, P A

1993-01-01

The guinea pig maximization test and the Buehler occluded patch test are used widely to identify the sensitization potential of new chemicals. This information enables toxicologists and/or regulatory authorities to determine whether a chemical should be classified formally as a skin sensitizer. Both to improve and to harmonize these assessments internationally, the OECD has recommended recently that moderate rather than strong contact sensitizers are used as positive control substances. The purpose is to ensure an adequate level of sensitivity in sensitization assays performed at specific testing establishments. Results from two laboratories reported here show that the minimum acceptable standard laid down by the OECD can be achieved and indeed commonly exceeded by a substantial margin. Furthermore, results with these positive controls in a new method, the local lymph node assay, also appear to satisfy similar criteria, suggesting results from this assay, including negative data, should be acceptable for classification purposes. However, a review of the way in which results with new chemicals will be interpreted for regulatory purposes, in the context of positive control data, reveals that considerable inadequacies still exist. It is recommended that ultimately, sensitization data can only be interpreted meaningfully (i.e. to protect humans from sensitization hazards) by considering the potency of the contact allergen in the context of the sensitivity of the assay performed at the particular testing institution.

Evaluation of a toxicogenomic approach to the local lymph node assay (LLNA).

PubMed

Boverhof, Darrell R; Gollapudi, B Bhaskar; Hotchkiss, Jon A; Osterloh-Quiroz, Mandy; Woolhiser, Michael R

2009-02-01

Genomic technologies have the potential to enhance and complement existing toxicology endpoints; however, assessment of these approaches requires a systematic evaluation including a robust experimental design with genomic endpoints anchored to traditional toxicology endpoints. The present study was conducted to assess the sensitivity of genomic responses when compared with the traditional local lymph node assay (LLNA) endpoint of lymph node cell proliferation and to evaluate the responses for their ability to provide insights into mode of action. Female BALB/c mice were treated with the sensitizer trimellitic anhydride (TMA), following the standard LLNA dosing regimen, at doses of 0.1, 1, or 10% and traditional tritiated thymidine ((3)HTdR) incorporation and gene expression responses were monitored in the auricular lymph nodes. Additional mice dosed with either vehicle or 10% TMA and sacrificed on day 4 or 10, were also included to examine temporal effects on gene expression. Analysis of (3)HTdR incorporation revealed TMA-induced stimulation indices of 2.8, 22.9, and 61.0 relative to vehicle with an EC(3) of 0.11%. Examination of the dose-response gene expression responses identified 9, 833, and 2122 differentially expressed genes relative to vehicle for the 0.1, 1, and 10% TMA dose groups, respectively. Calculation of EC(3) values for differentially expressed genes did not identify a response that was more sensitive than the (3)HTdR value, although a number of genes displayed comparable sensitivity. Examination of temporal responses revealed 1760, 1870, and 953 differentially expressed genes at the 4-, 6-, and 10-day time points respectively. Functional analysis revealed many responses displayed dose- and time-specific induction patterns within the functional categories of cellular proliferation and immune response, including numerous immunoglobin genes which were highly induced at the day 10 time point. Overall, these experiments have systematically illustrated the potential utility of genomic endpoints to enhance the LLNA and support further exploration of this approach through examination of a more diverse array of chemicals.

B cell increases and ex vivo IL-2 production as secondary endpoints for the detection of sensitizers in non-radioisotopic local lymph node assay using flow cytometry.

PubMed

Jung, Kyoung-Mi; Jang, Won-Hee; Lee, Yong-Kyoung; Yum, Young Na; Sohn, Soojung; Kim, Bae-Hwan; Chung, Jin-Ho; Park, Young-Ho; Lim, Kyung-Min

2012-03-25

Non-radioisotopic local lymph node assay (LLNA) using 5-bromo-2'-deoxyuridine (BrdU) with flow cytometry (FCM) is gaining attention since it is free from the regulatory issues in traditional LLNA (tLLNA) accompanying in vivo uses of radioisotope, (3)H-thymidine. However, there is also concern over compromised performance of non-radioisotopic LLNA, raising needs for additional endpoints to improve the accuracy. With the full 22 reference substances enlisted in OECD Test Guideline No. 429, we evaluated the performance of LLNA:BrdU-FCM along with the concomitant measurements of B/T cell ratio and ex vivo cytokine production from isolated lymph node cells (LNCs) to examine the utility of these markers as secondary endpoints. Mice (Balb/c, female) were topically treated with substances on both ears for 3 days and then, BrdU was intraperitoneally injected on day 5. After a day, lymph nodes were isolated and undergone FCM to determine BrdU incorporation and B/T cell sub-typing with B220+ and CD3e+. Ex vivo cytokine production by LNCs was measured such as IL-2, IL-4, IL-6, IL-12, IFN-γ, MCP-1, GM-CSF and TNFα. Mice treated with sensitizers showed preferential increases in B cell population and the selective production of IL-2, which matched well with the increases in BrdU incorporation. When compared with guinea pig or human data, BrdU incorporation, B cell increase and IL-2 production ex vivo could successfully identify sensitizers with the accuracy comparable to tLLNA, suggesting that these markers may be useful for improving the accuracy of LLNA:BrdU-FCM or as stand-alone non-radioisotopic endpoints. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Less than 12 lymph nodes in the surgical specimen after neoadjuvant chemo-radiotherapy: an indicator of tumor regression in locally advanced rectal cancer?

PubMed Central

Gurawalia, Jaiprakash; Nayak, Sandeep P.; Kurpad, Vishnu; Pandey, Arun

2016-01-01

Background The number of lymph node retrieved in the surgical specimen is important for tumor staging and has paramount impact on prognosis in colorectal cancer and imitates the adequacy of lymph node surgical clearance. The paucity of lymph node yields in patients undergoing resection after preoperative chemo radiotherapy (CRT) in rectal cancer has seen. Lower total number of lymph nodes in the total mesoractal excision (TME) specimen after CRT, could a marker of better tumor response. Methods We retrospectively reviewed the prospectively managed data of patients underwent excision for rectal cancer, who treated by neoadjuvant radiotherapy with or without chemotherapy in locally advanced rectal cancer. From 2010 to 2014, 364 patients underwent rectal cancer surgery, of which ninety-one treated with neoadjuvant treatment. Standard surgical and pathological protocols were followed. Patients were categorized into two groups based on the number of total harvested lymph nodes with group 1, having 12 or more nodes harvested, and group 2 including patients who had <12 lymph nodes harvested. The total number of lymph nodes retrieved from the surgical specimen was correlated with grade of tumor regression with neoadjuvant treatment. Results Out of 91 patients, 38 patients (42%) had less than 12 lymph nodes examined in specimen. The difference in median number of lymph nodes was observed significantly as 9 (range, 2–11) versus 16 (range, 12–32), in group 2 and 1, respectively (P<0.01). Patients with fewer lymph node group were comparable with respect to age, BMI, pre-operative staging, neoadjuvant treatment. Pathological complete response in tumor pCR was seen with significantly higher rate (40% vs. 26%, P<0.05) in group 2. As per Mandard criteria, there was significant difference in tumor regression grade (TRG) between both the groups (P<0.05). Among patients with metastatic lymph nodes, median LNR was lower in <12 lymph nodes group at 0.167 (range, 0.09–0.45) versus 0.187 (range, 0.05–0.54), difference was not statistically significant (P=0.81). Conclusions Retrieval of fewer than 12 lymph nodes in surgical specimen of rectal cancer who had received neo-adjuvant radiotherapy with or without chemotherapy should be considered as a good indicator of tumor response with better local disease control, and a good prognostic factor, rather than as a pointer of poor diligence of the surgical and pathological assessment. PMID:28078118

A critical review of variables affecting the accuracy and false-negative rate of sentinel node biopsy procedures in early breast cancer.

PubMed

Vijayakumar, Vani; Boerner, Philip S; Jani, Ashesh B; Vijayakumar, Srinivasan

2005-05-01

Radionuclide sentinel lymph node localization and biopsy is a staging procedure that is being increasingly used to evaluate patients with invasive breast cancer who have clinically normal axillary nodes. The most important prognostic indicator in patients with invasive breast cancer is the axillary node status, which must also be known for correct staging, and influences the selection of adjuvant therapies. The accuracy of sentinel lymph node localization depends on a number of factors, including the injection method, the operating surgeon's experience and the hospital setting. The efficacy of sentinel lymph node mapping can be determined by two measures: the sentinel lymph node identification rate and the false-negative rate. Of these, the false-negative rate is the most important, based on a review of 92 studies. As sentinel lymph node procedures vary widely, nuclear medicine physicians and radiologists must be acquainted with the advantages and disadvantages of the various techniques. In this review, the factors that influence the success of different techniques are examined, and studies which have investigated false-negative rates and/or sentinel lymph node identification rates are summarized.

Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay.

PubMed

Takeyoshi, Masahiro; Noda, Shuji; Yamazaki, Shunsuke; Kakishima, Hiroshi; Yamasaki, Kanji; Kimber, Ian

2004-01-01

Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes. Copyright 2004 John Wiley & Sons, Ltd.

[Technical points of laparoscopic splenic hilar lymph node dissection--The original intention of CLASS-04 research design].

PubMed

Huang, Changming; Lin, Mi

2018-02-25

According to Japanese gastric cancer treatment guidelines, the standard operation for locally advanced upper third gastric cancer is the total gastrectomy with D2 lymphadenectomy, which includes the dissection of the splenic hilar lymph nodes. With the development of minimally invasive ideas and surgical techniques, laparoscopic spleen-preserving splenic hilar lymph node dissection is gradually accepted. It needs high technical requirements and should be carried out by surgeons with rich experience of open operation and skilled laparoscopic techniques. Based on being familiar with the anatomy of splenic hilum, we should choose a reasonable surgical approach and standardized operating procedure. A favorable left-sided approach is used to perform the laparoscopic spleen-preserving splenic hilar lymph node dissection in Department of Gastric Surgery, Fujian Medical University Union Hospital. This means that the membrane of the pancreas is separated at the superior border of the pancreatic tail in order to reach the posterior pancreatic space, revealing the end of the splenic vessels' trunk. The short gastric vessels are severed at their roots. This enables complete removal of the splenic hilar lymph nodes and stomach. At the same time, based on the rich clinical practice of laparoscopic gastric cancer surgery, we have summarized an effective operating procedure called Huang's three-step maneuver. The first step is the dissection of the lymph nodes in the inferior pole region of the spleen. The second step is the dissection of the lymph nodes in the trunk of splenic artery region. The third step is the dissection of the lymph nodes in the superior pole region of the spleen. It simplifies the procedure, reduces the difficulty of the operation, improves the efficiency of the operation, and ensures the safety of the operation. To further explore the safety of laparoscopic spleen-preserving splenic hilar lymph node dissection for locally advanced upper third gastric cancer, in 2016, we launched a multicenter phase II( trial of safety and feasibility of laparoscopic spleen-preserving No.10 lymph node dissection for locally advanced upper third gastric cancer (CLASS-04). Through the multicenter prospective study, we try to provide scientific theoretical basis and clinical experience for the promotion and application of the operation, and also to standardize and popularize the laparoscopic spleen-preserving splenic hilar lymph node dissection to promote its development. At present, the enrollment of the study has been completed, and the preliminary results also suggested that laparoscopic spleen-preserving No.10 lymph node dissection for locally advanced upper third gastric cancer was safe and feasible. We believe that with the improvement of standardized operation training system, the progress of laparoscopic technology and the promotion of Huang's three-step maneuver, laparoscopic spleen-preserving splenic hilar lymph node dissection will also become one of the standard treatments for locally advanced upper third gastric cancer.

[Anatomy and histology characteristics of lymph node in nude mice].

PubMed

Sun, R; Gao, B; Guo, C B

2017-10-18

To compare the differences of anatomical and histological characteristics of lymph nodes between BALB/c nude mice and BALB/c mice. Firstly, twenty BALB/c nude mice and twenty BALB/c mice were dissected by using a surgical microscope. Secondly, the differences of T cells and B cells at the lymph node were compared by the expressions of CD 3 and CD 20 immunohistochemistry dyes. There were, on average, 23 nodes per mouse contained within the large lymph node assembly in the BALB/c nude mouse. The anatomical features of the lymph node distribution in the nude mice were mainly found in the neck with relatively higher density. There were two lymph nodes both in the submandible lymph nodes group and in the superficial cervical lymph nodes group (the constituent ratios were 95% and 90%, respectively) in the BALB/c nude mice, but there were four lymph nodes (the constituent ratios were 95% and 90%, respectively) in the BALB/c mice. There were significant difference between the BALB/c nude mice and the BALB/c mice. Mostly there were two lymph nodes of deep cervical lymph nodes both in the BALB/c nude mice and the BALB/c mice (the constituent ratios were 95% and 100%, respectively). There were no significant difference between the BALB/c nude mice and the BALB/c mice. We confirmed that the number of CD 3 -positive T lymphocytes in lymph nodes of the nude mice decreased greatly as compared with the BALB/c mice. Expressions of CD3 in T cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There were significant differences between the BALB/c nude mice and the BALB/c mice. Expressions of CD20 in B cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There was no significant difference between the BALB/c nude mice and BALB/c mice. The anatomical pictures of lymph node distribution in the nude mouse will be benefit to those who are interested. The anatomical features of the lymph node local higher density in neck of the nude mouse and lack of CD3-positive T lymphocytes would be useful for obtaining a better understanding of localized lymph node metastasis of oral transplant tumors.

9 CFR 311.9 - Actinomycosis and actinobacillosis.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., strictly localized, and without suppuration, fistulous tracts, or lymph node involvement, the tongue, if free from disease, may be passed, or, when the disease is slight and confined to the lymph nodes, the... corresponding lymph nodes, the head may be passed for human food after removal and condemnation of the tongue...

Potency values from the local lymph node assay: application to classification, labelling and risk assessment.

PubMed

Loveless, S E; Api, A-M; Crevel, R W R; Debruyne, E; Gamer, A; Jowsey, I R; Kern, P; Kimber, I; Lea, L; Lloyd, P; Mehmood, Z; Steiling, W; Veenstra, G; Woolhiser, M; Hennes, C

2010-02-01

Hundreds of chemicals are contact allergens but there remains a need to identify and characterise accurately skin sensitising hazards. The purpose of this review was fourfold. First, when using the local lymph node assay (LLNA), consider whether an exposure concentration (EC3 value) lower than 100% can be defined and used as a threshold criterion for classification and labelling. Second, is there any reason to revise the recommendation of a previous ECETOC Task Force regarding specific EC3 values used for sub-categorisation of substances based upon potency? Third, what recommendations can be made regarding classification and labelling of preparations under GHS? Finally, consider how to integrate LLNA data into risk assessment and provide a rationale for using concentration responses and corresponding no-effect concentrations. Although skin sensitising chemicals having high EC3 values may represent only relatively low risks to humans, it is not possible currently to define an EC3 value below 100% that would serve as an appropriate threshold for classification and labelling. The conclusion drawn from reviewing the use of distinct categories for characterising contact allergens was that the most appropriate, science-based classification of contact allergens according to potency is one in which four sub-categories are identified: 'extreme', 'strong', 'moderate' and 'weak'. Since draining lymph node cell proliferation is related causally and quantitatively to potency, LLNA EC3 values are recommended for determination of a no expected sensitisation induction level that represents the first step in quantitative risk assessment. 2009 Elsevier Inc. All rights reserved.

Differential gene expression responses distinguish contact and respiratory sensitizers and nonsensitizing irritants in the local lymph node assay.

PubMed

Adenuga, David; Woolhiser, Michael R; Gollapudi, B Bhaskar; Boverhof, Darrell R

2012-04-01

Genomic approaches have the potential to enhance the specificity and predictive accuracy of existing toxicology endpoints, including those for chemical sensitization. The present study was conducted to determine whether gene expression responses can distinguish contact sensitizers (1-chloro-2,4-dinitrobenzene [DNCB] and hexyl cinnamic aldehyde [HCA]), respiratory sensitizers (ortho-phthalaldehyde and trimellitic anhydride [TMA]), and nonsensitizing irritants (methyl salicylate [MS] and nonanoic acid [NA]) in the local lymph node assay (LLNA). Female Balb/c mice received doses of each chemical as per the standard LLNA dosing regimen on days 1, 2, and 3. Auricular lymph nodes were analyzed for tritiated thymidine ((3)HTdR) incorporation on day 6 and for gene expression responses on days 6 and 10. All chemicals induced dose-dependent increases in stimulation index, which correlated strongly with the number of differentially expressed genes. A majority of genes modulated by the irritants were similarly altered by the sensitizers, consistent with the irritating effects of the sensitizers. However, a select number of responses involved with immune-specific functions, such as dendritic cell activation, were unique to the sensitizers and may offer the ability to distinguish sensitizers from irritants. Genes for the mast cell proteases 1 and 8, Lgals7, Tim2, Aicda, Il4, and Akr1c18 were more strongly regulated by respiratory sensitizers compared with contact sensitizers and may represent potential biomarkers for discriminating between contact and respiratory sensitizers. Collectively, these data suggest that gene expression responses may serve as useful biomarkers to distinguish between respiratory and contact sensitizers and nonsensitizing irritants in the LLNA.

Development of LLNA:DAE: a new local lymph node assay that includes the elicitation phase, discriminates borderline-positive chemicals, and is useful for cross-sensitization testing.

PubMed

Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Itagaki, Hiroshi

2014-02-01

We developed a new local lymph node assay (LLNA) that includes the elicitation phase termed LLNA:DAE for discrimination of borderline-positive chemicals as classified by the LLNA modified by Daicel based on ATP content (LLNA:DA) and for cross-sensitization testing. Although the LLNA:DA method could help identify skin sensitizers, some skin irritants classified as non-sensitizers by the LLNA were classified as borderline positive. In addition, the evaluation for the cross-sensitization potential between chemicals was impossible. In the LLNA:DAE procedure, test group of mice received four applications of chemicals on the dorsum of the right ear for induction and one application on the dorsum of the left ear for elicitation. Control group of mice received one chemical application on the dorsum of the left ear. We evaluated the sensitizing potential by comparing the weights of the lymph nodes from the left ears between the two groups. The results of using the LLNA:DAE method to examine 24 chemicals, which contained borderline-positive chemicals, were consistent with those from the LLNA method, except for nickel chloride (NiCl2). Two chemical pairs, 2,4-dinitrochlorobenzene (DNCB) with 2,4-dinitrofluorobenzene (DNFB) and hydroquinone (HQ) with p-benzoquinone (p-BQ), showed clear cross-sensitization with each other, while another chemical pair, DNFB with hexylcinnamic aldehyde (HCA) did not. Taken together, our results suggest that the LLNA:DAE method is useful for discriminating borderline-positive chemicals and for determining chemical cross-sensitization.

The local lymph node assay and skin sensitization: a cut-down screen to reduce animal requirements?

PubMed

Kimber, Ian; Dearman, Rebecca J; Betts, Catherine J; Gerberick, G Frank; Ryan, Cindy A; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A

2006-04-01

The local lymph node assay (LLNA), an alternative approach to skin-sensitizing testing, has made a significant contribution to animal welfare by permitting a reduction and refinement of animal use. Although there is clearly an aspiration to eliminate the use of animals in such tests, it is appropriate also to consider other opportunities for refinement and reduction of animal use. We have therefore explored the use of a modified version of the LLNA for screening purposes when there is a need to evaluate the sensitizing activity of a large number of chemicals, as will be the case under the auspices of registration, evaluation and authorization of chemicals (REACH). Using an existing LLNA database of 211 chemicals, we have examined whether a cut-down assay comprising a single high-dose group and a concurrent vehicle control would provide a realistic approach for screening chemicals for sensitizing potential. The analyses reported here suggest this is the case. We speculate that the animal welfare benefits may be enhanced further by reducing the number of animals per experimental group. However, a detailed evaluation will be necessary to provide reassurance that a reduction in group size would provide adequate sensitivity across a range of skin sensitization potencies.

Evaluation of the performance of the reduced local lymph node assay for skin sensitization testing.

PubMed

Ezendam, Janine; Muller, Andre; Hakkert, Betty C; van Loveren, Henk

2013-06-01

The local lymph node assay (LLNA) is the preferred method for classification of sensitizers within REACH. To reduce the number of mice for the identification of sensitizers the reduced LLNA was proposed, which uses only the high dose group of the LLNA. To evaluate the performance of this method for classification, LLNA data from REACH registrations were used and classification based on all dose groups was compared to classification based on the high dose group. We confirmed previous examinations of the reduced LLNA showing that this method is less sensitive compared to the LLNA. The reduced LLNA misclassified 3.3% of the sensitizers identified in the LLNA and misclassification occurred in all potency classes and that there was no clear association with irritant properties. It is therefore not possible to predict beforehand which substances might be misclassified. Another limitation of the reduced LLNA is that skin sensitizing potency cannot be assessed. For these reasons, it is not recommended to use the reduced LLNA as a stand-alone assay for skin sensitization testing within REACH. In the future, the reduced LLNA might be of added value in a weight of evidence approach to confirm negative results obtained with non-animal approaches. Copyright © 2013 Elsevier Inc. All rights reserved.

Skin irritation, false positives and the local lymph node assay: a guideline issue?

PubMed

Basketter, David A; Kimber, Ian

2011-10-01

Since the formal validation and regulatory acceptance of the local lymph node assay (LLNA) there have been commentaries suggesting that the irritant properties of substances can give rise to false positives. As toxicology aspires to progress rapidly towards the age of in vitro alternatives, it is of increasing importance that issues relating to assay selectivity and performance are understood fully, and that true false positive responses are distinguished clearly from those that are simply unpalatable. In the present review, we have focused on whether skin irritation per se is actually a direct cause of true false positive results in the LLNA. The body of published work has been examined critically and considered in relation to our current understanding of the mechanisms of skin irritation and skin sensitisation. From these analyses it is very clear that, of itself, skin irritation is not a cause of false positive results. The corollary is, therefore, that limiting test concentrations in the LLNA for the purpose of avoiding skin irritation may lead, unintentionally, to false negatives. Where a substance is a true false positive in the LLNA, the classic example being sodium lauryl sulphate, explanations for that positivity will have to reach beyond the seductive, but incorrect, recourse to its skin irritation potential. Copyright © 2011 Elsevier Inc. All rights reserved.

Regional lymph node staging in breast cancer: the increasing role of imaging and ultrasound-guided axillary lymph node fine needle aspiration.

PubMed

Mainiero, Martha B

2010-09-01

The status of axillary lymph nodes is a key prognostic indicator in patients with breast cancer and helps guide patient management. Sentinel lymph node biopsy is increasingly being used as a less morbid alternative to axillary lymph node dissection. However, when sentinel lymph node biopsy is positive, axillary dissection is typically performed for complete staging and local control. Axillary ultrasound and ultrasound-guided fine needle aspiration (USFNA) are useful for detecting axillary nodal metastasis preoperatively and can spare patients sentinel node biopsy, because those with positive cytology on USFNA can proceed directly to axillary dissection or neoadjuvant chemotherapy. Internal mammary nodes are not routinely evaluated, but when the appearance of these nodes is abnormal on imaging, further treatment or metastatic evaluation may be necessary. Copyright © 2010 Elsevier Inc. All rights reserved.

Non-animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

PubMed

Roberts, David W; Patlewicz, Grace

2018-01-01

There is an expectation that to meet regulatory requirements, and avoid or minimize animal testing, integrated approaches to testing and assessment will be needed that rely on assays representing key events (KEs) in the skin sensitization adverse outcome pathway. Three non-animal assays have been formally validated and regulatory adopted: the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). There have been many efforts to develop integrated approaches to testing and assessment with the "two out of three" approach attracting much attention. Here a set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the three individual non-animal assays, their binary combinations and the "two out of three" approach in predicting skin sensitization potential. The most predictive approach was to use both the DPRA and h-CLAT as follows: (1) perform DPRA - if positive, classify as sensitizing, and (2) if negative, perform h-CLAT - a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 85% (local lymph node assay) and 93% (human) of non-sensitizer predictions were correct, whereas the "two out of three" approach had 69% (local lymph node assay) and 79% (human) of non-sensitizer predictions correct. The findings are consistent with the argument, supported by published quantitative mechanistic models that only the first KE needs to be modeled. All three assays model this KE to an extent. The value of using more than one assay depends on how the different assays compensate for each other's technical limitations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Correlation of N-myc downstream-regulated gene 1 subcellular localization and lymph node metastases of colorectal neoplasms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Yan; Lv, Liyang; Du, Juan

2013-09-20

Highlights: •We clarified NDRG1 subcellular location in colorectal cancer. •We found the changes of NDRG1 distribution during colorectal cancer progression. •We clarified the correlation between NDRG1 distribution and lymph node metastasis. •It is possible that NDRG1 subcellular localization may determine its function. •Maybe NDRG1 is valuable early diagnostic markers for metastasis. -- Abstract: In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily cytoplasmic protein, but it is also expressed on the cell membrane and in the nucleus. NDRG1 is involved in various stages of tumor development in colorectal cancer, and it is possible that the different subcellular localizationsmore » may determine the function of NDRG1 protein. Here, we attempt to clarify the characteristics of NDRG1 protein subcellular localization during the progression of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer patients in cancerous, non-cancerous, and corresponding lymph node tissues. Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with metastases than in those without metastases (P < 0.01). Nuclear NDRG1 expression in colorectal neoplasms was significantly higher than in the normal colorectal mucosa, and yet the normal colorectal mucosa showed no nuclear expression. Furthermore, our results showed higher cytoplasmic NDRG1 expression was better for differentiation, and higher membrane NDRG1 expression resulted in a greater possibility of lymph node metastasis. These data indicate that a certain relationship between the cytoplasmic and membrane expression of NDRG1 in lymph nodes exists with lymph node metastasis. NDRG1 expression may translocate from the membrane of the colorectal cancer cells to the nucleus, where it is involved in lymph node metastasis. Combination analysis of NDRG1 subcellular expression and clinical variables will help predict the incidence of lymph node metastasis.« less

A dual-modal magnetic nanoparticle probe for preoperative and intraoperative mapping of sentinel lymph nodes by magnetic resonance and near infrared fluorescence imaging

PubMed Central

Zhou, Zhengyang; Chen, Hongwei; Lipowska, Malgorzata; Wang, Liya; Yu, Qiqi; Yang, Xiaofeng; Tiwari, Diana; Yang, Lily; Mao, Hui

2016-01-01

The ability to reliably detect sentinel lymph nodes for sentinel lymph node biopsy and lymphadenectomy is important in clinical management of patients with metastatic cancers. However, the traditional sentinel lymph node mapping with visible dyes is limited by the penetration depth of light and fast clearance of the dyes. On the other hand, sentinel lymph node mapping with radionucleotide technique has intrinsically low spatial resolution and does not provide anatomic details in the sentinel lymph node mapping procedure. This work reports the development of a dual modality imaging probe with magnetic resonance and near infrared imaging capabilities for sentinel lymph node mapping using magnetic iron oxide nanoparticles (10 nm core size) conjugated with a near infrared molecule with emission at 830 nm. Accumulation of magnetic iron oxide nanoparticles in sentinel lymph nodes leads to strong T2 weighted magnetic resonance imaging contrast that can be potentially used for preoperative localization of sentinel lymph nodes, while conjugated near infrared molecules provide optical imaging tracking of lymph nodes with a high signal to background ratio. The new magnetic nanoparticle based dual imaging probe exhibits a significant longer lymph node retention time. Near infrared signals from nanoparticle conjugated near infrared dyes last up to 60 min in sentinel lymph node compared to that of 25 min for the free near infrared dyes in a mouse model. Furthermore, axillary lymph nodes, in addition to sentinel lymph nodes, can be also visualized with this probe, given its slow clearance and sufficient sensitivity. Therefore, this new dual modality imaging probe with the tissue penetration and sensitive detection of sentinel lymph nodes can be applied for preoperative survey of lymph nodes with magnetic resonance imaging and allows intraoperative sentinel lymph node mapping using near infrared optical devices. PMID:23812946

Lymph node dissection for melanoma using tumescence local anaesthesia: an observational study.

PubMed

Kofler, Lukas; Breuninger, Helmut; Häfner, Hans-Martin; Schweinzer, Katrin; Schnabl, Saskia M; Eigentler, Thomas K; Leiter, Ulrike

2018-04-01

The possibility that tumescence local anaesthesia (TLA) may lead to dissemination of tumour cells in lymph nodes is presently unclear. To evaluate whether infiltration by TLA influences metastatic spread and survival probability, compared to general anaesthesia (GA), based on lymph node dissection in melanoma patients. In total, 281 patients (GA: 162; TLA: 119) with cutaneous melanoma and clinically or histologically-confirmed metastases in regional lymph nodes were included. All patients underwent complete lymph node dissection. Median follow-up was 70 months. The rate of lymph node recurrence at the dissection site was 25.3% in the GA group and 17.6% in the TLA group (p = 0.082). No significant difference was found concerning 10-year melanoma-specific survival (GA: 56.2%, TLA: 67.4%; p = 0.09), disease-free survival (GA: 72.8 %, TLA: 81.1%; p = 0.095), or lymph node-free survival (GA: 72.8%, TLA: 81.1%; p = 0.095). Distant metastases-free survival appeared to be slightly reduced in the TLA group (GA: 49.9%, TLA: 64.0%; p = 0.025). No differences were identified between the GA and TLA groups regarding prognostic outcome for overall survival or disease-free survival.

Preclinical Evaluation of Robotic-Assisted Sentinel Lymph Node Fluorescence Imaging

PubMed Central

Liss, Michael A.; Farshchi-Heydari, Salman; Qin, Zhengtao; Hickey, Sean A.; Hall, David J.; Kane, Christopher J.; Vera, David R.

2015-01-01

An ideal substance to provide convenient and accurate targeting for sentinel lymph node (SLN) mapping during robotic-assisted surgery has yet to be found. We used an animal model to determine the ability of the FireFly camera system to detect fluorescent SLNs after administration of a dual-labeled molecular imaging agent. Methods We injected the footpads of New Zealand White rabbits with 1.7 or 8.4 nmol of tilmanocept labeled with 99mTc and a near-infrared fluorophore, IRDye800CW. One and 36 h after injection, popliteal lymph nodes, representing the SLNs, were dissected with the assistance of the FireFly camera system, a fluorescence-capable endoscopic imaging system. After excision of the paraaortic lymph nodes, which represented non-SLNs, we assayed all lymph nodes for radioactivity and fluorescence intensity. Results Fluorescence within all popliteal lymph nodes was easily detected by the FireFly camera system. Fluorescence within the lymph channel could be imaged during the 1-h studies. When compared with the paraaortic lymph nodes, the popliteal lymph nodes retain greater than 95% of the radioactivity at both 1 and 36 h after injection. At both doses (1.7 and 8.4 nmol), the popliteal nodes had higher (P < 0.050) optical fluorescence intensity than the paraaortic nodes at the 1- and 36-h time points. Conclusion The FireFly camera system can easily detect tilmanocept labeled with a near-infrared fluorophore at least 36 h after administration. This ability will permit image acquisition and subsequent verification of fluorescence-labeled SLNs during robotic-assisted surgery. PMID:25024425

Preclinical evaluation of robotic-assisted sentinel lymph node fluorescence imaging.

PubMed

Liss, Michael A; Farshchi-Heydari, Salman; Qin, Zhengtao; Hickey, Sean A; Hall, David J; Kane, Christopher J; Vera, David R

2014-09-01

An ideal substance to provide convenient and accurate targeting for sentinel lymph node (SLN) mapping during robotic-assisted surgery has yet to be found. We used an animal model to determine the ability of the FireFly camera system to detect fluorescent SLNs after administration of a dual-labeled molecular imaging agent. We injected the footpads of New Zealand White rabbits with 1.7 or 8.4 nmol of tilmanocept labeled with (99m)Tc and a near-infrared fluorophore, IRDye800CW. One and 36 h after injection, popliteal lymph nodes, representing the SLNs, were dissected with the assistance of the FireFly camera system, a fluorescence-capable endoscopic imaging system. After excision of the paraaortic lymph nodes, which represented non-SLNs, we assayed all lymph nodes for radioactivity and fluorescence intensity. Fluorescence within all popliteal lymph nodes was easily detected by the FireFly camera system. Fluorescence within the lymph channel could be imaged during the 1-h studies. When compared with the paraaortic lymph nodes, the popliteal lymph nodes retain greater than 95% of the radioactivity at both 1 and 36 h after injection. At both doses (1.7 and 8.4 nmol), the popliteal nodes had higher (P < 0.050) optical fluorescence intensity than the paraaortic nodes at the 1- and 36-h time points. The FireFly camera system can easily detect tilmanocept labeled with a near-infrared fluorophore at least 36 h after administration. This ability will permit image acquisition and subsequent verification of fluorescence-labeled SLNs during robotic-assisted surgery. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Herrada, J; Iyer, R B; Atkinson, E N; Sneige, N; Buzdar, A U; Hortobagyi, G N

1997-09-01

The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph nodes. The combination of physical examination with either mammography or sonography significantly improves the accuracy of noninvasive assessment of tumor dimensions.

Intraoperative Sentinel Lymph Node Evaluation: Implications of Cytokeratin 19 Expression for the Adoption of OSNA in Oral Squamous Cell Carcinoma.

PubMed

Shaw, Richard; Christensen, Anders; Java, Kapil; Maddani, Rehab El; Liloglou, Triantafillos; Asterios, Triantafyllou; von Buchwald, Christian; Wessel, Irene; Kiss, Katalin; Kjaer, Andreas; Lelkaitis, Giedrius; Long, Anna; Risk, Janet; Robinson, Max

2016-11-01

Intraoperative analysis of sentinel lymph nodes would enhance the care of early-stage oral squamous cell carcinoma (OSCC). We determined the frequency and extent of cytokeratin 19 (CK19) expression in OSCC primary tumours and surrounding tissues to explore the feasibility of a "clinic-ready" intraoperative diagnostic test (one step nucleic acid amplification-OSNA, sysmex). Two cohorts were assembled: cohort 1, OSCC with stage and site that closely match cases suitable for sentinel lymph node biopsy (SLNB); cohort 2, HNSCC with sufficient fresh tumour tissue available for the OSNA assay (>50 mg). CK19 assays included qRT-PCR, RNA in situ hybridisation (ISH), and immunohistochemistry (IHC), as well as OSNA. CK19 mRNA expression was detected with variable sensitivity, depending on method, in 60-80% of primary OSCC tumours, while protein expression was observed in only 50% of tumours. Discordance between different techniques indicated that OSNA was more sensitive than qRT-PCR or RNA-ISH, which in turn were more sensitive than IHC. OSNA results showed CK19 expression in 80% of primary cases, so if used for diagnosis of lymph node metastasis would lead to a false-negative result in 20% of patients with cervical lymph node metastases. OSNA in its current form is not suitable for use in OSCC SLNB due to inadequate expression of the CK19 target in all case. However, the same assay technology would likely be very promising if applied using a more ubiquitous squamous epithelial target.

Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice

PubMed Central

Sennino, Barbara; Ishiguro-Oonuma, Toshina; Schriver, Brian J.; Christensen, James G.; McDonald, Donald M.

2013-01-01

Inhibition of vascular endothelial growth factor (VEGF) signaling can promote lymph node metastasis in preclinical models, but the mechanism is not fully understood, and successful methods of prevention have not been found. Signaling of hepatocyte growth factor (HGF) and its receptor c-Met can promote the growth of lymphatics and metastasis of some tumors. We sought to explore the contributions of c-Met signaling to lymph node metastasis after inhibition of VEGF signaling. In particular, we examined whether c-Met is upregulated in lymphatics in or near pancreatic neuroendocrine tumors in RIP-Tag2 transgenic mice and whether lymph node metastasis can be reduced by concurrent inhibition of VEGF and c-Met signaling. Inhibition of VEGF signaling by anti-VEGF antibody or sunitinib in mice from age 14 to 17 weeks was accompanied by more intratumoral lymphatics, more tumor cells inside lymphatics, and more lymph node metastases. Under these conditions, lymphatic endothelial cells - like tumor cells - had strong immunoreactivity for c-Met and phospho-c-Met. c-Met blockade by the selective inhibitor PF-04217903 significantly reduced metastasis to local lymph nodes. Together, these results indicate that inhibition of VEGF signaling in RIP-Tag2 mice upregulates c-Met expression in lymphatic endothelial cells, increases the number of intratumoral lymphatics and number of tumor cells within lymphatics, and promotes metastasis to local lymph nodes. Prevention of lymph node metastasis by PF-04217903 in this setting implicates c-Met signaling in tumor cell spread to lymph nodes. PMID:23576559

A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer

PubMed Central

Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

2014-01-01

To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept. PMID:25485280

Modeling pre-metastatic lymphvascular niche in the mouse ear sponge assay

NASA Astrophysics Data System (ADS)

García-Caballero, Melissa; van de Velde, Maureen; Blacher, Silvia; Lambert, Vincent; Balsat, Cédric; Erpicum, Charlotte; Durré, Tania; Kridelka, Frédéric; Noel, Agnès

2017-01-01

Lymphangiogenesis, the formation of new lymphatic vessels, occurs in primary tumors and in draining lymph nodes leading to pre-metastatic niche formation. Reliable in vivo models are becoming instrumental for investigating alterations occurring in lymph nodes before tumor cell arrival. In this study, we demonstrate that B16F10 melanoma cell encapsulation in a biomaterial, and implantation in the mouse ear, prevents their rapid lymphatic spread observed when cells are directly injected in the ear. Vascular remodeling in lymph nodes was detected two weeks after sponge implantation, while their colonization by tumor cells occurred two weeks later. In this model, a huge lymphangiogenic response was induced in primary tumors and in pre-metastatic and metastatic lymph nodes. In control lymph nodes, lymphatic vessels were confined to the cortex. In contrast, an enlargement and expansion of lymphatic vessels towards paracortical and medullar areas occurred in pre-metastatic lymph nodes. We designed an original computerized-assisted quantification method to examine the lymphatic vessel structure and the spatial distribution. This new reliable and accurate model is suitable for in vivo studies of lymphangiogenesis, holds promise for unraveling the mechanisms underlying lymphatic metastases and pre-metastatic niche formation in lymph nodes, and will provide new tools for drug testing.

Mediastinal lymph node detection and station mapping on chest CT using spatial priors and random forest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jiamin; Hoffman, Joanne; Zhao, Jocelyn

2016-07-15

Purpose: To develop an automated system for mediastinal lymph node detection and station mapping for chest CT. Methods: The contextual organs, trachea, lungs, and spine are first automatically identified to locate the region of interest (ROI) (mediastinum). The authors employ shape features derived from Hessian analysis, local object scale, and circular transformation that are computed per voxel in the ROI. Eight more anatomical structures are simultaneously segmented by multiatlas label fusion. Spatial priors are defined as the relative multidimensional distance vectors corresponding to each structure. Intensity, shape, and spatial prior features are integrated and parsed by a random forest classifiermore » for lymph node detection. The detected candidates are then segmented by the following curve evolution process. Texture features are computed on the segmented lymph nodes and a support vector machine committee is used for final classification. For lymph node station labeling, based on the segmentation results of the above anatomical structures, the textual definitions of mediastinal lymph node map according to the International Association for the Study of Lung Cancer are converted into patient-specific color-coded CT image, where the lymph node station can be automatically assigned for each detected node. Results: The chest CT volumes from 70 patients with 316 enlarged mediastinal lymph nodes are used for validation. For lymph node detection, their system achieves 88% sensitivity at eight false positives per patient. For lymph node station labeling, 84.5% of lymph nodes are correctly assigned to their stations. Conclusions: Multiple-channel shape, intensity, and spatial prior features aggregated by a random forest classifier improve mediastinal lymph node detection on chest CT. Using the location information of segmented anatomic structures from the multiatlas formulation enables accurate identification of lymph node stations.« less

Sentinel lymph node biopsy in cutaneous melanoma of the head and neck using the indocyanine green SPY Elite system.

PubMed

Vahabzadeh-Hagh, Andrew M; Blackwell, Keith E; Abemayor, Elliot; St John, Maie A

2018-05-17

Lymph node status is the single most important prognostic factor for patients with early-stage cutaneous melanoma. Sentinel lymph node biopsy (SLNB) has become the standard of care for intermediate depth melanomas. Modern SLNB implementation includes technetium-99 lymphoscintigraphy combined with local administration of a vital blue dye. However, sentinel lymph nodes may fail to localize in some cases and false-negative rates range from 0 to 34%. Here we demonstrate the feasibility of a new sentinel lymph node biopsy technique using indocyanine green (ICG) and the SPY Elite near-infrared imaging system. Cases of primary cutaneous melanoma of the head and neck without locoregional metastasis, underwent SLNB at a single quaternary care institution between May 2016 and June 2017. Intraoperatively, 0.25 mL of ICG was injected intradermal in 4 quadrants around the primary lesion. 10-15 minute circulation time was permitted. SPY Elite identified the sentinel lymph node within the nodal basin marked by lymphoscintigraphy. Target first echelon lymph nodes were confirmed with a gamma probe and ICG fluorescence. 14 patients were included with T1a to T4b cutaneous melanomas. Success rates for sentinel lymph node identification using lymphoscintigraphy and the SPY Elite system were both 86%. Zero false negatives occurred. Median length of follow-up was 323 days. In this pilot study, Indocyanine green near-infrared fluorescence demonstrates a safe, and facile method of sentinel lymph node biopsy for cutaneous melanoma of the head and neck compared with lymphoscintigraphy and vital blue dyes. Copyright © 2018 Elsevier Inc. All rights reserved.

Sentinel lymph node mapping in melanoma with technetium-99m dextran.

PubMed

Neubauer, S; Mena, I; Iglesis, R; Schwartz, R; Acevedo, J C; Leon, A; Gomez, L

2001-06-01

The aim of this work is to evaluate the capability of Tc99m B Dextran as a lymphoscintigraphic agent in the detection of the sentinel node in skin lesions. Forty-one patients with melanomas (39) and Merkel cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours before surgery. Serial gamma camera images and a handheld gamma probe were used to direct sentinel node biopsy. In 39/41 patients, lymph channels and 52 sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one patient, with a dorsal melanoma, no lymph channels or lymph nodes could be demonstrated on the images and only minimal radioactivity was found in the regional nodes with the probe. Another patient with a facial lesion failed to demonstrate lymph channels or nodes. No adverse reactions were observed. Tc99m-Dextran provided good definition of lymph channels and sentinel node localization, without the risks related to the use of potentially hazardous labeled materials of biological origin.

Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery.

PubMed

Ashitate, Yoshitomo; Hyun, Hoon; Kim, Soon Hee; Lee, Jeong Heon; Henary, Maged; Frangioni, John V; Choi, Hak Soo

2014-01-01

The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We developed near-infrared fluorophores, which have fluorescence emission maxima either at 700 nm or at 800 nm. One was injected intravenously for identification of all regional lymph nodes in a basin, and the other was injected locally for identification of the SLN. Using the dual-channel FLARE intraoperative imaging system, we could identify and resect all PLNs and SLNs simultaneously. The technology we describe enables simultaneous, real-time visualization of both PLNs and SLNs in the same subject.

Characterization and evaluation of a modified local lymph node assay using ATP content as a non-radio isotopic endpoint.

PubMed

Idehara, Kenji; Yamagishi, Gaku; Yamashita, Kunihiko; Ito, Michio

2008-01-01

The murine local lymph node assay (LLNA) is an accepted and widely used method for assessing the skin-sensitizing potential of chemicals. Here, we describe a non-radio isotopic modified LLNA in which adenosine triphosphate (ATP) content is used as an endpoint instead of radioisotope (RI); the method is termed LLNA modified by Daicel based on ATP content (LLNA-DA). Groups of female CBA/JNCrlj mice were treated topically on the dorsum of both ears with test chemicals or a vehicle control on days 1, 2, and 3; an additional fourth application was conducted on day 7. Pretreatment with 1% sodium lauryl sulfate solution was performed 1 h before each application. On day 8, the amount of ATP in the draining auricular lymph nodes was measured as an alternative endpoint by the luciferin-luciferase assay in terms of bioluminescence (relative light units, RLU). A stimulation index (SI) relative to the concurrent vehicle control was derived based on the RLU value, and an SI of 3 was set as the cut-off value. Using the LLNA-DA method, 31 chemicals were tested and the results were compared with those of other test methods. The accuracy of LLNA-DA vs LLNA, guinea pig tests, and human tests was 93% (28/30), 80% (20/25), and 79% (15/19), respectively. The estimated concentration (EC) 3 value was calculated and compared with that of the original LLNA. It was found that the EC3 values obtained by LLNA-DA were almost equal to those obtained by the original LLNA. The SI value based on ATP content is similar to that of the original LLNA as a result of the modifications in the chemical treatment procedure, which contribute to improving the SI value. It is concluded that LLNA-DA is a promising non-RI alternative method for evaluating the skin-sensitizing potential of chemicals.

Ultrasonographic identification of the anatomical landmarks that define cervical lymph nodes spaces.

PubMed

Lenghel, Lavinia Manuela; Baciuţ, Grigore; Botar-Jid, Carolina; Vasilescu, Dan; Bojan, Anca; Dudea, Sorin M

2013-03-01

The localization of cervical lymph nodes is extremely important in practice for the positive and differential diagnosis as well as the staging of cervical lymphadenopathies. Ultrasonography represents the first line imaging method in the diagnosis of cervical lymphadenopathies due to its excellent resolution and high diagnosis accuracy. The present paper aims to illustrate the ultrasonographic identification of the anatomical landmarks used for the definition of cervical lymphatic spaces. The application of standardized views allows a delineation of clear anatomical landmarks and an accurate localization of the cervical lymph nodes.

Influence of reserpine on in vivo localization of injected lymph node cells in the mouse.

PubMed Central

Bellavia, A; Micklem, H S

1987-01-01

The effects of reserpine, and other agents that affect the storage and availability of 5-hydroxytryptamine (5HT), on the localization of injected 51Cr-labelled syngeneic lymph node cells have been investigated. A high dose (5 mg/kg) of reserpine to the recipients reduced localization in the lymph nodes and prevented the usual accumulation of lymphocytes in lymph nodes draining the site of an antigen (sheep erythrocytes: SE) injection. These effects were partially reversible by the monoamine oxidase inhibitor nialamide. This dose of reserpine produced deep sedation throughout the period of the experiment. Lower doses, up to 2.5 mg/kg, produced little sedation and had no effect on the localization of lymphocytes. Other workers had previously reported reduced localization of cells in delayed-type hypersensitivity (DTH) lesions after treatment of the recipients with 5 mg/kg reserpine, and had interpreted this in terms of a role of 5HT in promoting vascular permeability and egress of blood cells. The effect of lower doses of reserpine was not reported. We suggest that the effects on cell localization in both sets of experiments may have been secondary to the general state of sedation and not attributable to a direct local influence of 5HT. Other effects of reserpine included prolonged retention of lymphocytes in lungs and blood, and a reduction of cellularity and DNA synthesis in the thymus, spleen and lymph nodes. PMID:3817871

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay.

PubMed

Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao

2016-09-15

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. Copyright © 2016 Elsevier Inc. All rights reserved.

10 % fluorescein sodium vs 1 % isosulfan blue in breast sentinel lymph node biopsy.

PubMed

Ren, Lidong; Liu, Zhao; Liang, Mengdi; Wang, Li; Song, Xingli; Wang, Shui

2016-11-03

Sentinel lymph node biopsy (SLNB) is well accepted to be a standard procedure in breast cancer surgery with clinically negative lymph nodes. Isosulfan blue is the first dye approved by the USA Food and Drug Administration for the localization of the lymphatic system. Few alternative tracers have been investigated. In this study, we aimed to compare the differences between 10 % fluorescein sodium and 1 % isosulfan blue in breast sentinel lymph node biopsy and to investigate the feasibility of using 10 % fluorescein sodium as a new dye for breast sentinel lymph node biopsy. A total of 30 New Zealand rabbits were randomly divided into the fluorescein sodium group and the isosulfan blue group (15 rabbits per group). Fluorescein sodium or isosulfan blue was injected subcutaneously into the second pair of mammary areolas. The average fading time of the second lymph nodes in the isosulfan blue group was significantly shorter than that in the fluorescein sodium group. Moreover, the detection rates of SLNs were higher in the fluorescein sodium group than in the isosulfan blue group. No significant differences between the fluorescein sodium group and isosulfan blue group were observed regarding the distances between the detected sentinel lymph nodes and second pair of mammary areolas, the distances between the second lymph nodes and second pair of mammary areolas, the number of detected sentinel lymph nodes and second lymph nodes, the average dyeing time of the sentinel and the second lymph nodes, and the average fading time of the second lymph nodes. In summary, we first reported that fluorescein sodium is a potential new tracer for breast sentinel lymph node biopsy.

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases.

PubMed

Cavuslu, S; Goodlad, J; Hobbs, C; Connor, A M; Raju, K S; Best, J M; Cason, J

1997-10-01

Overexpression of p53 protein is common in cervical carcinoma. We investigated archival biopsies from 26 cervical cancer patients (24 with available lymph nodes) to determine the relationship between p53 overexpression and HPV infection at the cervix and lymph nodes. Twelve cervical carcinoma patients had p53 protein in cervical biopsies detectable by immunohistochemistry using monoclonal antibody DO-1, and 22 were positive for HPV DNA in polymerase chain reaction assays (16, contained HPV-16; 3, HPV-18; and, 3 HPV-X). Seven cervical cancer patients had one or more lymph nodes positive for p53 protein, and all but one of these were concordantly p53 positive at the cervix. However, detection of p53 protein in cervical biopsies was predictive neither of the expression of p53 at draining lymph nodes (P > 0.1) nor of the occurrence of metastases (P > 0.1). Fourteen patients were positive at one or more lymph nodes for HPV DNA. Cervical positivity for HPV DNA was associated significantly with concordant HPV positivity at the lymph nodes (P = 0.039) and was predictive of metastases (P = 0.019). There was no association between positivity for p53 and for HPV DNA at primary cervical carcinomas or at the lymph nodes (all P > 0.1). We conclude that, although detectable p53 protein is a common feature of cervical carcinomas, it is not predictive of metastases and is independent of HPV infection.

[Assessment of lymph node metastasis in gastric cancer: status quo, recent advances and new perspectives].

PubMed

Tu, Min; Zhu, Zhen-shu; Shi, Lin-sen; Jiang, Xi-qun; Wang, Hao; Guan, Wen-xian

2012-02-01

The precondition of accurate gastric cancer surgery is precise assessment of lymph node metastasis. To date, no imaging modality achieves both high sensitivity and high specificity in detecting lymph node metastasis in gastric cancer. Intraoperative sentinel node tracing and biopsy are the most popular method to identify the localization of tumor cell, but is limited to early gastric cancer. Nano-composite materials, designed for tumor imaging and tracing, show us a newly emerging domain for tumor detection in gastric cancer. The function of these nano-composite materials to detect lymph node metastasis in gastric cancer relies on the effective backflow of lymph system. However, the lymph vessels can be obstructed by tumor cells in advanced gastric cancer, which may restrain the application of these nanoparticles. Therefore, more methods to detect lymph node metastasis in gastric cancer should be explored. This review summarizes the characteristic of the targeted nanosphere. Based on the reported studies, a novel idea is conceived that targeted multifunctional nanosphere may be a potential method to achieve precise assessment of lymph node metastasis in gastric cancer.

Anatomic-histologic study of the floor of the mouth: the lingual lymph nodes.

PubMed

Ananian, Sargis G; Gvetadze, Shalva R; Ilkaev, Konstantin D; Mochalnikova, Valeria V; Zayratiants, Georgiy O; Mkhitarov, Vladimir A; Yang, Xin; Ciciashvili, Aleksandr M

2015-06-01

The lingual lymph nodes are inconstant nodes located within the fascial/intermuscular spaces of the floor of the mouth. Oral tongue squamous cell carcinoma has been reported to recur and metastasize in lingual lymph nodes with poor prognosis. Lingual lymph nodes are not currently included in basic tongue squamous cell carcinoma surgery. Twenty-one cadavers (7 males, 14 females) were studied, aged from 57 to 94 years (mean age 76.3 years). The gross specimen of the floor of the mouth was divided into blocks: A (median nodes), B, B' (parahyoid), C, C' (paraglandular). Serial histological microslides were cut and stained with hematoxylin-eosin. Frequency of lingual lymph nodes in each block and their microscopic features were assessed. The lingual lymph nodes in overall number of 7 were detected in 5 of the 21 cadavers (23.8%). The total incidence of lingual lymph node was 33.3% (7 nodes/21 cadavers). Block A failed to demonstrate any lymph nodes (0%); Blocks B, B'-2 nodes (9.5%) and 2 nodes (9.5%), respectively; Blocks C, C'-1 node (4.8%) and 2 nodes (9.5%), respectively. The mean lingual lymph node length was 4.1 mm (from 1.4 to 8.7 mm), the mean thickness was 2.8 mm (from 0.8 to 7.5 mm). Five cadavers (23.8%) revealed mucosa-associated lymphoid tissue. Atrophic changes appeared in 4 (57.1%) lingual lymph nodes. The presence of lymph node-bearing tissue in the floor of the mouth is demonstrated. In account of resection radicalism and better local control the fat tissue of the floor of the mouth should be removed in conjunction to glossectomy. Further anatomic and clinical research is required to establish the role of lingual lymph node in oral squamous cell carcinoma recurrence and metastasis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Molecular Diagnosis for Nodal Metastasis in Endoscopically Managed Cervical Cancer: The Accuracy of the APTIMA Test to Detect High-risk Human Papillomavirus Messenger RNA in Sentinel Lymph Nodes.

PubMed

Köhler, Christhardt; Le, Xin; Dogan, Nasuh Utku; Pfiffer, Tatiana; Schneider, Achim; Marnitz, Simone; Bertolini, Julia; Favero, Giovanni

2016-01-01

To evaluate the feasibility and accuracy of a commercially available test to detect E6/E7 mRNA of 14 subtypes of high-risk HPVs (APTIMA; Hologic, Bedford, MA) in the sentinel lymph nodes of CC patients laparoscopically operated. Prospective pilot study. The study was conducted in the Department of Advanced Operative and Oncologic Gynecology, Asklepios Hospital, Hamburg, Germany. 54 women with HPV-positive CC submitted to laparoscopic sentinel node biopsy alone or sentinel node biopsy followed by systematic pelvic and/or para-aortic endoscopic lymphadenectomy. All removed sentinel lymph nodes (SLNs) underwent sample collection by cytobrush for the APTIMA assay before frozen section. Results obtained with the HPV mRNA test were compared with the definitive histopathological analysis of the SLNs and additional lymph nodes removed. A total of 125 SLNs (119 pelvic and 6 paraaortic) were excised with a mean number of 2.3 SLNs per patient. Final histopathologic analysis confirmed nodal metastases in 10 SLNs from 10 different patients (18%). All the histologically confirmed metastatic lymph nodes were also HPV E6/E7 mRNA positive, resulting in a sensitivity of 100%. Four histologically free sentinel nodes were positive for HPV E6/E7 mRNA, resulting in a specificity of 96.4%. The HPV E6/E7 mRNA assay in the SLNs of patients with CC is feasible and highly accurate. The detection of HPV mRNA in 4 women with negative SLNs might denote a shift from microscopic identification of metastasis to the molecular level. The prognostic value of this findings awaits further verification. Copyright © 2016. Published by Elsevier Inc.

The local lymph node assay compared with the human maximization test as an indicator of allergic potency in humans using patch test clinic populations.

PubMed

Zaghi, Danny; Maibach, Howard I

2009-01-01

The human maximization test (HMT) is a method to evaluate potency in humans, while the local lymph node assay (LLNA) is a test method that allows for the measuring of the allergic potency of a substance in a rodent. It has been proposed that an EC3 value (the value obtained by the LLNA test, ie, the concentration of an allergen leading to a 3-fold increase of baseline proliferation rate) would be a reliable indicator for a compound's allergic potency in humans. This paper compares the correlation between the EC3 value of a compound and its allergic occurrence in the general population with the correlation between the HMT of the compound and its allergic occurrence in the general population, to determine the relationship to potency. The correlation values when outliers were removed from the sample were -0.56 and -0.71 for LLNA and HMT, respectively, suggesting that there is a possible 20% error margin in LLNA's ability to predict potency. The data also suggest that other factors (such as exposure) could play up to a 30% role in the determination of allergic occurrence in the general population. The potency assays might be made more clinically relevant for predicting allergic frequencies by including a frequency factor and other factors in its dermatotoxicological interpretation.

Further experience with the local lymph node assay using standard radioactive and nonradioactive cell count measurements.

PubMed

Kolle, Susanne N; Basketter, David; Schrage, Arnhild; Gamer, Armin O; van Ravenzwaay, Bennard; Landsiedel, Robert

2012-08-01

In a previous study, the predictive capacity of a modified local lymph node assay (LLNA) based on cell counts, the LNCC, was demonstrated to be closely similar to that of the original assay. In addition, a range of substances, including some technical/commercial materials and a range of agrochemical formulations (n = 180) have also been assessed in both methods in parallel. The results in the LNCC and LLNA were generally consistent, with 86% yielding an identical classification outcome. Discordant results were associated with borderline data and were evenly distributed between the two methods. Potency information derived from each method also demonstrated good consistency (n = 101), with 93% of predictions being close. Skin irritation was observed only infrequently and was most commonly associated with positive results; it was not associated with the discordant results. Where different vehicles were used with the same test material, the effect on sensitizing activity was modest, consistent with historical data. Analysis of positive control data indicated that the LNCC and LLNA displayed similar levels of biological variation. When taken in combination with the previously published results on LLNA Performance Standard chemicals, it is concluded that the LNCC provides a viable non-radioactive alternative to the LLNA for the assessment of substances, including potency predictions, as well as for the evaluation of preparations. Copyright © 2012 John Wiley & Sons, Ltd.

The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.

PubMed

Remenschneider, Aaron K; Dilger, Amanda E; Wang, Yingbing; Palmer, Edwin L; Scott, James A; Emerick, Kevin S

2015-04-01

Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. Blinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. A consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. Ninety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. SPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Automatic detection of pelvic lymph nodes using multiple MR sequences

NASA Astrophysics Data System (ADS)

Yan, Michelle; Lu, Yue; Lu, Renzhi; Requardt, Martin; Moeller, Thomas; Takahashi, Satoru; Barentsz, Jelle

2007-03-01

A system for automatic detection of pelvic lymph nodes is developed by incorporating complementary information extracted from multiple MR sequences. A single MR sequence lacks sufficient diagnostic information for lymph node localization and staging. Correct diagnosis often requires input from multiple complementary sequences which makes manual detection of lymph nodes very labor intensive. Small lymph nodes are often missed even by highly-trained radiologists. The proposed system is aimed at assisting radiologists in finding lymph nodes faster and more accurately. To the best of our knowledge, this is the first such system reported in the literature. A 3-dimensional (3D) MR angiography (MRA) image is employed for extracting blood vessels that serve as a guide in searching for pelvic lymph nodes. Segmentation, shape and location analysis of potential lymph nodes are then performed using a high resolution 3D T1-weighted VIBE (T1-vibe) MR sequence acquired by Siemens 3T scanner. An optional contrast-agent enhanced MR image, such as post ferumoxtran-10 T2*-weighted MEDIC sequence, can also be incorporated to further improve detection accuracy of malignant nodes. The system outputs a list of potential lymph node locations that are overlaid onto the corresponding MR sequences and presents them to users with associated confidence levels as well as their sizes and lengths in each axis. Preliminary studies demonstrates the feasibility of automatic lymph node detection and scenarios in which this system may be used to assist radiologists in diagnosis and reporting.

Patterns of regional head and neck lymph node metastasis in primary conjunctival malignant melanoma

PubMed Central

Lim, M; Tatla, T; Hersh, D; Hungerford, J

2006-01-01

Objective To correlate patterns of regional lymph node metastasis with the site of origin in primary conjunctival malignant melanoma. Design Retrospective analysis (1990–2003) of clinical data. Setting Two London tertiary referral centres. Participants 12 patients presenting with regional metastases after failed local treatment for conjunctival malignant melanoma. Results 6 cases predominantly involving the temporal conjunctiva metastasised to the pre‐auricular lymph nodes. Two cases predominantly involving the nasal conjunctiva metastasised to the submandibular nodes. Of the two cases with purely multifocal disease, one metastasised to the pre‐auricular nodes and another to both submandibular and parotid nodes. One primary conjunctival malignant melanoma had its origin in temporal conjunctiva but metastasised to submandibular nodes, and another case originating from nasal conjunctiva metastasised to pre‐auricular nodes. Conclusions Temporal conjunctival melanotic lesions tend to metastasise clinically to pre‐auricular lymph nodes and nasal conjunctival melanotic lesions metastasise to the submandibular lymph nodes. Patterns appear consistent with laboratory‐based anatomically mapped lymphatic drainage basins of the conjunctiva. PMID:16928703

Unusual metastasis of left colon cancer: considerations on two cases.

PubMed

Gubitosi, Adelmo; Moccia, Giancarlo; Malinconico, Francesca Antonella; Gilio, Francesco; Iside, Giovanni; Califano, Umberto G A; Foroni, Fabrizio; Ruggiero, Roberto; Docimo, Giovanni; Parmeggiani, Domenico; Agresti, Massimo

2009-04-01

Usually, left colon cancer metastasis concerns liver, abdominal lymph nodes and lungs. Other localizations are quite rare occurrences. In spite of this, some uncommon metastasis sites are reported in literature, such as: peritoneum, ovaries, uterus, kidney testis, bones, thyroid, oral cavity and central nervous system. We report two cases of unusual localizations of left colon cancer metastasis localization, one into the retroperitoneal space and the other at the left axillary lynphnodes and between liver and pancreas. In the first reported case the diffusion pathway may have been the lymphatic mesocolic vessels, partially left in place from the previous surgery. In the second case the alleged metastatic lane may have been through the periumbilical lymph nodes to the parasternal lymph nodes and then to the internal mammary ones, finally reaching the axillary limph nodes.

Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

PubMed Central

Ma, Michelle W.; Medicherla, Ratna C.; Qian, Meng; de Miera, Eleazar Vega-Saenz; Friedman, Erica B.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Ott, Patrick A.; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod

2013-01-01

The sentinel lymph node is the initial site of metastasis. Down-regulation of anti-tumor immunity plays a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T-cells (Foxp3+) and dendritic cells (conventional: CD11c+, mature: CD86+) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunologic primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared to those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T-cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathologic variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Anti-tumor immunity was down-regulated in the positive sentinel lymph node with an increase in regulatory T-cells compared to the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared to the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T-cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions. PMID:22425909

Immune stimulation following dermal exposure to unsintered indium tin oxide

PubMed Central

Brock, Kristie; Anderson, Stacey E.; Lukomska, Ewa; Long, Carrie; Anderson, Katie; Marshall, Nikki; Meade, B. Jean

2015-01-01

In recent years, several types of pulmonary pathology, including alveolar proteinosis, fibrosis, and emphysema, have been reported in workers in the indium industry. To date, there remains no clear understanding of the underlying mechanism(s). Pulmonary toxicity studies in rats and mice have demonstrated the development of mediastinal lymph node hyperplasia and granulomas of mediastinal lymph nodes and bronchus-associated lymphoid tissues following exposure to indium tin oxide. Given the association between exposure to other metals and the development of immune-mediated diseases, these studies were undertaken to begin to investigate the immuno-modulatory potential of unsintered indium tin oxide (uITO) in a mouse model. Using modifications of the local lymph node assay, BALB/c mice (five animals/group) were exposed topically via intact or breached skin or injected intradermally at the base of the ear pinnae with either vehicle or increasing concentrations 2.5–10% uITO (90:10 indium oxide/tin oxide, particle size <50 nm). Dose-responsive increases in lymphocyte proliferation were observed with a calculated EC3 of 4.7% for the intact skin study. Phenotypic analysis of draining lymph node cells following intradermal injection with 5% uITO yielded a profile consistent with a T-cell-mediated response. These studies demonstrate the potential for uITO to induce sensitization and using lymphocyte proliferation as a biomarker of exposure, and demonstrate the potential for uITO to penetrate both intact and breached skin. PMID:24164313

Application of carbon nanoparticles in laparoscopic sentinel lymph node detection in patients with early-stage cervical cancer.

PubMed

Lu, Yan; Wei, Jin-Ying; Yao, De-Sheng; Pan, Zhong-Mian; Yao, Yao

2017-01-01

To investigate the value of carbon nanoparticles in identifying sentinel lymph nodes in early-stage cervical cancer. From January 2014 to January 2016, 40 patients with cervical cancer stage IA2-IIA, based on the International Federation of Gynecology and Obstetrics (FIGO) 2009 criteria, were included in this study. The normal cervix around the tumor was injected with a total of 1 mL of carbon nanoparticles (CNP)at 3 and 9 o'clock. All patients then underwent laparoscopic pelvic lymph node dissection and radical hysterectomy. The black-dyed sentinel lymph nodes were removed for routine pathological examination and immunohistochemical staining. Among the 40 patients, 38 patients had at least one sentinel lymph node (SLN). The detection rate was 95% (38/40). One hundred seventy-three SLNs were detected with an average of 3.9 SLNs per side. 25 positive lymph nodes, which included 21 positive SLNs, were detected in 8 (20%) patients. Sentinel lymph nodes were localized in the obturator (47.97%), internal lilac (13.87%), external lilac (26.59%), parametrial (1.16%), and common iliac (8.67%) regions. The sensitivity of the SLN detection was 100% (5/5), the accuracy was 97.37% (37/38), and the negative predictive value was 100. 0% and the false negative rate was 0%. Sentinel lymph nodes can be used to accurately predict the pathological state of pelvic lymph nodes in early cervical cancer. The detection rates and accuracy of sentinel lymph node were high. Carbon nanoparticles can be used to trace the sentinel lymph node in early cervical cancer.

Experimental Study of Magnetic Multi-Walled Carbon Nanotube-Doxorubicin Conjugate in a Lymph Node Metastatic Model of Breast Cancer.

PubMed

Ji, Jian; Liu, Minfeng; Meng, Yue; Liu, Runqi; Yan, Yan; Dong, Jianyu; Guo, Zhaoze; Ye, Changsheng

2016-07-07

BACKGROUND The lymphatic system plays a significant role in the defense of a subject against breast cancer and is one of the major pathways for the metastasis of breast cancer. To improve the prognosis, many means, including surgery, radiotherapy, and chemotherapy, have been used. However, the combination of all these modalities has limited efficacy. Lymph nodes, therefore, have become an exceptionally potential target organ in cancer chemotherapy. MATERIAL AND METHODS A lymph node metastatic model of breast cancer was established in BALB/c mice. Magnetic multi-walled carbon nanotube carrier with good adsorption and lymph node-targeting capacity was prepared and conjugated with doxorubicin to make the magnetic multi-walled carbon nanotube-doxorubicin suspension. Dispersions of doxorubicin, magnetic multi-walled carbon nanotube-doxorubicin, and magnetic multi-walled carbon nanotube were injected into lymph node metastatic mice to compare their inhibitory effects on tumor cells in vivo. Inhibition of these dispersions on EMT-6 breast cancer cells was detected via MTT assay in vitro. RESULTS Although no significant difference was found between the effects of doxorubicin and magnetic multi-walled carbon nanotube-doxorubicin with the same concentration of doxorubicin on EMT-6 breast cancer cells in vitro, in terms of sizes of metastatic lymph nodes and xenograft tumors, apoptosis in metastatic lymph nodes, and adverse reactions, the magnetic multi-walled carbon nanotube-doxorubicin group differed significantly from the other groups. CONCLUSIONS The magnetic multi-walled carbon nanotube-doxorubicin clearly played an inhibitory role in lymph node metastases to EMT-6 breast cancer cells.

Automatic localization of IASLC-defined mediastinal lymph node stations on CT images using fuzzy models

NASA Astrophysics Data System (ADS)

Matsumoto, Monica M. S.; Beig, Niha G.; Udupa, Jayaram K.; Archer, Steven; Torigian, Drew A.

2014-03-01

Lung cancer is associated with the highest cancer mortality rates among men and women in the United States. The accurate and precise identification of the lymph node stations on computed tomography (CT) images is important for staging disease and potentially for prognosticating outcome in patients with lung cancer, as well as for pretreatment planning and response assessment purposes. To facilitate a standard means of referring to lymph nodes, the International Association for the Study of Lung Cancer (IASLC) has recently proposed a definition of the different lymph node stations and zones in the thorax. However, nodal station identification is typically performed manually by visual assessment in clinical radiology. This approach leaves room for error due to the subjective and potentially ambiguous nature of visual interpretation, and is labor intensive. We present a method of automatically recognizing the mediastinal IASLC-defined lymph node stations by modifying a hierarchical fuzzy modeling approach previously developed for body-wide automatic anatomy recognition (AAR) in medical imagery. Our AAR-lymph node (AAR-LN) system follows the AAR methodology and consists of two steps. In the first step, the various lymph node stations are manually delineated on a set of CT images following the IASLC definitions. These delineations are then used to build a fuzzy hierarchical model of the nodal stations which are considered as 3D objects. In the second step, the stations are automatically located on any given CT image of the thorax by using the hierarchical fuzzy model and object recognition algorithms. Based on 23 data sets used for model building, 22 independent data sets for testing, and 10 lymph node stations, a mean localization accuracy of within 1-6 voxels has been achieved by the AAR-LN system.

Intraoperative Fluorescence Imaging for Detection of Sentinel Lymph Nodes and Lymphatic Vessels during Open Prostatectomy using Indocyanine Green.

PubMed

Yuen, Keiji; Miura, Tetsuya; Sakai, Iori; Kiyosue, Akiko; Yamashita, Masuo

2015-08-01

We investigated the feasibility and validity of intraoperative fluorescence imaging using indocyanine green for the detection of sentinel lymph nodes and lymphatic vessels during open prostatectomy. Indocyanine green was injected into the prostate under transrectal ultrasound guidance just before surgery. Intraoperative fluorescence imaging was performed using a near-infrared camera system in 66 consecutive patients with clinically localized prostate cancer after a 10-patient pilot test to optimize indocyanine green dosing, observation timing and injection method. Lymphatic vessels were visualized and followed to identify the sentinel lymph nodes. Confirmatory pelvic lymph node dissection including all fluorescent nodes and open radical prostatectomy were performed in all patients. Lymphatic vessels were successfully visualized in 65 patients (98%) and sentinel lymph nodes in 64 patients (97%). Sentinel lymph nodes were located in the obturator fossa, internal and external iliac regions, and rarely in the common iliac and presacral regions. A median of 4 sentinel lymph nodes per patient was detected. Three lymphatic pathways, the paravesical, internal and lateral routes, were identified. Pathological examination revealed metastases to 9 sentinel lymph nodes in 6 patients (9%). All pathologically positive lymph nodes were detected as sentinel lymph nodes using this imaging. No adverse reactions due to the use of indocyanine green were observed. Intraoperative fluorescence imaging using indocyanine green during open prostatectomy enables the detection of lymphatic vessels and sentinel lymph nodes with high sensitivity. This novel method is technically feasible, safe and easy to apply with minimal additional operative time. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2014 CFR

2014-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2013 CFR

2013-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2012 CFR

2012-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization.

PubMed

Roberts, David W; Patlewicz, Grace; Kern, Petra S; Gerberick, Frank; Kimber, Ian; Dearman, Rebecca J; Ryan, Cindy A; Basketter, David A; Aptula, Aynur O

2007-07-01

The goal of eliminating animal testing in the predictive identification of chemicals with the intrinsic ability to cause skin sensitization is an important target, the attainment of which has recently been brought into even sharper relief by the EU Cosmetics Directive and the requirements of the REACH legislation. Development of alternative methods requires that the chemicals used to evaluate and validate novel approaches comprise not only confirmed skin sensitizers and non-sensitizers but also substances that span the full chemical mechanistic spectrum associated with skin sensitization. To this end, a recently published database of more than 200 chemicals tested in the mouse local lymph node assay (LLNA) has been examined in relation to various chemical reaction mechanistic domains known to be associated with sensitization. It is demonstrated here that the dataset does cover the main reaction mechanistic domains. In addition, it is shown that assignment to a reaction mechanistic domain is a critical first step in a strategic approach to understanding, ultimately on a quantitative basis, how chemical properties influence the potency of skin sensitizing chemicals. This understanding is necessary if reliable non-animal approaches, including (quantitative) structure-activity relationships (Q)SARs, read-across, and experimental chemistry based models, are to be developed.

Analysis of the Local Lymph Node Assay (LLNA) variability for assessing the prediction of skin sensitisation potential and potency of chemicals with non-animal approaches.

PubMed

Dumont, Coralie; Barroso, João; Matys, Izabela; Worth, Andrew; Casati, Silvia

2016-08-01

The knowledge of the biological mechanisms leading to the induction of skin sensitisation has favoured in recent years the development of alternative non-animal methods. During the formal validation process, results from the Local Lymph Node Assay (LLNA) are generally used as reference data to assess the predictive capacity of the non-animal tests. This study reports an analysis of the variability of the LLNA for a set of chemicals for which multiple studies are available and considers three hazard classification schemes: POS/NEG, GHS/CLP and ECETOC. As the type of vehicle used in a LLNA study is known to influence to some extent the results, two analyses were performed: considering the solvent used to test the chemicals and without considering the solvent. The results show that the number of discordant classifications increases when a chemical is tested in more than one solvent. Moreover, it can be concluded that study results leading to classification in the strongest classes (1A and EXT) seem to be more reliable than those in the weakest classes. This study highlights the importance of considering the variability of the reference data when evaluating non-animal tests. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluation of 4-methylcyclohexanemethanol (MCHM) in a combined irritancy and Local Lymph Node Assay (LLNA) in mice.

PubMed

Johnson, Victor J; Auerbach, Scott S; Luster, Michael I; Waidyanatha, Suramya; Masten, Scott A; Wolfe, Mary S; Burleson, Florence G; Burleson, Gary R; Germolec, Dori R

2017-07-01

4-Methylcyclohexanemethanol (MCHM) is a flotation reagent used in fine coal beneficiation. On January 9, 2014, crude MCHM, a mixture containing predominantly MCHM, was inadvertently released into the Elk River, a municipal water source that serves about 300,000 people in the Charleston, WV area, resulting in temporary contamination of 15 percent of the state's tap water and causing significant dermal exposure. The current studies were undertaken to determine whether crude MCHM or MCHM has the potential to produce dermal irritancy and/or sensitization. BALB/c female mice were treated daily for 3 consecutive days by direct epicutaneous application of 25 μL of various concentrations of crude MCHM or MCHM to the dorsum of each ear. A mouse ear-swelling test was used to determine irritancy potential and was undertaken in combination with the standardized Local Lymph Node Assay (LLNA) to determine skin sensitizing potential. MCHM was found to produce skin irritation at concentrations above 20% and did not produce sensitization. Crude MCHM also produced irritation, although weaker, and in addition was found to be a weak to moderate skin sensitizer. The results are discussed in terms of potential human health hazard. Copyright © 2017 Elsevier Ltd. All rights reserved.

TIMES-SS--recent refinements resulting from an industrial skin sensitisation consortium.

PubMed

Patlewicz, G; Kuseva, C; Mehmed, A; Popova, Y; Dimitrova, G; Ellis, G; Hunziker, R; Kern, P; Low, L; Ringeissen, S; Roberts, D W; Mekenyan, O

2014-01-01

The TImes MEtabolism Simulator platform for predicting Skin Sensitisation (TIMES-SS) is a hybrid expert system, first developed at Bourgas University using funding and data from a consortium of industry and regulators. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic 3D QSARs. The model estimates semi-quantitative skin sensitisation potency classes and has been developed with the aim of minimising animal testing, and also to be scientifically valid in accordance with the OECD principles for (Q)SAR validation. In 2007 an external validation exercise was undertaken to fully address these principles. In 2010, a new industry consortium was established to coordinate research efforts in three specific areas: refinement of abiotic reactions in the skin (namely autoxidation) in the skin, refinement of the manner in which chemical reactivity was captured in terms of structure-toxicity rules (inclusion of alert reliability parameters) and defining the domain based on the underlying experimental data (study of discrepancies between local lymph node assay Local Lymph Node Assay (LLNA) and Guinea Pig Maximisation Test (GPMT)). The present paper summarises the progress of these activities and explains how the insights derived have been translated into refinements, resulting in increased confidence and transparency in the robustness of the TIMES-SS predictions.

Distribution of prostate nodes: a PET/CT-derived anatomic atlas of prostate cancer patients before and after surgical treatment.

PubMed

Hegemann, Nina-Sophie; Wenter, Vera; Spath, Sonja; Kusumo, Nadia; Li, Minglun; Bartenstein, Peter; Fendler, Wolfgang P; Stief, Christian; Belka, Claus; Ganswindt, Ute

2016-03-11

In order to define adequate radiation portals in nodal positive prostate cancer a detailed knowledge of the anatomic lymph-node distribution is mandatory. We therefore systematically analyzed the localization of Choline PET/CT positive lymph nodes and compared it to the RTOG recommendation of pelvic CTV, as well as to previous work, the SPECT sentinel lymph node atlas. Thirty-two patients being mostly high risk patients with a PSA of 12.5 ng/ml (median) received PET/CT before any treatment. Eighty-seven patients received PET/CT for staging due to biochemical failure with a median PSA of 3.12 ng/ml. Each single PET-positive lymph node was manually contoured in a "virtual" patient dataset to achieve a 3-D visualization, resulting in an atlas of the cumulative PET positive lymph node distribution. Further the PET-positive lymph node location in each patient was assessed with regard to the existence of a potential geographic miss (i.e. PET-positive lymph nodes that would not have been treated adequately by the RTOG consensus on CTV definition of pelvic lymph nodes). Seventy-eight and 209 PET positive lymph nodes were detected in patients with no prior treatment and in postoperative patients, respectively. The most common sites of PET positive lymph nodes in patients with no prior treatment were external iliac (32.1 %), followed by common iliac (23.1 %) and para-aortic (19.2 %). In postoperative patients the most common sites of PET positive lymph nodes were common iliac (24.9 %), followed by external iliac (23.0 %) and para-aortic (20.1 %). In patients with no prior treatment there were 34 (43.6 %) and in postoperative patients there were 77 (36.8 %) of all detected lymph nodes that would not have been treated adequately using the RTOG CTV. We compared the distribution of lymph nodes gained by Choline PET/CT to the preexisting SPECT sentinel lymph node atlas and saw an overall good congruence. Choline PET/CT and SPECT sentinel lymph node atlas are comparable to each other. More than one-third of the PET positive lymph nodes in patients with no prior treatment and in postoperative patients would not have been treated adequately using the RTOG CTV. To reduce geographical miss, image based definition of an individual target volume is necessary.

Adenocarcinoma arising at a colostomy site with inguinal lymph node metastasis: report of a case.

PubMed

Iwamoto, Masayoshi; Kawada, Kenji; Hida, Koya; Hasegawa, Suguru; Sakai, Yoshiharu

2015-02-01

Inguinal lymph node metastasis from adenocarcinoma arising at a colostomy site is extremely rare, and the significance of surgical resection for metastatic inguinal lymph nodes has not been established. An 82-year-old woman who had undergone abdominoperineal resection 27 years earlier was admitted to our hospital complaining of bleeding from a colostomy. Physical examination revealed that a tumor at the colostomy site directly invaded into the peristomal skin, and that a left inguinal lymph node was firm and swollen. Positron emission tomography/computed tomography scan demonstrated accumulation of (18)F-fluorodeoxy glucose into both the colostomy tumor and the left swollen inguinal lymph node, while there was no evidence of metastasis to liver or lungs. She underwent open left hemicolectomy with wide local resection of the colostomy, and dissection of left inguinal lymph nodes. Histological diagnosis was a moderately differentiated adenocarcinoma that directly invaded into the surrounding skin and metastasized to the left inguinal lymph node. The patient has been followed up for >5 years without any sign of recurrence. In general, inguinal lymph node metastasis from colorectal cancers is regarded as a systemic disease with a poor prognosis, and so systemic chemotherapy and radiotherapy, but not surgical lymph node dissection, are recommended. Considering the lymphatic drainage route in the present case, inguinal lymph node metastasis does not represent a systemic disease but rather a sentinel nodal metastasis from adenocarcinoma at a colostomy site. Surgical dissection of metastatic inguinal lymph nodes should be considered to enable a favorable prognosis in the absence of distant metastasis to other organs. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sampling versus systematic full lymphatic dissection in surgical treatment of non-small cell lung cancer.

PubMed

Koulaxouzidis, Georgios; Karagkiouzis, Grigorios; Konstantinou, Marios; Gkiozos, Ioannis; Syrigos, Konstantinos

2013-04-22

The extent of mediastinal lymph node assessment during surgery for non-small cell cancer remains controversial. Different techniques are used, ranging from simple visual inspection of the unopened mediastinum to an extended bilateral lymph node dissection. Furthermore, different terms are used to define these techniques. Sampling is the removal of one or more lymph nodes under the guidance of pre-operative findings. Systematic (full) nodal dissection is the removal of all mediastinal tissue containing the lymph nodes systematically within anatomical landmarks. A Medline search was conducted to identify articles in the English language that addressed the role of mediastinal lymph node resection in the treatment of non-small cell lung cancer. Opinions as to the reasons for favoring full lymphatic dissection include complete resection, improved nodal staging and better local control due to resection of undetected micrometastasis. Arguments against routine full lymphatic dissection are increased morbidity, increase in operative time, and lack of evidence of improved survival. For complete resection of non-small cell lung cancer, many authors recommend a systematic nodal dissection as the standard approach during surgery, and suggest that this provides both adequate nodal staging and guarantees complete resection. Whether extending the lymph node dissection influences survival or recurrence rate is still not known. There are valid arguments in favor in terms not only of an improved local control but also of an improved long-term survival. However, the impact of lymph node dissection on long-term survival should be further assessed by large-scale multicenter randomized trials.

Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay.

PubMed

Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi

2015-12-01

The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross-sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was < 10%. Therefore, these chemicals were classified as moderate skin sensitizers in the LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE.

The added value of a portable gamma camera for intraoperative detection of sentinel lymph node in squamous cell carcinoma of the oral cavity: A case report.

PubMed

Mayoral, M; Paredes, P; Sieira, R; Vidal-Sicart, S; Marti, C; Pons, F

2014-01-01

The use of sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity is still subject to debate although some studies have reported its feasibility. The main reason for this debate is probably due to the high false-negative rate for floor-of-mouth tumors per se. We report the case of a 54-year-old man with a T1N0 floor-of-mouth squamous cell carcinoma who underwent the sentinel lymph node procedure. Lymphoscintigraphy and SPECT/CT imaging were performed for lymphatic mapping with a conventional gamma camera. Sentinel lymph nodes were identified at right Ib, left IIa and Ia levels. However, these sentinel lymph nodes were difficult to detect intraoperatively with a gamma probe owing to the activity originating from the injection site. The use of a portable gamma camera made it possible to localize and excise all the sentinel lymph nodes. This case demonstrates the usefulness of this tool to improve sentinel lymph node detecting in floor-of-mouth tumors, especially those close to the injection area. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Effects of a Diphtheria-Tetanus-Acellular Pertussis Vaccine on Immune Responses in Murine Local Lymph Node and Lung Allergy Models▿

PubMed Central

Vandebriel, Rob J.; Gremmer, Eric R.; van Hartskamp, Michiel; Dormans, Jan A. M. A.; Mooi, Frits R.

2007-01-01

We have previously shown that in mice, diphtheria-tetanus-acellular pertussis (DTaP) vaccination before Bordetella pertussis infection resulted in, besides effective clearance, immediate hypersensitivity (lung eosinophilia, increased total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production by cells from the bronchial lymph nodes). To better appreciate the extent of these findings, we measured DTaP vaccination effects in the local lymph node assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were vaccinated or adjuvant treated before being sensitized with trimellitic anhydride (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing a Th1-directed response). Compared to the adjuvant-treated controls, the vaccinated mice showed a decreased response to TMA and (to a much lesser extent) an increased response to DNCB. The decreased response to TMA coincided with increased transforming growth factor β levels. With the exception of filamentous hemagglutinin, all vaccine constituents contributed to the decreased response to TMA. In the lung allergy model, sensitization induced OVA-specific IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy. PMID:17202304

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients.

PubMed

Ryan, Marisa; Crow, Jennifer; Kahmke, Russel; Fisher, Samuel R; Su, Zuowei; Lee, Walter T

2014-01-01

1) Assess FoxP3/indoleamine 2,3-dioxygenase immunoreactivity in head and neck melanoma sentinel lymph nodes and 2) correlate FoxP3/indoleamine 2,3-dioxygenase with sentinel lymph node metastasis and clinical recurrence. Retrospective cohort study. Patients with sentinel lymph node biopsy for head and neck melanoma between 2004 and 2011 were identified. FoxP3/indoleamine 2,3-dioxygenase prevalence and intensity were determined from the nodes. Poor outcome was defined as local, regional or distant recurrence. The overall immunoreactivity score was correlated with clinical recurrence and sentinel lymph node metastasis using the chi-square test for trend. Fifty-six sentinel lymph nodes were reviewed, with 47 negative and 9 positive for melanoma. Patients with poor outcomes had a statistically significant trend for higher immunoreactivity scores (p=0.03). Positive nodes compared to negative nodes also had a statistically significant trend for higher immunoreactivity scores (p=0.03). Among the negative nodes, there was a statistically significant trend for a poor outcome with higher immunoreactivity scores (p=0.02). FoxP3/indoleamine 2,3-dioxygenase immunoreactivity correlates with sentinel lymph node positivity and poor outcome. Even in negative nodes, higher immunoreactivity correlated with poor outcome. Therefore higher immunoreactivity may portend a worse prognosis even without metastasis in the sentinel lymph node. This could identify a subset of patients that may benefit from future trials and treatment for melanoma through Treg and IDO suppression. Published by Elsevier Inc.

[Management of penile cancer patients: new aspects of a rare tumour entity].

PubMed

Roiner, M; Maurer, O; Lebentrau, S; Gilfrich, C; Schäfer, C; Haberl, C; Brookman-May, S D; Burger, M; May, M; Hakenberg, O W

2018-06-01

Over the past few decades, some principles in the treatment of penile cancer have changed fundamentally. While 15 years ago a negative surgical margin of at least 2 cm was considered mandatory, organ-sparing surgery permitting minimal negative surgical margins has a high priority nowadays. The current treatment principle requires as much organ preservation as possible and as much radicality as necessary. The implementation of organ-sparing and reconstructive surgical techniques has improved the quality of life of surviving patients. However, oncological and functional outcomes are still unsatisfactory. Alongside with adequate local treatment of the primary tumour, a consistent management of inguinal lymph nodes is of fundamental prognostic significance. In particular, clinically inconspicuous inguinal lymph nodes staged T1b and upwards need a surgical approach. Sentinel node biopsy, minimally-invasive surgical techniques and modified inguinal lymphadenectomy have reduced morbidity compared to conventional inguinal lymph node dissection. Multimodal treatment with surgery and chemotherapy is required in all patients with lymph node-positive disease; neoadjuvant chemotherapy has been established for patients with locally advanced lymph node disease, and adjuvant treatment after radical inguinal lymphadenectomy for lymph node-positive disease. An increasing understanding of the underlying tumour biology, in particular the role of the human papilloma virus (HPV) and epidermal growth factor receptor (EGFR) status, has led to a new pathological classification and may further enhance treatment options. This review summarises current aspects in the therapeutic management of penile cancer. © Georg Thieme Verlag KG Stuttgart · New York.

The local lymph node assay: current position in the regulatory classification of skin sensitizing chemicals.

PubMed

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is being used increasingly in the identification of skin sensitizing chemicals for regulatory purposes. In the context of new chemicals legislation (REACH) in Europe, it is the preferred assay. The rationale for this is that the LLNA quantitative and objective approach to skin sensitization testing allied with the important animal welfare benefits that the method offers. However, as with certain guinea pig sensitization tests before it, this increasing use also brings experience with an increasingly wide range of industrial and other chemicals where the outcome of the assay does not always necessarily meet with the expectations of those conducting it. Sometimes, the result appears to be a false negative, but rather more commonly, the complaint is that the chemical represents a false positive. Against this background we have here reviewed a number of instances where false positive and false negative results have been described and have sought to reconcile science with expectation. Based on these analyses, it is our conclusion that false positives and false negatives do occur in the LLNA, as they do with any other skin sensitization assay (and indeed with all tests used for hazard identification), and that this occurs for a number of reasons. We further conclude, however, that false positive results in the LLNA, as with the guinea pig maximization test, arise most commonly via failure to distinguish what is scientifically correct from that which is unpalatable. The consequences of this confusion are discussed in the article, particularly in relation to the need to integrate both potency measurement and risk assessments into classification and labelling schemes that aim to manage potential risks to human health.

Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter.

PubMed

Hirota, Morihiko; Ashikaga, Takao; Kouzuki, Hirokazu

2018-04-01

It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential. Copyright © 2017 John Wiley & Sons, Ltd.

Paracoccidioides brasiliensis-associated dermatitis and lymphadenitis in a dog.

PubMed

Headley, Selwyn Arlington; Pretto-Giordano, Lucienne Garcia; Di Santis, Giovana Wingeter; Gomes, Lucas Alécio; Macagnan, Rafaela; da Nóbrega, Daniela Farias; Leite, Katherine Moura; de Alcântara, Brígida Kussumoto; Itano, Eiko Nakagawa; Alfieri, Amauri Alcindo; Ono, Mario Augusto

2017-04-01

Paracoccidioidomycosis (PCM) is an endemic disease of humans from Latin America that is caused by Paracoccidioides brasiliensis and P. lutzii, with most cases of PCM in domestic animals being associated with P. brasiliensis. This study presents the clinical, cytological, mycological, serological, and molecular findings associated with P. brasiliensis in a dog from Southern Brazil. Fine needle biopsies were collected from the skin and several lymph nodes of a 5-year-old female Labrador dog that had enlargement of most superficial lymph nodes. Cytology of the skin and lymph nodes revealed pyogranulomatous dermatitis and lymphadenitis associated with fine-necked, budding fungal structures consistent with the Paracoccidioides genus of organisms; mycological culture derived from the lymph node aspirate demonstrated similar budding structures. Serological assays using exoantigens obtained from the fungal culture demonstrated that the fungal organisms derived from the lymph node were antigenically similar to P. brasiliensis by immunodiffusion and Western blot. A PCR assay, using the fungal culture as input, amplified a partial segment of the internal transcribed spacer 1 and 2 regions of P. brasiliensis; direct sequencing and phylogenetic analyses confirmed the PCR product as P. brasiliensis. The combined cytological, mycological, serological, and molecular findings confirmed a diagnosis of fungal dermatitis and lymphadenitis due to P. brasiliensis in this dog. This case represents the third description of clinical PCM in dogs and the first confirmation of mycotic dermatitis associated with P. brasiliensis in this species. The participation of dogs in the possible dissemination of PCM is reviewed, and it is proposed that dogs are probable accidental hosts in the epidemiological cycle associated with P. brasiliensis.

Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

PubMed

Kuang, Y H; Liu, Y J; Tang, L L; Wang, S M; Yan, G J; Liao, L Q

2018-05-25

Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

Molecular strategy for the diagnosis of infectious lymphadenitis.

PubMed

Prudent, Elsa; La Scola, Bernard; Drancourt, Michel; Angelakis, Emmanouil; Raoult, Didier

2018-06-01

Molecular methods have been considered to be the gold standard for the diagnosis of infectious lymphadenitis. However, culture remains critical in the case of low bacterial concentrations. We used molecular assays and culture to examine fresh lymph node biopsies from patients with suspected infectious lymphadenopathy. We analyzed 1762 lymph node biopsies of which 522 (30%) samples were found positive by real-time PCR; the most commonly amplified bacteria were Bartonella henselae (n = 438, 84%), Francisella tularensis (n = 46, 9%), and Mycobacterium spp. (n = 29, 6%). PCR amplification and sequencing of the 16S rDNA were positive for 359 (20%) lymph node specimens including mainly B. henselae (n = 167, 47%), Staphylococcus spp. (n = 77, 21%), and Streptococcus spp. (n = 41, 11%). In total, 351 lymph nodes were cultured on agar plates and 77 (22%) were positive. Significantly more lymph nodes infected by Gram-positive easy-growing agents were diagnosed by culture (n = 45) than by 16S rDNA PCR (p = 0.02). Culture remains critical for the diagnosis of easy-growing bacteria and mycobacteria; clinicians should be aware that a negative molecular result does not imply absence of infection.

The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow

PubMed Central

Ibrahim, Marwa K.; Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Travi, Bruno L.; Peniche, Alex G.; Osorio, E. Yaneth; Ahuja, Seema S.; Melby, Peter C.

2013-01-01

In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c+dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2+ macrophages, and CD169+ subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system. PMID:23967356

Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads.

PubMed

Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

2014-05-21

Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes.

Comparison of BALB/c and CBA/J mice for the local lymph node assay using bromodeoxyuridine with flow cytometry (LLNA: BrdU-FCM).

PubMed

Lee, Yong Sun; Yi, Jung-Sun; Seo, Souk Jin; Kim, Joo Hwan; Jung, Mi-Sook; Seo, Im-Kwon; Ahn, Ilyoung; Ko, Kyungyuk; Kim, Tae Sung; Lim, Kyung Min; Sohn, Soojung

2017-02-01

The local lymph node assay using 5-bromo-2-deoxyuridine (BrdU) with flow cytometry (LLNA: BrdU-FCM) is a modified LLNA that is used to identify skin sensitizers by counting BrdU-incorporated lymph node cells (LNCs) with flow cytometry. Unlike other LLNA methods (OECD TG 429, 442A and 442B) in which the CBA/J mouse strain is used, LLNA: BrdU-FCM was originally designed to be compatible with BALB/c, a mouse strain that is more widely used in many countries. To justify the substitution of CBA/J for BALB/c, the equivalence of the test results between two strains shall be established prior to the official implementation of LLNA: BrdU-FCM. This study aims to compare the test results of LLNA: BrdU-FCM produced in BALB/c mice with those in CBA/J mice for 18 reference substances, including 13 sensitizers and 5 non-sensitizers, listed in OECD Test Guideline 429. Based on the LLNA: BrdU-FCM test procedure, we selected an appropriate solvent and then performed preliminary tests to determine the non-irritating dose ranges for the main study, which revealed the difference in the irritation responses to 8 of the 18 chemicals between the two strains. In the main study, we measured the changes in the number of total LNCs, which indicated differences in the responses to test chemicals between the two strains. However, the stimulation index obtained with the counts of BrdU-incorporated LNCs with 7-AAD using flow cytometry yielded comparable results and 100% concordance between the BALB/c and CBA/J mouse strains was achieved, suggesting that the performance of LLNA: BrdU-FCM using BALB/c mice was equivalent to that with CBA/J mice. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of vehicle on the relative potency of skin-sensitizing chemicals in the local lymph node assay.

PubMed

Jowsey, Ian R; Clapp, Catherine J; Safford, Bob; Gibbons, Ben T; Basketter, David A

2008-01-01

The identification and characterization of chemicals that possess skin-sensitizing potential are typically performed using predictive tests. However, human exposure to skin-sensitizing chemicals often occurs via a matrix (vehicle) that differs from that used in these tests. It is thus important to account for the potential impact of vehicle differences when undertaking quantitative risk assessment for skin sensitization. This is achieved through the application of a specific sensitization assessment factor (SAF), scaled between 1 and 10, when identifying an acceptable exposure level. The objective of the analysis described herein is to determine the impact of vehicle differences on local lymph node assay (LLNA) EC3 values (concentrations of test chemical required to provoke a 3-fold increase in lymph node cell proliferation). Initially, the inherent variability of the LLNA was investigated by examining the reproducibility of EC3 values for 14 chemicals that have been tested more than once in the same vehicle (4:1 acetone:olive oil, AOO). This analysis reveals that the variability in EC3 value for these chemicals following multiple assessments is <5-fold. Next, data from the literature and previously unpublished studies were compiled for 18 chemicals that had been assessed in the LLNA using at least 2 of 15 different vehicles. These data demonstrate that often the variability in EC3 values observed for a given chemical in different vehicles is no greater than the 5-fold inherent variability observed when assessing a chemical in the same vehicle on multiple occasions. However, there are examples where EC3 values for a chemical differ by a factor of more than 10 between different vehicles. These observations were often associated with an apparent underestimation of potency (higher EC3 values) with predominantly aqueous vehicles or propylene glycol. These data underscore the need to consider vehicle effects in the context of skin-sensitization risk assessments.

Predictive capacity of a non-radioisotopic local lymph node assay using flow cytometry, LLNA:BrdU-FCM: Comparison of a cutoff approach and inferential statistics.

PubMed

Kim, Da-Eun; Yang, Hyeri; Jang, Won-Hee; Jung, Kyoung-Mi; Park, Miyoung; Choi, Jin Kyu; Jung, Mi-Sook; Jeon, Eun-Young; Heo, Yong; Yeo, Kyung-Wook; Jo, Ji-Hoon; Park, Jung Eun; Sohn, Soo Jung; Kim, Tae Sung; Ahn, Il Young; Jeong, Tae-Cheon; Lim, Kyung-Min; Bae, SeungJin

2016-01-01

In order for a novel test method to be applied for regulatory purposes, its reliability and relevance, i.e., reproducibility and predictive capacity, must be demonstrated. Here, we examine the predictive capacity of a novel non-radioisotopic local lymph node assay, LLNA:BrdU-FCM (5-bromo-2'-deoxyuridine-flow cytometry), with a cutoff approach and inferential statistics as a prediction model. 22 reference substances in OECD TG429 were tested with a concurrent positive control, hexylcinnamaldehyde 25%(PC), and the stimulation index (SI) representing the fold increase in lymph node cells over the vehicle control was obtained. The optimal cutoff SI (2.7≤cutoff <3.5), with respect to predictive capacity, was obtained by a receiver operating characteristic curve, which produced 90.9% accuracy for the 22 substances. To address the inter-test variability in responsiveness, SI values standardized with PC were employed to obtain the optimal percentage cutoff (42.6≤cutoff <57.3% of PC), which produced 86.4% accuracy. A test substance may be diagnosed as a sensitizer if a statistically significant increase in SI is elicited. The parametric one-sided t-test and non-parametric Wilcoxon rank-sum test produced 77.3% accuracy. Similarly, a test substance could be defined as a sensitizer if the SI means of the vehicle control, and of the low, middle, and high concentrations were statistically significantly different, which was tested using ANOVA or Kruskal-Wallis, with post hoc analysis, Dunnett, or DSCF (Dwass-Steel-Critchlow-Fligner), respectively, depending on the equal variance test, producing 81.8% accuracy. The absolute SI-based cutoff approach produced the best predictive capacity, however the discordant decisions between prediction models need to be examined further. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunocytochemical localization of cytokines and inducible nitric oxide synthase (iNOS) in oral mucosa and lymph nodes of patients with paracoccidioidomycosis.

PubMed

Neworal, E P M; Altemani, A; Mamoni, R L; Noronha, I L; Blotta, M H S L

2003-03-07

Paracoccidioidomycosis (PCM) is a deep mycosis caused by Paracoccidioides brasiliensis, with high incidence in Brazil. In order to examine the immune response in lesional tissue from patients with PCM, we analyzed cytokines as well as the phenotype of the cell infiltrate. Paraffin-embedded tissue from the oral mucosa of eight patients with the localized adult form (AF) of PCM and from the lymph nodes of 10 patients with the juvenile form (JF) of PCM was analyzed by immunohistochemistry to detect tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10). Most of the inflammatory cells in the lymph nodes were CD68+ (macrophages, epithelioid and giant cells), while a mixed infiltrate with macrophages, plasma cells and neutrophils was detected in the oral mucosa. TNF-alpha as well as iNOS expression was similar in lymph nodes and oral mucosa, whereas TGF-beta and IL-10 were observed in a larger number of macrophages, epithelioid and giant cells in the lymph nodes, where numerous yeast cells were visualized. The higher expression of anti-inflammatory cytokines (IL-10 and TGF-beta) in lesions of patients with the JF of PCM (lymph nodes) may represent a mechanism by which the fungus evades the host immune response, contributing to a more severe and disseminated form of the disease.

Cat scratch disease and lymph node tuberculosis in a colon patient with cancer.

PubMed

Matias, M; Marques, T; Ferreira, M A; Ribeiro, L

2013-12-12

A 71-year-old man operated for a sigmoid tumour remained in the surveillance after adjuvant chemotherapy. After 3 years, a left axillary lymph node was visible on CT scan. The biopsy revealed a necrotising and abscessed granulomatous lymphadenitis, suggestive of cat scratch disease. The patient confirmed having been scratched by a cat and the serology for Bartonella henselae was IgM+/IgG-. Direct and culture examinations for tuberculosis were negative. The patient was treated for cat scratch disease. One year later, the CT scan showed increased left axillary lymph nodes and a left pleural effusion. Direct and cultural examinations to exclude tuberculosis were again negative. Interferon-γ release assay testing for tuberculosis was undetermined and then positive. Lymph node and pleural tuberculosis were diagnosed and treated with a good radiological response. This article has provides evidence of the importance of continued search for the right diagnosis and that two diagnoses can happen in the same patient.

The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Chad G., E-mail: chad.rusthoven@ucdenver.edu; Carlson, Julie A.; Waxweiler, Timothy V.

2014-04-01

Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated,more » with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. Conclusions: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.« less

Safety Assessment of Allergic Contact Dermatitis Hazards: An Analysis Supporting Reduced Animal Use for the Murine Local Lymph Node Assay

PubMed Central

Haseman, Joseph K.; Strickland, Judy; Allen, David; Salicru, Eleni; Paris, Michael; Tice, Raymond R.; Stokes, William S.

2011-01-01

The original Organisation for Economic Co-operation and Development Test Guideline 429 (OECD TG 429) for the murine local lymph node assay (LLNA) required five mice/group if mice were processed individually. We used data from 83 LLNA tests (275 treated groups) to determine the impact on the LLNA outcome of reducing the group size from five to four. From DPM measurements, we formed all possible four-mice and five-mice combinations for the treated and control groups. Stimulation index (SI) values from each four-mice combination were compared with those from five-mice combinations, and agreement (both SI < 3 or both SI ≥ 3) determined. Average agreement between group sizes was 97.5% for the 275 treated groups. Compared test-by-test, 90% (75/83) of the tests had 100% agreement; agreement was 83% for the remaining eight tests. Disagreement was due primarily to variability in animal responses and closeness of the SI to three (positive response threshold) rather than to group size reduction. We conclude that using four rather than five mice per group would reduce animal use by 20% without adversely impacting LLNA performance. This analysis supported the recent update to OECD TG 429 allowing a minimum of four mice/group when each mouse is processed individually. PMID:20974208

Safety assessment of allergic contact dermatitis hazards: an analysis supporting reduced animal use for the murine local lymph node assay.

PubMed

Haseman, Joseph K; Strickland, Judy; Allen, David; Salicru, Eleni; Paris, Michael; Tice, Raymond R; Stokes, William S

2011-02-01

The original Organisation for Economic Co-operation and Development Test Guideline 429 (OECD TG 429) for the murine local lymph node assay (LLNA) required five mice/group if mice were processed individually. We used data from 83 LLNA tests (275 treated groups) to determine the impact on the LLNA outcome of reducing the group size from five to four. From DPM measurements, we formed all possible four- and five-mice combinations for the treated and control groups. Stimulation index (SI) values from each four-mice combination were compared with those from five-mice combinations, and agreement (both SI<3 or both SI ≥ 3) determined. Average agreement between group sizes was 97.5% for the 275 treated groups. Compared test-by-test, 90% (75/83) of the tests had 100% agreement; agreement was 83% for the remaining eight tests. Disagreement was due primarily to variability in animal responses and closeness of the SI to three (positive response threshold) rather than to group size reduction. We conclude that using four rather than five mice per group would reduce animal use by 20% without adversely impacting LLNA performance. This analysis supported the recent update to OECD TG 429 allowing a minimum of four mice/group when each mouse is processed individually. Published by Elsevier Inc.

The reduced local lymph node assay: the impact of group size.

PubMed

Ryan, Cindy A; Chaney, Joel G; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A; Betts, Catherine J; Dearman, Rebecca J; Kimber, Ian; Gerberick, G Frank

2008-05-01

The local lymph node assay (LLNA) is a skin sensitization test that provides animal welfare benefits. To reduce animal usage further, a modified version (rLLNA) was proposed. Conducting the rLLNA as a screening test with a single high dose group and vehicle control differentiated accurately between skin sensitizers and non-sensitizers. This study examined whether a reduction in animal number/group is feasible. Historical data were utilized to examine the impact of conducting the rLLNA with two mice/group. To assess the effect on the stimulation index (SI) 41 datasets with individual animal data derived using five mice/group were analysed. SIs were calculated on all possible combinations of two control and two high dose group disintegrations per minute (dpm) values. For 25 of 33 sensitizer datasets, > 96% of possible dpm combinations resulted in a calculated SI > 3. The lowest percentages of positive SIs were observed with weak allergens when, in the standard LLNA, the mean SIs would have been nearer to the threshold value of 3. The results indicate that moderate, strong and extreme allergens are more likely than weak allergens to be identified as sensitizers when group sizes of two mice are used within the rLLNA. It is concluded that a rLLNA with two mice/group would display decreased sensitivity and is inappropriate for use in hazard identification. Copyright (c) 2007 John Wiley & Sons, Ltd.

Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

2005-07-01

We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.

Evaluation of allergenicity of constituents of myoga using the murine local lymph node assay.

PubMed

Wei, Q J; Wei, C N; Harada, K; Minamoto, K; Okamoto, Y; Otsuka, M; Ueda, A

2010-01-01

Myoga (Zingiber Myoga Roscoe) is a perennial plant with a pungent smell from its flower buds. It is native to East Asia and has been reported to cause allergic contact dermatitis. The purpose of this study is to assess the allergenicity of myoga related to its major chemical components, alpha-pinene, beta-pinene, limonene, limonene oxide and beta-phellandrene, which are supposed to be the causative agents of contact dermatitis among myoga cultivators. We performed a toxicity study of the volatile constituents of myoga using the local lymph node assay (LLNA), in which limonene, limonene oxide and beta-phellandrene had positive responses and the EC3 was 35.8%, 8.22%, and 0.54%, respectively. EC3 for both alpha-pinene and beta-pinene was over 100%. Both chemicals failed to induce positive responses in the LLNA. While the maximization rating of limonene, limonene oxide and phellandrene were evaluated as moderate, extreme, and extreme respectively, alpha-pinene and beta-pinene were evaluated as weak in the previously reported GPMT. The usage of LLNA was also confirmed by comparing with previously reported GPMT results to detect the allergenicity of myoga constituents. The actual risk of humans developing an allergy to myoga constituents depends on many factors. The concentration of the compounds, the frequency and duration of exposure and the condition of the skin are supposed to be important factors.

Chemical applicability domain of the local lymph node assay (LLNA) for skin sensitisation potency. Part 4. Quantitative correlation of LLNA potency with human potency.

PubMed

Roberts, David W; Api, Anne Marie

2018-07-01

Prediction of skin sensitisation potential and potency by non-animal methods is the target of many active research programmes. Although the aim is to predict sensitisation potential and potency in humans, data from the murine local lymph node assay (LLNA) constitute much the largest source of quantitative data on in vivo skin sensitisation. The LLNA has been the preferred in vivo method for identification of skin sensitising chemicals and as such is potentially valuable as a benchmark for assessment of non-animal approaches. However, in common with all predictive test methods, the LLNA is subject to false positives and false negatives with an overall level of accuracy said variously to be approximately 80% or 90%. It is also necessary to consider the extent to which, for true positives, LLNA potency correlates with human potency. In this paper LLNA potency and human potency are compared so as to express quantitatively the correlation between them, and reasons for non-agreement between LLNA and human potency are analysed. This leads to a better definition of the applicability domain of the LLNA, within which LLNA data can be used confidently to predict human potency and as a benchmark to assess the performance of non-animal approaches. Copyright © 2018. Published by Elsevier Inc.

Investigation of the dermal sensitization potential of various essential oils in the local lymph node assay.

PubMed

Lalko, J; Api, A M

2006-05-01

Essential oils are commonly used fragrance ingredients. The oils themselves are complex mixtures, which may contain naturally occurring contact sensitizers. The local lymph node assay was used to evaluate the dermal sensitization potential of basil, citronella, clove leaf, geranium, litsea cubeba, lemongrass, and palmarosa oils. Three of the major components--citral, eugenol, and geraniol--were included to investigate any difference in sensitization potential arising from their exposure in a mixture. Each fragrance material was tested at five concentration ranging from 2.5% to 50% w/v in 1:3 ethanol:diethyl phthalate. The stimulation index (SI) values were calculated for each dose level, an SI > or = 3 was considered a positive response. The estimated concentration (EC3) required to elicit a positive was calculated and taken as a measure of relative potency. The EC3 values and potency classification for basil, clove leaf, litsea cubeba, lemongrass and palmarosa oils were calculated to be <2.5% (> or = moderate), 7.1% (weak), 8.4% (weak), 6.5% (weak) and 9.6% (weak), respectively. Citronella and geranium oils were negative. The individual components citral, eugenol and geraniol resulted in EC3 values of 6.3%, 5.4% and 11.4%, respectively. In general, the potency of each essential oil did not differ significantly from that observed for its main individual component.

Treatment of Metastatic Lymph Nodes in the Neck from Papillary Thyroid Carcinoma with Percutaneous Laser Ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mauri, Giovanni, E-mail: vanni.mauri@gmail.com; Cova, Luca; Ierace, Tiziana

2016-07-15

PurposeTo assess the effectiveness of percutaneous laser ablation (PLA) of cervical lymph node metastases from papillary thyroid carcinoma.Materials and Methods24 patients (62.3 ± 13.2 year; range 32–80) previously treated with thyroidectomy, neck dissection, and radioiodine ablation underwent ultrasound-guided PLA of 46 {sup 18}FDG-PET/CT—positive metachronous nodal metastases. All patients were at high surgical risk or refused surgery and were unsuitable for additional radioiodine ablation. A 300 µm quartz fiber and a continuous-wave Nd-YAG laser operating at 1.064 mm were used. Technical success, rate of complications, rate of serological conversion, and local control at follow-up were derived. Fisher’s exact test and Mann–Whitney U test were used andmore » Kaplan–Meier curve calculated.ResultsTechnical success was obtained in all 46 lymph nodes (100 %). There were no major complications. Thyroglobulin levels decreased from 8.40 ± 9.25 ng/ml before treatment to 2.73 ± 4.0 ng/ml after treatment (p = 0.011), with serological conversion in 11/24 (45.8 %) patients. Overall, local control was obtained in 40/46 (86.9 %) lymph nodes over 30 ± 11 month follow-up, with no residual disease seen at imaging in 19/24 (79.1 %) patients. Local control was achieved in 40/46 (86.9 %) lymph nodes at 1 year and in all of the 25 nodes (100 %) followed for 3 years. Estimated mean time to progression was 38.6 ± 2.7 m.ConclusionUltrasound-guided PLA is a feasible, safe, and effective therapy for the treatment of cervical lymph node metastases from papillary thyroid carcinoma.« less

Test battery with the human cell line activation test, direct peptide reactivity assay and DEREK based on a 139 chemical data set for predicting skin sensitizing potential and potency of chemicals.

PubMed

Takenouchi, Osamu; Fukui, Shiho; Okamoto, Kenji; Kurotani, Satoru; Imai, Noriyasu; Fujishiro, Miyuki; Kyotani, Daiki; Kato, Yoshinao; Kasahara, Toshihiko; Fujita, Masaharu; Toyoda, Akemi; Sekiya, Daisuke; Watanabe, Shinichi; Seto, Hirokazu; Hirota, Morihiko; Ashikaga, Takao; Miyazawa, Masaaki

2015-11-01

To develop a testing strategy incorporating the human cell line activation test (h-CLAT), direct peptide reactivity assay (DPRA) and DEREK, we created an expanded data set of 139 chemicals (102 sensitizers and 37 non-sensitizers) by combining the existing data set of 101 chemicals through the collaborative projects of Japan Cosmetic Industry Association. Of the additional 38 chemicals, 15 chemicals with relatively low water solubility (log Kow > 3.5) were selected to clarify the limitation of testing strategies regarding the lipophilic chemicals. Predictivities of the h-CLAT, DPRA and DEREK, and the combinations thereof were evaluated by comparison to results of the local lymph node assay. When evaluating 139 chemicals using combinations of three methods based on integrated testing strategy (ITS) concept (ITS-based test battery) and a sequential testing strategy (STS) weighing the predictive performance of the h-CLAT and DPRA, overall similar predictivities were found as before on the 101 chemical data set. An analysis of false negative chemicals suggested a major limitation of our strategies was the testing of low water-soluble chemicals. When excluded the negative results for chemicals with log Kow > 3.5, the sensitivity and accuracy of ITS improved to 97% (91 of 94 chemicals) and 89% (114 of 128). Likewise, the sensitivity and accuracy of STS to 98% (92 of 94) and 85% (111 of 129). Moreover, the ITS and STS also showed good correlation with local lymph node assay on three potency classifications, yielding accuracies of 74% (ITS) and 73% (STS). Thus, the inclusion of log Kow in analysis could give both strategies a higher predictive performance. Copyright © 2015 John Wiley & Sons, Ltd.

Modified vs. standard D2 lymphadenectomy in distal subtotal gastrectomy for locally advanced gastric cancer patients under 70 years of age.

PubMed

Zhang, Chun-Dong; Zong, Liang; Ning, Fei-Long; Zeng, Xian-Tao; Dai, Dong-Qiu

2018-01-01

The present study was conducted to investigate the prognosis and survival of patients with locally advanced gastric cancer who underwent distal subtotal gastrectomy with modified D2 (D1+) and D2 lymphadenectomy, under 70 years of age. The five-year overall survival rates of 390 patients were compared between those receiving D1+ and D2 lymphadenectomy. Univariate and multivariate analyses were used to identify factors that correlated with prognosis and lymph node metastasis. Tumor size (P=0.039), pT stage (P=0.011), pN stage (P<0.001), and lymphadenectomy (P=0.004) were identified as independent prognostic factors. Furthermore, tumor size (P=0.022), pT stage (P=0.012), and lymphadenectomy (P=0.028) were proven as independent factors predicting lymph node metastasis. In conclusion, cancers of larger size, higher pT stage, and with D1+ lymphadenectomy had a higher risk of lymph node metastasis. Standard D2 lymphadenectomy removes sufficient lymph nodes to improve staging accuracy and survival. Therefore, D2 lymphanectomy is recommended in distal subtotal gastrectomy for locally advanced gastric cancer, especially for cancers of larger size and higher pT stage.

Ultrasonographic detection of regional lymph node metastases in patients with intermediate or thick malignant melanoma.

PubMed

Brountzos, Elias N; Panagiotou, Irene E; Bafaloukos, Dimitrios I; Kelekis, Dimitrios A

2003-01-01

Careful monitoring of regional lymph nodes and early detection of metastases in malignant melanoma patients has an impact on their survival, since it may permit beneficial surgical therapy. Palpation is routinely used in clinical practice. The value of ultrasonography for routine follow-up of melanoma patients, still, is not generally accepted. The aim of our study was to assess the sensitivity and specificity of ultrasound and clinical examination respectively, in the detection of melanoma regional node metastases. Additionally, we evaluated whether early detection of metastases improved overall survival. One hundred and forty-eight melanoma patients with an intermediate or thick primary lesion were followed between January 1997 and May 2001. Clinical examination and concomitant regional lymph node ultrasonography were performed, every 3-4 months. If suspicious findings were identified, regional lymph node dissection was undertaken. Forty-four from the initial 148 patients relapsed with regional lymph nodal metastases. In 11 patients (25%) palpation failed to reveal the disease and metastases were depicted only by ultrasonography. In only 1 patient ultrasonography was false-negative. The sensitivity and specificity of palpation were 72.7 and 97% respectively, while those of ultrasonography were 97.7 (p<0.001) and 98% respectively. Ultrasonography was more sensitive in detecting lymph node metastases in the axilla (100%) and the groin (93.3%). When overall survival of patients presenting with local-regional recurrence was calculated--depending on the number of involved lymph nodes--a survival benefit (p<0.05) was found for patients with only one lymph node metastasis. In conclusion, ultrasonography is superior to clinical examination in the early detection of regional lymph node metastases from an intermediate or thick malignant melanoma and should be a part of those patients' surveillance.

SU-F-P-40: Analysis of Pelvic Lymph Node Margin Using Prostate Fiducial Markers, for SBRT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torres, J; Castro Pena, P; Garrigo, E

2016-06-15

Purpose: The use of fiducials markers in prostate treatment allows a precise localization of this volume. Typical prostate SBRT margins with fiducials markers are 5mm in all directions, except toward the rectum, where 3mm is used. For some patients nearby pelvic lymph nodes with 5mm margin need to be irradiate assuming that its localization is linked to the prostate fiducial markers instead of bony anatomy. The purpose of this work was to analyze the geometric impact of locate the lymph node regions through the patient positioning by prostate fiducial markers. Methods: 10 patients with prostate SBRT with lymph nodes irradiationmore » were selected. Each patient had 5 implanted titanium fiducial markers. A Novalis TX (BrainLAB-Varian) with ExacTrac and aSi1000 portal image was used. Treatment plan uses 11 beams with a dose prescription (D95%) of 40Gy to the prostate and 25Gy to the lymph node in 5 fractions. Daily positioning was carried out by ExacTrac system based on the implanted fiducials as the reference treatment position; further position verification was performed using the ExacTrac and two portal images (gantry angle 0 and 90) based on bony structures. Comparison between reference position with bony based ExacTrac and portal image localization, was done for each treatment fraction Results: A total of 50 positioning analysis were done. The average discrepancy between reference treatment position and ExacTrac based on bony anatomy (pubic area) was 4.2mm [0.3; 11.2]. The discrepancy was <5mm in 61% of the cases and <9mm in 92%. Using portal images the average discrepancy was 3.7mm [0.0; 11.1]. The discrepancy was <5mm in 69% of the cases and <9mm in 96%. Conclusion: Localizing lymph node by prostate fiducial markers may produce large discrepancy as large as 11mm compared to bony based localization. Dosimetric impact of this discrepancy should be studied.« less

CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma

PubMed Central

Xin, Qi; Zhang, Na; Yu, Hai-Bo; Zhang, Qin; Cui, Yan-Fen; Zhang, Chuan-Shan; Ma, Zhe; Yang, Yan; Liu, Wei

2017-01-01

AIM To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumor-adjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (χ2 = 6.669, P = 0.010; χ2 = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer. PMID:28533662

Management of the Regional Lymph Nodes Following Breast-Conservation Therapy for Early-Stage Breast Cancer: An Evolving Paradigm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Laura E.G.; Punglia, Rinaa S.; Wong, Julia S.

2014-11-15

Radiation therapy to the breast following breast conservation surgery has been the standard of care since randomized trials demonstrated equivalent survival compared to mastectomy and improved local control and survival compared to breast conservation surgery alone. Recent controversies regarding adjuvant radiation therapy have included the potential role of additional radiation to the regional lymph nodes. This review summarizes the evolution of regional nodal management focusing on 2 topics: first, the changing paradigm with regard to surgical evaluation of the axilla; second, the role for regional lymph node irradiation and optimal design of treatment fields. Contemporary data reaffirm prior studies showingmore » that complete axillary dissection may not provide additional benefit relative to sentinel lymph node biopsy in select patient populations. Preliminary data also suggest that directed nodal radiation therapy to the supraclavicular and internal mammary lymph nodes may prove beneficial; publication of several studies are awaited to confirm these results and to help define subgroups with the greatest likelihood of benefit.« less

The Value of Sentinel Lymph Node Biopsy in Oral Cavity Cancers

PubMed Central

Kaya, İsa; Göde, Sercan; Öztürk, Kerem; Turhal, Göksel; Aliyev, Araz; Akyıldız, Serdar; Duygun, Ülkem Yararbaş; Uluöz, Ümit; Yavuzer, Atilla

2015-01-01

Objective The aim of this study was to establish the effectiveness of sentinel lymph node biopsy in the detection of metastasis in N0 necks of T1–T2 early-stage oral cavity cancers. Materials and Methods Twenty neck dissections were performed in 18 patients diagnosed with T1 and T2 oral cavity cancer, with an indication for elective neck dissection between November 2007 and January 2011. The male to female ratio was 12:8, with a mean age of 54.5 years (range 28–76). Eight of the dissections were performed for lower lip cancer, 7 for tongue cancer, and 5 for floor of the mouth cancer. Sentinel lymph node biopsy was used to detect metastatic lymph nodes. Tc99m radionuclide injection was administered to the periphery of the tumor 24 h before the operation, and a lymphoscintigraphy image was obtained 30 min after the injection. Sentinel lymph nodes were localized and excised on the day of surgery using static lymphoscintigraphy images and a gamma probe. Sentinel lymph nodes were sent for a frozen section examination, and either a selective or a comprehensive neck dissection was performed for each neck according to the results. Results After the final histopathological examination of the specimens, the negative predictive value, the positive predictive value, the accuracy of the sentinel lymph node biopsy, and frozen section accuracy were found to be 100%. Conclusion Sentinel lymph node biopsy was found to be an efficient method in the pathological staging and management of the N0 neck in early T-stage oral cavity cancers. PMID:29391982

Three-dimensional Optical Coherence Tomography for Optical Biopsy of Lymph Nodes and Assessment of Metastatic Disease

PubMed Central

John, Renu; Adie, Steven G.; Chaney, Eric J.; Marjanovic, Marina; Tangella, Krishnarao V.; Boppart, Stephen A.

2013-01-01

Background Numerous techniques have been developed for localizing lymph nodes before surgical resection and for their histological assessment. Nondestructive high-resolution transcapsule optical imaging of lymph nodes offers the potential for in situ assessment of metastatic involvement, potentially during surgical procedures. Methods Three-dimensional optical coherence tomography (3-D OCT) was used for imaging and assessing resected popliteal lymph nodes from a preclinical rat metastatic tumor model over a 9-day time-course study after tumor induction. The spectral-domain OCT system utilized a center wavelength of 800 nm, provided axial and transverse resolutions of 3 and 12 µm, respectively, and performed imaging at 10,000 axial scans per second. Results OCT is capable of providing high-resolution labelfree images of intact lymph node microstructure based on intrinsic optical scattering properties with penetration depths of ~1–2 mm. The results demonstrate that OCT is capable of differentiating normal, reactive, and metastatic lymph nodes based on microstructural changes. The optical scattering and structural changes revealed by OCT from day 3 to day 9 after the injection of tumor cells into the lymphatic system correlate with inflammatory and immunological changes observed in the capsule, precortical regions, follicles, and germination centers found during histopathology. Conclusions We report for the first time a longitudinal study of 3-D transcapsule OCT imaging of intact lymph nodes demonstrating microstructural changes during metastatic infiltration. These results demonstrate the potential of OCT as a technique for intraoperative, real-time in situ 3-D optical biopsy of lymph nodes for the intraoperative staging of cancer. PMID:22688663

Investigations into the Immunotoxicity and Allergic Potential Induced by Topical Application of N-Butylbenzenesulfonamide (NBBS) in a Murine Model

PubMed Central

Marrocco, Antonella; Meade, B. Jean; Long, Carrie M.; Lukomska, Ewa; Marshall, Nikki B.; Anderson, Stacey E.

2015-01-01

N-Butylbenzene sulfonamide (NBBS) is a commonly used plasticizer found in numerous products. Due to its extensive use, lack of adequate toxicological data, and suspicion of toxicity based on the presence of structural alerts, it was nominated to the National Toxicology Program for comprehensive toxicological testing. The purpose of this study was to evaluate the potential for hypersensitivity and immune suppression following dermal exposure to NBBS using a murine model. NBBS tested negative in a combined irritancy/local lymph node assay (LLNA), classifying it as nonirritating and nonsensitizing. To estimate the immunosuppressive potential of NBBS, assays that assessed immunotoxicity were performed, including the immumnoglobulin (Ig) M response to T-cell-dependent antigen sheep red blood cells (SRBC), using the plaque-forming cell (PFC) assay and immune cell phenotyping. After a 28-d treatment with NBBS, mice exposed to the lowest concentration (25% NBBS) showed a significant increase in IgM-producing B cells in the spleen. No marked changes were identified in immune cell markers in the lymph node. In contrast to body weight, a significant elevation in kidney and liver weight was observed following dermal exposure to all concentrations of NBBS. These results demonstrate that dermal exposure to NBBS, other than liver and kidney toxicity, did not apparently induce immunotoxicity in a murine model. PMID:26291892

The LLNA: A Brief Review of Recent Advances and Limitations

PubMed Central

Anderson, Stacey E.; Siegel, Paul D.; Meade, B. J.

2011-01-01

Allergic contact dermatitis is the second most commonly reported occupational illness, accounting for 10% to 15% of all occupational diseases. This highlights the importance of developing rapid and sensitive methods for hazard identification of chemical sensitizers. The murine local lymph node assay (LLNA) was developed and validated for the identification of low molecular weight sensitizing chemicals. It provides several benefits over other tests for sensitization because it provides a quantitative endpoint, dose-responsive data, and allows for prediction of potency. However, there are also several concerns with this assay including: levels of false positive responses, variability due to vehicle, and predictivity. This report serves as a concise review which briefly summarizes the progress, advances and limitations of the assay over the last decade. PMID:21747867

Sentinel lymph node biopsy in malignant melanoma of the head and neck.

PubMed

Rahimi-Nedjat, Roman Kia; Al-Nawas, Bilal; Tuettenberg, Andrea; Sagheb, Keyvan; Grabbe, Stephan; Walter, Christian

2018-06-01

The aim of this retrospective study was to investigate sentinel lymph node biopsy in patients with head and neck melanoma. Patients who underwent SLNB between 2010 and 2016 were comprised. Epidemiological, radiological, and surgical data were collected and compared to histological findings. Patients who underwent primary complete lymph node dissection were excluded. 74 patients underwent SLNB during this period. The most common tumor localizations were the cheek (20.4%) and ears (20.4%). Overall, 256 sentinel lymph nodes (SLN) were detected and removed, most frequently in Robbins-levels IIA and IIB as well as in the surrounding of the parotid gland. 12.3% of the SLN showed a microscopic or macroscopic metastasis. In preoperative imaging all lymph nodes with macroscopic metastasis were described as suspect but only 4 of 11 lymph nodes with microscopic metastases were described as such. SLNB is an especially good procedure for the diagnosis of microscopically metastases as disease status is an important diagnostic and prognostic factor in early-stage melanoma patients. However, due to the complex lymphatic system in head and neck melanoma, a short follow-up interval is necessary in order to prevent delayed diagnosis of a nodal recurrence due to a false-negative SLN. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Sheep lymph-nodes as a biological indicator of environmental exposure to fluoro-edenite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ledda, Caterina, E-mail: cledda@unict.it; Hygiene and Public Health, Department of Medical Sciences, Surgical and Advanced Technologies “GF Ingrassia”, University of Catania, Catania; Loreto, Carla

A significantly increased incidence of pleural mesothelioma in Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite (FE), a fibrous amphibole extracted from a local stone quarry. The lymph-nodes draining the pulmonary lobes of sheep grazing around the town were examined, to gain insights into fibre diffusion. The pasture areas of six sheep flocks lying about 3 km from Biancavilla were located using the global positioning system. The cranial tracheobronchial and one middle mediastinal lymph-node as well as four lung tissue samples were collected from 10 animals from each flock and from 10 control sheep for light and scanningmore » electron microscopy (SEM) examination. The lymph-nodes from exposed sheep were enlarged and exhibited signs of anthracosis. Histologically, especially at the paracortical level, they showed lymph-follicle hyperplasia with large reactive cores and several macrophages (coniophages) containing grey-brownish particulate interspersed with elements with a fibril structure, forming aggregates of varying dimensions (coniophage nodules). Similar findings were detected in some peribronchiolar areas of the lung parenchyma. SEM examination showed that FE fibres measured 8–41 µm in length and 0.4–1.39 µm in diameter in both lymph-nodes and lung tissue. Monitoring of FE fibres in sheep lymph-nodes using appropriate techniques can help set up environmental pollution surveillance. - Highlights: • Lymph-nodes draining sheep lung were used to assess environmental fluoro-edenite exposure. • Monitoring fluoro-edenite fibres in sheep lung nodes can provide pollution surveillance. • Our findings document a risk of fluoro-edenite fibre inhalation a few kilometres from the source. • Sheep appear to be a valuable bioindicator species.« less

First Case of the Cervical Lymph Node as the Only Site of Metastasis from Anal Cancer.

PubMed

Wang, Bo; Jaiswal, Sunny; Saif, Muhammad W

2017-05-30

Anal squamous cell carcinoma was a previously uncommon malignancy that has steadily increased in incidence with the increased prevalence of human papillomavirus (HPV) and human immunodeficiency virus (HIV). Anal squamous cell carcinoma is typically characterized by local and regional involvement and distant metastases are far less common. Here, we report a case of a 36-year-old female initially diagnosed with anal squamous cell carcinoma manifesting as an anal mass along with an enlarged inguinal lymph node. After receiving chemoradiation therapy, she remained disease-free until recently, when she presented with an isolated left infraclavicular lymph node found on physical examination followed by a biopsy that was consistent with recurrent anal squamous cell carcinoma. The positron emission tomography-computed tomography (PET-CT) uptake of her original left inguinal lymph node was decreased, suggesting improved regional disease, and no other metastases were found. Our case represents a rare occurrence of metastatic anal squamous cell carcinoma to an isolated distal lymph node and reminds physicians not to forget a unusual site of metastasis and prevent any delay in treatment.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.

CONSIDERATIONS ON ANATOMY AND PHYSIOLOGY OF LYMPH VESSELS OF UPPER AERO DIGESTIVE ORGANS AND CERVICAL SATELLITE LYMPH NODE GROUP.

PubMed

Ciupilan, Corina; Stan, C I

2016-01-01

The almost constant local regional development of the cancers of upper aero digestive organs requires the same special attention to cervical lymph node metastases, as well as to the primary neoplastic burning point. The surgical therapy alone or associated has a mutilating, damaging character, resulting in loss of an organ and function, most of the times with social implications, involving physical distortions with aesthetic consequences, which make the reintegration of the individual into society questionable. The problem of cervical lymph node metastases is vast and complex, reason why we approached several anatomical and physiological aspects of lymph vessels of the aero digestive organs. Among the available elements during treatment, the headquarters of the tumour, its histologic degree, and its infiltrative nature, each of them significantly influences the possibility of developing metastases.

Skin sensitization potency and cross-reactivity of p-phenylenediamine and its derivatives evaluated by non-radioactive murine local lymph node assay and guinea-pig maximization test.

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru

2009-04-01

p-Phenylenediamine (PPD)-related chemicals have been used as antioxidants in rubber products, and many cases of contact dermatitis caused by these chemicals have been reported. The aim of this study was to investigate relative sensitizing potency and cross-reactivity among PPD derivatives. Five PPD derivatives, p-aminodiphenylamine (PADPA), N,N'-diphenyl-p-phenylenediamine (DPPD), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (DMBPPD), N-(1-methylheptyl)-N'-phenyl-p-phenylenediamine (MHPPD), and the core chemical PPD were evaluated for their sensitizing potency and cross-reactivity using the non-radioactive murine local lymph node assay (LLNA) and the guinea-pig maximization test (GPMT). PPD and all the derivatives were identified as primary sensitizers in both tests. The order of potency in the LLNA was as follows: IPPD and PADPA > PPD > DMBPPD and MHPPD > DPPD. In the GPMT, all six groups of animals sensitized with one of these chemicals cross-reacted to four other derivatives. Specifically, the five groups that have a common basic PADPA structure, that is PADPA, DPPD, IPPD, DMBPPD, and MHPPD, all reacted to each other at almost the same scores, while none of them reacted to PPD. The cross-reactivity profile found in the study was to some extent different from that in previous human data, where distinction between cross-reaction and concomitant primary sensitization is not always clear.

Comparison of outcomes obtained in murine local lymph node assays using CBA/J or CBA/Ca mice.

PubMed

Maeda, Yosuke; Hirosaki, Haruka; Yakata, Naoaki; Takeyoshi, Masahiro

2016-08-01

CBA/J and CBA/Ca mice are the recommended strains for local lymph node assays (LLNAs). Here, we report quantitative and qualitative comparisons between both mouse strains to provide useful information for the strain selection of sensitization testing. LLNA was conducted, in accordance with Organisation for Economic Co-operation and Development Test Guideline No. 429, with CBA/J and CBA/Ca mice using five chemicals including typical contact sensitizers and non-sensitizers: 2,4-dinitrochlorobenzene (DNCB), isoeugenol, α-hexylcinnamic aldehyde (HCA), propylene glycol (PG), and hexane; then outcomes were compared based on the raw data (disintegrations per minute, DPM), stimulation index (SI) values, EC3 values and positive/negative decisions. Although a significant difference was noted between DPM values derived from each strain of mice, SI values exhibited no considerable difference. The EC3 values for DNCB in CBA/J and CBA/Ca mice were 0.04 and 0.03, those for isoeugenol were 1.4 and 0.9, and those for HCA were 7.7 and 6.0, respectively. All EC values derived from each test system were almost equivalent and were within the range of acceptance criteria of the ICCVAM performance standard for LLNA. Positive/negative outcomes for all test chemicals were consistent. In conclusion, no considerable differences were observed in the final outcomes derived from CBA/J and CBA/Ca mice in LLNA. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Skin sensitization potency of isoeugenol and its dimers evaluated by a non-radioisotopic modification of the local lymph node assay and guinea pig maximization test.

PubMed

Takeyoshi, Masahiro; Iida, Kenji; Suzuki, Keiko; Yamazaki, Shunsuke

2008-05-01

Allergic contact dermatitis is the serious unwanted effect arising from the use of consumer products such as cosmetics. Isoeugenol is a fragrance chemical with spicy, carnation-like scent, is used in many kinds of cosmetics and is a well-known moderate human sensitizer. It was previously reported that the dimerization of eugenol yielded two types of dimer possessing different sensitization potencies. This study reports the differences in skin sensitization potencies for isoeugenol and two types of dimer, beta-O-4-dilignol and dehydrodiisoeugenol (DIEG), as evaluated by the non-radioisotopic local lymph node assay (non-RI LLNA) and guinea pig maximization test. In the guinea pig maximization test, isoeugenol, beta-O-4-dilignol and DIEG were classified as extreme, weak and moderate sensitizers, respectively. As for the results of non-RI LLNA, the EC3 for isoeugenol, beta-O-4-dilignol and DIEG were calculated as 12.7%, >30% and 9.4%, respectively. The two types of isoeugenol dimer showed different sensitizing activities similar to the case for eugenol dimers. A reduction of sensitization potency achieved by dimerization may lead to developing safer cosmetic ingredients. Isoeugenol dimers are not currently used for fragrance chemicals. However, the dimerization of isoeugenol may yield a promising candidate as a cosmetic ingredient with low sensitization risk. The data may also provide useful information for the structure-activity relationship (SAR) in skin sensitization. Copyright (c) 2007 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goebel, Carsten, E-mail: goebel.c.1@pg.com; Troutman, John; Hennen, Jenny

The strong sensitizing potencies of the most important primary intermediates of oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2-methyl-PPD) are well established. They are considered as the key sensitizers in hair dye allergic contact dermatitis. While modification of their molecular structure is expected to alter their sensitizing properties, it may also impair their color performance. With introduction of a methoxymethyl side chain we found the primary intermediate 2-methoxymethyl-p-phenylenediamine (ME-PPD) with excellent hair coloring performance but significantly reduced sensitizing properties compared to PPD and PTD: In vitro, ME-PPD showed an attenuated innate immune response when analyzed for its proteinmore » reactivity and dendritic cell activation potential. In vivo, the effective concentration of ME-PPD necessary to induce an immune response 3-fold above vehicle control (EC3 value) in the local lymph node assay (LLNA) was 4.3%, indicating a moderate skin sensitizing potency compared to values of 0.1 and 0.17% for PPD and PTD, respectively. Finally, assessing the skin sensitizing potency of ME-PPD under consumer hair dye usage conditions through a quantitative risk assessment (QRA) indicated an allergy induction risk negligible compared to PPD or PTD. - Highlights: • Methoxymethyl side chain in p-phenylenediamine reduces its strong skin sensitizing properties. • Reduced protein reactivity and dendritic cell activation. • Reduced skin sensitizing potency in local lymph node assay (LLNA). • Negligible allergy induction risk under hair dye usage conditions.« less

Skin sensitisation, vehicle effects and the local lymph node assay.

PubMed

Basketter, D A; Gerberick, G F; Kimber, I

2001-06-01

Accurate risk assessment in allergic contact dermatitis is dependent on the successful prospective identification of chemicals which possess the ability to behave as skin sensitisers, followed by appropriate measurement of the relative ability to cause sensitisation; their potency. Tools for hazard identification have been available for many years; more recently, a novel approach to the quantitative assessment of potency--the derivation of EC3 values in the local lymph node assay (LLNA)--has been described. It must be recognised, however, that these evaluations of chemical sensitisers also may be affected by the vehicle matrix in which skin exposure occurs. In this article, our knowledge of this area is reviewed and potential mechanisms through which vehicle effects may occur are detailed. Using the LLNA as an example, it is demonstrated that the vehicle may have little impact on the accuracy of basic hazard identification; the data also therefore support the view that testing ingredients in specific product formulations is not warranted for hazard identification purposes. However, the effect on potency estimations is of greater significance. Although not all chemical allergens are affected similarly, for certain substances a greater than 10-fold vehicle-dependent change in potency is observed. Such data are vital for accurate risk assessment. Unfortunately, it does not at present appear possible to predict notionally the effect of the vehicle matrix on skin sensitising potency without recourse to direct testing, for example by estimation of LLNA EC3 data, which provides a valuable tool for this purpose.

Further evaluation of quantitative structure--activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens.

PubMed

Patlewicz, Grace Y; Basketter, David A; Pease, Camilla K Smith; Wilson, Karen; Wright, Zoe M; Roberts, David W; Bernard, Guillaume; Arnau, Elena Giménez; Lepoittevin, Jean-Pierre

2004-02-01

Fragrance substances represent a very diverse group of chemicals; a proportion of them are associated with the ability to cause allergic reactions in the skin. Efforts to find substitute materials are hindered by the need to undertake animal testing for determining both skin sensitization hazard and potency. One strategy to avoid such testing is through an understanding of the relationships between chemical structure and skin sensitization, so-called structure-activity relationships. In recent work, we evaluated 2 groups of fragrance chemicals -- saturated aldehydes and alpha,beta-unsaturated aldehydes. Simple quantitative structure-activity relationship (QSAR) models relating the EC3 values [derived from the local lymph node assay (LLNA)] to physicochemical properties were developed for both sets of aldehydes. In the current study, we evaluated an additional group of carbonyl-containing compounds to test the predictive power of the developed QSARs and to extend their scope. The QSAR models were used to predict EC3 values of 10 newly selected compounds. Local lymph node assay data generated for these compounds demonstrated that the original QSARs were fairly accurate, but still required improvement. Development of these QSAR models has provided us with a better understanding of the potential mechanisms of action for aldehydes, and hence how to avoid or limit allergy. Knowledge generated from this work is being incorporated into new/improved rules for sensitization in the expert toxicity prediction system, deductive estimation of risk from existing knowledge (DEREK).

Lack of evidence for contact sensitization by Pfiesteria extract.

PubMed

Patterson, Rachel M; Noga, Edward; Germolec, Dori

2007-07-01

Members of the estuarine dinoflagellate genus Pfiesteria are reported to have been responsible for massive fish kills in the southeastern United States. Some reports suggest that exposure to waters having Pfiesteria blooms or occupation-related exposure might result in Pfiesteria-induced dermal irritation and inflammation. Although the toxin has not been isolated and purified, the original data suggested both hydrophilic and hydrophobic toxic components. Some investigators propose that dermonecrotic properties are associated with a hydrophobic fraction. A bioactive C18-bound putative toxin (CPE) extracted from Pfiesteria-laden aquarium water during active fish-killing conditions was examined in the present study to evaluate its potential to produce inflammation and dermal sensitization and to determine whether the inflammation and dermatitis reported in early human exposure studies were allergic or irritant in nature. This fraction was cytotoxic to mouse Neuro-2A cells and primary human epidermal keratinocytes (NHEK) at a concentration of 1 mg/mL. Balb/C mice exposed to 50-200% CPE by skin painting exhibited a 6-10% increase in ear swelling relative to vehicle-treated mice in a primary irritancy assay. There was no increase in lymph node cell proliferation as measured using the local lymph node assay. Exposure to CPE in culture up-regulated interleukin-8 in NHEK, whereas granulocyte macrophage-colony-stimulating factor and tumor necrosis factor alpha were only minimally altered. This study suggests that CPE is cytotoxic to keratinocytes in culture at high concentrations and that it induces mild, localized irritation but not dermal sensitization.

Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer.

PubMed

Nabais, Celso; Figueiredo, Joana; Lopes, Paulina; Martins, Manuela; Araújo, António

2017-04-01

This study aimed to determine the relationship between CK19 mRNA copy number in sentinel lymph nodes (SLN) assessed by one-step nucleic acid amplification (OSNA) technique, and non-sentinel lymph nodes (NSLN) metastization in invasive breast cancer. A model using total tumor load (TTL) obtained by OSNA technique was also constructed to evaluate its predictability. We conducted an observational retrospective study including 598 patients with clinically T1-T3 and node negative invasive breast cancer. Of the 88 patients with positive SLN, 58 patients fulfill the inclusion criteria. In the analyzed group 25.86% had at least one positive NSLN in axillary lymph node dissection. Univariate analysis showed that tumor size, TTL and number of SLN macrometastases were predictive factors for NSLN metastases. In multivariate analysis just the TTL was predictive for positive NSLN (OR 2.67; 95% CI 1.06-6.70; P = 0.036). The ROC curve for the model using TTL alone was obtained and an AUC of 0.805 (95% CI 0.69-0.92) was achieved. For TTL >1.9 × 10 5 copies/μL we got 73.3% sensitivity, 74.4% specificity and 88.9% negative predictive value to predict NSLN metastases. When using OSNA technique to evaluate SLN, NSLN metastases can be predicted intraoperatively. This prediction tool could help in decision for axillary lymph node dissection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk of Subclinical Micrometastatic Disease in the Supraclavicular Nodal Bed According to the Anatomic Distribution in Patients With Advanced Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reed, Valerie K.; Cavalcanti, Jose L.; Strom, Eric A.

Purpose: To determine the anatomic distribution of gross supraclavicular nodes within the supraclavicular fossa using 2-deoxy-2-[F-18] fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, and to evaluate likely coverage of specific regions of the supraclavicular fossa using standard radiation fields. Methods and Materials: We identified 33 patients with advanced or metastatic breast cancer who had a PET/CT scan demonstrating hypermetabolic supraclavicular lymph nodes in 2005. The locations of the involved lymph nodes were mapped onto a single CT set of images of the supraclavicular fossa. These lymph nodes were also mapped onto the treatment-planning CT dataset of 4 patients treatedmore » in our institution (2 patients with biopsy-proven supraclavicular nodes and 2 patients with clinically negative supraclavicular nodes). Results: We were able to determine the distribution of 52 supraclavicular lymph nodes in 32 patients. Of 32 patients, 28 (87%) had a history of metastatic disease, and 2 patients had isolated nodal recurrences. Five patients had supraclavicular nodes posterior to the vertebral body transverse process, and several lymph nodes were in close proximity to the medial field border, raising the possibility of geographic miss in these areas. Conclusions: In patients with locally advanced disease, increased coverage of the supraclavicular fossa medially and posteriorly may be warranted.« less

Transfer of immunoglobulins through the mammary endothelium and epithelium and in the local lymph node of cows during the initial response after intramammary challenge with E. coli endotoxin.

PubMed

Ostensson, Karin; Lun, Shichun

2008-07-02

The first hours after antigen stimulation, interactions occur influencing the outcome of the immunological reaction. Immunoglobulins originate in blood and/or are locally synthesized. The transfer of Ig isotypes (Igs) in the udder has been studied previously but without the possibility to distinguish between the endothelium and the epithelium. The purpose of this study was to map the Ig transfer through each barrier, separately, and Ig transfer in the local lymph nodes of the bovine udder during the initial innate immune response. The content of IgG1, IgG2, IgM, IgA and albumin (BSA) was examined in peripheral/afferent mammary lymph and lymph leaving the supramammary lymph nodes, and in blood and milk before (0 h) and during 4 hours after intramammary challenge with Esherichia coli endotoxin in 5 cows. Igs increased most rapidly in afferent lymph resulting in higher concentrations than in efferent lymph at postinfusion hour (PIH) 2, contrary to before challenge. Ig concentrations in milk were lower than in lymph; except for IgA at 0 h; and they increased more slowly. Afferent lymph:serum and efferent lymph:serum concentration ratios (CR) of Igs were similar to those of BSA but slightly lower. Milk:afferent lymph (M:A) CRs of each Ig, except for IgG2, showed strikingly different pattern than those of BSA. The M:A CR of IgG1, IgM and IgA were higher than that of BSA before challenge and the CR of IgA and IgG1 remained higher also thereafter. At PIH 2 there was a drop in Ig CRs, except for IgG2, in contrast to the BSA CR which gradually increased. The M:A CR of IgM and Ig A decreased from 0 h to PIH 4, in spite of increasing permeability. The transfer of Igs through the endothelium appeared to be merely a result of diffusion although their large molecular size may hamper the diffusion. The transfer through the epithelium and the Ig concentrations in milk seemed more influenced by selective mechanisms and local sources, respectively. Our observations indicate a selective mechanism in the transfer of IgG1 through the epithelium also in lactating glands, not previously shown; a local synthesis of IgA and possibly of IgM, released primarily into milk, not into tissue fluid; that IgG2 transfer through both barriers is a result of passive diffusion only and that the content of efferent lymph is strongly influenced by IgG1, IgM and IgA in the mammary tissue, brought to the lymph node by afferent lymph.

Transfer of immunoglobulins through the mammary endothelium and epithelium and in the local lymph node of cows during the initial response after intramammary challenge with E. coli endotoxin

PubMed Central

Östensson, Karin; Lun, Shichun

2008-01-01

Background The first hours after antigen stimulation, interactions occur influencing the outcome of the immunological reaction. Immunoglobulins originate in blood and/or are locally synthesized. The transfer of Ig isotypes (Igs) in the udder has been studied previously but without the possibility to distinguish between the endothelium and the epithelium. The purpose of this study was to map the Ig transfer through each barrier, separately, and Ig transfer in the local lymph nodes of the bovine udder during the initial innate immune response. Methods The content of IgG1, IgG2, IgM, IgA and albumin (BSA) was examined in peripheral/afferent mammary lymph and lymph leaving the supramammary lymph nodes, and in blood and milk before (0 h) and during 4 hours after intramammary challenge with Esherichia coli endotoxin in 5 cows. Results Igs increased most rapidly in afferent lymph resulting in higher concentrations than in efferent lymph at postinfusion hour (PIH) 2, contrary to before challenge. Ig concentrations in milk were lower than in lymph; except for IgA at 0 h; and they increased more slowly. Afferent lymph:serum and efferent lymph:serum concentration ratios (CR) of Igs were similar to those of BSA but slightly lower. Milk:afferent lymph (M:A) CRs of each Ig, except for IgG2, showed strikingly different pattern than those of BSA. The M:A CR of IgG1, IgM and IgA were higher than that of BSA before challenge and the CR of IgA and IgG1 remained higher also thereafter. At PIH 2 there was a drop in Ig CRs, except for IgG2, in contrast to the BSA CR which gradually increased. The M:A CR of IgM and Ig A decreased from 0 h to PIH 4, in spite of increasing permeability. Conclusion The transfer of Igs through the endothelium appeared to be merely a result of diffusion although their large molecular size may hamper the diffusion. The transfer through the epithelium and the Ig concentrations in milk seemed more influenced by selective mechanisms and local sources, respectively. Our observations indicate a selective mechanism in the transfer of IgG1 through the epithelium also in lactating glands, not previously shown; a local synthesis of IgA and possibly of IgM, released primarily into milk, not into tissue fluid; that IgG2 transfer through both barriers is a result of passive diffusion only and that the content of efferent lymph is strongly influenced by IgG1, IgM and IgA in the mammary tissue, brought to the lymph node by afferent lymph. PMID:18597683

Comparison of Positron Emission Tomography Scanning and Sentinel Node Biopsy in the Detection of Inguinal Node Metastases in Patients With Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mistrangelo, Massimiliano, E-mail: mistrangelo@katamail.co; Centre of Minimally Invasive Surgery, University of Turin; Pelosi, Ettore

2010-05-01

Background: Inguinal lymph node metastases in patients with anal cancer are an independent prognostic factor for local failure and overall mortality. Inguinal lymph node status can be adequately assessed with sentinel node biopsy, and the radiotherapy strategy can subsequently be changed. We compared this technique vs. dedicated 18F-fluorodeoxyglucose positron emission tomography (PET) to determine which was the better tool for staging inguinal lymph nodes. Methods and Materials: In our department, 27 patients (9 men and 18 women) underwent both inguinal sentinel node biopsy and PET-CT. PET-CT was performed before treatment and then at 1 and 3 months after treatment. Results:more » PET-CT scans detected no inguinal metastases in 20 of 27 patients and metastases in the remaining 7. Histologic analysis of the sentinel lymph node detected metastases in only three patients (four PET-CT false positives). HIV status was not found to influence the results. None of the patients negative at sentinel node biopsy developed metastases during the follow-up period. PET-CT had a sensitivity of 100%, with a negative predictive value of 100%. Owing to the high number of false positives, PET-CT specificity was 83%, and positive predictive value was 43%. Conclusions: In this series of patients with anal cancer, inguinal sentinel node biopsy was superior to PET-CT for staging inguinal lymph nodes.« less

Dynamics of neutrophil migration in lymph nodes during infection.

PubMed

Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; van Dooren, Giel G; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin; Aaron, Holly; Striepen, Boris; Robey, Ellen A

2008-09-19

Although the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning-laser microscopy to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We found that neutrophils formed both small, transient and large, persistent swarms via a coordinated migration pattern. We provided evidence that cooperative action of neutrophils and parasite egress from host cells could trigger swarm formation. Neutrophil swarm formation coincided in space and time with the removal of macrophages that line the subcapsular sinus of the lymph node. Our data provide insights into the cellular mechanisms underlying neutrophil swarming and suggest new roles for neutrophils in shaping immune responses.

Dynamics of neutrophil migration in lymph nodes during infection

PubMed Central

Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; van Dooren, Giel G.; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin; Aaron, Holly; Striepen, Boris; Robey, Ellen A.

2008-01-01

Summary While the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes, or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning laser microscopy (TPSLM) to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We find that neutrophils form both small, transient or large, persistent swarms via a strikingly coordinated migration pattern. We provide evidence that cooperative action of neutrophils and parasite egress from host cells can trigger swarm formation. Neutrophil swarm formation coincides in space and time with the removal of macrophages that line the subcapsular sinus of the lymph node. Our data provide insights into the cellular mechanisms underlying neutrophil swarming and suggest new roles for neutrophils in shaping immune responses. PMID:18718768

Probabilistic hazard assessment for skin sensitization potency by dose–response modeling using feature elimination instead of quantitative structure–activity relationships

PubMed Central

McKim, James M.; Hartung, Thomas; Kleensang, Andre; Sá-Rocha, Vanessa

2016-01-01

Supervised learning methods promise to improve integrated testing strategies (ITS), but must be adjusted to handle high dimensionality and dose–response data. ITS approaches are currently fueled by the increasing mechanistic understanding of adverse outcome pathways (AOP) and the development of tests reflecting these mechanisms. Simple approaches to combine skin sensitization data sets, such as weight of evidence, fail due to problems in information redundancy and high dimension-ality. The problem is further amplified when potency information (dose/response) of hazards would be estimated. Skin sensitization currently serves as the foster child for AOP and ITS development, as legislative pressures combined with a very good mechanistic understanding of contact dermatitis have led to test development and relatively large high-quality data sets. We curated such a data set and combined a recursive variable selection algorithm to evaluate the information available through in silico, in chemico and in vitro assays. Chemical similarity alone could not cluster chemicals’ potency, and in vitro models consistently ranked high in recursive feature elimination. This allows reducing the number of tests included in an ITS. Next, we analyzed with a hidden Markov model that takes advantage of an intrinsic inter-relationship among the local lymph node assay classes, i.e. the monotonous connection between local lymph node assay and dose. The dose-informed random forest/hidden Markov model was superior to the dose-naive random forest model on all data sets. Although balanced accuracy improvement may seem small, this obscures the actual improvement in misclassifications as the dose-informed hidden Markov model strongly reduced "false-negatives" (i.e. extreme sensitizers as non-sensitizer) on all data sets. PMID:26046447

Photodegradation of dibenzoylmethanes: potential cause of photocontact allergy to sunscreens.

PubMed

Karlsson, Isabella; Hillerström, Lisa; Stenfeldt, Anna-Lena; Mårtensson, Jerker; Börje, Anna

2009-11-01

One of the most frequently observed photoallergens today is the sunscreen agent 4-tert-butyl-4'-methoxy dibenzoylmethane (1a). The structurally similar compound, 4-isopropyldibenzoylmethane (1b), was a common cause of sunscreen allergy in the eighties and early nineties but was removed from the market in 1993 and replaced with dibenzoylmethane 1a. We have studied the photodegradation of the dibenzoylmethane 1a, to better understand how these substances cause an immune reaction. Several expected degradation products were formed and identified. Of these, arylglyoxals and benzils were of particular interest because they were unexplored as potential contact allergens. The allergenic potential of photodegraded 1a was evaluated by screening the formed arylglyoxals and benzils for their sensitizing capacity in the murine local lymph node assay. The arylglyoxals were found to be strong sensitizers. They were also found to be highly reactive toward the nucleophile arginine, which indicates that the immunogenic hapten-protein complex could be formed via an electrophilic-nucleophilic pathway. By varying the electron-withdrawing or -donating capacity of the substituent in the para position of the arylglyoxal, the electronic effects were shown to have no significant impact on either the sensitizing or the electrophilic power of arylglyoxals. Thus, a change in the substitution pattern of the parent dibenzoylmethane will not influence the sensitizing capacity of the products formed from them upon photodegradation. Furthermore, the combined studies of benzils, using the local lymph node assay and a cell proliferation assay, indicate that the benzils are cytotoxic rather than allergenic. Taken together, this study presents strong indication that photocontact allergy to dibenzoylmethanes is caused by the arylglyoxals that are formed upon photodegradation.

Probabilistic hazard assessment for skin sensitization potency by dose-response modeling using feature elimination instead of quantitative structure-activity relationships.

PubMed

Luechtefeld, Thomas; Maertens, Alexandra; McKim, James M; Hartung, Thomas; Kleensang, Andre; Sá-Rocha, Vanessa

2015-11-01

Supervised learning methods promise to improve integrated testing strategies (ITS), but must be adjusted to handle high dimensionality and dose-response data. ITS approaches are currently fueled by the increasing mechanistic understanding of adverse outcome pathways (AOP) and the development of tests reflecting these mechanisms. Simple approaches to combine skin sensitization data sets, such as weight of evidence, fail due to problems in information redundancy and high dimensionality. The problem is further amplified when potency information (dose/response) of hazards would be estimated. Skin sensitization currently serves as the foster child for AOP and ITS development, as legislative pressures combined with a very good mechanistic understanding of contact dermatitis have led to test development and relatively large high-quality data sets. We curated such a data set and combined a recursive variable selection algorithm to evaluate the information available through in silico, in chemico and in vitro assays. Chemical similarity alone could not cluster chemicals' potency, and in vitro models consistently ranked high in recursive feature elimination. This allows reducing the number of tests included in an ITS. Next, we analyzed with a hidden Markov model that takes advantage of an intrinsic inter-relationship among the local lymph node assay classes, i.e. the monotonous connection between local lymph node assay and dose. The dose-informed random forest/hidden Markov model was superior to the dose-naive random forest model on all data sets. Although balanced accuracy improvement may seem small, this obscures the actual improvement in misclassifications as the dose-informed hidden Markov model strongly reduced " false-negatives" (i.e. extreme sensitizers as non-sensitizer) on all data sets. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of the tracing effect of carbon nanoparticle and carbon nanoparticle-epirubicin suspension in axillary lymph node dissection for breast cancer treatment.

PubMed

Du, Junze; Zhang, Yongsong; Ming, Jia; Liu, Jing; Zhong, Ling; Liang, Quankun; Fan, Linjun; Jiang, Jun

2016-06-22

Carbon nanoparticle suspension, using smooth carbon particles at a diameter of 21 nm added with suspending agents, is a stable suspension of carbon pellets of 150 nm in diameter. It is obviously inclined to the lymphatic system. There were some studies reporting that carbon nanoparticles are considered as superior tracers for sentinel lymph nodes because of their stability and operational feasibility. However, there were few study concerns about the potential treatment effect including tracing and local chemotherapeutic effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. In the current study, a randomized controlled analysis was performed to investigate the potential treatment effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. A total of 90 breast cancer patients were randomly divided into three equal groups: control, tracer, and drug-load groups. The control group patients did not receive any lymphatic tracers, the tracer group patients were subcutaneously injected with 1 ml carbon nanoparticle suspension, and the drug-load group patients were injected with 3 ml carbon nanoparticle-epirubicin suspension at four separate sites around the areola 24 h before surgery. Modified radical mastectomy, endoscopic subcutaneous mammary resection plus axillary lymph node dissection, and immediate reconstruction with implants or breast-conserving surgery were performed. The mean number of the dissected lymph nodes per patient was significantly higher in the tracer (21.3 ± 6.1) and drug-load (19.5 ± 3.7) groups than in the control group (16.7 ± 3.4) (P < 0.05). Most lymph nodes in the former two groups were stained black (75.7 and 73.3 %, respectively), but with no significant difference between the groups. Most metastatic lymph nodes were also stained black in the tracer group (68.6 %) and drug-load group (78.1 %) and with no significant difference between the groups (P = 0.198). Microscopic examination revealed that the carbon nanoparticles were localized around or among the cancer cell masses and residues of necrotized cancer cells surrounded by fibroblastic proliferation could be found within the stained lymph nodes in the drug-load group. The majority of axillary lymph nodes were stained black by the suspension of carbon nanoparticles, which helped identify the lymph nodes from the surrounding tissues and avoided aggressive axillary treatment. Thus, a combination therapy of carbon nanoparticles with epirubicin could play an important role in lymphatic chemotherapy without affecting tracing. ChiCTRTRC13003419.

The Effect of Ambient Titanium Dioxide Microparticle Exposure to the Ocular Surface on the Expression of Inflammatory Cytokines in the Eye and Cervical Lymph Nodes.

PubMed

Eom, Youngsub; Song, Jong Suk; Lee, Hyun Kyu; Kang, Boram; Kim, Hyeon Chang; Lee, Hyung Keun; Kim, Hyo Myung

2016-12-01

To investigate the ocular immune response following exposure to airborne titanium dioxide (TiO2) microparticles. Rats in the TiO2-exposed group (n = 10) were exposed to TiO2 particles for 2 hours twice daily for 5 days, while the controls (n = 10) were not. Corneal staining score and tear lactic dehydrogenase (LDH) activity were measured to evaluate ocular surface damage, serum immunoglobulin (Ig) G and E were assayed by using enzyme-linked immunosorbent assay, and the size of cervical lymph nodes was measured. In addition, the expression of interleukin (IL)-4, IL-17, and interferon (IFN)-γ in the anterior segment of the eyeball and cervical lymph nodes was measured by immunohistochemistry, real-time reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis. Median corneal staining score (3.0), tear LDH activity (0.24 optical density [OD]), and cervical lymph node size (36.9 mm2) were significantly higher in the TiO2-exposed group than in the control group (1.0, 0.13 OD, and 26.7 mm2, respectively). Serum IgG and IgE levels were found to be significantly elevated in the TiO2-exposed group (P = 0.021 and P = 0.021, respectively). Interleukin 4 expression was increased in the anterior segment of the eyeball and lymph nodes following TiO2 exposure, as measured by immunostaining, real-time RT-PCR, and Western blot. In addition, IL-17 and IFN-γ levels were also increased following TiO2 exposure compared to controls as measured by immunostaining. Exposure to airborne TiO2 induced ocular surface damage. The Type 2 helper T-cell pathway seems to play a dominant role in the ocular immune response following airborne TiO2 exposure.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

PubMed

Alongi, Filippo; Schipani, Stefano; Samanes Gajate, Ana Maria; Rosso, Alberto; Cozzarini, Cesare; Fiorino, Claudio; Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina; Di Muzio, Nadia

2010-01-01

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer.

PubMed

Fanfani, Francesco; Monterossi, Giorgia; Ghizzoni, Viola; Rossi, Esther D; Dinoi, Giorgia; Inzani, Frediano; Fagotti, Anna; Gueli Alletti, Salvatore; Scarpellini, Francesca; Nero, Camilla; Santoro, Angela; Scambia, Giovanni; Zannoni, Gian F

2018-01-01

The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC). From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides. Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found. The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.

[Correlation factors of lymph node metastasis in patients with clinical stage T1a non-small cell lung cancer].

PubMed

Ruochuan, Zang; Shugeng, Guo; Jie, He; Yousheng, Mao; Qi, Xue; Dali, Wang; Juwei, Mu; Jun, Zhao; Yonggang, Wang; Xiangyang, Liu; Fengwei, Tan; Gefei, Zhao; Qian, Zhang; Moyan, Zhang; Peng, Song

2015-04-01

To explore the relationship between the lymph node metastasis and clinicopathological features in patients with clinical stage T1a non-small cell lung cancer (NSCLC). Clinicopathological data of a total of 418 patients who underwent lobectomy and systematic lymph node dissection were retrospectively analyzed. Logistic regression was used to analyze the relationship between lymph node metastasis and clinicopathological features. Lymph node metastasis was observed in 25 patients. There were 122 patients who were diagnosed as ground glass opacity with no lymph node metastasis. 399 patients had subcarinal dissection, among them 7 patients were found to have lymph node metastasis. Univariate analysis showed that gender, smoking history, diameter of lymph node, ground glass opacity (GGO), differentiation of the tumor and tumor site were the factors affecting lymph node metastasis (all P < 0.05). Logistic regression analysis showed that diameter of lymph node, differentiation of the tumor and the site of lesion were independent risk factors for lymph node metastasis of NSCLC. Tumor in the left lung, poor differentiation, and diameter of lymph nodes ≥ 1 cm on the preoperative CT image are independent risk factors for lymph node metastasis of NSCLC, hence we should pay attention before surgery and systematic lymph node dissection should be done. For patients with poor differentiation and lymph nodes ≥ 1 cm, subcarinal lymph nodes dissection is recommended for the sake of higher possibility of lymph node metastasis. For patients with ground glass opacity ≤ 2 cm, the lymph node metastasis is extremely rare, therefore, selective lymph node dissection is reconmmended.

Sphincter-sparing local excision and hypofractionated radiation therapy for anorectal melanoma: a 20-year experience.

PubMed

Kelly, Patrick; Zagars, Gunar K; Cormier, Jancie N; Ross, Merrick I; Guadagnolo, B Ashleigh

2011-10-15

Anorectal melanoma is a rare disease with a poor prognosis. Because survival is determined by distant failure, many centers have adopted sphincter-sparing excision for primary tumor control. However, this approach is associated with high rates of local failure (∼50%). In this study, the authors report their 20-year experience with sphincter-sparing excision combined with radiation therapy (RT) for the treatment of localized anorectal melanoma. The authors reviewed the records of 54 patients with localized anorectal melanoma who were treated at the University of Texas MD Anderson Cancer Center from 1989 to 2008. All patients underwent definitive local excision with or without sentinel lymph node biopsy or lymph node dissection. RT (25-36 grays in 5-6 fractions) was delivered to extended fields that targeted the primary site and draining pelvic/inguinal lymphatics in 39 patients and to limited fields that targeted only the primary site in 15 patients. The 5-year rates of local control (LC), lymph node control (NC), and sphincter preservation were 82%, 88%, and 96%, respectively. However, because of the high rate of distant metastasis, the overall survival (OS) rate at 5 years was only 30%. Although there were no significant differences in LC, NC, or OS based on RT field extent, patients who received extended-field RT had higher rates of lymphedema than patients who received limited-field RT. The current results indicated that combined sphincter-sparing local excision and RT is a well tolerated approach that provides effective LC for patients with anorectal melanoma. Inclusion of the inguinal lymph node basins in the RT fields did not improve outcomes and was associated with an increased risk of lymphedema. Copyright © 2011 American Cancer Society.

Age-related changes in cell localization and proliferation in lymph nodes and spleen after antigenic stimulation.

PubMed Central

Ansell, J D; McDougall, C M; Micklem, H S; Inchley, C J

1980-01-01

Antigen-dependent localization of 51Cr-labelled lymphocytes, and the subsequent uptake of IUdR into lymphoid organs has been studied as a function of age. Measures of cell localization indicated that while old age can alter the patterns of entry of lymphocytes into lymph nodes and spleen, these changes are variable and probably not sufficient alone to explain decreased primary antibody responses in old animals. Proliferation of cells, however, was consistently affected in both organs and this phenomenon is discussed in terms of abnormal T-cell function. PMID:7429546

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Pan; Hongqian, Chu; Qinghe, Meng

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and themore » lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8{sup +} T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. - Highlights: • Lack of TAK1 in DC caused an abolished TCE-induced CHS response. • TAK1 in DCs was essential to maintain the homeostasis of T cells in TCE-induced CHS. • Intact TAK1 in DCs was critical to promote T-cell priming in TCE-induced CHS. • DC-specific TAK1 deficiency abolished the TCE-mediated phosphorylation of Jnk.« less

Diagnostic and prognostic value of additional SPECT/CT in sentinel lymph node mapping in breast cancer patients.

PubMed

Stanzel, Susanne; Pernthaler, Birgit; Schwarz, Thomas; Bjelic-Radisic, Vesna; Kerschbaumer, Stefan; Aigner, Reingard M

2018-06-01

of the study was to demonstrate the diagnostic and prognostic value of SPECT/CT in sentinel lymph node mapping (SLNM) in patients with invasive breast cancer. 114 patients with invasive breast cancer with clinically negative lymph nodes were included in this retrospective study as they were referred for SLNM with 99m Tc-nanocolloid. Planar image acquisition was accomplished in a one-day or two-day protocol depending on the schedule of the surgical procedure. Low dose SPECT/CT was performed after the planar images. The sentinel lymph node biopsy (SLNB) was considered false negative if a primary recurrence developed within 12 months after SLNB in the axilla from which a tumor-free SLN had been removed. Between December 2009 and December 2011, 114 patients (pts.) underwent SLNM with additional SPECT/CT. Planar imaging identified in 109 pts. 139 SLNs, which were tumor-positive in 42 nodes (n = 41 pts.). SPECT/CT identified in 81 pts. 151 additional SLNs, of which 19 were tumor-positive and led to therapy change (axillary lymph node dissection) in 11 pts. (9.6 %). Of overall 61 tumor-positive SLNs (n = 52 pts.) SPECT/CT detected all, whereas planar imaging detected only 42 of 61 ( P < 0.0001). No patient had lymph node metastasis within 12 months after SLNB in the axilla from which a tumor-free SLN had been removed resulting in a false-negative rate of 0 %. The local relapse rate was 1.8 % leading to a 4-year disease-free survival rate of 90 %. Among patients with breast cancer, the use of SPECT/CT-aided SLNM correlated due to a better anatomical localization and identification of planar not visible SLNs with a higher detection rate of SLNs. This led to therapeutic consequences and an excellent false-negative and 4-year disease-free survival rate. Schattauer GmbH.

[Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers].

PubMed

Wang, Fu-long; Wan, De-sen; Lu, Zhen-hai; Fang, Yu-jing; Li, Li-ren; Chen, Gong; Wu, Xiao-jun; Ding, Pei-rong; Kong, Ling-heng; Lin, Jun-zhong; Pan, Zhi-zhong

2013-04-01

To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques. Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis. The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis. VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

Detection of toxoplasmosis in experimentally infected goats by PCR.

PubMed

Sreekumar, C; Rao, J R; Mishra, A K; Ray, D; Joshi, P; Singh, R K

2004-05-15

PCR was used to diagnose toxoplasmosis in two pairs of Barbari goats infected by oral administration of doses of either 10(4) or 10(5) oocysts of Toxoplasma gondii. Blood and lymph node aspirates were collected from the infected goats and control goat at intervals, and tissues were also collected from a fetus that was aborted and a doe that died during the trial. Both processed and unprocessed samples were used for the PCR, using primers directed to the multicopy B1 gene. None of the blood samples was positive, but a specific signal was obtained from the lymph node aspirates after partial DNA extraction. Direct PCR of the lung, muscle and mesenteric lymph node of the doe and lung tissue of the aborted fetus yielded the target fragment. The simplified PCR protocols, including partial DNA extraction and direct assay of lung tissue, were effective for the diagnosis of toxoplasmosis.

Preoperative 18F-FDG-PET/CT imaging and sentinel node biopsy in the detection of regional lymph node metastases in malignant melanoma.

PubMed

Singh, Baljinder; Ezziddin, Samer; Palmedo, Holger; Reinhardt, Michael; Strunk, Holger; Tüting, Thomas; Biersack, Hans-Jürgen; Ahmadzadehfar, Hojjat

2008-10-01

The objective of this study was to evaluate the role of preoperative 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scanning, preoperative lymphoscintigraphy (LS), and sentinel lymph node biopsy in patients with malignant melanoma. Fifty-two patients (36 men: 16 women; mean age 55.0+/-13.0 years; median age 61 years; range 17-76 years) with malignant melanoma were selected. According to the latest version of the American Joint Committee on Cancer staging system, the disease in the study patients was initially classified as either stage I or II. The other primary tumor characteristics were mean Breslow depth=2.87 mm and median=2 mm; range 1-12.0 mm and Clarks levels III-V. None of the study patients had clinical or radiological evidence of regional lymph node metastatic disease. At least one sentinel node was identified in all patients. Preoperative LS detected a total of 111 sentinel lymph nodes (average 2.13 sentinel lymph node per patient) and demonstrated a single nodal draining basin in 38 (73%) patients and multiple (2-3 draining basins) in the remaining 14 (27%) patients. Fourteen out of the 52 patients (27%) had at least one involved sentinel node. Positron emission tomography was true positive in two patients with a sentinel node greater than 1 cm and false positive in two other patients. In this study, the detection of sentinel lymph node by LS and gamma probe had a sensitivity of 100%. In contrast, 18F-FDG-PET imaging demonstrated very low sensitivity (14.3%; 95% CI, 2.5 to 44%) and positive predictive value (50%; 95% CI, 9 to 90%) for localizing the subclinical nodal metastases. The specificity, net present value, and diagnostic accuracy were 94.7, 75, and 73%, respectively. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography imaging is not able to substitute LS/sentinel lymph node biopsy in patients at stage I or II.

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

PubMed Central

2012-01-01

Background SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients. Methods Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeamTM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan. Results All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded. Conclusions Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes. PMID:23216821

Preoperative endoscopic localization of colorectal cancer and tracing lymph nodes by using carbon nanoparticles in laparoscopy.

PubMed

Wang, Qingxuan; Chen, Endong; Cai, Yefeng; Chen, Chong; Jin, Wenxu; Zheng, Zhouci; Jin, Yixiang; Chen, Yao; Zhang, Xiaohua; Li, Quan

2016-08-30

The objective of this study is to evaluate the effectiveness of preoperative endoscopic localization of colorectal cancer and tracing lymph nodes by carbon nanoparticle tattooing in laparoscopic colorectal cancer surgery. From January 2013 to December 2014, 54 patients with colorectal cancer were recruited and divided into experimental (n = 27) and control (n = 27) groups. The patients in the experimental group were localized preoperatively by endoscopic carbon nanoparticle tattooing, whereas patients in the control group were not tattooed. All injection sites in the experimental group were visible to surgeons. No abdominal pain, fever, diarrhea, and other symptoms of infection were found in the experimental group. The time for detecting the tumor (2.71 ± 2.13 min versus 6.91 ± 5.16 min, p < 0.001), operation time (151.22 ± 30.66 min versus 170.26 ± 33.13 min, p = 0.033), and blood loss during the operation (125.04 ± 29.48 mL versus 147.52 ± 34.35 mL, p = 0.013) were lower in the experimental group than in the control group. Average numbers of dissected lymph nodes in the experimental group exceeded those in the control group (14.41 ± 3.32 versus 8.96 ± 2.90, p < 0.001), and the rate of dissected lymph nodes ≥12 was higher in the experimental group than in the control group (70.37 versus 37.04 %, p < 0.001). Moreover, no difference in postoperative complications was found between the two groups. Tattooing colorectal cancer with carbon nanoparticles in laparoscopic colorectal cancer surgery is safe and useful both in localization and lymph node tracing.

Syphilitic lymphadenitis clinically and histologically mimicking lymphogranuloma venereum.

PubMed

Wessels, Annesu; Bamford, Colleen; Lewis, David; Martini, Markus; Wainwright, Helen

2016-04-19

An inguinal lymph node was discovered incidentally during surgery for a suspected strangulated inguinal hernia. The patient had recently been treated for candidal balanoposthitis and was known to have a paraphimosis. A new foreskin ulcer was discovered when he was admitted for the hernia surgery. The lymph node histology showed stellate abscesses suggestive of lymphogranuloma venereum (LGV). Chlamydial serologic tests were negative. As the histological appearance and clinical details provided were thought to suggest LGV, tissue was also sent for a real-time quadriplex polymerase chain reaction assay. This was used to screen for Chlamydia trachomatis in conjunction with other genital ulcer-related pathogens. The assay was negative for C. trachomatis, but positive for Treponema pallidum. Further histochemical staining of the histological specimen confirmed the presence of spirochaetes.

Lymph node detection in IASLC-defined zones on PET/CT images

NASA Astrophysics Data System (ADS)

Song, Yihua; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Torigian, Drew A.

2016-03-01

Lymph node detection is challenging due to the low contrast between lymph nodes as well as surrounding soft tissues and the variation in nodal size and shape. In this paper, we propose several novel ideas which are combined into a system to operate on positron emission tomography/ computed tomography (PET/CT) images to detect abnormal thoracic nodes. First, our previous Automatic Anatomy Recognition (AAR) approach is modified where lymph node zones predominantly following International Association for the Study of Lung Cancer (IASLC) specifications are modeled as objects arranged in a hierarchy along with key anatomic anchor objects. This fuzzy anatomy model built from diagnostic CT images is then deployed on PET/CT images for automatically recognizing the zones. A novel globular filter (g-filter) to detect blob-like objects over a specified range of sizes is designed to detect the most likely locations and sizes of diseased nodes. Abnormal nodes within each automatically localized zone are subsequently detected via combined use of different items of information at various scales: lymph node zone model poses found at recognition indicating the geographic layout at the global level of node clusters, g-filter response which hones in on and carefully selects node-like globular objects at the node level, and CT and PET gray value but within only the most plausible nodal regions for node presence at the voxel level. The models are built from 25 diagnostic CT scans and refined for an object hierarchy based on a separate set of 20 diagnostic CT scans. Node detection is tested on an additional set of 20 PET/CT scans. Our preliminary results indicate node detection sensitivity and specificity at around 90% and 85%, respectively.

Dual time point 2-deoxy-2-[18F]fluoro-D-glucose PET/CT: nodal staging in locally advanced breast cancer.

PubMed

García Vicente, A M; Soriano Castrejón, A; Cruz Mora, M Á; Ortega Ruiperez, C; Espinosa Aunión, R; León Martín, A; González Ageitos, A; Van Gómez López, O

2014-01-01

To assess dual time point 2-deoxy-2-[(18)F]fluoro-D-glucose (18)(F)FDG PET-CT accuracy in nodal staging and in detection of extra-axillary involvement. Dual time point [(18)F] FDG PET/CT scan was performed in 75 patients. Visual and semiquantitative assessment of lymph nodes was performed. Semiquantitative measurement of SUV and ROC-analysis were carried out to calculate SUV(max) cut-off value with the best diagnostic performance. Axillary and extra-axillary lymph node chains were evaluated. Sensitivity and specificity of visual assessment was 87.3% and 75%, respectively. SUV(max) values with the best sensitivity were 0.90 and 0.95 for early and delayed PET, respectively. SUV(max) values with the best specificity were 1.95 and 2.75, respectively. Extra-axillary lymph node involvement was detected in 26.7%. FDG PET/CT detected extra-axillary lymph node involvement in one-fourth of the patients. Semiquantitative lymph node analysis did not show any advantage over the visual evaluation. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Castleman's disease of the spleen.

PubMed

Mantas, Dimitrios; Damaskos, Christos; Dailiani, Panagiota; Samarkos, Michael; Korkolopoulou, Penelope

2017-06-01

Castleman's disease (CD), also known as giant or angiofolicular lymphoid hyperplasia or lymphoid hamartoma, is a group of atypical lymphoproliferative disorders that share common lymph node histological features and may be localized either to a single lymph node (unicentric) or occur systemically (multicentric). Herein, we present a rare case of a of 75-year-old female patient who was referred to our department and after a thorough work-up, underwent splenectomy with synchronous resection of an accessory spleen, splenic artery lymph nodes, and splenic hilar lymph nodes due to splenic involvement in a multicentric CD. The pathology of the specimens led to the conclusion that it was a case of polycentric HHV-8-positive CD, affecting the spleen, the accessory spleen, and the lymph nodes. Incidence of this rare condition is believed to be approximately 0.001-0.05%. CD has been linked to the human immunodeficiency virus (HIV), human herpes virus 8 (HHV-8), and is associated with malignancies. The pathogenesis mechanism is considered to be a dysregulation and hypersecretion of cytokines, either idiopathic or secondary to a viral infection, with the latter considered the most frequent. Solid organ involvement is very rare as is splenic involvement.

Extraction and visualization of the central chest lymph-node stations

NASA Astrophysics Data System (ADS)

Lu, Kongkuo; Merritt, Scott A.; Higgins, William E.

2008-03-01

Lung cancer remains the leading cause of cancer death in the United States and is expected to account for nearly 30% of all cancer deaths in 2007. Central to the lung-cancer diagnosis and staging process is the assessment of the central chest lymph nodes. This assessment typically requires two major stages: (1) location of the lymph nodes in a three-dimensional (3D) high-resolution volumetric multi-detector computed-tomography (MDCT) image of the chest; (2) subsequent nodal sampling using transbronchial needle aspiration (TBNA). We describe a computer-based system for automatically locating the central chest lymph-node stations in a 3D MDCT image. Automated analysis methods are first run that extract the airway tree, airway-tree centerlines, aorta, pulmonary artery, lungs, key skeletal structures, and major-airway labels. This information provides geometrical and anatomical cues for localizing the major nodal stations. Our system demarcates these stations, conforming to criteria outlined for the Mountain and Wang standard classification systems. Visualization tools within the system then enable the user to interact with these stations to locate visible lymph nodes. Results derived from a set of human 3D MDCT chest images illustrate the usage and efficacy of the system.

[Incidence and influencing factors of distal external iliac lymph node metastasis in early cervical cancer].

PubMed

Yin, Yueju; Sheng, Xiugui; Li, Xinglan; Li, Dapeng; Han, Xiaoyun; Zhang, Xiaoling; Zhang, Tingting

2014-06-01

The distal external iliac lymph nodes are located along the external iliac artery between the deep circumflex iliac vein and the inguinal canal. Our study aimed to investigate the incidence of metastasis in distal external iliac lymph nodes and its association with clinicopathological factors in patients with early stage cervical cancer, and to determine the role of distal external iliac lymph nodes dissection in the surgery. Five hundred and twenty-four patients with early stage cervical cancer underwent radical hysterectomy and bilateral pelvic lymphadenectomy in the Shandong Province Cancer Hospital between June 1995 and December 2011, and their clinicopathological features were analyzed retrospectively. Of the 524 patients, 124 (23.7%) had pelvic lymph node metastasis. The metastasis rates were 16.2% (85 of 524 patients) in the obturator lymph nodes, 12.2% (64 of 524 patients) in the internal and external iliac lymph nodes, 2.9% (15 of 524 patients) in the common iliac lymph nodes, 2.1% (11 of 524 patients) in the distal external iliac lymph nodes, and 1.7% (9 of 524 patients) in the para-aortic nodes. The incidence of isolated positive distal external iliac lymph nodes was 0.2%. Univariate analysis showed that lymphovascular space invasion, pelvic lymph node metastases (excluding distal external iliac lymph nodes) were significantly associated with distal external iliac lymph node metastasis (P < 0.05). Logistic regression analysis showed that pelvic lymph node metastasis (excluding distal external iliac lymph nodes) was the independent risk factor for metastasis to distal external iliac lymph nodes. In early stage cervical cancer, distal external iliac lymph node metastasis is rare, especially in cases with stage IA or without pelvic lymph node metastasis. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operative complications and improve patients' quality of life. The deep circumflex iliac vein may be an appropriate landmark for the caudal limit of external iliac lymphadenectomy. However, if pelvic lymph node metastasis (excluding distal external iliac lymph nodes) is found by intraoperative rapid pathological diagnosis, systematic pelvic lymphadenectomy including removal of the distal external iliac lymph nodes should be performed in order to reduce the risk of distant metastasis.

Unusual late presentation of metastatic extrathoracic thymoma to gastrohepatic lymph node treated by surgical resection.

PubMed

Billè, Andrea; Sachidananda, Sandeep; Moreira, Andre L; Rizk, Nabil P

2017-02-01

In advanced stages, thymic tumors tend to spread locally. Distant metastatic disease is rare. We present the first report of single metastatic abdominal lymph node in a 37-year-old female patient and 5 years after an extrapleural pneumonectomy for stage IV thymoma followed by radiotherapy with no other evidence of abdominal disease successfully treated by robotic surgical resection.

Repeat sentinel lymph node biopsy in patients with ipsilateral recurrent breast cancer after breast-conserving therapy and negative sentinel lymph node biopsy: a prospective study.

PubMed

Folli, Secondo; Falco, Giuseppe; Mingozzi, Matteo; Buggi, Federico; Curcio, Annalisa; Ferrari, Guglielmo; Taffurelli, Mario; Regolo, Lea; Nanni, Oriana

2016-04-01

Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery with negative sentinel lymph node biopsy need a new axillary staging procedure. However, the best surgical option, i.e. repeat sentinel lymph node biopsy or axillary lymph node dissection, is still debated. Purpose of the study is to assess the performance of repeat sentinel lymph node biopsy. In a multicenter study, lymph node biopsy completed by back-up axillary lymph node dissection was undertaken for ipsilateral breast tumor recurrence or new ipsilateral primary tumor. Tracer uptake was used to identify and isolate the sentinel lymph node during surgery, and it was classified after staining with hematoxylin and eosin and monoclonal anti-cytokeratin antibodies. Aside from negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. A multicenter, prospective study was conducted performing 30 repeat sentinel lymph node biopsy completed by back-up axillary lymph node dissection for ipsilateral breast tumor recurrence or new ipsilateral primary tumor in patients formerly treated with previous breast conservative surgery and negative sentinel lymph node biopsy. Negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. Sentinel lymph nodes were mapped in 27 patients out of 30 (90%). Aberrant drainage pathways were observed in one patient (3.7%). Tracer uptake was sufficient to identify and isolate the sentinel lymph node during surgery in 23 cases (76.6%); the patients in whom lymphoscintigraphy failed or no sentinel lymph nodes could be isolated underwent axillary lymph node dissection. The negative predictive value was 95.2%, the accuracy was 95.6% and the false-negative rate was 33%. Repeat sentinel lymph node biopsy is feasible and accurate, with a high negative predictive value. Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery and negative sentinel lymph node biopsy can be treated with repeat sentinel lymph node biopsy for the axillary staging and can be spared axillary dissection in case of absence of metastases. However, repeat sentinel lymph node biopsy may prove technically impracticable in about one quarter of cases and thus axillary lymph node dissection remains the only viable option in such instance.

Sentinel lymph node biopsy under fluorescent indocyanin green guidance: Initial experience.

PubMed

Aydoğan, Fatih; Arıkan, Akif Enes; Aytaç, Erman; Velidedeoğlu, Mehmet; Yılmaz, Mehmet Halit; Sager, Muhammet Sait; Çelik, Varol; Uras, Cihan

2016-01-01

Sentinel lymph node biopsy can be applied by using either blue dye or radionuclide method or both in breast cancer. Fluorescent imaging with indocyanine green is a new defined method. This study evaluates the applicability of sentinel lymph node biopsy via fluorescent indocyanine green. IC-VIEW (Pulsion Medical Systems AG, Munich, Germany) infrared visualization system was used for imaging. Two mL of indocyanine green was injected to visualize sentinel lymph nodes. After injection, subcutaneous lymphatics were traced and sentinel lymph nodes were found with simultaneous imaging. Sentinel lymph nodes were excised under fluorescent light guidance, and excised lymph nodes were examined histopathologically. Patients with sentinel lymph node metastases underwent axillary dissection. Four patients with sentinel lymph node biopsy due to breast cancer were included in the study. Sentinel lymph nodes were visualized with indocyanine green in all patients. The median number of excised sentinel lymph node was 2 (2-3). Two patients with lymph node metastasis underwent axillary dissection. No metastasis was detected in lymph nodes other than the sentinel nodes in patients with axillary dissection. There was no complication during and after the operation related to the method. According to our limited experience, sentinel lymph node biopsy under fluorescent indocyanine green guidance, which has an advantage of simultaneous visualization, is technically feasible.

Lymph node staging of oral and maxillofacial neoplasms in 31 dogs and cats.

PubMed

Herring, Erin S; Smith, Mark M; Robertson, John L

2002-09-01

A retrospective study was performed to report the histologic examination results of regional lymph nodes of dogs and cats with oral or maxillofacial neoplasms. Twenty-eight dogs and 3 cats were evaluated. Histologic examination results of standard and serial tissue sectioning of regional lymph nodes were recorded. When available, other clinical parameters including mandibular lymph node palpation, thoracic radiographs, and pre- and postoperative fine needle aspiration of lymph nodes were compared with the histologic results. Squamous cell carcinoma, fibrosarcoma, and melanoma were the most common neoplasms diagnosed in dogs. Squamous cell carcinoma and fibrosarcoma were diagnosed in cats. Of the palpably enlarged mandibular lymph nodes, 17.0% had metastatic disease histologically. Radiographically evident thoracic metastatic disease was present in 7.4% of cases. Preoperative cytologic evaluation of the mandibular lymph node based on fine needle aspiration concurred with the histologic results in 90.5% of lymph nodes examined. Postoperative cytologic evaluation of fine needle aspirates of regional lymph nodes concurred with the histologic results in 80.6% of lymph nodes examined. Only 54.5% of cases with metastatic disease to regional lymph nodes had metastasis that included the mandibular lymph node. Serial lymph node sectioning provided additional information or metastasis detection. Cytologic evaluation of the mandibular lymph node correlates positively with histology, however results may fail to indicate the presence of regional metastasis. Assessment of all regional lymph nodes in dogs and cats with oral or maxillofacial neoplasms will detect more metastatic disease than assessing the mandibular lymph node only.

Detection of Wilms' tumor antigen--specific CTL in tumor-draining lymph nodes of patients with early breast cancer.

PubMed

Gillmore, Roopinder; Xue, Shao-An; Holler, Angelika; Kaeda, Jaspal; Hadjiminas, Dimitri; Healy, Vourneen; Dina, Roberto; Parry, Suzanne C; Bellantuono, Ilaria; Ghani, Yasmeen; Coombes, R Charles; Waxman, Jonathan; Stauss, Hans J

2006-01-01

The Wilms' tumor antigen (WT1) is overexpressed in approximately 90% of breast tumors and, thus, is a potential target antigen for the immunotherapy of breast cancer. We have tested the working hypotheses that WT1 can be immunogenic in patients with breast cancer and can stimulate CTL of sufficient avidity to kill tumor cells. Paired tumor-draining lymph node and peripheral blood samples were analyzed from five HLA-A2-positive patients with stage I/II breast cancer. Fluorescent HLA-A*0201/WT1 tetramers were used to quantify WT1-specific CTL and the functional capacity of the CTL was assessed using cytotoxicity assays and intracellular cytokine staining. WT1 tetramer-binding T cells expanded from all lymph node samples but none of the corresponding peripheral blood samples. Functional assays were carried out on T cells from the patient who had yielded the highest frequency of HLA-A*0201/WT1 tetramer-positive cells. The cytotoxicity assays showed WT1 peptide--specific killing activity of the CTL, whereas intracellular cytokine staining confirmed that the tetramer--positive T cells produced IFN-gamma after stimulation with WT1 peptide. These WT1-specific T cells killed HLA-A2-positive breast cancer cell lines treated with IFN-gamma but no killing was observed with untreated tumor cells. These results show that WT1-specific CTL can be expanded from the tumor-draining lymph nodes of breast cancer patients and that they can display peptide-specific effector function. However, the CTL only killed IFN-gamma-treated tumor targets expressing high levels of HLA-A2 and not tumor cells with low HLA expression. This suggests that induction of autologous WT1-specific CTL may offer only limited tumor protection and that strategies that allow a high level of peptide/MHC complex presentation and/or improve CTL avidity may be required.

Nothing is perfect, not even the local lymph node assay: a commentary and the implications for REACH.

PubMed

Basketter, David A; McFadden, John F; Gerberick, Frank; Cockshott, Amanda; Kimber, Ian

2009-02-01

For many regulatory authorities, the local lymph node assay (LLNA) is the preferred assay for the predictive identification of skin-sensitizing chemicals. It is the initial requirement for sensitization testing within the new REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances) regulations in the European Union. The primary reasons for the preferment of the LLNA are the animal welfare benefits it provides compared with traditional guinea-pig methods (refinement and reduction of animal usage) and the general performance characteristics of the assay with regard to overall reliability, accuracy, and interpretation. Moreover, a substantial published literature on the LLNA is available making it appropriate for use as a benchmark against which new approaches, including in vitro alternatives, can be evaluated and validated. There is, therefore, a view that the LLNA represents the 'gold standard' for skin sensitization testing. However, although this is probably correct, it is important to recognize and acknowledge that in common with all other predictive tests (whether they be validated or not), the LLNA has limitations, in addition to strengths, some of which were mentioned above. Arguably, it is the limitations (e.g., the occurrence of false positive and false negative results) of test methods that are most important to understand. With respect to the LLNA, these limitations are similar to those associated with guinea-pig skin sensitization methods. Among these are the occurrence of false positive and false negative results, susceptibility of results to changes in vehicle, and the possibility that interspecies differences may confound interpretation. In this commentary, these issues are reviewed and their impact on the utility of the LLNA for identification, classification, and potency assessment of skin sensitizers are considered. In addition, their relevance for the future development and validation of novel in vitro and in silico alternatives is explored.

Differential Motion Between Mediastinal Lymph Nodes and Primary Tumor in Radically Irradiated Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaake, Eva E.; Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam; Rossi, Maddalena M.G.

2014-11-15

Purpose/Objective: In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction. Methods and Materials: Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancermore » during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets. Results: Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and −2%, 15%, and 7% for the tumor if an online carina registration protocol replaced a protocol based on bony anatomy registration. Conclusions: Detailed analysis revealed considerable lymph node position variability, differential motion, and respiratory motion. Planning target volume margins can be reduced up to 27% in lung cancer patients when the carina registration replaces bony anatomy registration.« less

Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases

PubMed Central

Jeong, Han-Sin; Jones, Dennis; Liao, Shan; Wattson, Daniel A.; Cui, Cheryl H.; Duda, Dan G.; Willett, Christopher G.; Jain, Rakesh K.

2015-01-01

Background: To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported. Methods: Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes (n = 9–12). We further test our results in patient samples (n = 20 colon cancer patients; n = 20 head and neck cancer patients). Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW. All statistical tests were two-sided. Results: Using the CLNW, we reveal the surprising lack of sprouting angiogenesis during metastatic growth, despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases (day 10: untreated mean = 1.2%, 95% confidence interval [CI] = 0.7% to 1.7%; control mean = 0.7%, 95% CI = 0.1% to 1.3%; DC101 mean = 0.4%, 95% CI = 0.0% to 3.3%; sunitinib mean = 0.5%, 95% CI = 0.0% to 1.0%, analysis of variance P = .34). We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab (no bevacizumab group mean = 257 vessels/mm2, 95% CI = 149 to 365 vessels/mm2; bevacizumab group mean = 327 vessels/mm2, 95% CI = 140 to 514 vessels/mm2, P = .78). Conclusion: We provide preclinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, and thus reveals a new mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The targets of clinically approved angiogenesis inhibitors are not active during early cancer progression in the lymph node, suggesting that inhibitors of sprouting angiogenesis as a class will not be effective in treating lymph node metastases. PMID:26063793

The use of artificial intelligence technology to predict lymph node spread in men with clinically localized prostate carcinoma.

PubMed

Crawford, E D; Batuello, J T; Snow, P; Gamito, E J; McLeod, D G; Partin, A W; Stone, N; Montie, J; Stock, R; Lynch, J; Brandt, J

2000-05-01

The current study assesses artificial intelligence methods to identify prostate carcinoma patients at low risk for lymph node spread. If patients can be assigned accurately to a low risk group, unnecessary lymph node dissections can be avoided, thereby reducing morbidity and costs. A rule-derivation technology for simple decision-tree analysis was trained and validated using patient data from a large database (4,133 patients) to derive low risk cutoff values for Gleason sum and prostate specific antigen (PSA) level. An empiric analysis was used to derive a low risk cutoff value for clinical TNM stage. These cutoff values then were applied to 2 additional, smaller databases (227 and 330 patients, respectively) from separate institutions. The decision-tree protocol derived cutoff values of < or = 6 for Gleason sum and < or = 10.6 ng/mL for PSA. The empiric analysis yielded a clinical TNM stage low risk cutoff value of < or = T2a. When these cutoff values were applied to the larger database, 44% of patients were classified as being at low risk for lymph node metastases (0.8% false-negative rate). When the same cutoff values were applied to the smaller databases, between 11 and 43% of patients were classified as low risk with a false-negative rate of between 0.0 and 0.7%. The results of the current study indicate that a population of prostate carcinoma patients at low risk for lymph node metastases can be identified accurately using a simple decision algorithm that considers preoperative PSA, Gleason sum, and clinical TNM stage. The risk of lymph node metastases in these patients is < or = 1%; therefore, pelvic lymph node dissection may be avoided safely. The implications of these findings in surgical and nonsurgical treatment are significant.

[Peripheral lymphadenopathy in childhood--recommendations for diagnostic evaluation].

PubMed

Benesch, M; Kerbl, R; Wirnsberger, A; Stünzner, D; Mangge, H; Schenkeli, R; Deutsch, J

2000-01-01

Enlargement of peripheral lymph nodes most commonly caused by a local inflammatory process is frequently seen in childhood. The aim of the present study was to analyze the most common causes of peripheral lymphadenopathy and to develop a simple algorithm for the primary diagnostic evaluation of peripheral lymph node enlargement in this age group. Between April and September 1999 87 unselected children (median age: 5 1/2 years) with peripheral lymphadenopathy were referred to the Department of Pediatrics, University of Graz, for further investigation. EBV infection was diagnosed in 20 (23.0%) children. 19 (21.8%) patients had acute bacterial lymphadenitis. In 21 (24.1%) patients lymph node enlargement was classified as "post/parainfectious (viral)". Four patients each had toxoplasmosis and cat scratch disease. In 11 (12.6%) patients neither physical nor laboratory examinations revealed pathologic results. Among the remaining 8 children sarcoidosis and Hodgkin disease was diagnosed in one patient each. Small, soft, mobile, nontender, cervical, axillary or inguinal lymph nodes do not require further investigations. In case of enlarged, tender lymph nodes with overlying skin erythema and fever diagnostic evaluation should include complete blood count, erythrocyte sedimentation rate and/or c-reactive protein level, supplemented by appropriate antibody testing (EBV, CMV, Toxoplasma gondii, Bartonella henselae). Firm, enlarged, painless lymph nodes which are matted together and fixed to the skin or underlying tissues necessitate a more detailed diagnostic evaluation in order to exclude malignant or granulomatous diseases. Our study demonstrated that primary diagnostic evaluation of childhood peripheral lymphadenopathy is mainly based on clinical grounds. In most cases a small number of additionally performed laboratory tests allow to correctly identify the cause of the peripheral lymph node enlargement.

Occurrence of lymph node metastasis in early-stage parotid gland cancer.

PubMed

Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

2012-02-01

Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

The impact of previous para-areolar incision in the upper outer quadrant of the breast on the localization of the sentinel lymph node in a canine model

PubMed Central

Vasques, Paulo Henrique Diógenes; Pinheiro, Luiz Gonzaga Porto; de Meneses e Silva, João Marcos; de Moura Torres-de-Melo, José Ricardo; Pinheiro, Karine Bessa Porto; Rocha, João Ivo Xavier

2011-01-01

OBJECTIVES: This paper discusses the influence of a para-areolar incision in the upper outer quadrant of the breast on the location of the sentinel lymph node in a canine model. METHODS: The sentinel lymph node was marked with technetium-99, which was injected into the subareolar skin of the cranial breast. After the marker had migrated to the axilla, an arcuate para-areolar incision was performed 2 cm from the nipple in the upper outer quadrant. Patent blue dye was then injected above the upper border of the incision. At the marked site, an axillary incision was made, and the sentinel lymph node was identified by gamma probe and/or by direct visualization of the dye. The agreement between the two injection sites and the two sentinel lymph node identification methods was determined. Our sample group consisted of 40 cranial breasts of 23 adult females of the species Canis familiaris. The data were analyzed by using the McNemar test and by determining the kappa agreement coefficient. RESULT: Our findings showed that in 95% of the breasts, the sentinel lymph node was identified by the injection of technetium-99 m into the subareolar region, and in 82% of the cases, the sentinel lymph node was identified by the injection of patent blue dye above the upper border of the incision. The methods agreed 82% of the time. CONCLUSIONS: Previous para-areolar incisions in the upper outer quadrant did not interfere significantly with the biopsy when the dye was injected above the upper border of the incision. PMID:21915493

Sentinel lymph node biopsy under fluorescent indocyanin green guidance: Initial experience

PubMed Central

Aydoğan, Fatih; Arıkan, Akif Enes; Aytaç, Erman; Velidedeoğlu, Mehmet; Yılmaz, Mehmet Halit; Sager, Muhammet Sait; Çelik, Varol; Uras, Cihan

2016-01-01

Objective: Sentinel lymph node biopsy can be applied by using either blue dye or radionuclide method or both in breast cancer. Fluorescent imaging with indocyanine green is a new defined method. This study evaluates the applicability of sentinel lymph node biopsy via fluorescent indocyanine green. Material and Methods: IC-VIEW (Pulsion Medical Systems AG, Munich, Germany) infrared visualization system was used for imaging. Two mL of indocyanine green was injected to visualize sentinel lymph nodes. After injection, subcutaneous lymphatics were traced and sentinel lymph nodes were found with simultaneous imaging. Sentinel lymph nodes were excised under fluorescent light guidance, and excised lymph nodes were examined histopathologically. Patients with sentinel lymph node metastases underwent axillary dissection. Results: Four patients with sentinel lymph node biopsy due to breast cancer were included in the study. Sentinel lymph nodes were visualized with indocyanine green in all patients. The median number of excised sentinel lymph node was 2 (2–3). Two patients with lymph node metastasis underwent axillary dissection. No metastasis was detected in lymph nodes other than the sentinel nodes in patients with axillary dissection. There was no complication during and after the operation related to the method. Conclusion: According to our limited experience, sentinel lymph node biopsy under fluorescent indocyanine green guidance, which has an advantage of simultaneous visualization, is technically feasible. PMID:26985159

Clinicopathologic risk factors for right paraesophageal lymph node metastasis in patients with papillary thyroid carcinoma.

PubMed

Yu, Q A; Ma, D K; Liu, K P; Wang, P; Xie, C M; Wu, Y H; Dai, W J; Jiang, H C

2018-03-17

To investigate risk factors associated with right paraesophageal lymph node (RPELN) metastasis in patients with papillary thyroid carcinoma (PTC) and to determine the indications for right lymph node dissection. Clinicopathologic data from 829 patients (104 men and 725 women) with PTC, operated on by the same thyroid surgery team at the First Affiliated Hospital of Harbin Medical University from January 2013 to May 2017, were analyzed. Overall, 309 patients underwent total thyroidectomy with bilateral lymph node dissection, 488 underwent right thyroid lobe and isthmic resection with right central compartment lymph node dissection, and 32 underwent near-total thyroidectomy (ipsilateral thyroid lobectomy with contralateral near-total lobectomy) with bilateral lymph node dissection. The overall rate of central compartment lymph node metastasis was 43.5% (361/829), with right central compartment lymph node and RPELN metastasis rates of 35.5% (294/829) and 19.1% (158/829), respectively. Tumor size, number, invasion, and location, lymph node metastasis, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis were associated with RPELN in the univariate analysis, whereas age and sex were not. Multivariate analysis identified tumors with a diameter ≥ 1 cm, multiple tumors, tumors located in the right lobe, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis as independent risk factors for RPELN metastasis. Lymph node dissection, including RPELN dissection, should be performed for patients with PTC with a tumor diameter ≥ 1 cm, multiple tumors, right-lobe tumors, right central compartment lymph node metastasis, or suspected lateral compartment lymph node metastasis.

Categorical QSAR models for skin sensitization based on local lymph node assay measures and both ground and excited state 4D-fingerprint descriptors

NASA Astrophysics Data System (ADS)

Liu, Jianzhong; Kern, Petra S.; Gerberick, G. Frank; Santos-Filho, Osvaldo A.; Esposito, Emilio X.; Hopfinger, Anton J.; Tseng, Yufeng J.

2008-06-01

In previous studies we have developed categorical QSAR models for predicting skin-sensitization potency based on 4D-fingerprint (4D-FP) descriptors and in vivo murine local lymph node assay (LLNA) measures. Only 4D-FP derived from the ground state (GMAX) structures of the molecules were used to build the QSAR models. In this study we have generated 4D-FP descriptors from the first excited state (EMAX) structures of the molecules. The GMAX, EMAX and the combined ground and excited state 4D-FP descriptors (GEMAX) were employed in building categorical QSAR models. Logistic regression (LR) and partial least square coupled logistic regression (PLS-CLR), found to be effective model building for the LLNA skin-sensitization measures in our previous studies, were used again in this study. This also permitted comparison of the prior ground state models to those involving first excited state 4D-FP descriptors. Three types of categorical QSAR models were constructed for each of the GMAX, EMAX and GEMAX datasets: a binary model (2-state), an ordinal model (3-state) and a binary-binary model (two-2-state). No significant differences exist among the LR 2-state model constructed for each of the three datasets. However, the PLS-CLR 3-state and 2-state models based on the EMAX and GEMAX datasets have higher predictivity than those constructed using only the GMAX dataset. These EMAX and GMAX categorical models are also more significant and predictive than corresponding models built in our previous QSAR studies of LLNA skin-sensitization measures.

Lack of Evidence for Contact Sensitization by Pfiesteria Extract

PubMed Central

Patterson, Rachel M.; Noga, Edward; Germolec, Dori

2007-01-01

Background Members of the estuarine dinoflagellate genus Pfiesteria are reported to have been responsible for massive fish kills in the southeastern United States. Some reports suggest that exposure to waters having Pfiesteria blooms or occupation-related exposure might result in Pfiesteria-induced dermal irritation and inflammation. Although the toxin has not been isolated and purified, the original data suggested both hydrophilic and hydrophobic toxic components. Some investigators propose that dermonecrotic properties are associated with a hydrophobic fraction. Objectives A bioactive C18-bound putative toxin (CPE) extracted from Pfiesteria-laden aquarium water during active fish-killing conditions was examined in the present study to evaluate its potential to produce inflammation and dermal sensitization and to determine whether the inflammation and dermatitis reported in early human exposure studies were allergic or irritant in nature. Results This fraction was cytotoxic to mouse Neuro-2A cells and primary human epidermal keratinocytes (NHEK) at a concentration of 1 mg/mL. Balb/C mice exposed to 50–200% CPE by skin painting exhibited a 6–10% increase in ear swelling relative to vehicle-treated mice in a primary irritancy assay. There was no increase in lymph node cell proliferation as measured using the local lymph node assay. Exposure to CPE in culture up-regulated interleukin-8 in NHEK, whereas granulocyte macrophage–colony-stimulating factor and tumor necrosis factor α were only minimally altered. Conclusions This study suggests that CPE is cytotoxic to keratinocytes in culture at high concentrations and that it induces mild, localized irritation but not dermal sensitization. PMID:17637917

The local lymph node assay in practice: a current regulatory perspective.

PubMed

Cockshott, A; Evans, P; Ryan, C A; Gerberick, G F; Betts, C J; Dearman, R J; Kimber, I; Basketter, D A

2006-07-01

Following the formal acceptance of the local lymph node assay (LLNA) as an Organization for Economic Cooperation and Development (OECD) guideline in April 2002, the UK Health and Safety Executive (HSE) informed notifiers that this was now the method of choice for the assessment of skin sensitization potential under the EU notification scheme for new industrial chemicals (NONS). This paper summarizes the experience of the HSE for the 2-year period immediately following the issuing of this statement, during which 48 LLNA study reports were assessed for notification purposes. The issues discussed here include adherence to the OECD guideline, interpretation of results, and classification outcomes. Generally, notifying laboratories followed the OECD guideline successfully, with regard to the sex/ strain/numbers of mice used, the precise process used for measurement of cell proliferation, and the use of recommended vehicles and positive controls. Initially, use of the individual animal approach (measuring the cell proliferation in each animal rather than for a pooled dose group) highlighted problems caused by technical inexperience, but these were overcome by practice. Toxicity or irritation were found to be minor factors in dose selection; more important was the choice of vehicle to correctly maximize the test substance concentration, while maintaining appropriate application properties. Contrary to concerns that the LLNA would prove to be less sensitive or more sensitive than the traditionally used Guinea Pig Maximization Test (GPMT), the proportion of new substances classified as skin sensitizers was within the range observed in previous years. Although the sample size is relatively small, the experience of the HSE indicates that the LLNA is satisfactory for routine regulatory use.

4D-Fingerprint Categorical QSAR Models for Skin Sensitization Based on Classification Local Lymph Node Assay Measures

PubMed Central

Li, Yi; Tseng, Yufeng J.; Pan, Dahua; Liu, Jianzhong; Kern, Petra S.; Gerberick, G. Frank; Hopfinger, Anton J.

2008-01-01

Currently, the only validated methods to identify skin sensitization effects are in vivo models, such as the Local Lymph Node Assay (LLNA) and guinea pig studies. There is a tremendous need, in particular due to novel legislation, to develop animal alternatives, eg. Quantitative Structure-Activity Relationship (QSAR) models. Here, QSAR models for skin sensitization using LLNA data have been constructed. The descriptors used to generate these models are derived from the 4D-molecular similarity paradigm and are referred to as universal 4D-fingerprints. A training set of 132 structurally diverse compounds and a test set of 15 structurally diverse compounds were used in this study. The statistical methodologies used to build the models are logistic regression (LR), and partial least square coupled logistic regression (PLS-LR), which prove to be effective tools for studying skin sensitization measures expressed in the two categorical terms of sensitizer and non-sensitizer. QSAR models with low values of the Hosmer-Lemeshow goodness-of-fit statistic, χHL2, are significant and predictive. For the training set, the cross-validated prediction accuracy of the logistic regression models ranges from 77.3% to 78.0%, while that of PLS-logistic regression models ranges from 87.1% to 89.4%. For the test set, the prediction accuracy of logistic regression models ranges from 80.0%-86.7%, while that of PLS-logistic regression models ranges from 73.3%-80.0%. The QSAR models are made up of 4D-fingerprints related to aromatic atoms, hydrogen bond acceptors and negatively partially charged atoms. PMID:17226934

A comparative evaluation of in vitro skin sensitisation tests: the human cell-line activation test (h-CLAT) versus the local lymph node assay (LLNA).

PubMed

Ashikaga, Takao; Sakaguchi, Hitoshi; Sono, Sakiko; Kosaka, Nanae; Ishikawa, Makie; Nukada, Yuko; Miyazawa, Masaaki; Ito, Yuichi; Nishiyama, Naohiro; Itagaki, Hiroshi

2010-08-01

We previously developed the human cell-line activation test (h-CLAT) in vitro skin sensitisation test, based on our reported finding that a 24-hour exposure of THP-1 cells (a human monocytic leukaemia cell line) to sensitisers is sufficient to induce the augmented expression of CD86 and CD54. The aim of this study is to confirm the predictive value of h-CLAT for skin sensitisation activity by employing a larger number of test chemicals. One hundred chemicals were selected, according to their categorisation in the local lymph node assay (LLNA), as being: extreme, strong, moderate and weak sensitisers, and non-sensitisers. The correlation of the h-CLAT results with the LLNA results was 84%. There were some false negatives (e.g. benzoyl peroxide, hexyl cinnamic aldehyde) and some false positives (e.g. 1-bromobutane, diethylphthalate). Eight out of the 9 false negatives (89%) were water-insoluble chemicals. The h-CLAT could positively predict not only extreme and strong sensitisers, but also moderate and weak sensitisers, though the detection rates of weak sensitisers and non-sensitisers were comparatively low. Some sensitisers enhanced both CD86 and CD54 levels, and some enhanced the level of only one of them. The use of the combination of CD86 and CD54 induction as a positive indicator, improved the accuracy of the test. In conclusion, the h-CLAT is expected to be a useful cell-based in vitro method for predicting skin sensitisation potential. 2010 FRAME.

Sentinel Lymph Nodes for Breast Carcinoma: A Paradigm Shift.

PubMed

Maguire, Aoife; Brogi, Edi

2016-08-01

-Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.

[Skin sensitization of 3, 4-bis (4'-aminofurazano-3') furoxan in mice evaluated by BrdU-ELISA local lymph node assay].

PubMed

Wang, H; Gao, J H; Liu, Z Y; Yue, H; Gao, Y C; Xue, Z; Zhang, Z Z; Zhou, Y S

2016-08-20

Objective: To investigate skin sensitization of 3, 4-bis (4'-aminofurazano-3') furoxan (DATF) in mice using 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay (BrdU-ELISA) . Methods: A total of 30 specific pathogen-free BALB/C mice were randomly divided into high-, medium-, and low-dose DATF groups, positive control group, and solvent control group, with six mice in each group. The mice in the high-, medium-, and low-dose DATF groups were treated with 50%, 25%, and 10% (0.5, 0.25, and 0.10 g/ml) DATF solution, those in the positive control group were treated with 1% 2, 4-dinitrochlorobenzol (DNCB) , and those in the solvent control group were treated with acetone/olive oil (4∶1) . After treatment, retroauricular lymph nodes were collected and cell suspension was prepared. ELISA was used to measure the level of cell proliferation after the addition of 5-bromo-2'-deoxyuridine (BrdU) , and the BrdU labeling index (LI) and test substance concentration at a stimulation index (SI) of 1.6 (EC 1.6 ) were calculated. Results: There were no significant differences in auricular thickness between groups ( P >0.05) , and DAFT did not have skin irritation. Compared with the solvent control group, the high-dose DATF group and the positive control group showed significant increases in the weight of lymph nodes ( P <0.05) . Compared with the solvent control group, all the other groups showed significant increases in BrdU LI ( P <0.01) . The low-, medium-, and high-dose DATF groups had SIs of 6.1, 8.8, and 12.1, respectively, and the EC 1.6 of DATF was 2.2%, which suggested that DATF had strong sensitization. Conclusion: DATF has strong skin sensitization in mice, with reference to the guideline of Organization for Economic Co-operation and Development Item No. 442B (OECD TG 442B) .

Prognostic value of lymph node involvement in oral cancers: a study of 137 cases.

PubMed

Tankéré, F; Camproux, A; Barry, B; Guedon, C; Depondt, J; Gehanno, P

2000-12-01

The aim of this study was to assess the prognostic value of lymph node involvement in patients with squamous cell carcinoma of the oral cavity. Retrospective study of 137 patients with T4 squamous cell carcinoma of the oral cavity treated by surgery and radiotherapy (84 N0, 23 N1, 16 N2,14 N3). Twenty-three patients in the N0 group had a history of surgery or radiotherapy. One hundred fourteen patients underwent limited or radical neck dissection unilaterally or bilaterally. The histological charts were reviewed and correlated with preoperative lymph node clinical stage. The local failure rate and the overall survival curves were calculated with respect to clinical and histological stages. The causes of death were analyzed. No evidence of lymph node metastasis was found in 47.4% of cases (54 of 114 patients). Among the node-positive (N+) patients, 39 had rupture of the lymph node capsule (R+). In the N0 group, 27.8% of patients were N+. Regional control rates after surgery and radiotherapy were 95% at 1 year and 85.4% at 5 years. The local failure rates were 6% in N0, 8.7% in N1, 31.2% in N2, 51.7% in N3, 9% in node-negative (N-), and 29% in N+R+ patients. The overall survival rates at 3 and 5 years were, respectively, 44.7% and 34.8% in the N0 group, 37.7% and 37.7% (same rate at 3 and 5 years) in the N1 group, and 31.2% and 15.8% in the N2 group. None of the patients in the N3 group survived beyond 2 years. The overall survival rates at 5 years were 42.8% and 17.5% in the N- and N+ groups, respectively. In patients with locally advanced tumors (T4), clinical nodal status and histological nodal invasion were key prognostic factors. The presence of occult metastases in the N0 group justifies routine neck dissection.

Definition and automatic anatomy recognition of lymph node zones in the pelvis on CT images

NASA Astrophysics Data System (ADS)

Liu, Yu; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Guo, Shuxu; Attor, Rosemary; Reinicke, Danica; Torigian, Drew A.

2016-03-01

Currently, unlike IALSC-defined thoracic lymph node zones, no explicitly provided definitions for lymph nodes in other body regions are available. Yet, definitions are critical for standardizing the recognition, delineation, quantification, and reporting of lymphadenopathy in other body regions. Continuing from our previous work in the thorax, this paper proposes a standardized definition of the grouping of pelvic lymph nodes into 10 zones. We subsequently employ our earlier Automatic Anatomy Recognition (AAR) framework designed for body-wide organ modeling, recognition, and delineation to actually implement these zonal definitions where the zones are treated as anatomic objects. First, all 10 zones and key anatomic organs used as anchors are manually delineated under expert supervision for constructing fuzzy anatomy models of the assembly of organs together with the zones. Then, optimal hierarchical arrangement of these objects is constructed for the purpose of achieving the best zonal recognition. For actual localization of the objects, two strategies are used -- optimal thresholded search for organs and one-shot method for the zones where the known relationship of the zones to key organs is exploited. Based on 50 computed tomography (CT) image data sets for the pelvic body region and an equal division into training and test subsets, automatic zonal localization within 1-3 voxels is achieved.

Factors affecting sentinel lymph node metastasis in Turkish breast cancer patients: Predictive value of Ki-67 and the size of lymph node.

PubMed

Ozemir, I A; Orhun, K; Eren, T; Baysal, H; Sagiroglu, J; Leblebici, M; Ceyran, A B; Alimoglu, O

We aimed to analyze the factors that affect the axillary lymph node involvement in Turkish breast cancer patients with clinically non-palpable axillary lymph node. Sentinel lymph node biopsy is the gold standard technique to evaluate the axillary lymph node status that directly influences the prognosis and the treatment options in breast cancer. Breast cancer patients without axillary lymph node involvement in clinic examination were enrolled the study. Patients were categorized into the two groups according to existence of axillary lymph node metastasis or not. Demographic, histopathological and clinical data of patients were revealed retrospectively. One-hundred and eighty-seven patients were analyzed and 101 of patients fulfilled the criteria and were included the study. Metastatic lymph node was detected in 38 (37.6 %) patients (Group 1), and was negative in 63 (62.4 %) patients (Group 2). Sentinel lymph node metastasis were statistically significant higher in patients with Ki-67 ≥ 14 % than patients with Ki-67 < 14 % (51.9 % vs 22.4 %; p < 0.01). Likewise, the mean size of the sentinel lymph node was statistically significant higher in Group 1 compared to Group 2 (p < 0.01). Ki-67 proliferation index and sentinel lymph node size may provide a higher prediction about the sentinel lymph node involvement in patients with clinically negative axillary lymph nodes (Tab. 3, Fig. 1, Ref. 31).

Early diagnosis of lymph node metastasis: Importance of intranodal pressures.

PubMed

Miura, Yoshinobu; Mikada, Mamoru; Ouchi, Tomoki; Horie, Sachiko; Takeda, Kazu; Yamaki, Teppei; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

2016-03-01

Regional lymph node status is an important prognostic indicator of tumor aggressiveness. However, early diagnosis of metastasis using intranodal pressure, at a stage when lymph node size has not changed significantly, has not been investigated. Here, we use an MXH10/Mo-lpr/lpr mouse model of lymph node metastasis to show that intranodal pressure increases in both the subiliac lymph node and proper axillary lymph node, which are connected by lymphatic vessels, when tumor cells are injected into the subiliac lymph node to induce metastasis to the proper axillary lymph node. We found that intranodal pressure in the subiliac lymph node increased at the stage when metastasis was detected by in vivo bioluminescence, but when proper axillary lymph node volume (measured by high-frequency ultrasound imaging) had not increased significantly. Intravenously injected liposomes, encapsulating indocyanine green, were detected in solid tumors by in vivo bioluminescence, but not in the proper axillary lymph node. Basic blood vessel and lymphatic channel structures were maintained in the proper axillary lymph node, although sinus histiocytosis was detected. These results show that intranodal pressure in the proper axillary lymph node increases at early stages when metastatic tumor cells have not fully proliferated. Intranodal pressure may be a useful parameter for facilitating early diagnosis of lymph node metastasis. © 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Frequency of an accessory popliteal efferent lymphatic pathway in dogs.

PubMed

Mayer, Monique N; Sweet, Katherine A; Patsikas, Michael N; Sukut, Sally L; Waldner, Cheryl L

2018-05-01

Staging and therapeutic planning for dogs with malignant disease in the popliteal lymph node are based on the expected patterns of lymphatic drainage from the lymph node. The medial iliac lymph nodes are known to receive efferent lymph from the popliteal lymph node; however, an accessory popliteal efferent pathway with direct connection to the sacral lymph nodes has also been less frequently reported. The primary objective of this prospective, anatomic study was to describe the frequency of various patterns of lymphatic drainage of the popliteal lymph node. With informed client consent, 50 adult dogs with no known disease of the lymphatic system underwent computed tomographic lymphography after ultrasound-guided, percutaneous injection of 350 mg/ml iohexol into a popliteal lymph node. In all 50 dogs, the popliteal lymph node drained directly to the ipsilateral medial iliac lymph node through multiple lymphatic vessels that coursed along the medial thigh. In 26% (13/50) of dogs, efferent vessels also drained from the popliteal lymph node directly to the internal iliac and/or sacral lymph nodes, coursing laterally through the gluteal region and passing over the dorsal aspect of the pelvis. Lymphatic connections between the right and left medial iliac and right and left internal iliac lymph nodes were found. Based on our findings, the internal iliac and sacral lymph nodes should be considered when staging or planning therapy for dogs with malignant disease in the popliteal lymph node. © 2018 American College of Veterinary Radiology.

Prognostic value of total number of lymph nodes retrieved differs between left-sided colon cancer and right-sided colon cancer in stage III patients with colon cancer.

PubMed

Yang, Lin; Xiong, Zhenchong; Xie, Qiankun; He, Wenzhuo; Liu, Shousheng; Kong, Pengfei; Jiang, Chang; Guo, Guifang; Xia, Liangping

2018-05-11

The consensus is that a minimum of 12 lymph nodes should be analyzed at colectomy for colon cancer. However, right colon cancer and left colon cancer have different characteristics, and this threshold value for total number of lymph nodes retrieved may not be universally applicable. The data of 63,243 patients with colon cancer treated between 2004 and 2012 were retrieved from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Multivariate Cox regression analysis was used to determine the predictive value of total number of lymph nodes for survival after adjusting for lymph nodes ratio. The predictive value in left-sided colon cancer and right-sided colon cancer was compared. The optimal total number of lymph nodes cutoff value for prediction of overall survival was identified using the online tool Cutoff Finder. Survival of patients with high total number of lymph nodes (≥12) and low total number of lymph nodes (< 12) was compared by Kaplan-Meier analysis. After stratifying by lymph nodes ratio status, total number of lymph nodes≥12 remained an independent predictor of survival in the whole cohort and in right-sided colon cancer, but not in left-sided colon cancer. The optimal cutoff value for total number of lymph nodes was determined to be 11. Low total number of lymph nodes (< 11) was associated with significantly poorer survival after adjusting for lymph nodes ratio in all subgroups except in the subgroup with high lymph nodes ratio (0.5-1.0). Previous reports of the prognostic significance of total number of lymph nodes on node-positive colon cancer were confounded by lymph nodes ratio. The 12-node standard for total number of lymph nodes may not be equally applicable in right-sided colon cancer and left-sided colon cancer.

Factors Predictive of Sentinel Lymph Node Involvement in Primary Breast Cancer.

PubMed

Malter, Wolfram; Hellmich, Martin; Badian, Mayhar; Kirn, Verena; Mallmann, Peter; Krämer, Stefan

2018-06-01

Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in patients with early-stage breast cancer. The need for therapeutic ALND is the subject of ongoing debate especially after the publication of the ACOSOG Z0011 trial. In a retrospective trial with univariate and multivariate analyses, factors predictive of sentinel lymph node involvement should be analyzed in order to define tumor characteristics of breast cancer patients, where SLNB should not be spared to receive important indicators for adjuvant treatment decisions (e.g. thoracic wall irradiation after mastectomy with or without reconstruction). Between 2006 and 2010, 1,360 patients with primary breast cancer underwent SLNB with/without ALND with evaluation of tumor localization, multicentricity and multifocality, histological subtype, tumor size, grading, lymphovascular invasion (LVI), and estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status. These characteristics were retrospectively analyzed in univariate and multivariate logistic regression models to define significant predictive factors for sentinel lymph node involvement. The multivariate analysis demonstrated that tumor size and LVI (p<0.001) were independent predictive factors for metastatic sentinel lymph node involvement in patients with early-stage breast cancer. Because of the increased risk for metastatic involvement of axillary sentinel nodes in cases with larger breast cancer or diagnosis of LVI, patients with these breast cancer characteristics should not be spared from SLNB in a clinically node-negative situation in order to avoid false-negative results with a high potential for wrong indication of primary breast reconstruction or wrong non-indication of necessary post-mastectomy radiation therapy. The prognostic impact of avoidance of axillary staging with SLNB is analyzed in the ongoing prospective INSEMA trial. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Sentinel Lymph Nodes for Breast Carcinoma A Paradigm Shift

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

Context Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. Objective To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. Data Sources Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. Conclusions The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin–stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non–sentinel lymph node involvement. This information is important to decide on further axillary treatment. PMID:27472237

International Registry for Patients With Castleman Disease

ClinicalTrials.gov

2017-07-12

Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymph Node Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH; Hyperplasia, Giant Lymph Node; Lymph Node Hyperplasia, Giant

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

PubMed Central

Sgourakis, George; Gockel, Ines; Lang, Hauke

2013-01-01

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. “Neural networks” as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the “feature selection and root cause analysis”, was used to identify the most important predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559), P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206 ± 0.6249 vs SCC: 4.1356 ± 0.4038, P < 0.05). The odds for re-classification of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC, respectively. Local tumor recurrence was best predicted by grade 3 differentiation and piecemeal resection, metachronous cancer development by the carcinoma in situ component, and lymph node positivity by lymphovascular invasion. With regard to surgically resected patients: Significant differences in patients with positive lymph nodes were observed between ADC and SCC [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P < 0.01). In contrast, lymphovascular and microvascular invasion and grade 3 patients between histologic types were comparable, the respective rank order of the predictors of lymph node positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type (ADC/SCC) was not included in the model. The best predictors for SCC lymph node positivity were Sm3 invasion and (V+). For ADC, the most important predictor was (L+). CONCLUSION: Local tumor recurrence is predicted by grade 3, metachronous cancer by the carcinoma in-situ component, and lymph node positivity by L+. T1b cancer should be treated with surgical resection. PMID:23539431

[The Role of Supraclavicular lymph node dissection in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis].

PubMed

Zhang, W; Qi, X M; Chen, A X; Zhang, P; Cao, X C; Xiao, C H

2017-05-23

Objective: In this study, we evaluated the effect of supraclavicular lymph node dissection in breast cancer patients who presented with ipsilateral supraclavicular lymph node metastasis (ISLM) without distant metastasis. Methods: A total of 90 patients with synchronous ISLM without distant metastasis between 2000 and 2009 were retrospectively analyzed. Patients were retrospectively divided into two groups, namely supraclavicular lymph node dissection group(34 patients) and non-dissection group(56 patients), according to whether they underwentsupraclavicular lymph node dissection or not.The Kaplan-Meier method was applied to analyze the locoregional relapse free survival (LRFS) and overall survival(OS). Results: Median follow-upwas 85 months(range, 6 to 11 months). Local recurrence in 32 cases, 47 cases of distant metastasis, of which 25 patients were accompanied by both locoregional relapse and distant metastasis. Of the 32 patients with locoregional relapse, 11 patients were in the lymph node dissection group and 21 patients in the control group. Of the 47 patients with distant metastases, 17 were treated with lymph node dissection, 30 in the control group. Thirty-two patients died in the whole group and 16 patients underwentlymph node dissection and 16 patients didn't. There was no significant difference between the rate of 5-year LRFS and 5-year OS ( P =0.359, P =0.246). For patients of ER negative, the 5-year loco-regional relapse free survival rates were 63.7% and 43.3% in supraclavicular lymph node dissection group and control group, respectively. The 5-year overall survival rates were 52.1% and 52.3%, respectively, and there were no statistically significant differences ( P =0.118, P =0.951). For patients of PR negative, the 5-yearloco-regional relapse free rates were 59.8% and 46.2%, respectively, and the 5-year overall survival rates were 50.6% and 43.2%, respectively, and there was no significant difference between the two groups ( P =0.317, P =0.973). The 5-year recurrence-free survival rates of human epidermal growth factor receptor 2 (HER2)-positive patients were 61.2% and 48.0%( P =0.634), respectively, and the 5-year overall survival rates were 37.2% and 65.4%( P =0.032). Forty-seven patients suffered distant metastases and the 5-year metastases free survival rates were 37.3% and 38.5% in supraclavicular lymph node dissection group and control group, respectively. Conclusion: Supraclavicular lymph node dissection maybe an effective approach to improve the loco-regional control for the patients with ISLM, especially for ER negative and PR negative subtypes, but it might has adverseeffects for the patients with negative HER2 status.

Management of Axillary Lymph Nodes in Breast Cancer

PubMed Central

Brenin, David R.; Morrow, Monica; Moughan, Jennifer; Owen, Jean B.; Wilson, J. Frank; Winchester, David P.

1999-01-01

Objective To determine the rates of axillary lymph node dissection (ALND) and axillary irradiation (AI) in patients with breast cancer and to identify the factors influencing them. Summary Background Data Routine performance of ALND in the treatment of breast cancer has become controversial. AI has been proposed as an alternative to ALND, and it has been suggested that AI in addition to ALND may decrease local failure in high-risk patients. Methods A joint study was conducted by the Commission on Cancer of the American College of Surgeons and the American College of Radiology. A total of 17,151 patients with stage I and II breast cancer treated at 819 institutions in 1994 were studied. Results A total of 15,992 patients underwent ALND (93%). The mean ages of patients who did and did not undergo ALND were 60.4 and 73.0 years. Univariate analysis demonstrated significantly decreased rates of ALND for women age 70 or older (86%vs. 97%), patients with clinical T1a tumors (81%vs. 93%), grade I histology (90%vs. 95%), and patients with favorable tumor types (88%vs. 94%). The ALND rate did not vary between palpable and nonpalpable tumors. Multivariate analysis of variables affecting the rate of ALND identified type of surgery, age, tumor size, histology, and payer status as significant. A total of 889 patients received AI. Patients not undergoing ALND were more likely to receive AI (10%vs. 5%). A total of 1.6% of patients with no lymph node metastasis underwent AI, 8.9% of those with one to three positive nodes underwent AI, 24.0% of those with four to nine positive lymph nodes underwent AI, and 29.9% of those with ≥10 positive lymph nodes underwent AI. Multivariate analysis of variables affecting the proportion of patients who received AI and had undergone ALND identified nodal status and type of surgery as significant. Conclusions Axillary lymph node dissection continues to be routinely applied in the treatment of breast cancer, and AI remains underused in patients at high risk for local regional relapse. PMID:10561093

Anatomical classification of breast sentinel lymph nodes using computed tomography-lymphography.

PubMed

Fujita, Tamaki; Miura, Hiroyuki; Seino, Hiroko; Ono, Shuichi; Nishi, Takashi; Nishimura, Akimasa; Hakamada, Kenichi; Aoki, Masahiko

2018-05-03

To evaluate the anatomical classification and location of breast sentinel lymph nodes, preoperative computed tomography-lymphography examinations were retrospectively reviewed for sentinel lymph nodes in 464 cases clinically diagnosed with node-negative breast cancer between July 2007 and June 2016. Anatomical classification was performed based on the numbers of lymphatic routes and sentinel lymph nodes, the flow direction of lymphatic routes, and the location of sentinel lymph nodes. Of the 464 cases reviewed, anatomical classification could be performed in 434 (93.5 %). The largest number of cases showed single route/single sentinel lymph node (n = 296, 68.2 %), followed by multiple routes/multiple sentinel lymph nodes (n = 59, 13.6 %), single route/multiple sentinel lymph nodes (n = 53, 12.2 %), and multiple routes/single sentinel lymph node (n = 26, 6.0 %). Classification based on the flow direction of lymphatic routes showed that 429 cases (98.8 %) had outward flow on the superficial fascia toward axillary lymph nodes, whereas classification based on the height of sentinel lymph nodes showed that 323 cases (74.4 %) belonged to the upper pectoral group of axillary lymph nodes. There was wide variation in the number of lymphatic routes and their branching patterns and in the number, location, and direction of flow of sentinel lymph nodes. It is clinically very important to preoperatively understand the anatomical morphology of lymphatic routes and sentinel lymph nodes for optimal treatment of breast cancer, and computed tomography-lymphography is suitable for this purpose.

Variant allele of CHEK2 is associated with a decreased risk of esophageal cancer lymph node metastasis in a Chinese population.

PubMed

Gu, Haiyong; Qiu, Wanshan; Wan, Ying; Ding, Guowen; Tang, Weifeng; Liu, Chao; Shi, Yijun; Chen, Yijang; Chen, Suocheng

2012-05-01

Growing evidence suggests that the checkpoint kinase 2 (CHEK2) signaling pathway occupies a central position in the signaling networks of DNA-damage signaling. Many functional and molecular epidemiological studies have evaluated the association between genetic variants of CHEK2 and various cancers. To evaluate the relationship between CHEK2 functional genetic variants and esophageal cancer risk and the risk of lymph node metastasis among a Chinese population. We genotyped CHEK2 rs738722, rs2236141 and rs2236142 single nucleotide polymorphisms (SNPs) using the matrix assisted laser desorption/ionization time-of-flight mass spectrometry assay in a case-controlled study, including 380 esophageal cancer cases and 380 healthy controls in a Chinese population. We found that none of the three polymorphisms achieved significant difference in their distributions between esophageal cancer cases and controls. Multiple logistic regression analyses revealed that esophageal cancer risk was not associated significantly with the variant genotypes of the three CHEK2 polymorphisms as compared with their wild-type genotypes. However, we found that functional variant rs738722 and rs2236142 in CHEK2 might contribute to susceptibility to lymph node metastasis. Our data did not support a significant association between CHEK2 SNPs and the risk of esophageal cancer. Functional variant CHEK2 rs738722 and rs2236142 might contribute to lymph node metastasis susceptibility. The CT allele of SNP rs738722 and the GC allele of SNP rs2236142 might be a protective factor of the risk for lymph node metastasis of esophageal cancer.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update

PubMed Central

Krop, Ian; Ismaila, Nofisat; Andre, Fabrice; Bast, Robert C.; Barlow, William; Collyar, Deborah E.; Hammond, M. Elizabeth; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Wolff, Antonio C.; Stearns, Vered

2018-01-01

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor–positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki. PMID:28692382

Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

PubMed

Harris, M; Patenaude, P; Cooperberg, P; Filipenko, D; Thorne, A; Raboud, J; Rae, S; Dailey, P; Chernoff, D; Todd, J; Conway, B; Montaner, J S

1997-11-01

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

Impact of affected lymph nodes on long-term outcome after surgical therapy of alveolar echinococcosis.

PubMed

Hillenbrand, Andreas; Beck, Annika; Kratzer, Wolfgang; Graeter, Tilmann; Barth, Thomas F E; Schmidberger, Julian; Möller, Peter; Henne-Bruns, Doris; Gruener, Beate

2018-06-16

Alveolar echinococcosis (AE) is a life-threatening helminthic disease. In humans, AE mostly affects the liver; the regional hepatic lymph nodes may be involved, indicating dissemination of AE from the liver. To achieve complete removal of the disease, enlarged hepatic lymph nodes may be resected during surgical treatment. We evaluated the frequency of affected lymph nodes by conventional microscopic and immunohistochemical analyses including detection of small particles of Echinococcus multilocularis (spem). Furthermore, we analyzed the association of resection of enlarged and affected lymph nodes with long-term outcome after surgical therapy of patients who underwent surgery with curative intent. We identified 43 patients who underwent hepatic surgery with curative intent with lymph node resection for AE. We analyzed the cohort for the manifestation of the parasite in the resected lymph nodes by conventional histology and by immunohistochemistry and compared these data with the further course of AE. Microscopically infected lymph nodes (laminar layer visible) were found in 7 out of these 43 patients (16%). In more than three quarters (25/32) of all specimens investigated, lymph nodes showed spems when stained with antibody against Em2G11, a monoclonal antibody specific for the Em2 antigen of the Echinococcus multilocularis metacestode. Most frequently, lymph nodes were resected due to enlargement. The median size of microscopically affected lymph nodes was 2 cm (range, 1.2 to 2.5 cm), the median size of immunohistochemically and non-affected lymph nodes was 1.3 cm each (range, "small" to 2.3 or 2.5 cm, respectively). Median follow-up was 8 years for all patients, 5 years for patients with lymph node resection, and 4 years for patients with infested lymph nodes. Overall, recurrent disease was seen in ten patients (10/109; 9%) after a median period of 1.5 years (range, 4 months to 4 years). None of the seven patients with conventionally microscopically affected lymph nodes suffered from recurrent disease. One patient with negative resected nodes and one patient with spems showed recurrent disease after 4 and 35 months, respectively. Lymph node involvement in AE is frequent, particularly when evaluated by immunohistochemical examination of lymph nodes with the monoclonal antibody Em2G11. Affected lymph nodes tend to be larger in size. Lymph node involvement is not associated with recurrent disease and therefore warrants further analysis of the biological significance of lymph node involvement.

Ultrasonography of the medial iliac lymph nodes in the dog.

PubMed

Llabrés-Díaz, Francisco J

2004-01-01

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

Molecular mechanisms of lymphocyte extravasation. II. Studies of in vitro lymphocyte adherence to high endothelial venules.

PubMed

Braaten, B A; Spangrude, G J; Daynes, R A

1984-07-01

Lymphocyte migration from the blood into the lymph nodes in most species occurs across post-capillary high endothelial venules (HEV). In a previous study, we proposed that lymphocyte extravasation involves receptor-mediated binding followed by adenylate cyclase-dependent activation of lymphocyte motility. This hypothesis was, in part, based on observations of in vitro lymphocyte adherence to HEV by employing pertussigen, which is a known inhibitor of lymphocyte recirculation. In vitro lymphocyte-HEV binding requires a cold (6 degrees C) incubation step and binding is poor to nil if the assay is attempted at room (23 degrees C) or physiologic temperature. We decided to investigate why this assay is temperature restricted, because of the possibility that pertussigen or fucoidin -treated lymphocytes might interact with HEV differently at higher temperatures. We now report that O.C.T. compound (OCT), the embedding matrix generally used to cut frozen lymph node sections, is toxic to lymphocytes at temperatures above 6 degrees C. Exclusion of OCT from the assay system will allow lymphocyte-HEV binding to occur at 23 degrees C and to a lesser extent at 37 degrees C. With this modified protocol, lymphocytes treated with either pertussigen, fucoidin , or neuraminidase were tested for adherence to HEV at 23 degrees C. No essential difference in binding properties was observed from what had been reported at 6 degrees C. In contrast, trypsin-treated lymphocytes that did not bind to HEV with the standard technique at 6 degrees C did adhere to a minimal extent to HEV at 23 degrees C using the modified procedure. We also report some preliminary work, using the modified assay, on in vitro lymphocyte-HEV binding of rat, rabbit, and guinea pig lymphocytes to sections of lymph nodes from the respective species.

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

PubMed

Lee, Young Chan; Na, Se Young; Park, Gi Cheol; Han, Ju Hyun; Kim, Seung Woo; Eun, Young Gyu

2017-02-01

The impact of occult lymph node metastasis on regional recurrence after prophylactic central neck dissection for preoperative, nodal-negative papillary thyroid cancer is controversial. We investigated risk factors for regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Analysis was according to clinicopathologic characteristics and occult lymph node metastasis patterns. This multicenter study enrolled 211 consecutive patients who underwent total thyroidectomy with bilateral prophylactic central neck dissection for papillary thyroid cancer without evidence of central lymph node metastasis on preoperative imaging. Clinicopathologic features and central lymph node metastasis patterns were analyzed for predicting regional recurrence. Multivariate Cox regression analysis was used to identify independent factors for recurrence. Median follow-up time was 43 months (24-95 months). Ten patients (4.7%) showed regional lymph node recurrence. The estimated 5-year, regional recurrence-free survival was 95.2%. Tumor size ≥1 cm, central lymph node metastasis, lymph node ratio, and prelaryngeal lymph node metastasis were associated with regional recurrence in univariate analysis (P < .05). In multivariate analysis, a lymph node ratio ≥ 0.26 was a significant risk factor for regional lymph node recurrence (odds ratio = 11.63, P = .003). Lymph node ratio ≥ 0.26 was an independent predictor of worse recurrence-free survival on Cox regression analysis (hazard ratio = 11.49, P = .002). Although no significant association was observed between the presence of occult lymph node metastasis and regional recurrence, lymph node ratio ≥ 0.26 was an independent predictor of regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Copyright © 2016 Elsevier Inc. All rights reserved.

German, Austrian and Swiss consensus conference on the diagnosis and local treatment of the axilla in breast cancer.

PubMed

Hoffmann, Jürgen; Souchon, Rainer; Lebeau, Annette; Öhlschlegel, Christian; Gruber, Günther; Rageth, Christoph; Weber, Walter; Harbeck, Nadia; Janni, Wolfgang; Kreipe, Hans; Fitzal, Florian; Resch, Alexandra; Bago-Horvath, Zsuzsanna; Peintinger, Florentia

2013-07-01

The German, Austrian and Swiss (D.A.CH) Societies of Senology gathered together in 2012 to address dwelling questions regarding axillary clearance in breast cancer patients. The Consensus Panel consisted of 14 members of these societies and included surgical oncologists, gynaecologists, pathologists and radiotherapists. With regard to omitting axillary lymph node dissection in sentinel lymph node macrometastases, the Panel consensually accepted this option for low-risk patients only. A simple majority voted against extending radiotherapy to the axilla after omitting axillary dissection in N1 disease. Consensus was yielded for the use of axillary ultrasound and prospective registers for such patients in the course of follow-up. The questions regarding neoadjuvant therapy and the timing of sentinel lymph node biopsy failed to yield consensus, yet both options (before or after) are possible in clinically node-negative disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lymph Node Assessment in Endometrial Cancer: Towards Personalized Medicine

PubMed Central

Vidal, Fabien; Rafii, Arash

2013-01-01

Endometrial cancer (EC) is the most common malignancy of the female reproductive tract and is increasing in incidence. Lymphovascular invasion and lymph node (LN) status are strong predictive factors of recurrence. Therefore, the determination of the nodal status of patients is mandatory to optimally tailor adjuvant therapies and reduce local and distant recurrences. Imaging modalities do not yet allow accurate lymph node staging; thus pelvic and aortic lymphadenectomies remain standard staging procedures. The clinical data accumulated recently allow us to define low- and high-risk patients based on pre- or peroperative findings that will allow the clinician to stratify the patients for their need of lymphadenectomies. More recently, several groups have been introducing sentinel node mapping with promising results as an alternative to complete lymphadenectomy. Finally, the use of peroperative algorithm for risk determination could improve patient's staging with a reduction of lymphadenectomy-related morbidity. PMID:24191159

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

PubMed Central

Goldstein, Lori J.; Gray, Robert; Badve, Sunil; Childs, Barrett H.; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L.; Ravdin, Peter M.; Davidson, Nancy E.; Sledge, George W.; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Sparano, Joseph A.

2008-01-01

Purpose Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. Patients and Methods A sample of 465 patients with hormone receptor (HR) –positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Results Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). Conclusion The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments. PMID:18678838

Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.

PubMed

Goldstein, Lori J; Gray, Robert; Badve, Sunil; Childs, Barrett H; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L; Ravdin, Peter M; Davidson, Nancy E; Sledge, George W; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Sparano, Joseph A

2008-09-01

Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

PubMed

Hou, Fenxia; Xing, Caihong; Li, Bin; Cheng, Juan; Chen, Wei; Zhang, Man

2015-01-01

Allergic contact dermatitis (ACD) is a skin disease characterized by eczema and itching. A considerable proportion of chemicals induce ACD in humans. More than 10,000 substances should be tested for skin sensitization potential under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation. The Local Lymph Node Assay (LLNA) has been designated as the first-choice in vivo assay for sensitization testing by REACH. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the LLNA. For both the LLNA and the LLNA:BrdU-ELISA, CBA/JN mouse is the preferred mouse strain recommended in the regulatory guidelines. However, the availability of CBA/JN mouse in China is only limited to a few animal suppliers, which makes the mouse difficult to obtain. BALB/c mouse, which is widely commercially available, is considered for alternative use but it can only be used in the assay after it has been evaluated by formal validation study. Thus, a validation study was conducted in our laboratory to determine if BALB/c mouse could also be used in the LLNA:BrdU-ELISA. Forty-three test substances including 32 LLNA sensitizers and 11 LLNA non-sensitizers, their vehicles and each concentration used were the same as that used in the formal validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. Female BALB/c mice of 8-10 weeks old were randomly allocated to groups (four mice per group). The test substance (25 μl) or the vehicle alone was applied to the dorsum of both ears daily for 3 consecutive days. A single intraperitoneal injection of 0.5 ml of BrdU (10mg/ml) solution was given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was excised, weighed and stored at -20°C until BrdU-ELISA was conducted. This validation study for the LLNA:BrdU-ELISA using BALB/c mouse correctly identified 30 of 31 sensitizers and 8 of 11 non-sensitizers. The accuracy, sensitivity, specificity, false positive rate, false negative rate, positive predictivity values and negative predictivity values in this study, which could indicate the performance of the LLNA:BrdU-ELISA using BALB/c mouse, were not different statistically from that of the validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. This validation study indicates that BALB/c mouse could be used alternatively in the LLNA:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals. Copyright © 2015 Elsevier Inc. All rights reserved.

RTOG GU Radiation Oncology Specialists Reach Consensus on Pelvic Lymph Node Volumes for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A.F.; Michalski, Jeff; El-Naqa, Issam

2009-06-01

Purpose: Radiation therapy to the pelvic lymph nodes in high-risk prostate cancer is required on several Radiation Therapy Oncology Group (RTOG) clinical trials. Based on a prior lymph node contouring project, we have shown significant disagreement in the definition of pelvic lymph node volumes among genitourinary radiation oncology specialists involved in developing and executing current RTOG trials. Materials and Methods: A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data were presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop clinical target volume (CTV) pelvic lymphmore » node consensus. Results: Consensus was obtained resulting in computed tomography image-based pelvic lymph node CTVs. Based on this consensus, the pelvic lymph node volumes to be irradiated include: distal common iliac, presacral lymph nodes (S{sub 1}-S{sub 3}), external iliac lymph nodes, internal iliac lymph nodes, and obturator lymph nodes. Lymph node CTVs include the vessels (artery and vein) and a 7-mm radial margin being careful to 'carve out' bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on dose-volume histogram constraints for OARs was also attained. Conclusions: Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based computed tomography images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.« less

Confirmation of Sentinel Lymph Node Identity by Analysis of Fine-Needle Biopsy Samples Using Inductively Coupled Plasma–Mass Spectrometry

PubMed Central

Beavis, Alison; Dawson, Michael; Doble, Philip; Scolyer, Richard A.; Bourne, Roger; Li, Ling-Xi L.; Murali, Rajmohan; Stretch, Jonathan R.; Lean, Cynthia L.; Uren, Roger F.

2008-01-01

Background The sentinel lymph node (SLN) biopsy technique is a reliable means of determining the tumor-harboring status of regional lymph nodes in melanoma patients. When technetium 99 m-labeled antimony trisulfide colloid (99 mTc-Sb2S3) particles are used to perform preoperative lymphoscintigraphy for SLN identification, they are retained in the SLN but are absent or present in only tiny amounts in non-SLNs. The present study investigated the potential for a novel means of assessing the accuracy of surgical identification of SLNs. This involved the use of inductively coupled plasma–mass spectrometry (ICP-MS) to analyze antimony concentrations in fine-needle biopsy (FNB) samples from surgically procured lymph nodes. Methods A total of 47 FNB samples from surgically excised lymph nodes (32 SLNs and 15 non-SLNs) were collected. The SLNs were localized by preoperative lymphoscintigraphy that used 99 mTc-Sb2S3, blue dye, and gamma probe techniques. The concentrations of antimony were measured in the FNB samples by ICP-MS. Results The mean and median antimony concentrations (in parts per billion) were .898 and .451 in the SLNs, and .015 and .068 in the non-SLNs, the differences being highly statistically significant (P < .00005). Conclusions Our results show that ICP-MS analysis of antimony concentrations in FNB specimens from lymph nodes can accurately confirm the identity of SLNs. Used in conjunction with techniques such as proton magnetic resonance spectroscopy for the nonsurgical evaluation of SLNs, ICP-MS analysis of antimony concentrations in FNB samples could potentially serve as a minimally invasive alternative to surgery and histopathologic evaluation to objectively classify a given node as sentinel or nonsentinel and determine its tumor-harboring status. PMID:18172734

Confirmation of sentinel lymph node identity by analysis of fine-needle biopsy samples using inductively coupled plasma-mass spectrometry.

PubMed

Beavis, Alison; Dawson, Michael; Doble, Philip; Scolyer, Richard A; Bourne, Roger; Li, Ling-Xi L; Murali, Rajmohan; Stretch, Jonathan R; Lean, Cynthia L; Uren, Roger F; Thompson, John F

2008-03-01

The sentinel lymph node (SLN) biopsy technique is a reliable means of determining the tumor-harboring status of regional lymph nodes in melanoma patients. When technetium 99 m-labeled antimony trisulfide colloid (99 mTc-Sb2S3) particles are used to perform preoperative lymphoscintigraphy for SLN identification, they are retained in the SLN but are absent or present in only tiny amounts in non-SLNs. The present study investigated the potential for a novel means of assessing the accuracy of surgical identification of SLNs. This involved the use of inductively coupled plasma-mass spectrometry (ICP-MS) to analyze antimony concentrations in fine-needle biopsy (FNB) samples from surgically procured lymph nodes. A total of 47 FNB samples from surgically excised lymph nodes (32 SLNs and 15 non-SLNs) were collected. The SLNs were localized by preoperative lymphoscintigraphy that used 99 mTc-Sb2S3, blue dye, and gamma probe techniques. The concentrations of antimony were measured in the FNB samples by ICP-MS. The mean and median antimony concentrations (in parts per billion) were .898 and .451 in the SLNs, and .015 and .068 in the non-SLNs, the differences being highly statistically significant (P < .00005). Our results show that ICP-MS analysis of antimony concentrations in FNB specimens from lymph nodes can accurately confirm the identity of SLNs. Used in conjunction with techniques such as proton magnetic resonance spectroscopy for the nonsurgical evaluation of SLNs, ICP-MS analysis of antimony concentrations in FNB samples could potentially serve as a minimally invasive alternative to surgery and histopathologic evaluation to objectively classify a given node as sentinel or nonsentinel and determine its tumor-harboring status.

Postmastectomy radiation therapy for lymph node-negative, locally advanced breast cancer after modified radical mastectomy: analysis of the NCI Surveillance, Epidemiology, and End Results database.

PubMed

Yu, James B; Wilson, Lynn D; Dasgupta, Tina; Castrucci, William A; Weidhaas, Joanne B

2008-07-01

The role of postmastectomy radiotherapy (PMRT) for lymph node-negative locally advanced breast carcinoma (T3N0M0) after modified radical mastectomy (MRM) with regard to improvement in survival remains an area of controversy. The 1973-2004 National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database was examined for patients with T3N0M0 ductal, lobular, or mixed ductal and lobular carcinoma of the breast who underwent MRM, treated from 1988-2003. Patients who were men, who had positive lymph nodes, who survived < or =6 months, for whom breast cancer was not the first malignancy, who had nonbeam radiation, intraoperative or preoperative radiation were excluded. The average treatment effect of PMRT on mortality was estimated with a propensity score case-matched analysis. In all, 1777 patients were identified; 568 (32%) patients received PMRT. Median tumor size was 6.3 cm. The median number of lymph nodes examined was 14 (range, 1-49). Propensity score matched case-control analysis showed no improvement in overall survival with the delivery of PMRT in this group. Older patients, patients with ER- disease (compared with ER+), and patients with high-grade tumors (compared with well differentiated) had increased mortality. The use of PMRT for T3N0M0 breast carcinoma after MRM is not associated with an increase in overall survival. It was not possible to analyze local control in this study given the limitations of the SEER database. The impact of potential improvement in local control as it relates to overall survival should be the subject of further investigation. (Copyright) 2008 American Cancer Society.

MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection.

PubMed

Soderberg, Kelly A; Linehan, Melissa M; Ruddle, Nancy H; Iwasaki, Akiko

2004-08-01

The members of the lymphotoxin (LT) family of molecules play a critical role in lymphoid organogenesis. Whereas LT alpha-deficient mice lack all lymph nodes and Peyer's patches, mice deficient in LT beta retain mesenteric lymph nodes and cervical lymph nodes, suggesting that an LT beta-independent pathway exists for the generation of mucosal lymph nodes. In this study, we describe the presence of a lymph node in LT beta-deficient mice responsible for draining the genital mucosa. In the majority of LT beta-deficient mice, a lymph node was found near the iliac artery, slightly misplaced from the site of the sacral lymph node in wild-type mice. The sacral lymph node of the LT beta-deficient mice, as well as that of the wild-type mice, expressed the mucosal addressin cell adhesion molecule-1 similar to the mesenteric lymph node. Following intravaginal infection with HSV type 2, activated dendritic cells capable of stimulating a Th1 response were found in this sacral lymph node. Furthermore, normal HSV-2-specific IgG responses were generated in the LT beta-deficient mice following intravaginal HSV-2 infection even in the absence of the spleen. Therefore, an LT beta-independent pathway exists for the development of a lymph node associated with the genital mucosa, and such a lymph node serves to generate potent immune responses against viral challenge.

Cervical lymphadenopathy in the dental patient: a review of clinical approach.

PubMed

Parisi, Ernesta; Glick, Michael

2005-06-01

Lymph node enlargement may be an incidental finding on examination, or may be associated with a patient complaint. It is likely that over half of all patients examined each day may have enlarged lymph nodes in the head and neck region. There are no written guidelines specifying when further evaluation of lymphadenopathy is necessary. With such a high frequency of occurrence, oral health care providers need to be able to determine when lymphadenopathy should be investigated further. Although most cervical lymphadenopathy is the result of a benign infectious etiology, clinicians should search for a precipitating cause and examine other nodal locations to exclude generalized lymphadenopathy. Lymph nodes larger than 1 cm in diameter are generally considered abnormal. Malignancy should be considered when palpable lymph nodes are identified in the supraclavicular region, or when nodes are rock hard, rubbery, or fixed in consistency. Patients with unexplained localized cervical lymphadenopathy presenting with a benign clinical picture should be observed for a 2- to 4-week period. Generalized lymphadenopathy should prompt further clinical investigation. This article reviews common causes of lymphadenopathy, and presents a methodical clinical approach to a patient with cervical lymphadenopathy.

Efficacy of Sentinel Lymph Node Biopsy in Detecting Axillary Metastasis in Breast Cancer Using Methylene Blue.

PubMed

Nandu, Vipul V; Chaudhari, Milind S

2017-06-01

Breast cancer is the leading malignancy and the second leading cause of cancer-related deaths. Axillary lymph node status is a very important prognostic factor in breast cancer patients; nodal evaluation is therefore a critical part of breast cancer management. Axillary lymph node dissection results in significant morbidity. Sentinel lymph node biopsy (SLNB) is being used in many centers to stage the axilla in planning axillary dissection management of patients and hence plays an important part in reducing morbidity among patients with carcinoma breast. The objectives of this paper is to study the (1) efficacy of sentinel lymph node biopsy in detecting axillary metastasis, (2) location of sentinel lymph node in the axilla, (3) rate of involvement of sentinel lymph nodes, and (4) incidence of skip metastasis. Thirty-five patients with breast cancer with clinically node-negative axilla were selected for the study. Methylene blue dye was injected intralesional and perilesional 20 min prior to surgery. All patients underwent modified radical mastectomy with sentinel lymph node biopsy and axillary dissection and after pathological examination diagnostic statics, namely sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were computed. Sentinel lymph node was identified in all of these patients. Sixty percent patients had pathologically positive lymph nodes in the axilla. 90.48% patients of these had sentinel lymph nodes positive for malignant cells. Incidence of skip metastasis is 9.52%. 88.57% patients had sentinel lymph node mapped to level I lymph nodes. Sensitivity of SLNB is 90.48%, specificity is 85.71%, PPV of is 90.48%, NPV is 85.71%, and accuracy is 88.57%. Sentinel lymph node biopsy is an effective method of staging the axilla and deciding on axillary clearance in patients of carcinoma breast. Unnecessary axillary dissection and associated complications can be prevented in most of patients due to sentinel lymph node biopsy.

Aggressive squamous cell carcinoma in Kindler syndrome.

PubMed

Emanuel, Patrick O; Rudikoff, Donald; Phelps, Robert G

2006-01-01

A 57-year-old Hispanic man with a personal and family history of bullae and photosensitivity presented with a fungating, ulcerated squamous cell carcinoma on his left hand (Figure 1). Physical examination showed conjunctival injection, ectropion, symblepharon, urethral stricture, loss of teeth, short stature, and nail dystrophy. There was reticulated erythema, atrophy, hyperpigmentation and hypopigmentation, and telangiectasia of sun-exposed skin of the face, neck, and hands consistent with poikiloderma (Figure 2). In addition, there was foreshortening of the left thumb and sclerodermoid changes of his hands (Figure 3). Radiation therapy was applied to shrink the tumor before a local excision was performed. However, a local recurrence followed and axillary lymph nodes became clinically palpable, necessitating amputation and lymph node dissection. Extensive histologic evaluation of the specimen obtained following left arm amputation and lymph node dissection showed moderate-to-poorly differentiated deeply invasive squamous cell carcinoma. Two of 3 axillary lymph nodes were positive for metastatic carcinoma. A random biopsy of the trunk showed epidermal atrophy, telangiectasia, a perivascular lymphocytic infiltration, and pigment-laden macrophages consistent with poikiloderma. Electron microscopy illustrated extensive reduplication of the basement membrane, with loops, curls, and free extensions of the basal lamina in the superficial dermis; reduced numbers of hemidesmosomes and anchoring fibrils; and a basement membrane focally devoid of basal cells (Figure 4). On the basis of the clinical features and the characteristic basement zone changes, a diagnosis of Kindler syndrome was made.

Long-term prognoses and outcomes of axillary lymph node recurrence in 2,578 sentinel lymph node-negative patients for whom axillary lymph node dissection was omitted: results from one Japanese hospital.

PubMed

Ogiya, Akiko; Kimura, Kiyomi; Nakashima, Eri; Sakai, Takehiko; Miyagi, Yumi; Iijima, Kotaro; Morizono, Hidetomo; Makita, Masujiro; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji

2016-03-01

Axillary dissection omission for sentinel lymph node-negative patients has been a practice at Cancer Institute Hospital, Japanese Foundation for Cancer Research since 2003. We examined the long-term results of omission of axillary dissection in sentinel lymph node-negative patients treated at our hospital, as well as their axillary lymph node recurrence characteristics and outcomes. Our study included 2,578 patients with cTis or T1-T3N0M0 primary breast cancer for whom dissection was omitted because they were sentinel lymph node negative. The median observation period was 75 months. In sentinel lymph node-negative patients for whom dissection was omitted, the rates of axillary lymph node recurrence, distant recurrence, and breast cancer mortality were 0.9, 2, and 1 %, respectively. Eighteen patients underwent additional dissection if axillary lymph node recurrence was observed at the first recurrence. Four triple-negative (TN) patients experienced distant recurrence after additional dissection. All four patients were administered anticancer agents after axillary lymph node recurrence and experienced recurrence within 1 year of additional dissection. The axillary lymph node recurrence rate was 0.8 % for luminal and 4.5 % for TN subtypes. The long-term prognoses of patients for whom dissection was omitted owing to negative sentinel lymph node metastases were similar to those reported previously-low recurrence and mortality rates. The frequency of axillary lymph node recurrence and the post-recurrence outcome differed between luminal and TN cases, with recurrence being more frequent in patients with the TN subtype. TN patients also had poorer prognoses, even after receiving additional dissection and anticancer agents after recurrence.

Potential role for carbon nanoparticles to guide central neck dissection in patients with papillary thyroid cancer.

PubMed

Yu, Wenbin; Cao, XiaoLi; Xu, Guihu; Song, Yuntao; Li, Guojun; Zheng, Hongliang; Zhang, Naisong

2016-09-01

The purpose of this study was to investigate the use and clinical utility of carbon nanoparticles as a lymph node tracer in the central neck lymph node dissection of patients with papillary thyroid cancer. One hundred forty consecutive patients were divided into a carbon nanoparticle group (n = 70) and a control group (n = 70). All patients underwent total or near-total thyroidectomy with bilateral central neck dissection. The carbon nanoparticle and control groups had different rates of metastatic lymph nodes (P = .017), total detected numbers of lymph nodes (P = .0001), total numbers of dissected lymph nodes <5 mm (P = .0001), and numbers of metastatic lymph nodes <5 mm (P = .0001). Of the 682 lymph nodes dissected in the carbon nanoparticle group, 579 (85%) were stained black, and of these, 147 (25%) were metastatic lymph nodes. There were 63 metastatic lymph nodes <5 mm among the black-stained metastatic lymph nodes, while there were 12 non-black-stained metastatic lymph nodes <5 mm. Of the total number of metastatic lymph nodes (n = 193), 147 (76%) were stained black. Moreover, pathologic results revealed that 5 accidental parathyroid resections occurred in the carbon nanoparticle group, compared with 14 in the control group (P = .046). Carbon nanoparticles might help to detect lymph nodes and increase the number of metastatic lymph nodes visualized and preserved. Therefore, use of carbon nanoparticles may reflect the metastatic condition of the central neck and have the potential to protect parathyroid glands. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of Indocyanine Green for Sentinel Lymph Node Biopsy: Case Series and Methods Comparison.

PubMed

McGregor, Andrew; Pavri, Sabrina N; Tsay, Cynthia; Kim, Samuel; Narayan, Deepak

2017-11-01

Sentinel lymph node biopsy is indicated for patients with biopsy-proven thickness melanoma greater than 1.0 mm. Use of lymphoscintigraphy along with vital blue dyes is the gold standard for identifying sentinel lymph nodes intraoperatively. Indocyanine green (ICG) has recently been used as a method of identifying sentinel lymph nodes. We herein describe a case series of patients who have successfully undergone ICG-assisted sentinel lymph node biopsy for melanoma. We compare 2 imaging systems that are used for ICG-assisted sentinel lymph node biopsy. Fourteen patients underwent ICG-assisted sentinel lymph node biopsy for melanoma using the SPY Elite system (Novadaq, Mississigua, Canada) and the Hamamatsu PDE-Neo probe system (Mitaka USA, Park City, Utah). We analyzed costs for 2 systems that utilize ICG for sentinel lymph node biopsies. Intraoperative use of ICG for sentinel lymph node biopsies was successful in correctly identifying sentinel lymph nodes. There was no difference between the Hamamatsu PDE-Neo probe and SPY Elite systems in the ability to detect sentinel lymph nodes; however, the former was associated with a lower operating cost and ease of use compared with the latter. ICG-assisted sentinel lymph biopsy using the SPY Elite or the Hamamatsu PDE-Neo probe systems for melanoma are comparable in terms of sentinel node detection. The Neo probe system delivers pertinent clinical data with the advantages of lower cost and ease of operation.

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes.

PubMed

Walk, Elyse L; McLaughlin, Sarah L; Weed, Scott A

2015-07-25

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal systems. HFUS has the ability to detect structures as small as 30 µm, a property that has been utilized for visualizing superficial lymph nodes in rodents in brightness (B)-mode. Combining power Doppler with B-mode imaging allows for measuring circulatory blood flow within lymph nodes and other organs. While HFUS has been utilized for lymph node imaging in a number of mouse  model systems, a detailed protocol describing HFUS imaging and characterization of the cervical lymph nodes in mice has not been reported. Here, we show that HFUS can be adapted to detect and characterize cervical lymph nodes in mice. Combined B-mode and power Doppler imaging can be used to detect increases in blood flow in immunologically-enlarged cervical nodes. We also describe the use of B-mode imaging to conduct fine needle biopsies of cervical lymph nodes to retrieve lymph tissue for histological  analysis. Finally, software-aided steps are described to calculate changes in lymph node volume and to visualize changes in lymph node morphology following image reconstruction. The ability to visually monitor changes in cervical lymph node biology over time provides a simple and powerful technique for the non-invasive monitoring of cervical lymph node alterations in preclinical mouse models of oral cavity disease.

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

PubMed

Wang, Na-Na; Yang, Zheng-Jun; Wang, Xue; Chen, Li-Xuan; Zhao, Hong-Meng; Cao, Wen-Feng; Zhang, Bin

2018-04-25

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P < 0.001), and the number of negative sentinel lymph nodes (OR = 0.686, 95% CI 0.575-0.817; P < 0.001) were independent statistically significant predictors of non-sentinel lymph node metastasis. Furthermore, luminal B (OR = 3.311, 95% CI 1.593-6.884; P = 0.001) and HER2 overexpression (OR = 4.308, 95% CI 1.097-16.912; P = 0.036) were independent and statistically significant predictor of non-sentinel lymph node metastasis versus luminal A. A regression model based on the results of multivariate analysis was established to predict the risk of non-sentinel lymph node metastasis, which had an AUC of 0.8188. The model was validated in the validation cohort and showed excellent diagnostic performance. The mathematical prediction model that incorporates five variables including breast cancer molecular subtype demonstrates excellent diagnostic performance in assessing the risk of non-sentinel lymph node metastasis in sentinel lymph node-positive patients. The prediction model could be of help surgeons in evaluating the risk of non-sentinel lymph node involvement for breast cancer patients; however, the model requires further validation in prospective studies.

Clinical Impact of Re-irradiation with Carbon-ion Radiotherapy for Lymph Node Recurrence of Gynecological Cancers.

PubMed

Shiba, Shintaro; Okonogi, Noriyuki; Kato, Shingo; Wakatsuki, Masaru; Kobayashi, Daijiro; Kiyohara, Hiroki; Ohno, Tatsuya; Karasawa, Kumiko; Nakano, Takashi; Kamada, Tadashi

2017-10-01

To evaluate the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for lymph node recurrence of gynecological cancers after definitive radiotherapy. Data regarding patients with unresectable and isolated recurrent lymph node from gynecological cancer after definitive radiotherapy were analyzed. Total dose of C-ion RT was 48-57.6 Gy (RBE) in 12 or 16 fractions. Sixteen patients received re-irradiation by C-ion RT were analyzed. Median follow-up was 37 months. Median tumor size was 27 mm. None developed Grade 1 or higher acute toxicities and Grade 3 or higher late toxicities. The 3-year overall survival, local control and disease-free survival rates after C-ion RT were 74%, 94% and 55%, respectively. Re-irradiation with C-ion RT for lymph node recurrence of gynecological cancers after definitive radiotherapy can be safe and effective. This result suggested that C-ion RT could be a curative treatment option for conventionally difficult-to-cure patients. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer.

PubMed

Mikosiński, Sławomir; Pomorski, Lech; Oszukowska, Lidia; Makarewicz, Jacek; Adamczewski, Zbigniew; Sporny, Stanisław; Lewiński, Andrzej

2006-01-01

Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.

Penile Cancer: Contemporary Lymph Node Management.

PubMed

O'Brien, Jonathan S; Perera, Marlon; Manning, Todd; Bozin, Mike; Cabarkapa, Sonja; Chen, Emily; Lawrentschuk, Nathan

2017-06-01

In penile cancer, the optimal diagnostics and management of metastatic lymph nodes are not clear. Advances in minimally invasive staging, including dynamic sentinel lymph node biopsy, have widened the diagnostic repertoire of the urologist. We aimed to provide an objective update of the recent trends in the management of penile squamous cell carcinoma, and inguinal and pelvic lymph node metastases. We systematically reviewed several medical databases, including the Web of Science® (with MEDLINE®), Embase® and Cochrane databases, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines. The search terms used were penile cancer, lymph node, sentinel node, minimally invasive, surgery and outcomes, alone and in combination. Articles pertaining to the management of lymph nodes in penile cancer were reviewed, including original research, reviews and clinical guidelines published between 1980 and 2016. Accurate and minimally invasive lymph node staging is of the utmost importance in the surgical management of penile squamous cell carcinoma. In patients with clinically node negative disease, a growing body of evidence supports the use of sentinel lymph node biopsies. Dynamic sentinel lymph node biopsy exposes the patient to minimal risk, and results in superior sensitivity and specificity profiles compared to alternate nodal staging techniques. In the presence of locoregional disease, improvements in inguinal or pelvic lymphadenectomy have reduced morbidity and improved oncologic outcomes. A multimodal approach of chemotherapy and surgery has demonstrated a survival benefit for patients with advanced disease. Recent developments in lymph node management have occurred in penile cancer, such as minimally invasive lymph node diagnosis and intervention strategies. These advances have been met with a degree of controversy in the contemporary literature. Current data suggest that dynamic sentinel lymph node biopsy provides excellent sensitivity and specificity for detecting lymph node metastases. More robust long-term data on multicenter patient cohorts are required to determine the optimal management of lymph nodes in penile cancer. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed

Van den Broeck, Wim; Derore, Annie; Simoens, Paul

2006-05-30

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.

Lymph node clearance of plutonium from subcutaneous wounds in beagles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dagle, G.E.

1973-08-01

The lymph node clearance of /sup 239/Pu O/sub 2/ administered as insoluble particles from subcutaneous implants was studied in adult beagles to simulate accidental contamination of hand wounds. External scintillation data were collected from the popliteal lymph nodes of each dog after 9.2 to 39.4 mu Ci of plutonium oxide was subcutaneously implanted into the left or right hind paws. The left hind paw was armputated 4 weeks after implantation to prevent continued deposition of plutonium oxide particles in the left popliteal lymph node. Groups of 3 dogs were sacrificed 4, 8, 16, and 32 weeks after plutonium implantation formore » histopathologic, electron microscopic, and radiochemical analysis of regional lymph nodes. An additional group of dogs received treatment with the chelating agent diethyenetriaminepentaacetic acid (DTPA). Plutonium rapidly accumulated in the popliteal lymph nodes after subcutaneous injection into the hind paw, and 1 to 10% of the implant dose was present in the popliteal lymph nodes at the time of necropsy. Histopathologic changes in the popliteal lymph nodes with plutonium particles were characterized primarily by reticular cell hyperplasia, increased numbers of macrophages, necrosis, and fibroplasia. Eventually, the plutonium particles became sequestered by scar tissue that often replaced the entire architecture of the lymph node. Light microscopic autoradiographs of the popliteal lymph nodes showed a time-related increase in number of alpha tracks per plutonium source. Electron microscopy showed that the plutonium particles were aggregated in phagolysosomes of macrophages. There was slight clearance of plutonium from the popliteal lymph nodes of dogs monitored for 32 weeks. The clearance of plutonium particles from the popliteal lymph nodes was associated with necrosis of macrophages. The external iliac lymph nodes contained fewer plutonium particles than the popliteal lymph nodes and histopathologic changes were less severe. The superficial inguinal lymph nodes of one dog contained appreciable amounts of plutonium. Treatment with diethylenetriaminepentaacetic acid (DTPA) did not have a measurable effect on the clearance of plutonium from the popliteal lymph nodes. (60 references) (auth)« less

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

PubMed

Faries, Mark B; Thompson, John F; Cochran, Alistair J; Andtbacka, Robert H; Mozzillo, Nicola; Zager, Jonathan S; Jahkola, Tiina; Bowles, Tawnya L; Testori, Alessandro; Beitsch, Peter D; Hoekstra, Harald J; Moncrieff, Marc; Ingvar, Christian; Wouters, Michel W J M; Sabel, Michael S; Levine, Edward A; Agnese, Doreen; Henderson, Michael; Dummer, Reinhard; Rossi, Carlo R; Neves, Rogerio I; Trocha, Steven D; Wright, Frances; Byrd, David R; Matter, Maurice; Hsueh, Eddy; MacKenzie-Ross, Alastair; Johnson, Douglas B; Terheyden, Patrick; Berger, Adam C; Huston, Tara L; Wayne, Jeffrey D; Smithers, B Mark; Neuman, Heather B; Schneebaum, Schlomo; Gershenwald, Jeffrey E; Ariyan, Charlotte E; Desai, Darius C; Jacobs, Lisa; McMasters, Kelly M; Gesierich, Anja; Hersey, Peter; Bines, Steven D; Kane, John M; Barth, Richard J; McKinnon, Gregory; Farma, Jeffrey M; Schultz, Erwin; Vidal-Sicart, Sergi; Hoefer, Richard A; Lewis, James M; Scheri, Randall; Kelley, Mark C; Nieweg, Omgo E; Noyes, R Dirk; Hoon, Dave S B; Wang, He-Jing; Elashoff, David A; Elashoff, Robert M

2017-06-08

Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

Decline in Frozen Section Diagnosis for Axillary Sentinel Lymph Nodes as a Result of the American College of Surgeons Oncology Group Z0011 Trial.

PubMed

Bishop, Julie Anne; Sun, Jihong; Ajkay, Nicolas; Sanders, Mary Ann G

2016-08-01

-Results of the American College of Surgeons Oncology Group Z0011 trial showed that patients with early-stage breast cancer and limited sentinel node metastasis treated with breast conservation and systemic therapy did not benefit from axillary lymph node dissection. Subsequently, most pathology departments have likely seen a decrease in frozen section diagnosis of sentinel lymph nodes. -To determine the effect of the Z0011 trial on pathology practice and to examine the utility of intraoperative sentinel lymph node evaluation for this subset of patients. -Pathology reports from cases of primary breast cancer that met Z0011 clinical criteria and were initially treated with lumpectomy and sentinel lymph node biopsy from 2009 to 2015 were collected. Clinicopathologic data were recorded. -Sentinel lymph node biopsies sent for frozen section diagnosis occurred in 22 of 22 cases (100%) in 2009 and 15 of 22 cases (68%) in 2010 during the pre-Z0011 years, and in 3 of 151 cases (2%) collected in 2011 through 2015, considered to be post-Z0011 years. Of the 151 post-Z0011 cases, 28 (19%) had sentinel lymph nodes with metastasis, and 147 (97%) were spared axillary lymph node dissection. -Following Z0011, intraoperative sentinel lymph node evaluation has significantly decreased at our institution. Prior to surgery, all patients had clinically node-negative disease. After sentinel lymph node evaluation, 97% (147 of 151) of the patients were spared axillary lymph node dissection. Therefore, routine frozen section diagnosis for sentinel lymph node biopsies can be avoided in these patients.

Evaluation of radioisotopic and non-radioisotopic versions of local lymph node assays for subcategorization of skin sensitizers compliant to UN GHS rev 4.

PubMed

Ha, Soojin; Ahn, Il Young; Kim, Da-Eun; Lee, Jong Kwon; Sohn, Soojung; Jung, Mi-Sook; Heo, Yong; Omori, Takashi; Bae, SeungJin; Lim, Kyung-Min

2017-04-01

Recently UN GHS has introduced the sub-categorization of skin sensitizers for which ECt (concentration estimated to induce stimulation index above threshold) of the murine local lymph node assay (LLNA) is used as criteria. Non-radioisotopic variants of LLNA, LLNA: DA, LLNA: BrdU-ELISA, LNCC and LLNA: BrdU-FCM were developed yet their utilities for potency sub-categorization are not established. Here we assessed the agreement of LLNA variants with LLNA or human data in potency sub-categorization for 22 reference substances of OECD TG429. Concordance of sub-categorization with LLNA was highest for LLNA: BrdU-FCM(91%, κ = 0.833, weighted kappa) followed by LLNA: BrdU-ELISA (82%, κ = 0.744) and LLNA: DA (73%, κ = 0.656) whereas LNCC only showed a modest association (64%, κ = 0.441). With human data, LLNA agreed best (77%) followed by LLNA: DA and LLNA: BrdU-FCM(73%), LLNA: BrdU-ELISA (68%) and LNCC(55%). Bland-Altman plot revealed that ECt's of LLNA variants largely agreed with LLNA where most values fell within 95% limit of agreement. Correlation between ECt's of LLNA and LLNA variants were high except for LNCC(pair-wise with LLNA, LLNA: DA, r = 0.848, LLNA: BrdU-ELISA, r = 0.744, LLNA: BrdU-FCM, r=0.786, and LNCC, r = 0.561 by Pearson). Collectively, these results demonstrated that LLNA variants exhibit performance comparable to LLNA in the potency sub-categorization although additional substances shall be analyzed in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel approach for classifying chemicals according to skin sensitizing potency by non-radioisotopic modification of the local lymph node assay.

PubMed

Takeyoshi, Masahiro; Iida, Kenji; Shiraishi, Keiji; Hoshuyama, Satsuki

2005-01-01

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone sensitization test for determining the sensitizing potential of chemicals, and it has the advantage of yielding a quantitative endpoint that can be used to predict the sensitization potency of chemicals. The EC3 has been proposed as a parameter for classifying chemicals according to the sensitization potency. We previously developed a non-radioisotopic endpoint for the LLNA based on 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA), and we are proposing a new procedure to predict the sensitization potency of chemicals based on comparisons with known human contact allergens. Nine chemicals (i.e. diphencyclopropenone, p-phenylenediamine, glutaraldehyde, cinnamicaldehyde, citral, eugenol, isopropyl myristate, propyleneglycol and hexane) categorized as human contact allergen classes 1-5 were tested by the non-RI LLNA with the following reference allergens: 2,4-dinitrochlorobenzene (DNCB) as a class 1 human contact allergen, isoeugenol as a class 2 human contact allergen and alpha-hexylcinnamic aldehyde (HCA) as a class 3 human contact allergen. Consequently, nine test chemicals were almost assigned to their correct allergen class. The results suggested that the new procedure for non-RI LLNA can provide correct sensitization potency data. Sensitization potency data are useful for evaluating the sensitization risk to humans of exposure to new chemical products. Accordingly, this approach would be an effective modification of LLNA with regard to its experimental design. Moreover, this procedure can be applied also to the standard LLNA with radioisotopes and to other modifications of the LLNA. Copyright 2005 John Wiley & Sons, Ltd.

Inter-laboratory validation of the modified murine local lymph node assay based on 5-bromo-2'-deoxyuridine incorporation.

PubMed

Kojima, Hajime; Takeyoshi, Masahiro; Sozu, Takashi; Awogi, Takumi; Arima, Kazunori; Idehara, Kenji; Ikarashi, Yoshiaki; Kanazawa, Yukiko; Maki, Eiji; Omori, Takashi; Yuasa, Atsuko; Yoshimura, Isao

2011-01-01

The murine local lymph node assay (LLNA) is a well-established alternative to the guinea pig maximization test (GPMT) or Buehler test (BT) for the assessment of the skin sensitizing ability of a drug, cosmetic material, pesticide or industrial chemical. Instead of radioisotope using in this method, Takeyoshi M. et al. (2001) has developed a modified LLNA based on the 5-bromo-2'-deoxyuridine (BrdU) incorporation (LLNA:BrdU-ELISA). The LLNA:BrdU-ELISA is practically identical to the LLNA methodology excluding the use of BrdU, for which a single intraperitoneal injection of BrdU is made on day 4, and colorimetric detection of cell turnover. We conducted the validation study to evaluate the reliability and relevance of LLNA:BrdU-ELISA. The experiment involved 7 laboratories, wherein 10 chemicals were examined under blinded conditions. In this study, 3 chemicals were examined in all laboratories and the remaining 7 were examined in 3 laboratories. The data were expressed as the BrdU incorporation using an ELISA method for each group, and the stimulation index (SI) for each chemical-treated group was determined as the increase in the BrdU incorporation relative to the concurrent vehicle control group. An SI of 2 was set as the cut-off value for exhibiting skin sensitization activity. The results obtained in the experiments conducted for all 10 chemicals were sufficiently consistent with small variations in their SI values. The sensitivity, specificity, and accuracy of LLNA:BrdU-ELISA against those of GPMT/BT were 7/7 (100%), 3/3 (100%), and 10/10 (100%), respectively. Copyright © 2010 John Wiley & Sons, Ltd.

Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy.

PubMed

Ramírez-Backhaus, Miguel; Mira Moreno, Alejandra; Gómez Ferrer, Alvaro; Calatrava Fons, Ana; Casanova, Juan; Solsona Narbón, Eduardo; Ortiz Rodríguez, Isabel María; Rubio Briones, José

2016-11-01

We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph fluorescent analysis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The role of CEUS in characterization of superficial lymph nodes: a single center prospective study

PubMed Central

de Stefano, Giorgio; Scognamiglio, Umberto; Di Martino, Filomena; Parrella, Roberto; Scarano, Francesco; Signoriello, Giuseppe; Farella, Nunzia

2016-01-01

Accurate lymph node characterization is important in a large number of clinical settings. We evaluated the usefulness of Contrast Enhanced Ultrasound (CEUS) in distinguishing between benign and malignant lymph nodes compared with conventional ultrasonography in the differential diagnosis of superficial lymphadenopathy. We present our experience for 111 patients enrolled in a single center. 111 superficial lymph nodes were selected and only 1 lymph node per patient underwent CEUS. A definitive diagnosis for all lymph nodes was obtained by ultrasonographically guided biopsy and/or excision biopsy. The size of the lymph nodes, the site (neck, axilla, inguinal region) being easily accessible for biopsy, and the US and color Doppler US characteristics guided us in selecting the nodes to be evaluated by CEUS. In our study we identified different enhancement patterns in benign and malignant lymph nodes, with a high degree of diagnostic accuracy for superficial lymphadenopathy in comparison with conventional US. PMID:27191746

Use of a Local Immunotherapy as an Adjunctive Tool for the Generation of Human Monoclonal Antibodies from Regional Lymph Nodes of Colonic Cancer Patients

PubMed Central

Yagyu, Toshio; Monden, Takushi; Tamaki, Yasuhiro; Morimoto, Hideki; Takeda, Tsutomu; Kobayashi, Tetsuro; Shimano, Takashi; Murakami, Hiroki; Mori, Takesada

1992-01-01

Human hybridomas were generated through the fusion of the human B‐lymphoblastoid cell line HO‐323 with the regional lymph node lymphocytes of colonic cancer patients who had received a local immunotherapy. A total of 353 hybridomas were obtained from 4 patients and 116 of these were found to secrete ≧ 100 ng/ml human immunoglobulin. The efficiency was remarkably high as compared with that from patients without the local immunotherapy. Further immunohistological examination showed that 5 hybridomas secreted IgM which selectively reacted with colonic cancers. The results indicate that local immunotherapy could be an adjunctive tool for the generation of highly potent human hybridomas through augmenting the host's immunity. PMID:1544869

Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

PubMed Central

Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

2014-01-01

Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

A grid matrix-based Raman spectroscopic method to characterize different cell milieu in biopsied axillary sentinel lymph nodes of breast cancer patients.

PubMed

Som, Dipasree; Tak, Megha; Setia, Mohit; Patil, Asawari; Sengupta, Amit; Chilakapati, C Murali Krishna; Srivastava, Anurag; Parmar, Vani; Nair, Nita; Sarin, Rajiv; Badwe, R

2016-01-01

Raman spectroscopy which is based upon inelastic scattering of photons has a potential to emerge as a noninvasive bedside in vivo or ex vivo molecular diagnostic tool. There is a need to improve the sensitivity and predictability of Raman spectroscopy. We developed a grid matrix-based tissue mapping protocol to acquire cellular-specific spectra that also involved digital microscopy for localizing malignant and lymphocytic cells in sentinel lymph node biopsy sample. Biosignals acquired from specific cellular milieu were subjected to an advanced supervised analytical method, i.e., cross-correlation and peak-to-peak ratio in addition to PCA and PC-LDA. We observed decreased spectral intensity as well as shift in the spectral peaks of amides and lipid bands in the completely metastatic (cancer cells) lymph nodes with high cellular density. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to create an automated smart diagnostic tool for bench side screening of sampled lymph nodes. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to develop an automated smart diagnostic tool for bench side screening of sampled lymph nodes supported by ongoing global research in developing better technology and signal and big data processing algorithms.

Assessment of statistic analysis in non-radioisotopic local lymph node assay (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example.

PubMed

Takeyoshi, Masahiro; Sawaki, Masakuni; Yamasaki, Kanji; Kimber, Ian

2003-09-30

The murine local lymph node assay (LLNA) is used for the identification of chemicals that have the potential to cause skin sensitization. However, it requires specific facility and handling procedures to accommodate a radioisotopic (RI) endpoint. We have developed non-radioisotopic (non-RI) endpoint of LLNA based on BrdU incorporation to avoid a use of RI. Although this alternative method appears viable in principle, it is somewhat less sensitive than the standard assay. In this study, we report investigations to determine the use of statistical analysis to improve the sensitivity of a non-RI LLNA procedure with alpha-hexylcinnamic aldehyde (HCA) in two separate experiments. Consequently, the alternative non-RI method required HCA concentrations of greater than 25% to elicit a positive response based on the criterion for classification as a skin sensitizer in the standard LLNA. Nevertheless, dose responses to HCA in the alternative method were consistent in both experiments and we examined whether the use of an endpoint based upon the statistical significance of induced changes in LNC turnover, rather than an SI of 3 or greater, might provide for additional sensitivity. The results reported here demonstrate that with HCA at least significant responses were, in each of two experiments, recorded following exposure of mice to 25% of HCA. These data suggest that this approach may be more satisfactory-at least when BrdU incorporation is measured. However, this modification of the LLNA is rather less sensitive than the standard method if employing statistical endpoint. Taken together the data reported here suggest that a modified LLNA in which BrdU is used in place of radioisotope incorporation shows some promise, but that in its present form, even with the use of a statistical endpoint, lacks some of the sensitivity of the standard method. The challenge is to develop strategies for further refinement of this approach.

Quantitative relationship between the local lymph node assay and human skin sensitization assays.

PubMed

Schneider, K; Akkan, Z

2004-06-01

The local lymph node assay (LLNA) is a new test method which allows for the quantitative assessment of sensitizing potency in the mouse. Here, we investigate the quantitative correlation between results from the LLNA and two human sensitization tests--specifically, human repeat insult patch tests (HRIPTs) and human maximization tests (HMTs). Data for 57 substances were evaluated, of which 46 showed skin sensitizing properties in human tests, whereas 11 yielded negative results in humans. For better comparability data from mouse and human tests were transformed to applied doses per skin area, which ranged over four orders of magnitude for the substances considered. Regression analysis for the 46 human sensitizing substances revealed a significant positive correlation between the LLNA and human tests. The correlation was better between LLNA and HRIPT data (n=23; r=0.77) than between LLNA and HMT data (n=38; r=0.65). The observed scattering of data points is related to various uncertainties, in part associated with insufficiencies of data from older HMT studies. Predominantly negative results in the LLNA for another 11 substances which showed no skin sensitizing activity in human maximization tests further corroborate the correspondence between LLNA and human tests. Based on this analysis, the LLNA can be considered a reliable basis for relative potency assessments for skin sensitizers. Proposals are made for the regulatory exploitation of the LLNA: four potency groups can be established, and assignment of substances to these groups according to the outcome of the LLNA can be used to characterize skin sensitizing potency in substance-specific assessments. Moreover, based on these potency groups, a more adequate consideration of sensitizing substances in preparations becomes possible. It is proposed to replace the current single concentration limit for skin sensitizers in preparations, which leads to an all or nothing classification of a preparation as sensitizing to skin ("R43") in the European Union, by differentiated concentration limits derived from the limits for the four potency groups.

Interlaboratory validation of 1% pluronic l92 surfactant as a suitable, aqueous vehicle for testing pesticide formulations using the murine local lymph node assay.

PubMed

Boverhof, Darrell R; Wiescinski, Connie M; Botham, Phil; Lees, David; Debruyne, Eric; Repetto-Larsay, Marina; Ladics, Gregory; Hoban, Denise; Gamer, Armin; Remmele, Marina; Wang-Fan, Weizheng; Ullmann, Ludwig G; Mehta, Jyotigna; Billington, Richard; Woolhiser, Michael R

2008-09-01

The mouse local lymph node assay (LLNA) has become the preferred test for evaluating the dermal sensitization potential of chemicals and requirements are now emerging for its use in the evaluation of their formulated products, especially in the European Union. However, despite its widespread use and extensive validation, the use of this assay for directly testing mixtures and formulated products has been questioned, which could lead to repeat testing using multiple animal models. As pesticide formulations are typically a specific complex blend of chemicals for use as aqueous-based dilutions, traditional vehicles prescribed for the LLNA may change the properties of these formulations leading to inaccurate test results and hazard identification. The objective of this study was to evaluate the effectiveness of an aqueous solution of Pluronic L92 block copolymer surfactant (L92) as a vehicle in the mouse LLNA across five laboratories. Three chemicals with known sensitization potential and four pesticide formulations for which the sensitization potential in guinea pigs and/or humans had previously been assessed were used. Identical LLNA protocols and test materials were used in the evaluation. Assessment of the positive control chemicals, hexylcinnamaldehyde, formaldehyde, and potassium dichromate revealed positive results when using 1% aqueous L92 as the vehicle. Furthermore, results for these chemicals were reproducible among the five laboratories and demonstrated consistent relative potency determinations. The four pesticide formulations diluted in 1% aqueous L92 also demonstrated reproducible results in the LLNA among the five laboratories. Results for these test materials were also consistent with those generated previously using guinea pigs or from human experience. These data support testing aqueous compatible chemicals or pesticide formulations using the mouse LLNA, and provide additional support for the use of 1% aqueous L92 as a suitable, aqueous-based vehicle.

Optimal MRI sequences for 68Ga-PSMA-11 PET/MRI in evaluation of biochemically recurrent prostate cancer.

PubMed

Lake, Spencer T; Greene, Kirsten L; Westphalen, Antonio C; Behr, Spencer C; Zagoria, Ronald; Small, Eric J; Carroll, Peter R; Hope, Thomas A

2017-09-19

PET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with 68 Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on 68 Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with 68 Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7.1 ± 6.6 months. Detection rates of anatomic correlates for prostate-specific membrane antigen (PSMA)-positive foci were evaluated on small field of view (FOV) T2, T1 post-contrast, and diffusion-weighted images. For prostate bed recurrences, the detection rate of dynamic contrast-enhanced (DCE) imaging for PSMA-positive foci was evaluated. Finally, the detection sensitivity for PSMA-avid foci on 3- and 8-min PET acquisitions was compared. PSMA-positive foci were detected in 89.1% (49/55) of patients evaluated. Small FOV T2 performed best for lymph nodes and detected correlates for all PSMA-avid lymph nodes. DCE imaging performed the best for suspected prostate bed recurrence, detecting correlates for 87.5% (14/16) of PSMA-positive prostate bed foci. The 8-min PET acquisition performed better than the 3-min acquisition for lymph nodes smaller than 1 cm, detecting 100% (57/57) of lymph nodes less than 1 cm, compared to 78.9% (45/57) for the 3-min acquisition. PSMA PET/MRI performed well for the detection of sites of suspected recurrent disease in patients with BCR. Of the MRI sequences obtained for localization, small FOV T2 images detected the greatest proportion of PSMA-positive abdominopelvic lymph nodes and DCE imaging detected the greatest proportion of PSMA-positive prostate bed foci. The 8-min PET acquisition was superior to the 3 min acquisition for detection of small lymph nodes.

Luciferase-tagged wild-type and tropism-deficient mouse cytomegaloviruses reveal early dynamics of host colonization following peripheral challenge.

PubMed

Farrell, Helen; Oliveira, Martha; Macdonald, Kate; Yunis, Joseph; Mach, Michael; Bruce, Kimberley; Stevenson, Philip; Cardin, Rhonda; Davis-Poynter, Nicholas

2016-12-01

Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal-foetal transfer, suggesting that their dissemination is a key target for antiviral intervention. Late clinical presentation has meant that human CMV (HCMV) dissemination is not well understood. Murine CMV (MCMV) provides a tractable model. Whole mouse imaging of virus-expressed luciferase has proved a useful way to track systemic infections. MCMV, in which the abundant lytic gene M78 was luciferase-tagged via a self-cleaving peptide (M78-LUC), allowed serial, unbiased imaging of systemic and peripheral infection without significant virus attenuation. Ex vivo luciferase imaging showed greater sensitivity than plaque assay, and revealed both well-known infection sites (the lungs, lymph nodes, salivary glands, liver, spleen and pancreas) and less explored sites (the bone marrow and upper respiratory tract). We applied luciferase imaging to tracking MCMV lacking M33, a chemokine receptor conserved in HCMV and a proposed anti-viral drug target. M33-deficient M78-LUC colonized normally in peripheral sites and local draining lymph nodes but spread poorly to the salivary gland, suggesting a defect in vascular transport consistent with properties of a chemokine receptor.

Potential Surgical and Oncologic Consequences Related to Skin Tattoos in the Treatment of Cervical Cancer.

PubMed

Köhler, Christhardt; Foiato, Tariane; Marnitz, Simone; Schneider, Achim; Le, Xin; Dogan, Nasuh Utku; Pfiffer, Tatiana; Jacob, Anna Elena; Mölgg, Andrea; Hagemann, Ingke; Favero, Giovanni

Skin tattoos on the feet, legs, and lower abdominal wall are progressively gaining popularity. Consequently, the number of tattooed women with cervical cancer has significantly increased in the last decade. However, pigments of tattoo ink can be transported to regional lymph nodes and potentially clog lymphatic pathways that might also be used by sentinel labeling substances. Therefore, here we report whether the presence of tattoo ink affected pelvic lymph nodes in women with early cervical cancer and discuss its potential oncologic and surgical consequences. Prospective observational study. University Hospital in Hamburg, Germany (Canadian Task Force classification II2). Women affected by cervical cancer. Between January 2014 and May 2016, 267 laparoscopic oncologic operations, including at least a pelvic sentinel or complete lymphadenectomy, were performed in the Department of Advanced Surgical and Oncologic Gynecology, Asklepios Hospital, Hamburg, Germany. Among these, 191 patients were affected by cervical cancer. Data of patients in whom dyed lymph nodes without the use of patent blue as a sentinel marker or different from blue-colored pelvic lymph nodes in the case of sentinel procedure were identified and prospectively collected. In 9 patients, skin tattoos localized in the lower extremities caused discoloration of at least 1 pelvic lymph node. This effect was observed in 40% of women (9/23) with tattoos in this area of the body. Mean patient age was 34 years (range, 27-56). All women had cutaneous tattoos on their feet or legs, and in 1 woman an additional tattoo situated on the inferior abdominal wall was observed. The stage of cervical cancer was FIGO IB1 in all cases. One woman was at the 16th week of gestation at the time of cancer diagnosis. On average, 26 pelvic lymph nodes (range, 11-51) were harvested from both pelvic basin sides. None of the removed lymph nodes was tumor involved. Three patients (33%) developed postoperatively infected lymphoceles on the side of the tattooed lymph nodes, and 1 woman had multiple episodes of fever without a clear origin. In women affected by cervical cancer with skin tattoos located in the lower limbs, the pelvic lymph nodes can be partially or totally occupied by the ink. This must be taken into consideration, especially for women scheduled exclusively for sentinel node biopsy. Infectious complications related to nodal dissection, in particular infected lymphoceles, may be more frequent in this population. Copyright © 2016. Published by Elsevier Inc.

Molecular analysis of Mycobacterium isolates from extrapulmonary specimens obtained from patients in Mexico

PubMed Central

Alvarado-Esquivel, Cosme; García-Corral, Nora; Carrero-Dominguez, David; Enciso-Moreno, José Antonio; Gurrola-Morales, Teodoro; Portillo-Gómez, Leopoldo; Rossau, Rudi; Mijs, Wouter

2009-01-01

Background Little information is available on the molecular epidemiology in Mexico of Mycobacterium species infecting extrapulmonary sites in humans. This study used molecular methods to determine the Mycobacterium species present in tissues and body fluids in specimens obtained from patients in Mexico with extrapulmonary disease. Methods Bacterial or tissue specimens from patients with clinical or histological diagnosis of extrapulmonary tuberculosis were studied. DNA extracts from 30 bacterial cultures grown in Löwenstein Jensen medium and 42 paraffin-embedded tissues were prepared. Bacteria were cultured from urine, cerebrospinal fluid, pericardial fluid, gastric aspirate, or synovial fluid samples. Tissues samples were from lymph nodes, skin, brain, vagina, and peritoneum. The DNA extracts were analyzed by PCR and by line probe assay (INNO-LiPA MYCOBACTERIA v2. Innogenetics NV, Gent, Belgium) in order to identify the Mycobacterium species present. DNA samples positive for M. tuberculosis complex were further analyzed by PCR and line probe assay (INNO-LiPA Rif.TB, Innogenetics NV, Gent, Belgium) to detect mutations in the rpoB gene associated with rifampicin resistance. Results Of the 72 DNA extracts, 26 (36.1%) and 23 (31.9%) tested positive for Mycobacterium species by PCR or line probe assay, respectively. In tissues, M. tuberculosis complex and M. genus were found in lymph nodes, and M. genus was found in brain and vagina specimens. In body fluids, M. tuberculosis complex was found in synovial fluid. M. gordonae, M. smegmatis, M. kansasii, M. genus, M. fortuitum/M. peregrinum complex and M. tuberculosis complex were found in urine. M. chelonae/M. abscessus was found in pericardial fluid and M. kansasii was found in gastric aspirate. Two of M. tuberculosis complex isolates were also PCR and LiPA positive for the rpoB gene. These two isolates were from lymph nodes and were sensitive to rifampicin. Conclusion 1) We describe the Mycobacterium species diversity in specimens derived from extrapulmonary sites in symptomatic patients in Mexico; 2) Nontuberculous mycobacteria were found in a considerable number of patients; 3) Genotypic rifampicin resistance in M. tuberculosis complex infections in lymph nodes was not found. PMID:19272158

Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging-A prospective trial.

PubMed

Wagner, Lars M; Kremer, Nathalie; Gelfand, Michael J; Sharp, Susan E; Turpin, Brian K; Nagarajan, Rajaram; Tiao, Gregory M; Pressey, Joseph G; Yin, Julie; Dasgupta, Roshni

2017-01-01

Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single-photon emission computed tomography/computed tomography (SPECT-CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET-CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT-CT with PET-CT for the identification of nodal metastases in pediatric and AYA patients. Twenty-eight pediatric and AYA sarcoma patients underwent SLNB with SPECT-CT. The histological findings of the excised lymph nodes were then correlated with preoperative PET-CT imaging. A median of 2.4 sentinel nodes were sampled per patient. No wound infections or chronic lymphedema occurred. SLNB identified tumors in 7 of the 28 patients (25%), including 3 patients who had normal PET-CT imaging of the nodal basin. In contrast, PET-CT demonstrated hypermetabolic regional nodes in 14 patients, and this resulted in a positive predictive value of only 29%. The sensitivity and specificity of PET-CT for detecting histologically confirmed nodal metastases were only 57% and 52%, respectively. SLNB can safely guide the rational selection of nodes for biopsy in pediatric and AYA sarcoma patients and can identify therapy-changing nodal disease not appreciated with PET-CT. Cancer 2017;155-160. © 2016 American Cancer Society. © 2016 American Cancer Society.

Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma.

PubMed

Kraft, John C; McConnachie, Lisa A; Koehn, Josefin; Kinman, Loren; Collins, Carol; Shen, Danny D; Collier, Ann C; Ho, Rodney J Y

2017-03-27

The aim of the present study was to determine whether a combination of anti-HIV drugs - tenofovir (TFV), lopinavir (LPV) and ritonavir (RTV) - in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma. Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analysed using a validated combination LC-MS/MS assay. For the two active drugs (TFV, LPV), plasma and PBMC intracellular drug levels persisted for over 2 weeks; PBMC drug exposures were three- to four-fold higher than those in plasma. Apparent terminal half-lives (t1/2) of TFV and LPV were 65.3 and 476.9 h in plasma, and 169.1 and 151.2 h in PBMCs. At 24 and 192 h, TFV and LPV drug levels in LNMCs were up to 79-fold higher than those in PBMCs. Analysis of PBMC intracellular TFV and its active metabolite TFV-diphosphate (TFV-DP) indicated that intracellular exposures of total TFV and TFV-DP were markedly higher and persisted longer than in humans and macaques dosed with oral TFV prodrugs, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). A simple, scalable three-drug combination, lipid-stabilized nanosuspension exhibited persistent drug levels in cells of lymph nodes and the blood (HIV host cells) and in plasma. With appropriate dose adjustment, TLC-ART101 may be a useful HIV treatment with a potential to impact residual virus in lymph nodes.

Renal lymph nodes for tumor staging: appraisal of 871 nephrectomies with examination of hilar fat.

PubMed

Mehta, Vikas; Mudaliar, Kumaran; Ghai, Ritu; Quek, Marcus L; Milner, John; Flanigan, Robert C; Picken, Maria M

2013-11-01

Despite decades of research, the role of lymphadenectomy in the management of renal cell carcinoma (RCC) is still not clearly defined. Before the implementation of targeted therapies, lymph node metastases were considered to be a portent of markedly decreased survival, regardless of the tumor stage. However, the role of lymphadenectomy and the relative benefit of retroperitoneal lymph node dissection in the context of modern adjunctive therapies have not been conclusively addressed in the clinical literature. The current pathologic literature does not offer clear recommendations with regard to the minimum number of lymph nodes that should be examined in order to accurately stage the pN in renal cell carcinoma. Although gross examination of the hilar fat to assess the nodal status is performed routinely, it has not yet been determined whether this approach is adequate. To evaluate the status of lymph nodes and their rate of identification in the pathologic examination of nephrectomy specimens in adult renal malignancies. We reviewed the operative and pathology reports of 871 patients with renal malignancies treated by nephrectomy. All tumors were classified according to the seventh edition of the Tumor-Nodes-Metastasis classification. Patients were divided into 3 groups: Nx, no lymph nodes recovered; N0, negative; and N1, with positive lymph nodes. Grossly visible lymph nodes were submitted separately; as per grossing protocol, hilar fatty tissue was submitted for microscopic examination. We evaluated the factors that affected the number of lymph nodes identified and the variables that allowed the prediction of nodal involvement. Lymph nodes were recovered in 333 of 871 patients (38%): hilar in 125 patients, nonhilar in 137 patients, and hilar and nonhilar in 71 patients. Patients with positive lymph nodes (n = 87) were younger, had larger primary tumors, and had lymph nodes of average size, as well as a higher pT stage, nuclear grade, and rate of metastases. Metastases were seen only in grossly identified lymph nodes (65% hilar, 16% nonhilar); all microscopic nodes were negative. Even with the microscopic examination of fat, hilar lymph nodes were recovered in only 22.5% of patients. A nonhilar route of node metastasis was suspected in 40 patients. Only grossly identifiable lymph nodes, both hilar and nonhilar, were positive for metastases. Although microscopic examination of the hilar fat increased the number of lymph nodes recovered, the identification rate of these nodes was low (22.5%), and such microscopic nodes were invariably negative. Hence, microscopic examination of the hilar fat may be unnecessary.

Lymph Node Size on Computed Tomography Images Is a Predictive Indicator for Lymph Node Metastasis in Patients with Colorectal Neuroendocrine Tumors.

PubMed

Tanaka, Toshiaki; Nozawa, Hiroaki; Kawai, Kazushige; Hata, Keisuke; Kiyomatsu, Tomomichi; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Murono, Koji; Watanabe, Toshiaki

2017-01-01

Colorectal neuroendocrine tumors (NET) are a rare manifestation of colorectal neoplasia, requiring for radical dissection of the regional lymph nodes along with colorectal resection similar to that required for colorectal cancer. However, thus far, no reports have described the ability of computed tomography (CT) to predict lymph node involvement. In this study, we revealed the prediction rate of lymph node metastasis using contrast-enhanced CT. A total of 21 patients with colorectal NET undergoing colorectal resection were recruited from January 2010 to June 2016. We compared the CT findings between samples with or without pathologically proven lymph node metastasis, in each field (pericolic/perirectal and intermediate nodes). Within the pericolic/perirectal field, any lymph node larger than 5 mm in the CT images was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and area under ROC curve (AUC) of 66.7%, 87.5%, and 0.844, respectively. Within the intermediate field, any visible lymph node on the CT was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and AUC of 100%, 76.4%, and 0.890, respectively. In addition, when we observed lymph nodes larger than 3 mm on the CT images, the sensitivity and specificity were 100% and 82.4%, respectively, with an AUC of 0.8971. CT images provide predictive information for lymph node metastasis with a high rate of accuracy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer.

PubMed

Dawson, L A; Anzai, Y; Marsh, L; Martel, M K; Paulino, A; Ship, J A; Eisbruch, A

2000-03-15

To analyze the patterns of local-regional recurrence in patients with head and neck cancer treated with parotid-sparing conformal and segmental intensity-modulated radiotherapy (IMRT). Fifty-eight patients with head and neck cancer were treated with bilateral neck radiation (RT) using conformal or segmental IMRT techniques, while sparing a substantial portion of one parotid gland. The targets for CT-based RT planning included the gross tumor volume (GTV) (primary tumor and lymph node metastases) and the clinical target volume (CTV) (postoperative tumor bed, expansions of the GTVs and lymph node groups at risk of subclinical disease). Lymph node targets at risk of subclinical disease included the bilateral jugulodigastric and lower jugular lymph nodes, bilateral retropharyngeal lymph nodes at risk, and high jugular nodes at the base of skull in the side of the neck at highest risk (containing clinical neck metastases and/or ipsilateral to the primary tumor). The CTVs were expanded by 5 mm to yield planning target volumes (PTVs). Planning goals included coverage of all PTVs (with a minimum of 95% of the prescribed dose) and sparing of a substantial portion of the parotid gland in the side of the neck at less risk. The median RT doses to the gross tumor, the operative bed, and the subclinical disease PTVs were 70.4 Gy, 61.2 Gy, and 50.4 Gy respectively. All recurrences were defined on CT scans obtained at the time of recurrence, transferred to the pretreatment CT dataset used for RT planning, and analyzed using dose-volume histograms. The recurrences were classified as 1) "in-field," in which 95% or more of the recurrence volume (V(recur)) was within the 95% isodose; 2) "marginal," in which 20% to 95% of V(recur) was within the 95% isodose; or 3) "outside," in which less than 20% of V(recur) was within the 95% isodose. With a median follow-up of 27 months (range 6 to 60 months), 10 regional recurrences, 5 local recurrences (including one noninvasive recurrence) and 1 stomal recurrence were seen in 12 patients, for a 2-year actuarial local-regional control rate of 79% (95% confidence interval 68-90%). Ten patients (80%) relapsed in-field (in areas of previous gross tumor in nine patients), and two patients developed marginal recurrences in the side of the neck at highest risk (one in the high retropharyngeal nodes/base of skull and one in the submandibular nodes). Four regional recurrences extended superior to the jugulodigastric node, in the high jugular and retropharyngeal nodes near the base of skull of the side of the neck at highest risk. Three of these were in-field, in areas that had received the dose intended for subclinical disease. No recurrences were seen in the nodes superior to the jugulodigastric nodes in the side of the neck at less risk, where RT was partially spared. The majority of local-regional recurrences after conformal and segmental IMRT were "in-field," in areas judged to be at high risk at the time of RT planning, including the GTV, the operative bed, and the first echelon nodes. These findings motivate studies of dose escalation to the highest risk regions.

Castleman Disease Collaborative Network Biobank

ClinicalTrials.gov

2017-07-12

Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymph Node Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH; Hyperplasia; Giant Lymph Node

Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

PubMed Central

Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

1995-01-01

Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

PubMed

Wallace, Anne M; Han, Linda K; Povoski, Stephen P; Deck, Kenneth; Schneebaum, Schlomo; Hall, Nathan C; Hoh, Carl K; Limmer, Karl K; Krontiras, Helen; Frazier, Thomas G; Cox, Charles; Avisar, Eli; Faries, Mark; King, Dennis W; Christman, Lori; Vera, David R

2013-08-01

Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance. A total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept. A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept. [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.

[Hidradenocarcinoma of the heel associated with inguinal metastases].

PubMed

Labbardi, W; Hali, F; Marnissi, F; Cribier, B; Chiheb, S

Hidradenocarcinoma is a rare malignant tumour involving the sweat glands. It classically arises de novo, only rarely resulting from pre-existing hidradenoma. The literature contains few reports of lymph node metastasis in this tumour. We report a case of a patient with hidradenocarcinoma of the heel associated with inguinal node metastases. We report the case of a 64-year-old patient with a history of chronic smoking, who in the last two years developed a painless nodule in his right heel, with no prior injury, and which gradually increased in size to become an ulcerated tumour. Physical examination revealed a rounded tumour mass, ulcerated in the centre, and associated with multiple inguinal adenopathies. Histological and immunohistochemical examination was suggestive of hidradenocarcinoma. The patient had undergone extensive local excision with inguinal lymphadenectomy. Histological examination showed infiltration of lymph nodes by the tumour with capsular rupture. Radiotherapy was subsequently given. The outcome was good without recurrence after 34 months of follow-up. Hidradenocarcinoma is a rare malignant tumour. Diagnosis is based on histological and immunohistochemical examination. However, hidradenocarcinoma may on occasion be difficult to differentiate from hidradenoma, a benign tumour, hence the interest of complete surgical resection with safety margins even in the absence of cytological malignancy. Local recurrences are common. The occurrence of lymph node metastasis during hidradenocarcinoma has been described only rarely in the literature. Such metastases usually occur after tumour resection. The specific features of our case are the rarity of lymph node metastases in hidradenocarcinoma coupled with the fact that these metastases were discovered upon diagnosis of the primary tumour. Copyright © 2017. Published by Elsevier Masson SAS.

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

PubMed

Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Extent of surgery for papillary thyroid cancer: preoperative imaging and role of prophylactic and therapeutic neck dissection.

PubMed

Cisco, Robin M; Shen, Wen T; Gosnell, Jessica E

2012-03-01

Papillary thyroid cancer (PTC) has an excellent prognosis, yet lymph node metastases are common. Most authors agree that central and/or lateral lymph node dissection should be undertaken in patients with abnormal lymph nodes detected on ultrasound, physical examination or intraoperative inspection. However the appropriate extent of prophylactic lymph node dissection for clinically node-negative patients remains the subject of controversy. There have been no randomized trials to date to offer guidance on this issue. The 2006 guidelines of the American Thyroid Association recommended consideration of prophylactic bilateral central lymph node dissection (CLND) for all patients undergoing thyroidectomy for PTC. However, the absence of compelling evidence for a benefit in terms of recurrence or survival, and the potential for increased morbidity, have led many, including our institution, to take an approach of selective central lymph node dissection. This approach is guided by the detection of abnormal lymph nodes on preoperative ultrasound, on physical examination, or during surgery. Postoperatively, ultrasound by an experienced ultrasonographer is the mainstay of evaluation for lymph node recurrence and is combined with monitoring of thyroglobulin and antithyroglobulin antibody levels. Reoperative lymph node dissection is typically undertaken upon detection and fine needle aspiration (FNA) of involved lymph nodes 0.8 cm or greater in size.

Cross-Disciplinary Analysis of Lymph Node Classification in Lung Cancer on CT Scanning.

PubMed

El-Sherief, Ahmed H; Lau, Charles T; Obuchowski, Nancy A; Mehta, Atul C; Rice, Thomas W; Blackstone, Eugene H

2017-04-01

Accurate and consistent regional lymph node classification is an important element in the staging and multidisciplinary management of lung cancer. Regional lymph node definition sets-lymph node maps-have been created to standardize regional lymph node classification. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a lymph node map to supersede all preexisting lymph node maps. Our aim was to study if and how lung cancer specialists apply the IASLC lymph node map when classifying thoracic lymph nodes encountered on CT scans during lung cancer staging. From April 2013 through July 2013, invitations were distributed to all members of the Fleischner Society, Society of Thoracic Radiology, General Thoracic Surgical Club, and the American Association of Bronchology and Interventional Pulmonology to participate in an anonymous online image-based and text-based 20-question survey regarding lymph node classification for lung cancer staging on CT imaging. Three hundred thirty-seven people responded (approximately 25% participation). Respondents consisted of self-reported thoracic radiologists (n = 158), thoracic surgeons (n = 102), and pulmonologists who perform endobronchial ultrasonography (n = 77). Half of the respondents (50%; 95% CI, 44%-55%) reported using the IASLC lymph node map in daily practice, with no significant differences between subspecialties. A disparity was observed between the IASLC definition sets and their interpretation and application on CT scans, in particular for lymph nodes near the thoracic inlet, anterior to the trachea, anterior to the tracheal bifurcation, near the ligamentum arteriosum, between the bronchus intermedius and esophagus, in the internal mammary space, and adjacent to the heart. Use of older lymph node maps and inconsistencies in interpretation and application of definitions in the IASLC lymph node map may potentially lead to misclassification of stage and suboptimal management of lung cancer in some patients. Published by Elsevier Inc.

[Establishment of lymph node metastasis of MDA-MB-231 breast cancer model in nude mice].

PubMed

Wang, Le; Mi, Chengrong; Wang, Wen

2015-06-16

To establish lymph node metastasis of breast cancer model in nude mices using MDA-MB-231 cell lines or tumor masses. Divided twelve female nude mices of five weeks into A, B groups randomly. A group had seven nude mices, B group had five nude mices. A group nude mices were injected with MDA-MB-231 cells suspension into the second right mammary fat pad. Two weeks after emerged tumors, the orthotopic tumors of two nude mices of A group were dissected and then implanted into the second right mammary fat pad of B group nude mices. The other mices of A group continued to be fed. After six weeks of inoculation, we excised the tumors and the swollen lymph nodes in right axilla of all nude mices to make pathological examination. ① A group have a 7/7 tumor formation rate 7 days after implanted, B group was 5/5 5 days after implanted. ② The tumor volumes between the two groups had evident difference (P = 0.023), and the tumor volume of B group was bigger than A group. ③ A group had three nude mices which had one tumid lymph node respectively, the lymph node enlargement rate was 3/5; B group only had one nude mice that had one tumid lymph node, the lymph node enlargement rate was 1/5, the lymph node enlargement rate between the two groups showed no significant difference (P = 0.524). ④ The result of pathology in the two groups testified the tumors were invasive ductal carcinoma. The swollen lymph nodes in A group were reactive hyperplasia lymph nodes; the swollen lymph nodes in B group was metastatic lymph node. The method of orthotopic implantation with MDA-MB-231 tumor mass to establish lymph node metastasis of breast cancer model in nude mice, can provide a useful mean to research the lymph node metastasis mechanism of breast cancer.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of non-lymph node thoracic lesions

PubMed Central

Yang, Huizhen; Zhao, Heng; Garfield, David H.; Teng, Jiajun; Han, Baohui; Sun, Jiayuan

2013-01-01

AIMS: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has shown excellent diagnostic capabilities for mediastinal and hilar lymphadenopathy. However, its value in thoracic non-lymph node lesions is less clear. This study was designed to assess the value of EBUS-TBNA in distinguishing malignant from benign thoracic non-lymph node lesions. METHODS: From October 2009 to August 2011, 552 patients underwent EBUS-TBNA under local anesthesia and with conscious sedation. We retrospectively reviewed 81 of these patients who had tracheobronchial wall-adjacent intrapulmonary or isolated mediastinal non-lymph node lesions. On-site cytological evaluation was not used. Immunohistochemistry (IHC) was performed to distinguish the origin or type of malignancy when necessary. RESULTS: EBUS-TBNA was performed in 68 tracheobronchial wall-adjacent intrapulmonary and 13 isolated mediastinal non-lymph node lesions. Of the 81 patients, 77 (95.1%, 60 malignancies and 17 benignancies) were diagnosed through EBUS-TBNA, including 57 primary lung cancers, 2 mediastinal tumors, 1 pulmonary metastatic adenocarcinoma, 7 inflammation, 5 tuberculosis, 3 mediastinal cysts, 1 esophageal schwannoma, and 1 focal fibrosis. There were four false-negative cases (4.9%). Of the 60 malignancies, there were 9 (15.0%) which originally had no definite histologic origin or type. Thus, IHC was performed, with 7 (77.8%) being subsequently confirmed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in distinguishing malignant from benign lesions were 93.4% (60/64), 100% (17/17), 100% (60/60), 81.0% (17/21), and 95.1% (77/81), respectively. CONCLUSION: EBUS-TBNA is a safe procedure with a high sensitivity for distinguishing malignant from benign thoracic non-lymph node lesions within the reach of EBUS-TBNA, with IHC usually providing a more definitive diagnosis. PMID:23439919

Enhancement of indocyanine green stability and cellular uptake by incorporating cationic lipid into indocyanine green-loaded nanoemulsions.

PubMed

Lee, Eun-Hye; Kim, Jin-Ki; Lim, Joon-Seok; Lim, Soo-Jeong

2015-12-01

Indocyanine green (ICG) is a near-infrared optical dye approved by the Food and Drug Administration. ICG has been investigated as a simultaneous color and fluorescence-imaging tracer for the intraoperative identification of sentinel lymph nodes, but its use has recently expanded to include application as a photosensitizer for the local photodynamic/thermal treatment of identified lymph node metastases. The current study was designed to develop an ICG-loaded nanoemulsion as an effective agent for both the diagnosis and treatment of lymph node metastases. Incorporating the cationic lipid stearylamine (SA) together with ICG in the shell of nanoemulsions did not affect the loaded ICG concentration, but changed the surface charge of nanoemulsions from a negative to a positive value and improved the physical stability of nanoemulsions. Loading ICG into SA-incorporated nanoemulsions more effectively blocked the aggregation and degradation of ICG compared to loading in SA-free nanoemulsions. SA incorporation also enhanced tumor cell uptake of ICG-loaded nanoemulsions, resulting in greater cell killing upon light irradiation. After subcutaneous injection into the footpad of mice, SA-incorporated nanoemulsions increased the concentration of ICG accumulated in popliteal lymph nodes to a greater extent than SA-free nanoemulsions without affecting the kinetics of lymph node uptake of nanoemulsions. These multiple beneficial effects of incorporating SA in nanoemulsions are likely attributable to the electrostatic interaction between anionic ICG and cationic SA, as well as the change in the nanoemulsion surface charge from negative to positive. Our findings indicate that SA-incorporated nanoemulsions are promising ICG carriers for combined diagnosis and treatment of lymph node metastases. Copyright © 2015 Elsevier B.V. All rights reserved.

Consistency mapping of 16 lymph node stations in gastric cancer by CT-based vessel-guided delineation of 255 patients.

PubMed

Xu, Shuhang; Feng, Lingling; Chen, Yongming; Sun, Ying; Lu, Yao; Huang, Shaomin; Fu, Yang; Zheng, Rongqin; Zhang, Yujing; Zhang, Rong

2017-06-20

In order to refine the location and metastasis-risk density of 16 lymph node stations of gastric cancer for neoadjuvant radiotherapy, we retrospectively reviewed the initial images and pathological reports of 255 gastric cancer patients with lymphatic metastasis. Metastatic lymph nodes identified in the initial computed tomography images were investigated by two radiologists with gastrointestinal specialty. A circle with a diameter of 5 mm was used to identify the central position of each metastatic lymph node, defined as the LNc (the central position of the lymph node). The LNc was drawn at the equivalent location on the reference images of a standard patient based on the relative distances to the same reference vessels and the gastric wall using a Monaco® version 5.0 workstation. The image manipulation software Medi-capture was programmed for image analysis to produce a contour and density atlas of 16 lymph node stations. Based on a total of 2846 LNcs contoured (31-599 per lymph node station), we created a density distribution map of 16 lymph node drainage stations of the stomach on computed tomography images, showing the detailed radiographic delineation of each lymph node station as well as high-risk areas for lymph node metastasis. Our mapping can serve as a template for the delineation of gastric lymph node stations when defining clinical target volume in pre-operative radiotherapy for gastric cancer.

Support Vector Machines Model of Computed Tomography for Assessing Lymph Node Metastasis in Esophageal Cancer with Neoadjuvant Chemotherapy.

PubMed

Wang, Zhi-Long; Zhou, Zhi-Guo; Chen, Ying; Li, Xiao-Ting; Sun, Ying-Shi

The aim of this study was to diagnose lymph node metastasis of esophageal cancer by support vector machines model based on computed tomography. A total of 131 esophageal cancer patients with preoperative chemotherapy and radical surgery were included. Various indicators (tumor thickness, tumor length, tumor CT value, total number of lymph nodes, and long axis and short axis sizes of largest lymph node) on CT images before and after neoadjuvant chemotherapy were recorded. A support vector machines model based on these CT indicators was built to predict lymph node metastasis. Support vector machines model diagnosed lymph node metastasis better than preoperative short axis size of largest lymph node on CT. The area under the receiver operating characteristic curves were 0.887 and 0.705, respectively. The support vector machine model of CT images can help diagnose lymph node metastasis in esophageal cancer with preoperative chemotherapy.

Endometrial Cancer and the Role of Lymphadenectomy.

PubMed

Clark, Leslie H; Soper, John T

2016-06-01

The role of lymph node dissection in early-stage endometrial cancer is highly debated, but staging and prognosis are dependent on knowledge of lymph node metastasis. We sought to review the available data on the use of lymph node assessment in presumed early-stage endometrial cancer. A comprehensive literature review was performed using MEDLINE, the Cochrane Collaborative Database, and PubMed. There is limited retrospective data that suggest a therapeutic benefit to lymphadenectomy. Prospective randomized trials have not shown a benefit to lymphadenectomy in low-risk patients, but found significant morbidity in patients undergoing lymphadenectomy. Selective lymph node assessment should be used in low-risk endometrial cancer. Sentinel lymph node assessment is emerging as a potential strategy for lymph node assessment. Selective use of lymphadenectomy in early-stage endometrial cancer can reduce the morbidity associated with lymph node dissection without compromising clinical outcomes. Multiple strategies are available including sentinel lymph nodes and risk factor based lymphadenectomy.

Active Lymphatic Drainage From the Eye Measured by Noninvasive Photoacoustic Imaging of Near-Infrared Nanoparticles.

PubMed

Yücel, Yeni H; Cardinell, Kirsten; Khattak, Shireen; Zhou, Xun; Lapinski, Michael; Cheng, Fang; Gupta, Neeru

2018-06-01

To visualize and quantify lymphatic drainage of aqueous humor from the eye to cervical lymph nodes in the dynamic state. A near-infrared tracer was injected into the right eye anterior chamber of 10 mice under general anesthesia. Mice were imaged with photoacoustic tomography before and 20 minutes, 2, 4, and 6 hours after injection. Tracer signal intensity was measured in both eyes and right and left neck lymph nodes at every time point and signal intensity slopes were calculated. Slope differences between right and left eyes and right and left nodes were compared using paired t-test. Neck nodes were examined with fluorescence optical imaging and histologically for the presence of tracer. Following right eye intracameral injection of tracer, an exponential decrease in tracer signal was observed from 20 minutes to 6 hours in all mice. Slope differences of the signal intensity between right and left eyes were significant (P < 0.001). Simultaneously, increasing tracer signal was observed in the right neck node from 20 minutes to 6 hours. Slope differences of the signal intensity between right and left neck nodes were significant (P = 0.0051). Ex vivo optical fluorescence imaging and histopathologic examination of neck nodes confirmed tracer presence within submandibular nodes. Active lymphatic drainage of aqueous from the eye to cervical lymph nodes was measured noninvasively by photoacoustic imaging of near-infrared nanoparticles. This unique in vivo assay may help to uncover novel drugs that target alternative outflow routes to lower IOP in glaucoma and may provide new insights into lymphatic drainage in eye health and disease.

High Occurrence of Aberrant Lymph Node Spread on Magnetic Resonance Lymphography in Prostate Cancer Patients With a Biochemical Recurrence After Radical Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Lin, Emile N. van; Debats, Oscar A.

2012-03-15

Purpose: To investigate the pattern of lymph node spread in prostate cancer patients with a biochemical recurrence after radical prostatectomy, eligible for salvage radiotherapy; and to determine whether the clinical target volume (CTV) for elective pelvic irradiation in the primary setting can be applied in the salvage setting for patients with (a high risk of) lymph node metastases. Methods and Materials: The charts of 47 prostate cancer patients with PSA recurrence after prostatectomy who had positive lymph nodes on magnetic resonance lymphography (MRL) were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines ofmore » the Radiation Therapy Oncology Group (RTOG) for delineation of the CTV for pelvic irradiation (RTOG-CTV). We defined four lymph node regions for positive nodes outside this RTOG-CTV: the para-aortal, proximal common iliac, pararectal, and paravesical regions. They were referred to as aberrant lymph node regions. For each patient, clinical and pathologic features were recorded, and their association with aberrant lymph drainage was investigated. The distribution of positive lymph nodes was analyzed separately for patients with a prostate-specific antigen (PSA) <1.0 ng/mL. Results: MRL detected positive aberrant lymph nodes in 37 patients (79%). In 20 patients (43%) a positive lymph node was found in the pararectal region. Higher PSA at the time of MRL was associated with the presence of positive lymph nodes in the para-aortic region (2.49 vs. 0.82 ng/mL; p = 0.007) and in the proximal common iliac region (1.95 vs. 0.59 ng/mL; p = 0.009). There were 18 patients with a PSA <1.0 ng/mL. Ten of these patients (61%) had at least one aberrant positive lymph node. Conclusion: Seventy-nine percent of the PSA-recurrent patients had at least one aberrant positive lymph node. Application of the standard RTOG-CTV for pelvic irradiation in the salvage setting therefore seems to be inappropriate.« less

Evaluation of non-radioactive endpoints of ex vivo local lymph node assay-BrdU to investigate select contact sensitizers.

PubMed

Ulker, Ozge Cemiloglu; Ates, Ilker; Atak, Aysegul; Karakaya, Asuman

2013-01-01

The present study sought to verify the utility of the non-radioactive endpoints LLNA BrdU (5-bromo-2'-deoxyuridine) ex vivo incorporation and cytokine release using auricular lymph node cells isolated from BALB/c mice topically treated with a strong (formaldehyde or p-phenylene-diamine [PPD]), moderate sensitizer (cinnamal), or weak sensitizer (eugenol). Stimulation index (SI) and EC₃ values were calculated for each agent. Based on the results of ex vivo LLNA-BrdU assays, EC₃ values were calculated to be 0.29, 0.09, 1.91, and 16.60% for formaldehyde, PPD, cinnamal, and eugenol, respectively. These results were in good agreement with data from previous standard radioactive LLNA. Cytokine analyses indicated T(H)1 and T(H)2 cytokine involvement in the regulation of murine contact allergy and these could be utilized as endpoints in assessments of contact allergy in mice. In conclusion, the current study provided evidence that the non-radioactive endpoint LLNA BrdU ex vivo incorporation could be of use as a viable alternative approach to assess the skin sensitization potential of test compound with respect to improving animal welfare. This is of particular importance in the case of any laboratory where it might be difficult to handle and/or readily employ radioisotopes. Further studies will be required to confirm--across test agents--the reproducibility as well as the limits of utility of this new ex vivo BrdU method.

[Measurement of intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer based on four-dimensional computed tomography (4D-CT)].

PubMed

Wang, Su-zhen; Li, Jian-bin; Zhang, Ying-jie; Li, Feng-xiang; Wang, Wei; Liu, Tong-hai

2012-09-01

To measure the intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer (NSCLC) based on four-dimensional computed tomography (4D-CT), and to provide the basis for the internal margin of metastatic mediastinal lymph nodes. Twenty-four NSCLC patients with mediastinal metastatic lymph nodes confirmed by contrast enhanced CT (short axis diameter ≥ 1 cm) were included in this study. 4D-CT simulation was carried out during free breathing and 10 image sets were acquired. The mediastinal metastatic lymph nodes and the dome of ipsilateral diaphragma were separately delineated on the CT images of 10 phases of breath cycle, and the lymph nodes were grouped as the upper, middle and lower mediastinal groups depending on the mediastinal station. Then the displacements of the lymph nodes in the left-right, anterior-posterior, superior-inferior directions and the 3-dimensional vector were measured. The differences of displacement in three directions for the same group of metastatic lymph nodes and in the same direction for different groups of metastatic lymph nodes were compared. The correlation between the displacement of ipsilateral diaphragma and mediastinal lymph nodes was analyzed in superior-inferior direction. The displacements in left-right, anterior-posterior and superior-inferior directions were (2.24 ± 1.55) mm, (1.87 ± 0.92) mm and (3.28 ± 2.59) mm for the total (53) mediastinal lymph nodes, respectively. The vectors were (4.70 ± 2.66) mm, (3.87 ± 2.45) mm, (4.97 ± 2.75) mm and (5.23 ± 2.67) mm for the total, upper, middle and lower mediastinal lymph nodes, respectively. For the upper mediastinal lymph nodes, the displacements in left-right, anterior-posterior and superior-inferior directions showed no significant difference between each other (P > 0.05). For the middle mediastinal lymph nodes, the displacements merely in anterior-posterior and superior-inferior directions showed significant difference (P = 0.005), while the displacements were not significantly different in the left-right and anterior-posterior, left-right and superior-inferior directions (P > 0.05). The displacements of the total and the lower mediastinal lymph nodes in left-right and superior-inferior, or anterior-posterior and superior-inferior directions were significantly different (P < 0.05), but was not significantly different in left-right and anterior-posterior directions (P > 0.05). The displacements of different group of mediastinal lymph nodes in a single direction or vector showed no significant difference (P > 0.05). In the superior-inferior direction, the correlation between the displacements of ipsilateral diaphragma and mediastinal lymph nodes were not statistically significant (P > 0.05). During free breathing, the differences between the intrafractional displacement of mediastinal metastatic lymph nodes in the same direction and its station were not statistically significant. The displacements of the total mediastinal metastatic lymph nodes in the superior-inferior direction were greater than that in the left-right and anterior-posterior directions, especially for the middle and lower mediastinal metastatic lymph nodes. There was no significant correlation between the displacements of ipsilateral diaphragma and the mediastinal metastatic lymph nodes in the superior-inferior direction, so it was unreasonable to estimate and predict the displacement of mediastinal metastatic lymph nodes by the displacement of ipsilateral diaphragma.

Feasibility of contrast-enhanced ultrasound-guided biopsy of sentinel lymph nodes in dogs.

PubMed

Gelb, Hylton R; Freeman, Lynetta J; Rohleder, Jacob J; Snyder, Paul W

2010-01-01

Our goal was to develop and validate a technique to identify the sentinel lymph nodes of the mammary glands of healthy dogs with contrast-enhanced ultrasound, and evaluate the feasibility of obtaining representative samples of a sentinel lymph node under ultrasound guidance using a new biopsy device. Three healthy intact female adult hounds were anesthetized and each received an injection of octafluoropropane-filled lipid microspheres and a separate subcutaneous injection of methylene blue dye around a mammary gland. Ultrasound was then used to follow the contrast agent through the lymphatic channel to the sentinel lymph node. Lymph node biopsy was performed under ultrasound guidance, followed by an excisional biopsy of the lymph nodes and a regional mastectomy procedure. Excised tissues were submitted for histopathologic examination and evaluated as to whether they were representative of the node. The ultrasound contrast agent was easily visualized with ultrasound leading up to the sentinel lymph nodes. Eight normal lymph nodes (two inguinal, one axillary in two dogs; two inguinal in one dog) were identified and biopsied. Lymphoid tissue was obtained from all biopsy specimens. Samples from four of eight lymph nodes contained both cortical and medullary lymphoid tissue. Contrast-enhanced ultrasound can be successfully used to image and guide minimally invasive biopsy of the normal sentinel lymph nodes draining the mammary glands in healthy dogs. Further work is needed to evaluate whether this technique may be applicable in patients with breast cancer or other conditions warranting evaluation of sentinel lymph nodes in animals.

Assessment of sensitization potential of monoterpenes using the rat popliteal lymph node assay.

PubMed

Friedrich, Karen; Delgado, Isabella F; Santos, Laísa M F; Paumgartten, Francisco J R

2007-08-01

The popliteal lymph node assay (PLNA) has been proposed as a screening test for detecting chemicals with potential of inducing allergic and auto-immune-like reactions in humans. In the present study, we used the rat PLNA to evaluate the immuno-sensitizing potential of 10 monoterpenes found in the essential oils of a variety of aromatic, edible and medicinal plants. The primary or direct PLNA was performed with the monoterpenes, and chlorpromazine (CPZ) and barbital were used as positive and negative controls, respectively. Female, 7-8 week-old Wistar rats were injected subcutaneously (50 microL) with the test substance (0.5, 2.5 or 5mg) into the right hind footpad while the contralateral footpad was injected with the vehicle (DMSO) alone. Weight (WI) and cellularity (CI) indices for draining PLNs were determined 7 days after treatment. PLNA was positive (WI >or= 2 and CI >or= 5) for CPZ, citral, alpha-terpinene, beta-myrcene and (-)-alpha-pinene, and negative for barbital, DMSO, (-)-menthol, 1,8-cineole, (+/-) citronellal, (+)-limonene, (+/-) camphor and terpineol. A secondary PLNA, a T-cell priming test, was carried out with the four substances that had been positive in the primary assay. Six weeks after being locally primed with 5 mg/paw, rats were sc injected into the same footpad with a dose (0.5 mg/paw) of the substance that had been previously found to be insufficient to cause a positive response. WI and CI were then calculated 4 and 7 days after the second injection. CPZ was also positive in the secondary assay thereby confirming that it is a sensitizing agent. Citral, alpha-terpinene, beta-myrcene and (-)-alpha-pinene, however, were negative in the secondary assay. In summary, citral, alpha-terpinene, beta-myrcene and (-)-alpha-pinene induced a clear immuno-stimulatory response due to their irritant properties but no monoterpene proved to be a sensitizing agent in the PLNA.

Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma.

PubMed

Mantel, Hendrik T J; Wiggers, Jim K; Verheij, Joanne; Doff, Jan J; Sieders, Egbert; van Gulik, Thomas M; Gouw, Annette S H; Porte, Robert J

2015-12-01

Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.

Irritancy and Allergic Responses Induced by Topical Application of ortho-Phthalaldehyde

PubMed Central

Anderson, Stacey E.; Umbright, Christina; Sellamuthu, Rajendran; Fluharty, Kara; Kashon, Michael; Franko, Jennifer; Jackson, Laurel G.; Johnson, Victor J.; Joseph, Pius

2010-01-01

Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG1. In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde. PMID:20176622

Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride

PubMed Central

Anderson, Stacey E.; Shane, Hillary; Long, Carrie; Lukomska, Ewa; Meade, B. Jean; Marshall, Nikki B.

2016-01-01

Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. PMID:27216637

INTRACELLULAR LOCALIZATION AND QUANTITATION OF TRITIATED ANTIGENS IN RETICULOENDOTHELIAL TISSUES OF MICE DURING SECONDARY AND HYPERIMMUNE RESPONSES

PubMed Central

Roberts, Audrey N.; Haurowitz, Felix

1962-01-01

Autoradiography and quantitative radiochemical techniques have been used to determine intracellular localization of tritium and the quantity of tissue-bound tritium, respectively, following injections of H3-aniline azo PGG or H3-arsanilazo PGG to yield hyperimmune or secondary response stimulation in mice. Autoradiography revealed intracytoplasmic localization of grains in macrophages of spleen and lung sections, and in Kupffer cells of liver sections following intravenous and subcutaneous injections of H3-aniline azo PGG. Quantitation of tissue section surface radioactivities in the windowless flow counter and scintillation counter, and of dissolved tissue section activities in the scintillation counter, showed that greatest radioactivity was present in lung tissue, with less in spleen, liver, and mesenteric lymph nodes from these hyperimmunized mice. Autoradiographic studies on tissue sections from mice in secondary response stimulation after subcutaneous foot-pad injections of H3-arsanilazo PGG, showed intracellular and extracellular grains over regional popliteal node sections, with intracytoplasmic grain localization over macrophages and pyroninophilic plasmacytes. Scattered macrophages in spleen and lung sections also contained intracytoplasmic radioactivity. Clusters of antibody-synthesizing cells in the regional lymph nodes were demonstrated with fluorescence microscopy, and these cells were compared to similar cells possessing radioactivity as observed in the section autoradiographs. An occasional Russell body plasma cell containing specific antibody was observed in splenic impressions. Windowless flow counting showed that greatest radioactivity was in regional node sections, with less in spleen and lung, and none in contralateral lymph nodes. A quantitative comparison between windowless flow counting and autoradiography revealed that 20 counts were required to yield one silver grain. PMID:13974279

Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang-Chesebro, Alice; Xia Ping; Coleman, Joy

2006-11-01

Purpose: The aim of this study was to quantify gains in lymph node coverage and critical structure dose reduction for whole-pelvis (WP) and extended-field (EF) radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for the first treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate. Methods and Materials: From January to August 2005, 35 patients with localized prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1 (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2 plans retrospectively generated:more » 1 WP 3DCRT plan using bony landmarks, and 1 EF 3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by group. Results: For Group 1, WP 3DCRT missed 25% of pelvic nodes with the prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy, whereas WP IMRT achieved V{sub 45Gy} = 98% and V{sub 42.75Gy} = 100%. Compared with WP 3DCRT, IMRT reduced bladder V{sub 45Gy} by 78%, rectum V{sub 45Gy} by 48%, and small bowel V{sub 45Gy} by 232 cm{sup 3}. EF 3DCRT achieved 95% coverage of nodes for all patients at high cost to critical structures. For Group 2, IMRT decreased bladder V{sub 45Gy} by 90%, rectum V{sub 45Gy} by 54% and small bowel V{sub 45Gy} by 455 cm{sup 3} compared with EF 3DCRT. Conclusion: In this study WP 3DCRT missed a significant percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage, it increased critical structure doses. IMRT improved pelvic nodal coverage while decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients with extended node involvement, IMRT especially decreases small bowel dose.« less

Ultrasonography and fine needle aspirate cytology of the mesenteric lymph node in normal domestic ferrets (Mustela putorius furo).

PubMed

Paul-Murphy, J; O'Brien, R T; Spaeth, A; Sullivan, L; Dubielzig, R R

1999-01-01

The large mesenteric lymph node of 28 normal ferrets was imaged with ultrasound. The large node, located in the mid-abdomen at the root of the mesentery, was round to ovoid and uniformly hyperechoic. Mean ultrasonographic dimensions of the lymph node were 12.6 +/- 2.6 mm by 7.6 +/- 2.0 mm. Fine needle aspirates of 20 lymph nodes were obtained either using ultrasound guided free-hand techniques or at necropsy. The cytological descriptions were compared to histological descriptions of 13 lymph node core biopsies obtained during laparotomy or necropsy as well as 10 peripheral blood smear differentials. The large mesenteric lymph node of ferrets could be easily imaged and measured by ultrasound and evaluated by fine needle aspirate cytology. Normal lymph node cytology may include an eosinophilic infiltrate.

Clinical utilities and biological characteristics of melanoma sentinel lymph nodes

PubMed Central

Han, Dale; Thomas, Daniel C; Zager, Jonathan S; Pockaj, Barbara; White, Richard L; Leong, Stanley PL

2016-01-01

An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient’s nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN. PMID:27081640

Value of lymph node biopsy in the diagnosis of acquired toxoplasmosis.

PubMed

Tuzuner, N; Doğusoy, G; Demirkesen, C; Ozkan, F; Altas, K

1996-04-01

Toxoplasmic lymphadenitis generally involves a solitary lymph node in the head and neck regions, without systemic symptoms. In order to determine the frequency of toxoplasmic lymphadenitis, we reviewed the histological sections of 731 consecutive patients with reactive lymph node hyperplasia. Amongst 731 patients, 112 had histological features supporting a diagnosis of toxoplasmic lymphadenitis (15.3 per cent). In 80 of these patients (71 per cent), either Indirect Haemaglutination test (IHA), in 37 cases, or the Enzyme-Linked Immunosorbent Assay (ELISA) for detecting toxoplasmic IgG or IgM antibodies, in 43 cases, were performed. In 76 out of 80 patients (95 per cent), histological features correlated well with serological studies. The IHA test was positive in 30 patients with a titre of 1/64 or higher. The IgG-ELISA test was positive in 11 whereas the IgM-ELISA test was positive in 28 patients. These results provide further evidence of the distinctive nature of the histological changes in toxoplasmic lymphadenitis, which should enable the clinician to make a confident diagnosis of acute acquired toxoplasmosis.

Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy.

PubMed

Kang, Young-Joon; Han, Wonshik; Park, Soojin; You, Ji Young; Yi, Ha Woo; Park, Sungmin; Nam, Sanggeun; Kim, Joo Heung; Yun, Keong Won; Kim, Hee Jeong; Ahn, Sei Hyun; Park, Seho; Lee, Jeong Eon; Lee, Eun Sook; Noh, Dong-Young; Lee, Jong Won

2017-11-01

Many breast cancer patients with positive axillary lymph nodes achieve complete node remission after neoadjuvant chemotherapy. The usefulness of sentinel lymph node biopsy in this situation is uncertain. This study evaluated the outcomes of sentinel biopsy-guided decisions in patients who had conversion of axillary nodes from clinically positive to negative following neoadjuvant chemotherapy. We reviewed the records of 1247 patients from five hospitals in Korea who had breast cancer with clinically axillary lymph node-positive status and negative conversion after neoadjuvant chemotherapy, between 2005 and 2012. Patients who underwent axillary operations with sentinel biopsy-guided decisions (Group A) were compared with patients who underwent complete axillary lymph node dissection without sentinel lymph node biopsy (Group B). Axillary node recurrence and distant recurrence-free survival were compared. There were 428 cases in Group A and 819 in Group B. Kaplan-Meier analysis showed that recurrence-free survivals were not significantly different between Groups A and B (4-year axillary recurrence-free survival: 97.8 vs. 99.0%; p = 0.148). Multivariate analysis also indicated the two groups had no significant difference in axillary and distant recurrence-free survival. For breast cancer patients who had clinical conversion of axillary lymph nodes from positive to negative following neoadjuvant chemotherapy, sentinel biopsy-guided axillary surgery, and axillary lymph node dissection without sentinel lymph node biopsy had similar rates of recurrence. Thus, sentinel biopsy-guided axillary operation in breast cancer patients who have clinically axillary lymph node positive to negative conversion following neoadjuvant chemotherapy is a useful strategy.

[Numbers of lymph nodes in large intestinal resections for colorectal carcinoma].

PubMed

Motycka, V; Ferko, A; Tycová, V; Nikolov, Hadzi; Sotona, O; Cecka, F; Dusek, T; Chobola, M; Pospísil, I

2010-03-01

Precise evaluation of lymph nodes in the surgical specimen is crucial for the staging and subsequent decision about the adjuvant therapy in colorectal cancer. Prognosis of the patients can be assessed only in cases when at least 12 lymph nodes in the surgical specimen are examined. To evaluate the radicalism of resections for colorectal carcinoma after introducing laparoscopic approach. We compared all resections for primary colorectal cancer and rectal cancer (C 18-C20) performed in the Department of Surgery in University Hospital Hradec Králové in the years 2005 and 2008 and we evaluated numbers of examined lymph nodes in the surgical specimens. The patients with recurrent tumours and the patients with complete pathological response (negative histology) after neoadjuvant therapy were excluded from the study. 117 patients were included in the study in 2005, 2 of them were operated laparoscopically. 155 patients (more by 32.5%) were included in the study in 2008, 53 of them (34.2%) were operated laparoscopically. In tumours of the right part of the colon (C180-C184) treated by right hemicolectomy: on an average 7.9 (+/- 5.3) lymph nodes were examined in the specimens in 2005, and 15.3 (+/- 7.0) lymph nodes in 2008. In tumours of the left part of the colon (C185-C186) treated by left hemicolectomy: 6.5 (+/- 5.1) lymph nodes were examined in 2005, and 19.6 (+/- 15.6) in 2008. In tumours of the sigmoid colon (C187) 9.1 (+/- 6.9) lymph nodes were examined in 2005,and 15.4 (+/- 7.9) in 2008. In tumours of the rectosigmoid junction (C19) 8.0 (+/- 6.9) lymph nodes were examined in 2005, and 17.8 (+/- 11.2) in 2008. In rectal cancer (C20) 5.2 (+/- 4.5) lymph nodes were examined in 2005, and 13.6 (+/- 12.5) in 2008. There is a significant difference in a number of examined lymph nodes in patients without neodadjuvant treatment compared to those with neoadjuvant chemoradiotherapy and neoadjuvant radiotherapy. In 2005, in an average 3.7 (+/- 3.3) lymph nodes were removed in rectal resections after neoadjuvant chemoradiotherapy, in 2008 in an average 7.6 (+/- 6.1) lymph nodes were removed. In 2005, in an average 5.1 (+/- 3.7) lymph nodes in rectal resections after neoadjuvant radiotherapy were removed, in 2008 6.3 (+/- 4.3) lymph nodes were removed. In 2005, in an average 7.0 (+/- 5.5) lymph nodes in rectal resections without neoadjuvant therapy were removed, in 2008 20.9 (+/- 14.1) lymph nodes were removed. Laparoscopic resections were comparable with open resections regarding the number of examined lymph nodes in our group of patients. Introducing the laparoscopic approach to resections of colorectal carcinomas did not decrease radicalism of the operation as to the number of removed lymph nodes.

Pancreas-preserving segmental duodenectomy for gastrointestinal stromal tumor of the duodenum and splenectomy for splenic angiosarcoma.

PubMed

Muroni, Mirko; Ravaioli, Matteo; Del Gaudio, Massimo; Nigri, Giuseppe; D'Angelo, Francesco; Uccini, Stefania; Ramacciato, Giovanni

2012-06-01

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. (111)In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes. We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence.

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma.

PubMed

Yu, Marc Gregory; Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines.

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma

PubMed Central

Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines. PMID:27746818

Phospholipid ether analogs for the detection of colorectal tumors.

PubMed

Deming, Dustin A; Maher, Molly E; Leystra, Alyssa A; Grudzinski, Joseph P; Clipson, Linda; Albrecht, Dawn M; Washington, Mary Kay; Matkowskyj, Kristina A; Hall, Lance T; Lubner, Sam J; Weichert, Jamey P; Halberg, Richard B

2014-01-01

The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×10(10) vs 3.27×10(9) respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.

Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiang, Li; Zhang, Jian-wen; Lin, Sheng

2015-08-01

Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planningmore » target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.« less

Inhibition of the development of metastases by dietary vitamin C:K3 combination.

PubMed

Taper, Henryk S; Jamison, James M; Gilloteaux, Jacques; Summers, Jack L; Calderon, Pedro Buc

2004-07-09

The tumor growth-inhibiting and chemo-potentiating effects of vitamin C and K(3)combinations have been demonstrated both in vitro and in vivo. The purpose of this study was to investigate the influence of orally administered vitamin C and K(3) on the metastasis of mouse liver tumor (T.L.T.) cells implanted in C3H mice. Adult male C3H mice were given water containing vitamin C and K3 (15 g/0.15 g dissolved in 1000 ml) beginning 2 weeks before tumor transplantation until the end of the experiment. T.L.T. cells (106) were implanted intramuscularly in the right thigh of mice. All mice were sacrificed 42 days after tumor transplantation. Primary tumor, lungs, lymph nodes and other organs or tissues suspected of harboring metastases were macroscopically examined. Samples of primary tumors, their local lymph nodes, lungs and main organs such as liver, kidneys, spleen were taken for histological examination. Forty-two percent of control mice exhibited lung metastases and 27% possessed metastases in local lymph nodes whereas 24% of vitamin-treated mice exhibited lung metastases and 10% possessed local lymph nodes metastases. The total number of lung metastases was 19 in control group and 10 in vitamin C and K(3)-treated mice. Histopathological examination of the metastatic tumors from the vitamin-treated mice revealed the presence of many tumor cells undergoing autoschizic cell death. These results demonstrate that oral vitamin C and K(3) significantly inhibited the metastases of T.L.T. tumors in C3H mice. At least a portion of this inhibition was due to tumor cell death by autoschizis.

Phospholipid Ether Analogs for the Detection of Colorectal Tumors

PubMed Central

Deming, Dustin A.; Maher, Molly E.; Leystra, Alyssa A.; Grudzinski, Joseph P.; Clipson, Linda; Albrecht, Dawn M.; Washington, Mary Kay; Matkowskyj, Kristina A.; Hall, Lance T.; Lubner, Sam J.; Weichert, Jamey P.; Halberg, Richard B.

2014-01-01

The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×1010 vs 3.27×109 respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease. PMID:25286226

Modified methylene blue injection improves lymph node harvest in rectal cancer.

PubMed

Liu, Jianpei; Huang, Pinjie; Zheng, Zongheng; Chen, Tufeng; Wei, Hongbo

2017-04-01

The presence of nodal metastases in rectal cancer plays an important role in accurate staging and prognosis, which depends on adequate lymph node harvest. The aim of this prospective study is to investigate the feasibility and survival benefit of improving lymph node harvest by a modified method with methylene blue injection in rectal cancer specimens. One hundred and thirty-one patients with rectal cancer were randomly assigned to the control group in which lymph nodes were harvested by palpation and sight, or to the methylene blue group using a modified method of injection into the superior rectal artery with methylene blue. Analysis of clinicopathologic records, including a long-term follow-up, was performed. In the methylene blue group, 678 lymph nodes were harvested by simple palpation and sight. Methylene blue injection added 853 lymph nodes to the total harvest as well as 32 additional metastatic lymph nodes, causing a shift to node-positive stage in four patients. The average number of lymph nodes harvested was 11.7 ± 3.4 in the control group and 23.2 ± 4.7 in the methylene blue group, respectively. The harvest of small lymph nodes (<5 mm) and the average number of metastatic nodes were both significantly higher in the methylene blue group. The modified method of injection with methylene blue had no impact on overall survival. The modified method with methylene blue injection improved lymph node harvest in rectal cancer, especially small node and metastatic node retrieval, which provided more accurate staging. However, it was not associated with overall survival. © 2014 Royal Australasian College of Surgeons.

The value of quantitative shear wave elastography in differentiating the cervical lymph nodes in patients with thyroid nodules.

PubMed

You, Jun; Chen, Juan; Xiang, Feixiang; Song, Yue; Khamis, Simai; Lu, Chengfa; Lv, Qing; Zhang, Yanrong; Xie, Mingxing

2018-04-01

This study aimed at evaluating the diagnostic performance of quantitative shear wave elastography (SWE) in differentiating metastatic cervical lymph nodes from benign nodes in patients with thyroid nodules. One hundred and forty-one cervical lymph nodes from 39 patients with thyroid nodules that were diagnosed as papillary thyroid cancer had been imaged with SWE. The shear elasticity modulus, which indicates the stiffness of the lymph nodes, was measured in terms of maximum shear elasticity modulus (maxSM), minimum shear elasticity modulus (minSM), mean shear elasticity modulus (meanSM), and standard deviation (SD) of the shear elasticity modulus. All the patients underwent thyroid surgery, 50 of the suspicious lymph nodes were resected, and 91 lymph nodes were followed up for 6 months. The maxSM value, minSM value, meanSM value, and SD value of the metastatic lymph nodes were significantly higher than those of the benign nodes. The area under the curve of the maxSM value, minSM value, meanSM value, and SD value were 0.918, 0.606, 0.865, and 0.915, respectively. SWE can differentiate metastasis from benign cervical lymph nodes in patients with thyroid nodules, and the maxSM, meanSM, and SD may be valuable quantitative indicators for characterizing cervical lymph nodes.

Patterns of Recurrence in Electively Irradiated Lymph Node Regions After Definitive Accelerated Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosch, Sven van den, E-mail: sven.vandenbosch@radboudumc.nl; Dijkema, Tim; Verhoef, Lia C.G.

Purpose: To provide a comprehensive risk assessment on the patterns of recurrence in electively irradiated lymph node regions after definitive radiation therapy for head and neck cancer. Methods and Materials: Two hundred sixty-four patients with stage cT2-4N0-2M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated with accelerated intensity modulated radiation therapy between 2008 and 2012 were included. On the radiation therapy planning computed tomography (CT) scans from all patients, 1166 lymph nodes (short-axis diameter ≥5 mm) localized in the elective volume were identified and delineated. The exact sites of regional recurrences were reconstructed and projected on the initial radiationmore » therapy planning CT scan by performing coregistration with diagnostic imaging of the recurrence. Results: The actuarial rate of recurrence in electively irradiated lymph node regions at 2 years was 5.1% (95% confidence interval 2.4%-7.8%). Volumetric analysis showed an increased risk of recurrence with increasing nodal volume. Receiver operating characteristic analysis demonstrated that the summed long- and short-axis diameter is a good alternative for laborious volume calculations, using ≥17 mm as cut-off (hazard ratio 17.8; 95% confidence interval 5.7-55.1; P<.001). Conclusions: An important risk factor was identified that can help clinicians in the pretreatment risk assessment of borderline-sized lymph nodes. Not overtly pathologic nodes with a summed diameter ≥17 mm may require a higher than elective radiation therapy dose. For low-risk elective regions (all nodes <17 mm), the safety of dose de-escalation below the traditional 45 to 50 Gy should be investigated.« less

Antigen-loaded dendritic cell migration: MR imaging in a pancreatic carcinoma model.

PubMed

Zhang, Zhuoli; Li, Weiguo; Procissi, Daniele; Li, Kangan; Sheu, Alexander Y; Gordon, Andrew C; Guo, Yang; Khazaie, Khashayarsha; Huan, Yi; Han, Guohong; Larson, Andrew C

2015-01-01

To test the following hypotheses in a murine model of pancreatic cancer: (a) Vaccination with antigen-loaded iron-labeled dendritic cells reduces T2-weighted signal intensity at magnetic resonance (MR) imaging within peripheral draining lymph nodes ( LN lymph node s) and (b) such signal intensity reductions are associated with tumor size changes after dendritic cell vaccination. The institutional animal care and use committee approved this study. Panc02 cells were implanted into the flanks of 27 C57BL/6 mice bilaterally. After tumors reached 10 mm, cell viability was evaluated, and iron-labeled dendritic cell vaccines were injected into the left hind footpad. The mice were randomly separated into the following three groups (n = 9 in each): Group 1 was injected with 1 million iron-labeled dendritic cells; group 2, with 2 million cells; and control mice, with 200 mL of phosphate-buffered saline. T1- and T2-weighted MR imaging of labeled dendritic cell migration to draining LN lymph node s was performed before cell injection and 6 and 24 hours after injection. The signal-to-noise ratio ( SNR signal-to-noise ratio ) of the draining LN lymph node s was measured. One-way analysis of variance ( ANOVA analysis of variance ) was used to compare Prussian blue-positive dendritic cell measurements in LN lymph node s. Repeated-measures ANOVA analysis of variance was used to compare in vivo T2-weighted SNR signal-to-noise ratio LN lymph node measurements between groups over the observation time points. Trypan blue assays showed no significant difference in mean viability indexes (unlabeled vs labeled dendritic cells, 4.32% ± 0.69 [standard deviation] vs 4.83% ± 0.76; P = .385). Thirty-five days after injection, the mean left and right flank tumor sizes, respectively, were 112.7 mm(2) ± 16.4 and 109 mm(2) ± 24.3 for the 1-million dendritic cell group, 92.2 mm(2) ± 9.9 and 90.4 mm(2) ± 12.8 for the 2-million dendritic cell group, and 193.7 mm(2) ± 20.9 and 189.4 mm(2) ± 17.8 for the control group (P = .0001 for control group vs 1-million cell group; P = .00007 for control group vs 2-million cell group). There was a correlation between postinjection T2-weighted SNR signal-to-noise ratio decreases in the left popliteal LN lymph node 24 hours after injection and size changes at follow-up for tumors in both flanks (R = 0.81 and R = 0.76 for left and right tumors, respectively). MR imaging approaches can be used for quantitative measurement of accumulated iron-labeled dendritic cell-based vaccines in draining LN lymph node s. The amount of dendritic cell-based vaccine in draining LN lymph node s correlates well with observed protective effects.

Expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer.

PubMed

Mikami, Koji; Hirano, Yukiko; Futami, Kitaro; Maekawa, Takafumi

2017-07-18

Mixed-type early gastric cancer (differentiated and undifferentiated components) incurs a higher risk of lymph node metastasis than pure-type early gastric cancer (only differentiated or only undifferentiated components). Therefore, we investigated the expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer in order to establish the most appropriate treatment for mixed-type cancer. We retrospectively analyzed 279 consecutive patients with submucosal invasive gastric cancer who underwent curative gastrectomy for gastric cancer between 1996 and 2015. We classified the patients into the mixed-type and pure-type groups according to histologic examination and evaluated the expansion of lymph node metastasis. The rate of lymph node metastasis was 23.7% (66/279) in the total patients, 36.4% (36/99) in the mixed-type group, and 16.6% (30/180) in the pure-type group. The significant independent risk factors for lymph node metastasis were tumor size ≥2.0 cm (P = 0.014), mixed-type gastric cancer (P < 0.001), and lymphatic invasion (P < 0.001). Lymphatic invasion and lymph node metastasis had a strong relationship in mixed-type group. The rates of no. 7 lymph node metastasis in the total patients and mixed-type group were 2.9% (8/279) and 5.1% (5/99), respectively; the rates of no. 8a lymph node metastasis were 1.4% (4/279) and 4.0% (4/99), respectively. Mixed histological type is an independent risk factor for lymph node metastasis. Lymph node metastasis in mixed-type gastric cancer involves expansion to the no. 7 and no. 8a lymph nodes. Therefore, lymphadenectomy for mixed-type submucosal invasive gastric cancer requires D1+ or D2 dissection. Copyright © 2017. Published by Elsevier Taiwan.

Magnetic Resonance Lymphography-Guided Selective High-Dose Lymph Node Irradiation in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Debats, Oscar A.; Kunze-Busch, Martina

2012-01-01

Purpose: To demonstrate the feasibility of magnetic resonance lymphography (MRL) -guided delineation of a boost volume and an elective target volume for pelvic lymph node irradiation in patients with prostate cancer. The feasibility of irradiating these volumes with a high-dose boost to the MRL-positive lymph nodes in conjunction with irradiation of the prostate using intensity-modulated radiotherapy (IMRT) was also investigated. Methods and Materials: In 4 prostate cancer patients with a high risk of lymph node involvement but no enlarged lymph nodes on CT and/or MRI, MRL detected pathological lymph nodes in the pelvis. These lymph nodes were identified and delineatedmore » on a radiotherapy planning CT to create a boost volume. Based on the location of the MRL-positive lymph nodes, the standard elective pelvic target volume was individualized. An IMRT plan with a simultaneous integrated boost (SIB) was created with dose prescriptions of 42 Gy to the pelvic target volume, a boost to 60 Gy to the MRL-positive lymph nodes, and 72 Gy to the prostate. Results: All MRL-positive lymph nodes could be identified on the planning CT. This information could be used to delineate a boost volume and to individualize the pelvic target volume for elective irradiation. IMRT planning delivered highly acceptable radiotherapy plans with regard to the prescribed dose levels and the dose to the organs at risk (OARs). Conclusion: MRL can be used to select patients with limited lymph node involvement for pelvic radiotherapy. MRL-guided delineation of a boost volume and an elective pelvic target volume for selective high-dose lymph node irradiation with IMRT is feasible. Whether this approach will result in improved outcome for these patients needs to be investigated in further clinical studies.« less

[Application of lymph node labeling with carbon nanoparticles by preoperative endoscopic subserosal injection in laparoscopic radical gastrectomy].

PubMed

Hong, Q; Wang, Y; Wang, J J; Hu, C G; Fang, Y J; Fan, X X; Liu, T; Tong, Q

2017-01-10

Objective: To evaluate the application value of carbon lymph node tracing technique by preoperative endoscopic subserosal injection in laparoscopic radical gastrectomy. Methods: From June 2013 to February 2015, seventy eight patients with gastric cancer were enrolled and randomly divided into trial group and control group. Subserosal injection of carbon nanoparticles around the tumor was performed by preoperative endoscopic subserosal injection one day before the operation in trial group, while the patients routinely underwent laparoscopic gastrectomy in control group. Results of harvested lymph nodes, postoperative complications were compared between the two groups. Carbon nanoparticle-related side effect was also evaluated. Results: The average number of harvested lymph node in trial group was significantly higher than that in control group (35.5±8.5 vs 29.5±6.5, P <0.05). The rate of overall black-dyed harvested lymph node was 74.7% (1 035/1 386) in trial group, the black-dyed lymph node rate in D1 lymph node was 80.1%, which was significantly higher than that in D2 lymph node (69.8%, χ 2 =19.38, P <0.01). When comparing the lymph node with and without black-dyed in trial group, the rate of metastasis lymph node was significantly higher in lymph node with black-dyed (17.3% vs 4.0%, χ 2 =38.67, P <0.01). There was no significant difference in postoperative complications rate between two group (trial group 10.2%; control group 12.8%, χ 2 =0.00, P >0.05), and no carbon nanoparticle-related side effect was observed. Conclusion: Given a higher harvested lymph node number and a similar rate of complications, preoperative endoscopic subserosal injection of carbon nanoparticles was safe and feasible.

Lymph nodes

MedlinePlus Videos and Cool Tools

... and conveying lymph and by producing various blood cells. Lymph nodes play an important part in the ... the microorganisms being trapped inside collections of lymph cells or nodes. Eventually, these organisms are destroyed and ...

Evaluation of the anaphylactoid potential of Andrographis paniculata extracts using the popliteal lymph node assay and P815 cell degranulation in vitro.

PubMed

Hu, Xuguang; Wen, Ya; Liu, Shasha; Luo, Jiabo; Tan, Xiaomei; Li, Zhiheng; Lu, Xinhua; Long, Xiaoying

2015-04-14

The anaphylactoid reactions induced by andrographis injection have repeatedly been reported. The aim of our study was to evaluate the immuno-sensitizing potential of extracts from Andrographis paniculata Nees and to screen for the constituent that is responsible for inducing the anaphylactoid reaction. In the direct popliteal lymph node assay (D-PLNA), female BALB/c mice were randomly divided into several groups with ten mice per group according to the experiment design, the right hind footpads of mice received a single subcutaneous injection of Andrographis paniculata (50 μl), and the left hind footpads received the same volume of vehicle. Seven days later, the mice were sacrificed by cervical dislocation, and the popliteal lymph nodes from both the left and right sides were removed. The weight (WI) and cellularity indices (CI) of the popliteal lymph nodes (PLNs) were then calculated, and the pathological changes of the PLNs were measured. In addition, P815 mast cells were collected for the in vitro cell degranulation experiment. The level of histamine, the percentage of cell degranulation and the ratio of ammonia glycosidase released were measured to further evaluate the potential allergenicity. Alcohol extract (AEE), ethyl acetate extract (EAE) and n-butanol extract (NBE) significantly increased the weight (WI > 2) and cell number (CI > 5) of PLNs (P < 0.05, P < 0.01). Additionally, all the three monomers of andrographis, namely NAD, AND, and DDA, significantly increased the weight (WI > 2) and cell number (CI > 5) of the PLNs (P < 0.05, P < 0.01). In the cell model, all of the different extract fractions (AEE, EAE and NBE) and the three monomers of andrographis markedly elevated the level of histamine, the percentage of cell degranulation and the ratio of ammonia glycosidase released. The diterpene lactone compounds of Andrographis paniculata Nees (total lactones of andrographolide) may have a potential sensitizing capacity in andrographis injection.

[Injection of methylene blue into inferior mesenteric artery improves lymph node harvest in rectal cancer after neoadjuvant chemotherapy].

PubMed

Liu, Jianpei; Huang, Pinjie; Huang, Jianglong; Chen, Tufeng; Wei, Hongbo

2015-06-09

To confirm the feasibility of improving lymph node harvest by injecting methylene blue into inferior mesenteric artery in rectal cancer after neoadjuvant therapy. Forty two ex vivo specimens were collected from rectal cancer patients with neoadjuvant therapy and radical operation at our hospital. Traditional method with palpation and injection of methylene blue into inferior mesenteric artery were employed. The data of lymph node harvest were analyzed by paired t and chi-square tests. The average number of detected lymph node in traditional method and methylene blue groups were 6.1 ± 4.3 and 15.2 ± 6.4 respectively (P<0.001). The proportions of lymph nodes <5 mm were 14.1% and 46.7% in traditional method and methylene blue groups respectively (P<0.001). And the injection of methylene blue added 13 extra metastatic lymph nodes and caused a shift to node-positive stage (P=0.89). Neoadjuvant therapy decrease lymph node retrieval in rectal cancer. Injecting methylene blue into inferior mesenteric artery improves lymph node harvest especially for small nodes and helps to acquire more metastatic nodes for accurate pathological staging.

Iodine-131: An Effective Method for Treating Lymph Node Metastases of Differentiated Thyroid Cancer.

PubMed

He, Ying; Pan, Ming-Zhi; Huang, Jian-Min; Xie, Peng; Zhang, Fang; Wei, Ling-Ge

2016-12-15

BACKGROUND The aim of this study was to assess the efficacy of radioactive iodine-131 (¹³¹I) therapy for lymph node metastasis of differentiated thyroid cancer (DTC) and to identify influential factors using univariate and multivariate analyses to determine if identified factors influence the efficacy of treatment. MATERIAL AND METHODS This study included a retrospective review of 218 patients with histologically proven DTC in the post-operation stage. After thyroid tissue remnants were eliminated with ¹³¹I therapy, patients' lymph node status was confirmed by ultrasound and by ¹³¹I whole body scan regarding lymph node metastasis, and then patients were treated with ¹³¹I as appropriate. The treatment efficacy was assessed and possible influencing factors were identified using univariate and multivariate analyses. RESULTS The total effective rate of ¹³¹I therapy was 88.07% (including a cure rate of 20.64% and an improvement rate of 67.43%). The non-effective rate was 11.93%. Of the total 406 lymph nodes of 218 patients, 319 lymph nodes (78.57%) were judged to be effectively cured, including 133 (32.75%) lymph nodes that were totally eliminated and 186 (45.82%) lymph nodes that shrank. Eighty-seven (21.43%) of the 406 lymph nodes had no obvious change. No lymph nodes were found to be in a continuously enlarging state. Distant metastasis, size of lymph node, human serum thyroglobulin (HTG) level, and condition of thyroid remnants ablation were identified as the independent factors influencing the efficacy of treatment using univariate and multivariate analyses. CONCLUSIONS The use of ¹³¹I is a promising treatment for lymph node metastasis of DCT. Distant metastasis, size of lymph nodes, HTG level, and condition of thyroid remnant ablation were independent factors influencing the treatment efficacy.

Surgical management of primary, metastatic and recurrent anal sac adenocarcinoma in the dog: 52 cases.

PubMed

Barnes, D C; Demetriou, J L

2017-05-01

To report the outcomes and complications of a cohort of dogs with primary and recurrent anal sac adenocarcinoma managed with surgery as the first-line treatment. To report the use of lymph node cytology for identification of metastatic disease. Retrospective review of case records of a single referral centre population of dogs diagnosed with anal sac adenocarcinoma. Fifty-two clinical cases were identified. Altered ultrasonographic appearance of lymph nodes was highly consistent with metastatic disease as assessed by cytology and histopathology. Seven of 58 (12%) perineal surgeries had reported minor complications and seven (12%) others required further surgical intervention. Minor controllable intraoperative bleeding was the only complication noted associated with lymph node extirpation in two of 39 (5%) metastectomy procedures. Six dogs (12%) suffered local recurrence and 22 (42%) developed subsequent or recurrent nodal metastatic disease. From the time of detection of disease recurrence, median additional survival associated with a second surgical intervention was 283 days. Coeliotomy for lymph node metastatectomy in dogs with adenocarcinoma of the anal sac has low morbidity and should be considered in patients presenting with evidence of regional metastatic disease both at initial presentation and with recurrent disease. © 2017 British Small Animal Veterinary Association.

Histological differential diagnosis between lymph node toxoplasmosis and other benign lymph node hyperplasias.

PubMed

Miettinen, M

1981-03-01

The material from 667 lymph nodes, originally suspected of toxoplasmosis, was histologically re-examined, to evaluate criteria for diagnosis and differential diagnosis. The results showed that at least 80% of benign lymph node enlargements containing small groups of epithelioid cells were associated with high titres of Toxoplasma antibodies. Furthermore, 85--95% of the lymph nodes in association with high Toxoplasma antibodies showed the typical histological appearances of toxoplasmosis. The histological diagnosis of toxoplasmosis is thus both fairly specific and sensitive. Other lymph node lesions with small groups of epithelioid cells must be considered in the differential diagnosis. Sarcoidosis and tuberculosis usually have a predominance of distinct large epithelioid cell granulomata. Lymph nodes with sinus histiocytosis showing the formation of small groups of epithelioid cells, do not demonstrate prominent hyperplasia and include sparse germinal centres and were not associated with toxoplasmosis. Lymph nodes with disturbed general structure and small groups of epithelioid cells must be carefully assessed because of the significant possibility of malignancy.

Nano-titanium dioxide modulates the dermal sensitization potency of DNCB

PubMed Central

2012-01-01

We determined the ability of a model nanoparticle (NP) (titanium dioxide, TiO2) to modulate sensitization induced by a known potent dermal sensitizer (dinitrochlorobenzene) using a variant of the local lymph node assay called lymph node proliferation assay. BALB/c mice received sub-cutaneous injections of vehicle (2.5 mM sodium citrate), TiO2 NPs (0.004, 0.04 or 0.4 mg/ml) or pigment particles (0.04 mg/ml) both stabilized in sodium citrate buffer at the base of each ear (2x50μl), before receiving dermal applications (on both ears) of 2,4-Dinitrochlorobenzene (DNCB) (2x25μl of 0.1%) or its vehicle (acetone olive oil – AOO (4:1)) on days 0, 1 and 2. On day 5, the stimulation index (SI) was calculated as a ratio of 3HTdR incorporation in lymphocytes from DNBC-treated mice and AOO-treated controls. In a second experiment the EC3-value for DNCB (0 to 0.1%) was assessed in the absence or presence of 0.04 mg/ml TiO2. In a third experiment, the lymphocyte subpopulations and the cytokine secretion profile were analyzed after TiO2 (0.04 mg/ml) and DNCB (0.1%) treatment. Injection of NPs in AOO-treated control mice did not have any effect on lymph node (LN) proliferation. DNCB sensitization resulted in LN proliferation, which was further increased by injection of TiO2 NPs before DNCB sensitization. The EC3 of DNCB, with prior injection of vehicle control was 0.041%, while injection with TiO2 decreased the EC3 of DNCB to 0.015%. TiO2 NPs pre-treatment did not alter the lymphocyte subpopulations, but significantly increased the level of IL-4 and decreased IL-10 production in DNCB treated animals. In conclusion, our study demonstrates that administration of nano-TiO2 increases the dermal sensitization potency of DNCB, by augmenting a Th2 response, showing the immunomodulatory abilities of NPs. PMID:22621278

A critical evaluation of lymph node ratio in head and neck cancer.

PubMed

de Ridder, M; Marres, C C M; Smeele, L E; van den Brekel, M W M; Hauptmann, M; Balm, A J M; van Velthuysen, M L F

2016-12-01

In head and neck squamous cell carcinoma (HNSCC), the search for better prognostic factors beyond TNM-stage is ongoing. Lymph node ratio (LNR) (positive lymph nodes/total lymph nodes) is gaining interest in view of its potential prognostic significance. All HNSCC patients at the Netherlands Cancer Institute undergoing neck dissection for lymph node metastases in the neck region between 2002 and 2012 (n = 176) were included. Based on a protocol change in specimen processing, the cohort was subdivided in two distinct consecutive periods (pre and post 2007). The prognostic value of LNR, N-stage, and number of positive lymph nodes for overall survival was assessed. The mean number of examined lymph nodes after 2007 was significantly higher (42.3) than before (35.8) (p = 0.024). The higher number concerned mostly lymph nodes in level V. The mean number of positive lymph nodes before 2007 was 3.3 vs. 3.6 after 2007 (p = 0.745). By multivariate analysis of both pre- and post-2007 cohort data, two factors remained associated with an increased hazard of dying: N2 [HR 2.1 (1.1-4.1) and 2.4 (1.0-5.8)] and >3 positive lymph nodes [HR 2.0 (1.1-3.5) and 3.1 (1.4-6.9)]. Hazard ratio for LNR >7 % was not significantly different: pre 2007 at 2.2 (1.3-3.8) and post 2007 at 2.1 (1.0-4.8, p = 0.053). In this study, changes in specimen processing influenced LNR values, but not the total number of tumor positive nodes found. Therefore, in HNSCC, the number of positive nodes seems a more reliable parameter than LNR, provided a minimum number of lymph nodes are examined.

Effectiveness of the Benign and Malignant Diagnosis of Mediastinal and Hilar Lymph Nodes by Endobronchial Ultrasound Elastography.

PubMed

Huang, Haidong; Huang, Zhiang; Wang, Qin; Wang, Xinan; Dong, Yuchao; Zhang, Wei; Zarogoulidis, Paul; Man, Yan-Gao; Schmidt, Wolfgang Hohenforst; Bai, Chong

2017-01-01

Background and Objectives: Endobronchial ultrasound elastography is a new technique for describing the stiffness of tissue during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The aims of this study were to investigate the diagnostic value of Endobronchial ultrasound (EBUS) elastography for distinguishing the difference between benign and malignant lymph nodes among mediastinal and hilar lymph node. Materials and Methods: From June 2015 to August 2015, 47 patients confirmed of mediastinal and hilar lymph node enlargement through examination of Computed tomography (CT) were enrolled, and a total of 78 lymph nodes were evaluated by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). EBUS-guided elastography of lymph nodes was performed prior to EBUS-TBNA. A convex probe EBUS was used with a new EBUS processor to assess elastographic patterns that were classified based on color distribution as follows: Type 1, predominantly non-blue (green, yellow and red); Type 2, part blue, part non-blue (green, yellow and red); Type 3, predominantly blue. Pathological determination of malignant or benign lymph nodes was used as the gold standard for this study. The elastographic patterns were compared with the final pathologic results from EBUS-TBNA. Results: On pathological evaluation of the lymph nodes, 45 were benign and 33 were malignant. The lymph nodes that were classified as Type 1 on endobronchial ultrasound elastography were benign in 26/27 (96.3%) and malignant in 1/27 (3.7%); for Type 2 lymph nodes, 15/20 (75.0%) were benign and 5/20 (25.0%) were malignant; Type 3 lymph nodes were benign in 4/31 (12.9%) and malignant in 27/31 (87.1%). In classifying Type 1 as 'benign' and Type 3 as 'malignant,' the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rates were 96.43%, 86.67%, 87.10%, 96.30%, 91.38%, respectively. Conclusion: EBUS elastography of mediastinal and hilar lymph nodes is a noninvasive technique that can be performed reliably and may be helpful in the prediction of benign and malignant lymph nodes among mediastinal and hilar lymph node during EBUS-TBNA.

PRC2/EED-EZH2 Complex Is Up-Regulated in Breast Cancer Lymph Node Metastasis Compared to Primary Tumor and Correlates with Tumor Proliferation In Situ

PubMed Central

Yu, Hongxiang; Simons, Diana L.; Segall, Ilana; Carcamo-Cavazos, Valeria; Schwartz, Erich J.; Yan, Ning; Zuckerman, Neta S.; Dirbas, Frederick M.; Johnson, Denise L.; Holmes, Susan P.; Lee, Peter P.

2012-01-01

Background Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression. Methodology/Principal Findings We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors. Conclusions/Significance This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens up epigenetic drug development possibilities for the treatment and prevention of lymph node metastasis in breast cancer. PMID:23251464

DIAGNOSIS AND IMPLICATIONS OF MYCOBACTERIUM BOVIS INFECTION IN BANDED MONGOOSES (MUNGOS MUNGO) IN THE KRUGER NATIONAL PARK, SOUTH AFRICA.

PubMed

Brüns, Angela C; Tanner, Manfred; Williams, Mark C; Botha, Louise; O'Brien, Amanda; Fosgate, Geoffrey T; van Helden, Paul D; Clarke, John; Michel, Anita L

2017-01-01

Bovine tuberculosis (bTB) was first diagnosed in the Kruger National Park (KNP) in 1990. Research has since focused on the maintenance host, the African buffalo ( Syncerus caffer ) and clinically affected lion ( Panthera leo ). However, little is known about the role of small predators in tuberculosis epidemiology. During 2011-12, we screened banded mongooses ( Mungos mungo ) in the bTB high-prevalence zone of the KNP for Mycobacterium tuberculosis complex members. Fecal swabs, tracheal swabs, and tracheal lavages of 76 banded mongooses caught in cage traps within a 2-km radius of Skukuza Rest Camp were submitted for Mycobacterium culture, isolation, and species identification. Lesions and lymph node samples collected from 12 animals at postmortem examination were submitted for culture and histopathology. In lung and lymph nodes of two banded mongooses, well demarcated, irregularly margined, gray-yellow nodules of up to 5 mm diameter were identified with either central necrosis or calcification, characterized on histopathology as caseating necrosis with epithelioid macrophages or necrogranuloma with calcified centre. No acid fast bacteria were identified with Ziehl-Neelsen stain. We isolated Mycobacterium bovis from lung, lymph node, and liver samples, as well as from tracheal lavages and tracheal swab from the same two banded mongooses. Blood samples were positive by ElephantTB STAT-PAK® Assay for 12 and Enferplex™ TB Assay for five animals. Only the two banded mongooses positive on pathology and M. bovis culture were positive on both serologic assays. We provide evidence of bTB infection in banded mongooses in the KNP, demonstrate their ability to shed M. bovis , and propose a possible antemortem diagnostic algorithm. Our findings open the discussion around possible sources of infection and their significance at the human/wildlife interface in and around Skukuza.

[Risk factors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node ≤ 2].

PubMed

Gao, Yajun; He, Yingjian; Fan, Zhaoqing; Ouyang, Tao

2014-08-13

To explore retrospectively the risk factors of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with sentinel lymph node metastasis ≤ 2 and examine the likelihood of non-sentinel lymph node prediction. A sentinel lymph node biopsy database containing 455 breast cancer patients admitted between July 2005 and February 2012 at Beijing Cancer Hospital was analyzed retrospectively. The patients had ≤ 2 positive sentinel lymph node and complete axillary lymph node dissection. The SLNS⁺/SLNS ratio (P = 0.001), histological grade (P = 0.075), size of mass (P = 0.023) and onset age (P = 0.074) were correlated with NSLN metastases. Only SLNS⁺/SLNS (OR 0.502 95% CI 0.322-0.7844) , histological grade ratio (histological grade ratio II, III and others vs grade I OR 2.696, 2.102, 3.662) were significant independent predictors for NSLN metastases . The ROC value was 0.62 (0.56, 0.68). For ≤ 2 positive sentinel lymph nodes of breast cancer, ratio of SLNS⁺/SLNS and histological grading are independent factors affecting NSLN metastases. However, the results remain unsatisfactory for predicting the status of NSLN.

Automatic identification of IASLC-defined mediastinal lymph node stations on CT scans using multi-atlas organ segmentation

NASA Astrophysics Data System (ADS)

Hoffman, Joanne; Liu, Jiamin; Turkbey, Evrim; Kim, Lauren; Summers, Ronald M.

2015-03-01

Station-labeling of mediastinal lymph nodes is typically performed to identify the location of enlarged nodes for cancer staging. Stations are usually assigned in clinical radiology practice manually by qualitative visual assessment on CT scans, which is time consuming and highly variable. In this paper, we developed a method that automatically recognizes the lymph node stations in thoracic CT scans based on the anatomical organs in the mediastinum. First, the trachea, lungs, and spines are automatically segmented to locate the mediastinum region. Then, eight more anatomical organs are simultaneously identified by multi-atlas segmentation. Finally, with the segmentation of those anatomical organs, we convert the text definitions of the International Association for the Study of Lung Cancer (IASLC) lymph node map into patient-specific color-coded CT image maps. Thus, a lymph node station is automatically assigned to each lymph node. We applied this system to CT scans of 86 patients with 336 mediastinal lymph nodes measuring equal or greater than 10 mm. 84.8% of mediastinal lymph nodes were correctly mapped to their stations.

Comparative study between ultrasound-guided fine needle aspiration cytology of axillary lymph nodes and sentinel lymph node histopathology in early-stage breast cancer

PubMed Central

Cardoso-Coelho, Lívio Portela; Borges, Rafael Soares; Alencar, Airlane Pereira; Cardoso-Campos-Verdes, Larysse Maira; da Silva-Sampaio, João Paulo; Borges, Umbelina Soares; Gebrim, Luiz Henrique; da Silva, Benedito Borges

2017-01-01

The replacement of sentinel lymph node biopsy (SNB) by ultrasound-guided fine-needle aspiration (US-guided FNA) cytology of axillary lymph nodes is controversial, despite the simplicity and reduced cost of the latter. In the present study, US-guided FNA was performed in 27 patients with early-stage breast cancer for comparison with SNB. Data were analyzed by calculation of sample proportions. Tumor subtypes included invasive ductal carcinoma (85%), invasive lobular carcinoma (7%), and tubular and metaplastic carcinoma (4%). FNA had a sensitivity of 45%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 73%. Axillary lymph node cytology obtained by US guided-FNA in patients with breast cancer had a specificity similar to that of sentinel lymph node histopathology in the presence of axillary node metastases. However, when lymph node cytology is negative, it does not exclude the existence of metastatic implants, due to its low sensitivity in comparison to sentinel lymph node histopathology. PMID:28521436

Evaluation of the GeneXpert MTB/RIF assay on extrapulmonary and respiratory samples other than sputum: a low burden country experience.

PubMed

Pandey, Sushil; Congdon, Jacob; McInnes, Bradley; Pop, Alina; Coulter, Christopher

2017-01-01

The aim of this study was to assess the performance of the GeneXpert MTB/RIF assay on extrapulmonary (EP) and respiratory (non-sputum) clinical samples of patients suspected of having tuberculosis (TB) from Queensland, Australia. A total of 269 EP and respiratory (non-sputum) clinical samples collected from Qld patients who were suspected of having TB were subjected to the GeneXpert MTB/RIF analysis, Ziehl-Neelsen (ZN) staining, Mycobacterium tuberculosis (MTB) culture and drug susceptibility testing. Phenotypic and genotypic data were compared. The overall performance analysis of the GeneXpert MTB/RIF assay for detection of MTB complex demonstrated sensitivity of 89%, specificity of 95%, PPV of 89% and NPV of 95% using culture as a reference standard. The GeneXpert MTB/RIF analysis of acid-fast bacilli (AFB) smear positive samples and AFB smear negative samples showed sensitivities of 100% and 77%, respectively. Looking at individual EP and respiratory (non-sputum) sample types, the sensitivity ranged from 60% to 100% although the specificity ranged from 33% to 100% with the specificity of lymph node tissue biopsy being the lowest. The GeneXpert MTB/RIF assay detected 11% more TB cases than culture and 27% more cases than ZN microscopy. Due to insufficient numbers of presenting rifampicin resistance cases, performance analysis of the GeneXpert MTB/RIF assay on rifampicin resistance could not be carried out. The GeneXpert MTB/RIF assay is potentially valuable for TB diagnosis in the majority of the EP and respiratory (other than sputum) samples in our setting. Although the GeneXpert MTB/RIF assay provides rapid diagnostic results, the overall sensitivity to rule out the disease is suboptimal for some specimen types. Performance varied according to specimen type and AFB smear status. The sensitivity and specificity of lymph node tissue was 63% and 33%. Care must be taken when using the GeneXpert MTB/RIF assay for detection of MTB in lymph node tissue samples. All samples should be cultured regardless of the GeneXpert MTB/RIF assay result. Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Dense volumetric detection and segmentation of mediastinal lymph nodes in chest CT images

NASA Astrophysics Data System (ADS)

Oda, Hirohisa; Roth, Holger R.; Bhatia, Kanwal K.; Oda, Masahiro; Kitasaka, Takayuki; Iwano, Shingo; Homma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Schnabel, Julia A.; Mori, Kensaku

2018-02-01

We propose a novel mediastinal lymph node detection and segmentation method from chest CT volumes based on fully convolutional networks (FCNs). Most lymph node detection methods are based on filters for blob-like structures, which are not specific for lymph nodes. The 3D U-Net is a recent example of the state-of-the-art 3D FCNs. The 3D U-Net can be trained to learn appearances of lymph nodes in order to output lymph node likelihood maps on input CT volumes. However, it is prone to oversegmentation of each lymph node due to the strong data imbalance between lymph nodes and the remaining part of the CT volumes. To moderate the balance of sizes between the target classes, we train the 3D U-Net using not only lymph node annotations but also other anatomical structures (lungs, airways, aortic arches, and pulmonary arteries) that can be extracted robustly in an automated fashion. We applied the proposed method to 45 cases of contrast-enhanced chest CT volumes. Experimental results showed that 95.5% of lymph nodes were detected with 16.3 false positives per CT volume. The segmentation results showed that the proposed method can prevent oversegmentation, achieving an average Dice score of 52.3 +/- 23.1%, compared to the baseline method with 49.2 +/- 23.8%, respectively.

Clinical significance of lymph node metastasis in gastric cancer

PubMed Central

Deng, Jing-Yu; Liang, Han

2014-01-01

Gastric cancer, one of the most common malignancies in the world, frequently reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection, which results in poor prognosis. Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer. Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials, it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year follow-up study. Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide, but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis. It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer. Besides, the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer. PMID:24744586

Comparison of four staging systems of lymph node metastasis in gastric cancer.

PubMed

Zhang, Ming; Zhu, Guanyu; Ma, Yan; Xue, Yingwei

2009-11-01

The classification of lymph node metastasis in patients with gastric cancer is still controversial. Our aim was to evaluate the relative merits of four staging systems of lymph node metastasis. In our study, the nodal status was classified according to the 5th edition of the tumor node metastasis (TNM) system, the Japanese Classification of Gastric Carcinoma (JCGC), the ratio of metastatic lymph nodes, and the size of the largest metastatic lymph node. Each staging system was scored as good (+2), fair (+1), or poor (0) with respect to the theoretical value (extent of the anatomical lymphatic tumor spread), convenience (simplicity), surgical applicability (extent of lymph node dissection), and prognostic value (ability to predict survival rate). In the multivariate analysis including the four staging systems and other potential prognostic factors, stepwise Cox regression revealed that the ratio of metastatic lymph nodes was the most independent prognostic factor. The TNM, ratio, and size systems were convenient because they had no consideration for the location of the tumor and lymph node. Although the JCGC system had advantages in theoretical value and surgical application, it was most optional due to the complexity of the system. Although all different staging systems are comparable, the metastatic lymph node ratio system is convenient, reproducible, and has the highest ability to predict survival.

Swollen lymph nodes

MedlinePlus

... lymph nodes, including: Seizure medicines such as phenytoin Typhoid immunization Which lymph nodes are swollen depends on ... hard, irregular, or fixed in place. You have fever, night sweats, or unexplained weight loss. Any node ...

[Clinico-morphological peculiarities of thyroid cancer among children exposed to the Chernobyl disaster radiation].

PubMed

Iakovleva, I N; Shishkov, R V; Poliakov, V G; Pankova, P A

2008-01-01

The paper deals with a comparison of clinico-morphological patterns of sporadic thyroid cancer and that in pediatric patients exposed to radiation during the Chernobyl disaster. The latter are highly prone to both local and regional metastatic spread to the lymph nodes (intrathyroid distribution--61%; extension through capsule--42%, and metastases to the neck lymph nodes--66%). However, these data do not differ significantly from those for intact areas. Yet, cancer occurs in exposed cohorts at an earlier stage: its incidence at age 4-6 is 2-3.5 higher and that of relapse such as presentation of latent metastases to the lymph nodes and tumor foci development in residual tumor tissue is 1.6 times the average. Also, morphological patterns have changed: typical papillary cancer incidence has dropped by half while the diffuse follicular variety has grown 1.8-fold.

INDIRECT COMPUTED TOMOGRAPHIC LYMPHOGRAPHY FOR ILIOSACRAL LYMPHATIC MAPPING IN A COHORT OF DOGS WITH ANAL SAC GLAND ADENOCARCINOMA: TECHNIQUE DESCRIPTION.

PubMed

Majeski, Stephanie A; Steffey, Michele A; Fuller, Mark; Hunt, Geraldine B; Mayhew, Philipp D; Pollard, Rachel E

2017-05-01

Sentinel lymph node mapping can help to direct surgical oncologic staging and metastatic disease detection in patients with complex lymphatic pathways. We hypothesized that indirect computed tomographic lymphography (ICTL) with a water-soluble iodinated contrast agent would successfully map lymphatic pathways of the iliosacral lymphatic center in dogs with anal sac gland carcinoma, providing a potential preoperative method for iliosacral sentinel lymph node identification in dogs. Thirteen adult dogs diagnosed with anal sac gland carcinoma were enrolled in this prospective, pilot study, and ICTL was performed via peritumoral contrast injection with serial caudal abdominal computed tomography scans for iliosacral sentinel lymph node identification. Technical and descriptive details for ICTL were recorded, including patient positioning, total contrast injection volume, timing of contrast visualization, and sentinel lymph nodes and lymphatic pathways identified. Indirect CT lymphography identified lymphatic pathways and sentinel lymph nodes in 12/13 cases (92%). Identified sentinel lymph nodes were ipsilateral to the anal sac gland carcinoma in 8/12 and contralateral to the anal sac gland carcinoma in 4/12 cases. Sacral, internal iliac, and medial iliac lymph nodes were identified as sentinel lymph nodes, and patterns were widely variable. Patient positioning and timing of imaging may impact successful sentinel lymph node identification. Positioning in supported sternal recumbency is recommended. Results indicate that ICTL may be a feasible technique for sentinel lymph node identification in dogs with anal sac gland carcinoma and offer preliminary data to drive further investigation of iliosacral lymphatic metastatic patterns using ICTL and sentinel lymph node biopsy. © 2017 American College of Veterinary Radiology.

[Application of digital 3D technique combined with nanocarbon-aided navigation in endoscopic sentinel lymph node biopsy for breast cancer].

PubMed

Zhang, Pu-Sheng; Luo, Yun-Feng; Yu, Jin-Long; Fang, Chi-Hua; Shi, Fu-Jun; Deng, Jian-Wen

2016-08-20

To study the clinical value of digital 3D technique combined with nanocarbon-aided navigation in endoscopic sentinel lymph node biopsy for breast cancer. Thirty-nine female patients with stage I/II breast cancer admitted in our hospital between September 2014 and September 2015 were recruited. CT lymphography data of the patients were segmented to reconstruct digital 3D models, which were imported into FreeForm Modeling Surgical System Platform for visual simulation surgery before operation. Endoscopic sentinel lymph node biopsy and endoscopic axillary lymph node dissection were then carried out, and the accuracy and clinical value of digital 3D technique in endoscopic sentinel lymph node biopsy were analyzed. s The 3D models faithfully represented the surgical anatomy of the patients and clearly displayed the 3D relationship among the sentinel lymph nodes, axillary lymph nodes, axillary vein, pectoralis major, pectoralis minor muscle and latissimus dorsi. In the biopsy, the detection rate of sentinel lymph nodes was 100% in the patients with a coincidence rate of 87.18% (34/39), a sensitivity of 91.67% (11/12), and a false negative rate of 8.33% (1/12). Complications such as limb pain, swelling, wound infection, and subcutaneouseroma were not found in these patients 6 months after the operation. Endoscopic sentinel lymph node biopsy assisted by digital 3D technique and nanocarbon-aided navigation allows a high detection rate of sentinel lymph nodes with a high sensitivity and a low false negative rate and can serve as a new method for sentinel lymph node biopsy for breast cancer.

[The historical perspective of the sentinel lymph node concept].

PubMed

Bekker, J; Meijer, S

2008-01-05

The sentinel lymph node procedure is currently standard care in the treatment of breast cancer. The introduction of this procedure in 1992 would not have been possible without the pioneering discoveries regarding lymph nodes and cancer. The Italian surgeon Gaspar Asellius (1581-1626) visualized the lymphatic vessels of a dog after it had been fed and shortly before dissection. At the end of the 17th century, the French anatomists Lauth and Sappey visualized the lymphatics by injecting deceased criminals with mercury. In 1858, the German pathologist Virchow (1821-1902) launched the theory that lymph nodes act as defensive barriers. He also made the first microscopical illustration ofa sentinel lymph node. Gould et al. and Cabaãs independently launched the precursors of the current modern sentinel lymph node concept in 1959 and 1977 respectively. Gould et al. were the first people to use the term "sentinel node'. Cabañas used lymphangiography for the visualisation of the sentinel lymph node. Controversies about the barrier function of the lymph nodes, the fear of skip metastasis and the difficulties of performing the Cabañas procedure, prevented a breakthrough of this concept. In 1992 Morton et al. rediscovered the valuable sentinel node biopsy concept and introduced blue dye for the investigation of patients with melanoma. The combination of lymphoscintigraphy, intra-operative gamma probe guidance and patent blue further increased the reliability of the sentinel lymph node biopsy procedure. Unnecessary lymph gland dissection procedures with considerable morbidity can be prevented by this procedure.

Intratumoral IL-12 and TNF-alpha-loaded microspheres lead to regression of breast cancer and systemic antitumor immunity.

PubMed

Sabel, Michael S; Skitzki, Joseph; Stoolman, Lloyd; Egilmez, Nejat K; Mathiowitz, Edith; Bailey, Nicola; Chang, Wen-Jian; Chang, Alfred E

2004-02-01

Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response. BALB/c mice with established MT-901 tumors underwent resection or treatment with a single intratumoral injection of PLAM containing IL-12, TNF-alpha, or GM-CSF, alone or in combination. Two weeks later, lymph nodes and spleens were harvested, activated with anti-CD3 monoclonal antibodies (mAb) and rhIL-2, and assessed for antitumor reactivity by an interferon gamma (IFNgamma) release assay. Tumor-infiltrating lymphocyte (TIL) analysis was performed on days 2 and 5 after treatment by mechanically processing the tumors to create a single cell suspension, followed by three-color fluorescence-activated cell sorter (FACS) analysis. Intratumoral injection of cytokine-loaded PLAM significantly suppressed tumor growth, with the combination of IL-12 and TNF-alpha leading to increased infiltration by polymorphonuclear cells and CD8+ T-cells in comparison with controls. The induction of tumor-specific reactive T-cells in the nodes and spleens, as measured by IFN-gamma production, was highest with IL-12 and TNF-alpha. This treatment resulted in resistance to tumor rechallenge. A single intratumoral injection of IL-12 and TNF-alpha-loaded PLAM into a breast tumor leads to infiltration by polymorphonuclear cells and CD8+ T-cells with subsequent tumor regression. In addition, this local therapy induces specific antitumor T-cells in the lymph nodes and spleens, resulting in memory immune response.

[Hidradenocarcinoma of the Scrotum with Lymph Node Metastasis].

PubMed

Simões, Maria Inês; Marcão, Isabel; Toscano, Mário; Borges, Luís

2018-03-29

Hidradenocarcinoma is a rare neoplasm of the eccrine cells of the sweat glands, usually asymptomatic with slow growing and higher incidence between 50 and 80 years, occurring in both sexes and preferentially located in the palmar, plantar, frontal, axillary and nuchal regions. It has an aggressive behavior, with high rate of local recurrence and distance metastasis, associated with a poor prognosis. We present a case of hidradenocarcinoma of the scrotum manifested by lymph node metastasis through an exercise of clinical and histological differential diagnosis of an inguinal adenopathy in a young adult.

Paired-agent fluorescent imaging to detect micrometastases in breast sentinel lymph node biopsy: experiment design and protocol development

NASA Astrophysics Data System (ADS)

Li, Chengyue; Xu, Xiaochun; Basheer, Yusairah; He, Yusheng; Sattar, Husain A.; Brankov, Jovan G.; Tichauer, Kenneth M.

2018-02-01

Sentinel lymph node status is a critical prognostic factor in breast cancer treatment and is essential to guide future adjuvant treatment. The estimation that 20-60% of micrometastases are missed by conventional pathology has created a demand for the development of more accurate approaches. Here, a paired-agent imaging approach is presented that employs a control imaging agent to allow rapid, quantitative mapping of microscopic populations of tumor cells in lymph nodes to guide pathology sectioning. To test the feasibility of this approach to identify micrometastases, healthy pig lymph nodes were stained with targeted and control imaging agent solution to evaluate the potential for the agents to diffuse into and out of intact nodes. Aby-029, an anti-EGFR affibody was labeled with IRDye 800CW (LICOR) as targeted agent and IRDye 700DX was hydrolyzed as a control agent. Lymph nodes were stained and rinsed by directly injecting the agents into the lymph nodes after immobilization in agarose gel. Subsequently, lymph nodes were frozen-sectioned and imaged under an 80-um resolution fluorescence imaging system (Pearl, LICOR) to confirm equivalence of spatial distribution of both agents in the entire node. The binding potentials were acquired by a pixel-by-pixel calculation and was found to be 0.02 +/- 0.06 along the lymph node in the absence of binding. The results demonstrate this approach's potential to enhance the sensitivity of lymph node pathology by detecting fewer than 1000 cell in a whole human lymph node.

Human relevance of an in vitro gene signature in HaCaT for skin sensitization.

PubMed

van der Veen, Jochem W; Hodemaekers, Henny; Reus, Astrid A; Maas, Wilfred J M; van Loveren, Henk; Ezendam, Janine

2015-02-01

The skin sensitizing potential of chemicals is mainly assessed using animal methods, such as the murine local lymph node assay. Recently, an in vitro assay based on a gene expression signature in the HaCaT keratinocyte cell line was proposed as an alternative to these animal methods. Here, the human relevance of this gene signature is assessed through exposure of freshly isolated human skin to the chemical allergens dinitrochlorobenzene (DNCB) and diphenylcyclopropenone (DCP). In human skin, the gene signature shows similar direction of regulation as was previously observed in vitro, suggesting that the molecular processes that drive expression of these genes are similar between the HaCaT cell line and freshly isolated skin, providing evidence for the human relevance of the gene signature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Financial aspects of sentinel lymph node biopsy in early breast cancer.

PubMed

Severi, S; Gazzoni, E; Pellegrini, A; Sansovini, M; Raulli, G; Corbelli, C; Altini, M; Paganelli, G

2012-02-01

At present, early breast cancer is treated with conservative surgery of the primary lesion (BCS) along with axillary staging by sentinel lymph node biopsy (SLNB). Although the scintigraphic method is standardized, its surgical application is different for patient compliance, work organization, costs, and diagnosis related group (DRG) reimbursements. We compared four surgical protocols presently used in our region: (A) traditional BCS with axillary lymph node dissection (ALND); (B) BCS with SLNB and concomitant ALND for positive sentinel nodes (SN); (C) BCS and SLNB under local anaesthesia with subsequent ALND under general anaesthesia according to the SN result; (D) SLNB under local anaesthesia with subsequent BCS under local anaesthesia for negative SN, or ALND under general anaesthesia for positive SN. For each protocol, patient compliance, use of consumables, resources and time spent by various dedicated professionals, were analyzed. Furthermore, a detailed breakdown of 1-/2-day hospitalization costs was calculated using specific DRGs. We reported a mean costs variation that ranged from 1,634 to 2,221 Euros (protocols C and D). The number of procedures performed and the pathologists' results are the most significant variables affecting the rate of DRG reimbursements, that were the highest for protocol D and the lowest for protocol B. In our experience protocol C is the most suitable in terms of patient compliance, impact of surgical procedures, and work organization, and is granted by an appropriate DRG. We observed that a multidisciplinary approach enhances overall patient care and that a revaluation of DRG reimbursements is opportune.

Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

PubMed

Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

2017-12-01

Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby construct self-adjuvanting polymer-based intranasal mRNA vaccines to enhance lymph node trafficking and further improve immune responses. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Role of gastrin-releasing peptides in breast cancer metastasis.

PubMed

Ni, Chunsheng; Zhao, Xiulan; Sun, Tao; Liu, Yanrong; Gu, Qiang; Sun, Baocun

2012-12-01

The gastrin-releasing peptide, which is an unfolded protein response regulator and functions as a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum, is a regulatory human peptide that elicits gastrin release and regulates gastric acid secretion and enteric motor function. It has been shown to exhibit mitogenic activity in small cell lung cancer and plays a role in a lot of other human cancers including tumors in colon, stomach, pancreas, breast, and prostate. This study investigated the gastrin-releasing peptide expression in breast cancer to demonstrate the role of this biomarker in breast cancer metastasis. Gastrin-releasing peptide was analyzed in breast cancer tissue microarray specimens, including 200 primary breast cancer specimens and the corresponding lymph nodes from the same patients, through immunohistochemistry. The effect of gastrin-releasing peptide on the invasion ability of MCF-7 cells was evaluated using transwell assays. Gastrin-releasing peptide was highly expressed in breast cancer patients with lymph node metastasis. Besides, among the patients with lymph node metastasis, the ones with higher expression of gastrin-releasing peptide had shorter survival time. Overexpression of gastrin-releasing peptide significantly enhanced cell invasiveness. Conversely, a knockdown of gastrin-releasing peptide through the short hairpin RNA approach remarkably reduced MCF-7 cell invasion. Gastrin-releasing peptide expression may be associated with lymph node metastasis and may be used as an indicator of undesirable prognosis in patients with breast cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience.

PubMed

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R; Chagpar, Anees B; Killelea, Brigid K; Lannin, Donald R

2017-01-01

Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

Intranasal Live Influenza Vaccine Priming Elicits Localized B Cell Responses in Mediastinal Lymph Nodes.

PubMed

Jegaskanda, Sinthujan; Mason, Rosemarie D; Andrews, Sarah F; Wheatley, Adam K; Zhang, Ruijun; Reynoso, Glennys V; Ambrozak, David R; Santos, Celia P; Luke, Catherine J; Matsuoka, Yumiko; Brenchley, Jason M; Hickman, Heather D; Talaat, Kawsar R; Permar, Sallie R; Liao, Hua-Xin; Yewdell, Jonathan W; Koup, Richard A; Roederer, Mario; McDermott, Adrian B; Subbarao, Kanta

2018-05-01

Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust neutralizing antibody response upon subsequent administration of a pandemic inactivated subunit vaccine (pISV). However, a difference was not detected in H5-specific memory B cells in the peripheral blood between pLAIV-primed and unprimed subjects prior to pISV boost. To investigate the mechanism underlying pLAIV priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically and in local draining lymph nodes (LN). The AGM model recapitulated the serologic observations from clinical studies. Interestingly, H5N1 pLAIV induced robust germinal center B cell responses in the mediastinal LN (MLN). Subsequent boosting with H5N1 pISV drove increases in H5-specific B cells in the axillary LN, spleen, and circulation in H5N1 pLAIV-primed animals. Thus, H5N1 pLAIV primes localized B cell responses in the MLN that are recalled systemically following pISV boost. These data provide mechanistic insights for the generation of robust humoral responses via prime-boost vaccination. IMPORTANCE We have previously shown that pandemic live attenuated influenza vaccines (pLAIV) prime for a rapid and robust antibody response on subsequent administration of inactivated subunit vaccine (pISV). This is observed even in individuals who had undetectable antibody (Ab) responses following the initial vaccination. To define the mechanistic basis of pLAIV priming, we turned to a nonhuman primate model and performed a detailed analysis of B cell responses in systemic and local lymphoid tissues following prime-boost vaccination with pLAIV and pISV. We show that the nonhuman primate model recapitulates the serologic observations from clinical studies. Further, we found that pLAIVs induced robust germinal center B cell responses in the mediastinal lymph node. Subsequent boosting with pISV in pLAIV-primed animals resulted in detection of B cells in the axillary lymph nodes, spleen, and peripheral blood. We demonstrate that intranasally administered pLAIV elicits a highly localized germinal center B cell response in the mediastinal lymph node that is rapidly recalled following pISV boost into germinal center reactions at numerous distant immune sites. Copyright © 2018 American Society for Microbiology.

[Acute toxoplasmosis in coexistent non-Hodgkin lymphoma].

PubMed

Welge-Lüssen, A; Hauser, R

1999-06-01

There are many reasons for cervical lymph node enlargement. In particular, the large group of infectious diseases must be considered along with malignant diseases. The coexistence of an uncommon infectious disease with malignant disease is a rare event. We report the case of an otherwise healthy 69-year-old man with marked enlargement of his cervical lymph nodes. A diagnosis of a recent toxoplasmosis infection was made based on positive IgG and IgM toxoplasma titers and the results of fine-needle aspiration from a lymph node. Since the enlarged lymph nodes persisted for more than weeks, the lymph node was excised. Histological examination revealed a non-Hodgkin's lymphoma. IgM titers in toxoplasmosis can persist up to 1 year. In cases with rare infectious diseases like toxoplasmosis in immunocompromised patients, swollen lymph nodes that persist or grow should lead to the suspicion of additional disease. A diagnosis can be confirmed by removing a lymph node for histology.

Murine chronic lymph node window for longitudinal intravital lymph node imaging.

PubMed

Meijer, Eelco F J; Jeong, Han-Sin; Pereira, Ethel R; Ruggieri, Thomas A; Blatter, Cedric; Vakoc, Benjamin J; Padera, Timothy P

2017-08-01

Chronic imaging windows in mice have been developed to allow intravital microscopy of many different organs and have proven to be of paramount importance in advancing our knowledge of normal and disease processes. A model system that allows long-term intravital imaging of lymph nodes would facilitate the study of cell behavior in lymph nodes during the generation of immune responses in a variety of disease settings and during the formation of metastatic lesions in cancer-bearing mice. We describe a chronic lymph node window (CLNW) surgical preparation that allows intravital imaging of the inguinal lymph node in mice. The CLNW is custom-made from titanium and incorporates a standard coverslip. It allows stable longitudinal imaging without the need for serial surgeries while preserving lymph node blood and lymph flow. We also describe how to build and use an imaging stage specifically designed for the CLNW to prevent (large) rotational changes as well as respiratory movement during imaging. The entire procedure takes approximately half an hour per mouse, and subsequently allows for longitudinal intravital imaging of the murine lymph node and surrounding structures for up to 14 d. Small-animal surgery experience is required to successfully carry out the protocol.

Prognostic Significance of the Location of Lymph Node Metastases in Patients With Adenocarcinoma of the Distal Esophagus or Gastroesophageal Junction.

PubMed

Anderegg, Maarten C J; Lagarde, Sjoerd M; Jagadesham, Vamshi P; Gisbertz, Suzanne S; Immanuel, Arul; Meijer, Sybren L; Hulshof, Maarten C C M; Bergman, Jacques J G H M; van Laarhoven, Hanneke W M; Griffin, S Michael; van Berge Henegouwen, Mark I

2016-11-01

To identify the prognostic significance of the location of lymph node metastases in patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma treated with neoadjuvant therapy followed by esophagectomy. Detection of lymph node metastases in the upper mediastinum and around the celiac trunk after neoadjuvant therapy and resection does not alter the TNM classification of esophageal carcinoma. The impact of these distant lymph node metastases on survival remains unclear. Between March 2003 and September 2013, 479 consecutive patients with adenocarcinoma of the distal esophagus or GEJ who underwent transthoracic esophagectomy with en bloc 2-field lymphadenectomy after neoadjuvant therapy were included, and survival was analyzed according to the location of positive lymph nodes in the resection specimen. Two hundred fifty-three patients had nodal metastases in the resection specimen. Of these patients, 92 patients had metastases in locoregional nodes, 114 patients in truncal nodes, 21 patients in the proximal field of the chest, and 26 patients had both positive truncal and proximal field nodes. Median disease-free survival was 170 months in the absence of nodal metastases, 35 months for metastases limited to locoregional nodes, 16 months for positive truncal nodes, 15 months for positive nodes in the proximal field, and 8 months for nodal metastases in both truncal and the proximal field. On multivariate analysis, location of lymph node metastases was independently associated with survival. Location of lymph node metastases is an independent predictor for survival. Relatively distant lymph node metastases along the celiac axis and/or the proximal field have a negative impact on survival. Location of lymph node metastases should therefore be considered in future staging systems of esophageal and GEJ adenocarcinoma.

Intra-lymph node injection of biodegradable polymer particles.

PubMed

Andorko, James I; Tostanoski, Lisa H; Solano, Eduardo; Mukhamedova, Maryam; Jewell, Christopher M

2014-01-02

Generation of adaptive immune response relies on efficient drainage or trafficking of antigen to lymph nodes for processing and presentation of these foreign molecules to T and B lymphocytes. Lymph nodes have thus become critical targets for new vaccines and immunotherapies. A recent strategy for targeting these tissues is direct lymph node injection of soluble vaccine components, and clinical trials involving this technique have been promising. Several biomaterial strategies have also been investigated to improve lymph node targeting, for example, tuning particle size for optimal drainage of biomaterial vaccine particles. In this paper we present a new method that combines direct lymph node injection with biodegradable polymer particles that can be laden with antigen, adjuvant, or other vaccine components. In this method polymeric microparticles or nanoparticles are synthesized by a modified double emulsion protocol incorporating lipid stabilizers. Particle properties (e.g. size, cargo loading) are confirmed by laser diffraction and fluorescent microscopy, respectively. Mouse lymph nodes are then identified by peripheral injection of a nontoxic tracer dye that allows visualization of the target injection site and subsequent deposition of polymer particles in lymph nodes. This technique allows direct control over the doses and combinations of biomaterials and vaccine components delivered to lymph nodes and could be harnessed in the development of new biomaterial-based vaccines.

Morphological analysis of lymph nodes in Odontocetes from north and northeast coast of Brazil.

PubMed

De Oliveira e Silva, Fernanda Menezes; Guimarães, Juliana Plácido; Vergara-Parente, Jociery Einhardt; Carvalho, Vitor Luz; De Meirelles, Ana Carolina Oliveira; Marmontel, Miriam; Ferrão, Juliana Shimara Pires; Miglino, Maria Angelica

2014-05-01

The morphology and location of lymph nodes from seven species of Odontocetes, of both sexes and different age groups, were described. All animals were derived from stranding events along the North and Northeastern coasts of Brazil. After the identification of lymph nodes in situ, tissue samples were analyzed for light and electron microscopy. Vascular volume density (VVD) and vascular length density (VLD) were evaluated in the mesenteric lymph nodes. Lymph nodes occurred as solitary nodules or in groups, varying in shape and size. In addition to using the nomenclature recommended by Nomina Anatomica Veterinaria, new nomenclatures were suggested based on the lymph nodes topography. Lymph nodes were covered by a highly vascularized and innervated capsule of dense connective tissue, below which muscle fibers were observed, inconsistently, in all studied species. There was no difference in VLD among different age groups. However, VVD was higher in adults. Lymph nodes parenchyma was divided into an outer cortex, containing lymph nodules and germinal centers; a paracortical region, transition zone with dense lymphoid tissue; and an inner medulla, composed of small irregular cords of lymphatic tissue, blood vessels, and diffuse lymphoid tissue. Abundant collagen fibers were observed around arteries and arterioles. Germinal centers were more evident and developed in calves and young animals, being more discrete and sparse in adults. The morphology of lymph nodes in Odontocetes was typical of that observed in other terrestrial mammals. However, new groups of lymph nodes were described for seven species occurring in the Brazilian coast. Copyright © 2014 Wiley Periodicals, Inc.

Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67.

PubMed

Thangarajah, Fabinshy; Malter, Wolfram; Hamacher, Stefanie; Schmidt, Matthias; Krämer, Stefan; Mallmann, Peter; Kirn, Verena

2016-12-01

Since the introduction of the sentinel node technique for breast cancer in the 1990s patient's morbidity was reduced. Tracer uptake is known to be dependent from lymph node integrity and activity of macrophages. The aim of this study was to assess whether radioactivity of the tracer can predict sentinel lymph node metastases. Furthermore, a potential association with Ki-67 index was examined. Non-invasive prediction of lymph node metastases could lead to a further decrease of morbidity. We retrospectively analyzed patients with primary breast cancer who underwent surgery at the Department of Obstetrics and Gynecology in the University Hospital of Cologne between 2012 and 2013. Injection of radioactive tracer was done a day before surgery in the department of Nuclear Medicine. Clinical data and radioactivity of the sentinel node measured the day before and intraoperatively were abstracted from patient's files. Of 246 patients, 64 patients had at least one, five patients had two and one patient had three positive sentinel lymph nodes. Occurrence of sentinel lymph node metastases was not associated with preoperative tracer activity (p = 0,319), intraoperative tracer activity of first sentinel node (p = 0,086) or with loss of tracer activity until operation (p = 0,909). There was no correlation between preoperative Ki-67 index and occurrence of lymph node metastases (p = 0,403). In our cohort, there was no correlation between radioactivity and sentinel node metastases. Tracer uptake might not only be influenced by lymph node metastases and does not predict metastatic lymph node involvement. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Chemotherapy on Retroperitoneal Lymph Nodes in Ovarian Cancer.

PubMed

Keyver-Paik, Mignon-Denise; Arden, Janne Myriam; Lüders, Christine; Thiesler, Thore; Abramian, Alina; Hoeller, Tobias; Hecking, Thomas; Ayub, Tiyasha Hosne; Doeser, Anna; Kaiser, Christina; Kuhn, Walther

2016-04-01

Complete cytoreduction is the most important prognostic factor in ovarian cancer. However, there exist conflicting data on whether the removal of microscopic tumor metastasis in macroscopically unsuspicious retroperitoneal lymph nodes is beneficial. Ovarian cancer tissues and tissues from lymph node metastasis of 30 patients with FIGO IIIC or IV disease undergoing neoadjuvant chemotherapy (NACT) were obtained and assessed using a validated regression score. Histopathological markers, size of largest tumor focus, and overall score were evaluated in lymph node and ovarian tissue. Regression and known prognostic factors were analyzed for influence on survival. No difference in the overall score between lymph nodes and ovarian tissue was shown, however, single parameters such as fibrosis and pattern of tumor infiltration, were significantly different. The pattern of tumor regression in lymph nodes and ovarian tissue are of prognostic value. Lymph node dissection even of unsuspicious nodes should, therefore, be performed. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

PubMed

Klerkx, Wenche M; Geldof, Albert A; Heintz, A Peter; van Diest, Paul J; Visser, Fredy; Mali, Willem P; Veldhuis, Wouter B

2011-05-01

To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes. Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically. The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5-7 mm(3) at baseline to 25 mm(3) at day 14, while the control node remained 5 mm(3). The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%-32%), but this decrease was also seen in reactive nodes. Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values. Copyright © 2011 Wiley-Liss, Inc.

Ultrasound texture analysis: Association with lymph node metastasis of papillary thyroid microcarcinoma.

PubMed

Kim, Soo-Yeon; Lee, Eunjung; Nam, Se Jin; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Han, Kyung Hwa; Kwak, Jin Young

2017-01-01

This retrospective study aimed to evaluate whether ultrasound texture analysis is useful to predict lymph node metastasis in patients with papillary thyroid microcarcinoma (PTMC). This study was approved by the Institutional Review Board, and the need to obtain informed consent was waived. Between May and July 2013, 361 patients (mean age, 43.8 ± 11.3 years; range, 16-72 years) who underwent staging ultrasound (US) and subsequent thyroidectomy for conventional PTMC ≤ 10 mm between May and July 2013 were included. Each PTMC was manually segmented and its histogram parameters (Mean, Standard deviation, Skewness, Kurtosis, and Entropy) were extracted with Matlab software. The mean values of histogram parameters and clinical and US features were compared according to lymph node metastasis using the independent t-test and Chi-square test. Multivariate logistic regression analysis was performed to identify the independent factors associated with lymph node metastasis. Tumors with lymph node metastasis (n = 117) had significantly higher entropy compared to those without lymph node metastasis (n = 244) (mean±standard deviation, 6.268±0.407 vs. 6.171±.0.405; P = .035). No additional histogram parameters showed differences in mean values according to lymph node metastasis. Entropy was not independently associated with lymph node metastasis on multivariate logistic regression analysis (Odds ratio, 0.977 [95% confidence interval (CI), 0.482-1.980]; P = .949). Younger age (Odds ratio, 0.962 [95% CI, 0.940-0.984]; P = .001) and lymph node metastasis on US (Odds ratio, 7.325 [95% CI, 3.573-15.020]; P < .001) were independently associated with lymph node metastasis. Texture analysis was not useful in predicting lymph node metastasis in patients with PTMC.

Results of Sentinel Lymph Node Biopsy in Patients with Breast Cancer in 10-Year Own Material of the 4th Military Teaching Hospital with Polyclinic in Wrocław.

PubMed

Kabziński, Piotr; Rac, Jacek; Dorobisz, Tadeusz; Pawłowski, Wiktor; Ziomek, Agnieszka; Chabowski, Mariusz; Janczak, Dawid; Leśniak, Michał; Janczak, Dariusz

2016-05-01

At present, sentinel lymph node biopsy is a standard procedure to assess the advancement of breast cancer and cutaneous melanoma. The aim of the study was to assess the role of the sentinel lymph node biopsy in the treatment of patients with breast cancer in our own material. Analyzed was medical documentation of 258 patients with initially operable breast cancer, qualified for operation with sentinel lymph node biopsy in 2004-2014 in the Department of Surgery of the 4th Military Teaching Hospital. A few hours prior to the planned surgery, radioisotope (technitium-99 sulfur colloid) was applied in the area of tumor or under the areola. 1-2 hours after administering the tracer, the lymphoscintigraphy with the labelling of the sentinel lymph node on the skin was performed. On the basis of the gathered material, obtained were the following parameters: sensitivity - 100%, and specificity - 94.6%. Four cases were false negative (5.5%). 1. Marking the sentinel lymph node in breast cancer, based on the single visualisation method with the use of radioisotope, is a useful and effective technique. 2. The factor influencing the results of the sentinel lymph node biopsy (true positive and negative results and false negative result) was the number of the excised lymph nodes except for the sentinel lymph node. 3. Patients with estrogen receptor expression had often metastases to sentinel lymph node (145 cases - 56%). 4. The false negative rate, i.e. 5.5% in our material, is within the limits of acceptability given in the literature. 5. The sentinel lymph node biopsy performed by the experienced surgical team is a reliable diagnostic tool with a low complication rate.

[Selective biopsy of the sentinel lymph node in patients with breast cancer and previous excisional biopsy: is there a change in the reliability of the technique according to time from surgery?].

PubMed

Sabaté-Llobera, A; Notta, P C; Benítez-Segura, A; López-Ojeda, A; Pernas-Simon, S; Boya-Román, M P; Bajén, M T

2015-01-01

To assess the influence of time on the reliability of sentinel lymph node biopsy (SLNB) in breast cancer patients with previous excisional biopsy (EB), analyzing both the sentinel lymph node detection and the lymph node recurrence rate. Thirty-six patients with cT1/T2 N0 breast cancer and previous EB of the lesion underwent a lymphoscintigraphy after subdermal periareolar administration of radiocolloid, the day before SLNB. Patients were classified into two groups, one including 12 patients with up to 29 days elapsed between EB and SLNB (group A), and another with the remaining 24 in which time between both procedures was of 30 days or more (group B). Scintigraphic and surgical detection of the sentinel lymph node, histological status of the sentinel lymph node and of the axillary lymph node dissection, if performed, and lymphatic recurrences during follow-up, were analyzed. Sentinel lymph node visualization at the lymphoscintigraphy and surgical detection were 100% in both groups. Histologically, three patients showed macrometastasis in the sentinel lymph node, one from group A and two from group B. None of the patients, not even those with malignancy of the sentinel lymph node, relapsed after a medium follow-up of 49.5 months (24-75). Time elapsed between EB and SLNB does not influence the reliability of this latter technique as long as a superficial injection of the radiopharmaceutical is performed, proving a very high detection rate of the sentinel lymph node without evidence of lymphatic relapse during follow-up. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Lymph node toxoplasmosis. Follow-up of 237 histologically diagnosed and serologically verified cases.

PubMed

Miettinen, M; Saxén, L; Saxén, E

1980-01-01

The clinical features, histology and follow-up of lymph node toxoplasmosis are presented in the light of 237 histologically and serologically verified cases. Lymph node toxoplasmosis is a disease with mild symptoms, and in most patients the enlarged lymph nodes were the only sign. Three fourths of the patients were women and the majority were under 40 years of age. The clinical picture was not specific, but suggestive features included a relatively short history, presence of the nodes in the neck and relative lymphocytosis in peripheral blood. Histological changes in the lymph nodes were characteristic. The most important features were strong hyperplasia but preserved general structure with small groups of epithelioid cells both in the paracortical area and in the germinal centers. Strands of monocytoid cells were usually found. 80% of the cases with typical histology also had high antibody titers, and in more than 85% of the cases with high antibodies, the lymph nodes presented a typical picture of toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis is a disease without complications, nor is there any connection with malignant lymphomas.

Effect of Neoadjuvant Chemotherapy on Axillary Lymph Node Positivity and Numbers in Breast Cancer Cases.

PubMed

Uyan, Mikail; Koca, Bulent; Yuruker, Savas; Ozen, Necati

2016-01-01

The aim of this study is to compare the numbers of axillary lymph nodes (ALN) taken out by dissection between patients with breast cancer operated on after having neoadjuvant chemotherapy (NAC) treatment and otherswithout having neoadjuvant chemotherapy, and to investigate factors affecting lymph node positivity. A total of 49 patients operated due to advanced breast cancer after neoadjuvant chemotherapy and 144 patients with a similar stage of the cancer having primary surgical treatment without chemotherapy at the general surgery clinic of Ondokuz Mayis University Medicine Faculty between the dates 01.01.2006 and 31.10.2012 were included in the study. The total number of lymph nodes taken out by axillary dissection (ALND) was categorized as the number of positive lymph nodes and divided into <10 and ≥10. The variables to be compared were analysed using the program SPSS 15.0 with P<0.05 accepted as significant. Median number of dissected lymph nodes from the patient group having neoadjuvant chemotherapy was 16 (16-33) while it was 20 (5-55) without chemotherapy. The respective median numbers of positive lymph nodes were 5 ( 0-19) and 10 (0-51). In 8 out of 49 neoadjuvant chemotherapy patients (16.3%), the number of dissected lymph nodes was below 10, and it was below 10 in 17 out of 144 primary surgery patients. Differences in numbers of dissected total and positive lymph nodes between two groups were significant, but this was not the case for numbers of <10 lymph nodes. The number of dissected lymph nodes from the patients with breast cancer having neoadjuvant chemotherapy may be less than without chemotherapy. This may not always be attributed to an inadequate axillary dissection. More research to evaluate the numbers of positive lymph nodes are required in order to increase the reliability of staging in the patients with breast cancer undergoing neoadjuvant chemotherapy.

Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors (pNET)

PubMed Central

Krampitz, Geoffrey W.; Norton, Jeffrey A.; Poultsides, George A.; Visser, Brendan C.; Sun, Lixian; Jensen, Robert T.

2012-01-01

Background The significance of lymph node metastases on survival of patients with pNET is controversial. Hypothesis Lymph node metastases decrease survival in patients with pNET. Design Prospective databases of the National Institutes of Health (NIH) and Stanford University Hospital (SUH) were queried. Main Outcome Measures Overall survival, disease-related survival, and time to development of liver metastases Results 326 underwent surgical exploration for pNET at the NIH (n=216) and SUH (n=110). 40 (13%) and 305 (94%) underwent enucleation and resection, respectively. Of the patients who underwent resection, 117 (42%) had partial pancreatectomy and 30 (11%) had a Whipple procedure. 41 also had liver resections, 21 wedge resections and 20 lobectomies. Average follow-up was 8 years (range 0.3–28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (p<0.001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared to those with none (p<0.001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (p<0.0001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of number of lymph nodes involved (p=0.004). Conclusion As expected, liver metastases decrease survival of patients with pNET. Patients with lymph node metastases alone have a shorter time to development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease disease-related survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNET. PMID:22987171

The use of isotope injections in sentinel node biopsy for breast cancer: are the 1- and 2-day protocols equally effective?

PubMed

Dodia, Nazera; El-Sharief, Deena; Kirwan, Cliona C

2015-01-01

Sentinel lymph nodes are mapped using (99m)Technetium, injected on day of surgery (1-day protocol) or day before (2-day protocol). This retrospective cohort study compares efficacy between the two protocols. Histopathology for all unilateral sentinel lymph node biopsies (March 2012-March 2013) in a single centre were reviewed. Number of sentinel lymph nodes, non-sentinel lymph nodes and pathology was compared. 2/270 (0.7 %) in 1-day protocol and 8/192 (4 %) in 2-day protocol had no sentinel lymph nodes removed (p = 0.02). The median (range) number of sentinel lymph nodes removed per patient was 2 (0-7) and 1 (0-11) in the 1- and 2-day protocols respectively (p = 0.08). There was a trend for removing more non-sentinel lymph nodes in 2-day protocol [1-day: 52/270 (19 %); 2-day: 50/192 (26 %), p = 0.07]. Using 2-day, sentinel lymph node identification failure rate is higher, although within acceptable rates. The 1 and 2 day protocols are both effective, therefore choice of protocol should be driven by patient convenience and hospital efficiency. However, this study raises the possibility that 1-day may be preferable when higher sentinel lymph node count is beneficial, for example following neoadjuvant chemotherapy.

[Analysis of the patterns of cervical lymph node recurrence in patients with cN0 papillary thyroid carcinoma after central neck lymph node dissection].

PubMed

Huang, Hui; Xu, Zhengang; Wang, Xiaolei; Wu, Yuehuang; Liu, Shaoyan

2015-10-01

To retrospectively analyze the long-term results of prophylactic central lymph node dissection in cN0 papillary thyroid carcinoma (PTC), and investigate the treatment method of the cervical lymph nodes for cN0 PTC. One hundred and thirty-six patients with cN0 PTC were treated by surgery at the Cancer Hospital of Chinese Academy of Medical Sciences from 2000 to 2006. Their clinicopathological characteristics, surgical procedures and survival outcomes were collected and analyzed. The occult lymph node metastasis rate in central compartment was 61.0%. The average number of positive lymph nodes was 2.47 (1-13), in which 54 patients had 1-2 and 29 patients had ≥ 3 positive lymph nodes. Multiple logistic regression analysis showed that age less than 45 (P=0.001, OR 3.571, 95% CI 1.681-7.587)and extracapsular spread (ECS) (P=0.015, OR 2.99, 95% CI 1.241-7.202)were independent risk factors for lymph node metastasis in the central compartment. The ten-year cumulative overall survival rate was 98.3% and cumulative lateral neck metastasis rate was 25.2%. Multivariate analysis with Cox regression model showed that ECS (P=0.001, OR 5.211, 95% CI1.884-14.411) and positive lymph nodes in the central compartment ≥ 3 (P=0.009, OR 4.005, 95% CI 1.419-11.307) were independent risk factors for lymph node recurrence in the lateral neck region. The distribution of recurrent lymph nodes: level IV (82.4%), level III (64.7%), level II (29.4%) and level V (11.8%). Routine central lymph node dissection, at least unilateral, should be conducted for cN0 papillary thyroid carcinoma. Attention should be paid to the treatment of lateral neck region in patients with cN0 papillary thyroid carcinoma. Selective neck dissection is suggested for cN0 PTC with ECS or positive central lymph nodes ≥ 3, or both. The range of dissection should include level III and IV at least.

Interval sentinel lymph nodes in melanoma: a digital pathology analysis of Ki67 expression and microvascular density.

PubMed

Marinaccio, Christian; Giudice, Giuseppe; Nacchiero, Eleonora; Robusto, Fabio; Opinto, Giuseppina; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Domenico

2016-08-01

The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest that the correlation between tumor cell proliferation and neo-angiogenesis in interval sentinel lymph nodes in melanoma could be used as a good predictive marker to distinguish interval positive sentinel lymph nodes with micrometastasis from interval positive lymph nodes with macrometastasis subgroups.

Sentinel lymph node biopsy in breast cancer

PubMed Central

Alsaif, Abdulaziz A.

2015-01-01

Objectives: To report our experience in sentinel lymph node biopsy (SLNB) in early breast cancer. Methods: This is a retrospective study conducted at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between January 2005 and December 2014. There were 120 patients who underwent SLNB with frozen section examination. Data collected included the characteristics of patients, index tumor, and sentinel node (SN), SLNB results, axillary recurrence rate and SLNB morbidity. Results: There were 120 patients who had 123 cancers. Sentinel node was identified in 117 patients having 120 tumors (97.6% success rate). No SN was found intraoperatively in 3 patients. Frozen section results showed that 95 patients were SN negative, those patients had no immediate axillary lymph node dissection (ALND), whereas 25 patients were SN positive and subsequently had immediate ALND. Upon further examination of the 95 negative SN’s by hematoxylin & eosin (H&E) and immunohistochemical staining for doubtful H&E cases, 10 turned out to have micrometastases (6 had delayed ALND and 4 had no further axillary surgery). Median follow up of patients was 35.5 months and the mean was 38.8 months. There was one axillary recurrence observed in the SN negative group. The morbidity of SLNB was minimal. Conclusion: The obtainable results from our local experience in SLNB in breast cancer, concur with that seen in published similar literature in particular the axillary failure rate. Sentinel lymph node biopsy resulted in minimal morbidity. PMID:26318461

Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism

PubMed Central

Ganusov, Vitaly V.; Auerbach, Jeremy

2014-01-01

The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours). Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism. PMID:24830705

Predictors of axillary lymph node metastases in women with early breast cancer in Singapore.

PubMed

Tan, L G L; Tan, Y Y; Heng, D; Chan, M Y

2005-12-01

The presence of axillary lymph node metastases is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) is an emerging method for the staging of the axilla. It is hoped that with SLNB, the morbidity from axillary lymph node dissection (ALND) can be avoided without compromising the staging and management of early breast cancer. However, only patients found to be SLNB negative benefit from this procedure, as those with positive SLNB may still require ALND. Our objective is to study the various clinico-pathological factors to find predictive factors for axillary lymph node involvement in early breast cancer. It is hoped that with these factors, we will be better able to identify groups of patients most likely to benefit from SLNB. A retrospective study of 380 early breast cancer cases (stage T1 and T2, N0, N1, M0) in women treated in the Department of General Surgery, Tan Tock Seng Hospital, between January 1999 and August 2002, was conducted. Incidence of nodal metastases was correlated with clinico-pathological factors, and analysed by univariate and multivariate analyses. Approximately 35 percent of the 380 cases of early breast cancer had nodal metastases. Multivariate analyses revealed four independent predictors of node positivity: tumour size (p-value equals 0.0001), presence of lymphovascular invasion (p-value is less than 0.0001), tumours with histology other than invasive ductal or lobular carcinoma (p-value equals 0.04), and presence of progesterone receptors (p-value equals 0.05). We have found independent preoperative predictive factors in our local population for the presence of nodal metastases. This information can aid patient selection for SLNB and improve patient counselling.

A prospective single-center study of sentinel lymph node detection in cervical carcinoma: is there a place in clinical practice?

PubMed

Devaja, Omer; Mehra, Gautam; Coutts, Michael; Montalto, Stephen Attard; Donaldson, John; Kodampur, Mallikarjun; Papadopoulos, Andreas John

2012-07-01

To establish the accuracy of sentinel lymph node (SLN) detection in early cervical cancer. Sentinel lymph node detection was performed prospectively over a 6-year period in 86 women undergoing surgery for cervical carcinoma by the combined method (Tc-99m and methylene blue dye). Further ultrastaging was performed on a subgroup of 26 patients who had benign SLNs on initial routine histological examination. The SLN was detected in 84 (97.7%) of 86 women by the combined method. Blue dye uptake was not seen in 8 women (90.7%). Sentinel lymph nodes were detected bilaterally in 63 women (73.3%), and the external iliac region was the most common anatomic location (48.8%). The median SLN count was 3 nodes (range, 1-7). Of the 84 women with sentinel node detection, 65 also underwent bilateral pelvic lymph node dissection, and in none of these cases was a benign SLN associated with a malignant non-SLN (100% negative predictive value). The median non-SLN count for all patients was 19 nodes (range, 8-35). Eighteen patients underwent removal of the SLN without bilateral pelvic lymph node dissection. Nine women (10.5%) had positive lymph nodes on final histology. One patient had bulky pelvic nodes on preoperative imaging and underwent removal of the negative bulky malignant lymph nodes and a benign SLN on the contralateral side. This latter case confirms the unreliability of the SLN method with bulky nodes. The remaining 8 patients had positive SLNs with negative nonsentinel lymph nodes. Fifty-nine SLNs from 26 patients, which were benign on initial routine histology, underwent ultrastaging, but no further disease was identified. Four patients (5%) relapsed after a median follow-up of 28 months (range, 8-80 months). Sentinel lymph node detection is an accurate and safe method in the assessment of nodal status in early cervical carcinoma.

Sentinel Node Biopsy for the Head and Neck Using Contrast-Enhanced Ultrasonography Combined with Indocyanine Green Fluorescence in Animal Models: A Feasibility Study.

PubMed

Kogashiwa, Yasunao; Sakurai, Hiroyuki; Akimoto, Yoshihiro; Sato, Dai; Ikeda, Tetsuya; Matsumoto, Yoshifumi; Moro, Yorihisa; Kimura, Toru; Hamanoue, Yasuhiro; Nakamura, Takehiro; Yamauchi, Koichi; Saito, Koichiro; Sugasawa, Masashi; Kohno, Naoyuki

2015-01-01

Sentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast-enhanced ultrasonography and indocyanine green fluorescence in animal models. This was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically. Sentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically. The combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted.

Semi-automatic central-chest lymph-node definition from 3D MDCT images

NASA Astrophysics Data System (ADS)

Lu, Kongkuo; Higgins, William E.

2010-03-01

Central-chest lymph nodes play a vital role in lung-cancer staging. The three-dimensional (3D) definition of lymph nodes from multidetector computed-tomography (MDCT) images, however, remains an open problem. This is because of the limitations in the MDCT imaging of soft-tissue structures and the complicated phenomena that influence the appearance of a lymph node in an MDCT image. In the past, we have made significant efforts toward developing (1) live-wire-based segmentation methods for defining 2D and 3D chest structures and (2) a computer-based system for automatic definition and interactive visualization of the Mountain central-chest lymph-node stations. Based on these works, we propose new single-click and single-section live-wire methods for segmenting central-chest lymph nodes. The single-click live wire only requires the user to select an object pixel on one 2D MDCT section and is designed for typical lymph nodes. The single-section live wire requires the user to process one selected 2D section using standard 2D live wire, but it is more robust. We applied these methods to the segmentation of 20 lymph nodes from two human MDCT chest scans (10 per scan) drawn from our ground-truth database. The single-click live wire segmented 75% of the selected nodes successfully and reproducibly, while the success rate for the single-section live wire was 85%. We are able to segment the remaining nodes, using our previously derived (but more interaction intense) 2D live-wire method incorporated in our lymph-node analysis system. Both proposed methods are reliable and applicable to a wide range of pulmonary lymph nodes.

Rapid detection of metastatic melanoma in lymph nodes using proton magnetic resonance spectroscopy of fine needle aspiration biopsy specimens.

PubMed

Lean, Cynthia L; Bourne, Roger; Thompson, John F; Scolyer, Richard A; Stretch, Jonathan; Li, Ling-Xi Lawrence; Russell, Peter; Mountford, Carolyn

2003-06-01

Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histological examination to identify disease. A rapid, accurate and cost-effective non-surgical technique able to detect micrometastatic deposits of melanoma in regional lymph nodes would be of great benefit. Fine needle aspiration biopsies and tissue specimens were obtained from lymph nodes from 18 patients undergoing node resection for metastatic melanoma and five patients undergoing radical retropubic prostatectomy. One-dimensional proton magnetic resonance spectroscopy was undertaken at 360 MHz (8.5 T). Lymph nodes were cut into 3 mm thick slices and embedded. Four sequential 5 microm tissue sections were cut from each block and stained, with haematoxylin and eosin, for S100 protein, for HMB45, and again with haematoxylin and eosin, respectively. Proton magnetic resonance spectroscopy distinguished between benign and malignant lymph node tissue (P < 0.001, separate t-test) and benign and malignant lymph node fine needle aspiration biopsy (P < 0.012) based on the ratio of the integrals of resonances from lipid/other metabolites (1.8-2.5 p.p.m. region) and 'choline' (3.1-3.3 p.p.m. region). In conclusion, one-dimensional proton magnetic resonance spectroscopy on a simple fine needle aspiration biopsy can distinguish lymph nodes containing metastatic melanoma from uninvolved nodes, providing a rapid, accurate and cost-effective non-surgical technique to assess regional lymph nodes in patients with melanoma.

Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.

PubMed

Lemieux, Aaron; Kedarisetty, Suraj; Raju, Sharat; Orosco, Ryan; Coffey, Charles

2016-03-01

Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Case series with chart review. Administrative database analysis. The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Impact of false-negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma.

PubMed

Caracò, C; Marone, U; Celentano, E; Botti, G; Mozzillo, N

2007-09-01

Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.

Numeric pathologic lymph node classification shows prognostic superiority to topographic pN classification in esophageal squamous cell carcinoma.

PubMed

Sugawara, Kotaro; Yamashita, Hiroharu; Uemura, Yukari; Mitsui, Takashi; Yagi, Koichi; Nishida, Masato; Aikou, Susumu; Mori, Kazuhiko; Nomura, Sachiyo; Seto, Yasuyuki

2017-10-01

The current eighth tumor node metastasis lymph node category pathologic lymph node staging system for esophageal squamous cell carcinoma is based solely on the number of metastatic nodes and does not consider anatomic distribution. We aimed to assess the prognostic capability of the eighth tumor node metastasis pathologic lymph node staging system (numeric-based) compared with the 11th Japan Esophageal Society (topography-based) pathologic lymph node staging system in patients with esophageal squamous cell carcinoma. We retrospectively reviewed the clinical records of 289 patients with esophageal squamous cell carcinoma who underwent esophagectomy with extended lymph node dissection during the period from January 2006 through June 2016. We compared discrimination abilities for overall survival, recurrence-free survival, and cancer-specific survival between these 2 staging systems using C-statistics. The median number of dissected and metastatic nodes was 61 (25% to 75% quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3), respectively. The eighth tumor node metastasis pathologic lymph node staging system had a greater ability to accurately determine overall survival (C-statistics: tumor node metastasis classification, 0.69, 95% confidence interval, 0.62-0.76; Japan Esophageal Society classification; 0.65, 95% confidence interval, 0.58-0.71; P = .014) and cancer-specific survival (C-statistics: tumor node metastasis classification, 0.78, 95% confidence interval, 0.70-0.87; Japan Esophageal Society classification; 0.72, 95% confidence interval, 0.64-0.80; P = .018). Rates of total recurrence rose as the eighth tumor node metastasis pathologic lymph node stage increased, while stratification of patients according to the topography-based node classification system was not feasible. Numeric nodal staging is an essential tool for stratifying the oncologic outcomes of patients with esophageal squamous cell carcinoma even in the cohort in which adequate numbers of lymph nodes were harvested. Copyright © 2017 Elsevier Inc. All rights reserved.

Reliability and cost-effectiveness of sentinel lymph node excision under local anaesthesia versus general anaesthesia for malignant melanoma: a retrospective analysis in 300 patients with malignant melanoma AJCC Stages I and II.

PubMed

Stoffels, I; Dissemond, J; Körber, A; Hillen, U; Poeppel, T; Schadendorf, D; Klode, J

2011-03-01

Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions, as it is a cost-intensive surgical intervention with potentially significant morbidity. The present retrospective study seeks to clarify the effectiveness and reliability of SLNE performed under tumescent local anaesthesia (TLA) and whether SLNE performed under TLA can reduce costs and morbidity. Therefore, our study is a comparison of SLNE performed under TLA and general anaesthesia (GA). We retrospectively analysed data from 300 patients with primary malignant melanoma with a Breslow index of ≥1.0 mm. Altogether, 211 (70.3%) patients underwent SLNE under TLA and 89 (29.7%) patients underwent SLNE under GA. A total of 637 sentinel lymph nodes (SLN) were removed. In the TLA group 1.98 SLN/patient and in the GA group 2.46 SLN/patient were removed (median value). Seventy patients (23.3%) had a positive SLN. No major complications occurred. The costs for SLNE were significantly less for the SLNE in a procedures room performed under TLA (mean € 30.64) compared with SLNE in an operating room under GA (mean € 326.14, P<0.0001). In conclusion, SLNE performed under TLA is safe, reliable, and cost-efficient and could become the new gold standard in sentinel lymph node diagnostic procedures. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Intraoperative sentinel node identification in early stage cervical cancer using a combination of radiolabeled albumin injection and isosulfan blue dye injection.

PubMed

Martínez-Palones, José M; Gil-Moreno, Antonio; Pérez-Benavente, María A; Roca, Isabel; Xercavins, Jordi

2004-03-01

We investigated the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled human serum albumin and isosulfan blue dye injection in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between September 2000 and October 2002, 25 patients with cervical cancer FIGO stage I (n=24) or stage II (n=1) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (technetium-99m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with blue dye and a handheld or laparoscopic gamma probe. Complete pelvic or paraaortic lymphadenectomy was performed in all cases by open surgery or laparoscopic surgery. In 23 evaluable patients, a total of 51 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.21 nodes per patient). Intraoperatively, 61 sentinel lymph nodes were identified, with a mean of 2.52 nodes per patient by gamma probe and a mean of 1.94 nodes per patient after isosulfan blue injection. Forty percent of sentinel nodes were found in the interiliac region and 25% in the external iliac area. Microscopic nodal metastases (four nodes) were confirmed in 12% of cases. All these lymph nodes were previously detected as sentinel lymph nodes. The remaining 419 nodes after pelvic lymphadenectomy were histologically negative. Sentinel lymph node identification with technetium-99m-labeled nanocolloid combined with blue dye injection is feasible and showed a 100% negative predictive value, and potentially identified women in whom lymph node dissection can be avoided.

What Is a False Negative Sentinel Node Biopsy: Definition, Reasons and Ways to Minimize It?

PubMed

Kataria, Kamal; Srivastava, Anurag; Qaiser, Darakhshan

2016-10-01

Sentinel node biopsy helps in assessing the involvement of axillary lymph node without the morbidity of full axillary lymph node dissection, namely arm and shoulder pain, paraesthesia and lymphoedema. The various methods described in the literature identify the sentinel lymph nodes in approximately 96 % of cases and associated with a false negativity rate of 5 to 10 %. A false negative sentinel node is defined as the proportion of cases in whom sentinel node biopsy is reported as negative, but the rest of axillary lymph node(s) harbours cancer cells. The possible causes of a false negative sentinel lymph node may be because of blocked lymphatics either by cancer cells or following fibrosis of previous surgery/radiotherapy, and an alternative pathway opens draining the blue dye or isotope to another uninvolved node . The other reasons may be two lymphatic pathways for a tumour area, the one opening to a superficial node and the other in deep nodes. Sometimes, lymphatics do not relay into a node but traverse it going to a higher node. In some patients, the microscopic focus of metastasis inside a lymph node is so small-micrometastasis (i.e. between 0.2 and 2 mm) or isolated tumour cells (i.e. less than 0.2 mm) that is missed by the pathologist. The purpose of this review is to clear some fears lurking in the mind of most surgeons about the false negative sentinel lymph node (FNSLN).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chernyshova, A. L.; Lyapunov, A. Yu., E-mail: Lyapunov1720.90@mail.ru; Kolomiets, L. A.

The study included 26 patients with FIGO stage Ia1–Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

Allergenicity evaluation of fragrance mix and its ingredients by using ex vivo local lymph node assay-BrdU endpoints.

PubMed

Ulker, Ozge Cemiloglu; Kaymak, Yesim; Karakaya, Asuman

2014-03-01

The present studies were performed to compare the differences between sensitization potency of fragrance mix and its ingredients (oak moss absolute, isoeugenol, eugenol, cinnamal, hydroxycitronellal, geraniol, cinnamic alcohol, alpha amyl cinnamal), by using ex vivo LLNA-BrdU ELISA. The SI and EC3 values were calculated and potency classification was found for the mixture and for each ingredients. TH1 cytokines (IL-2, IFN-γ) and TH2 cytokines (IL-4, IL-5) releases from lymph node cell culture were also investigated as contact sensitization endpoints. The EC3 values were calculated and the potency of contact sensitization were classified for fragrance mix, oak moss absolute, isoeugenol, eugenol, cinnamal, hydroxycitronellal, geraniol, cinnamic alcohol, alpha amyl cinnamal respectively: 4.4% (moderate), 3.4% (moderate), 0.88% (strong), 16.6% (weak), 1.91% (moderate), 9.77% (moderate), 13.1% (weak), 17.93% (weak), 7.74% (moderate). According to our results it should be concluded that exposure to fragrance mix does not constitute an evidently increased hazard compared to exposure to each of the eight fragrance ingredients separately. Cytokine analyses results indicate that both TH1 and TH2 cytokines are involved in the regulation of murine contact allergy and can be considered as useful endpoints. Copyright © 2014 Elsevier Ltd. All rights reserved.

A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study.

PubMed

Rossi, Emma C; Kowalski, Lynn D; Scalici, Jennifer; Cantrell, Leigh; Schuler, Kevin; Hanna, Rabbie K; Method, Michael; Ade, Melissa; Ivanova, Anastasia; Boggess, John F

2017-03-01

Sentinel-lymph-node mapping has been advocated as an alternative staging technique for endometrial cancer. The aim of this study was to measure the sensitivity and negative predictive value of sentinel-lymph-node mapping compared with the gold standard of complete lymphadenectomy in detecting metastatic disease for endometrial cancer. In the FIRES multicentre, prospective, cohort study patients with clinical stage 1 endometrial cancer of all histologies and grades undergoing robotic staging were eligible for study inclusion. Patients received a standardised cervical injection of indocyanine green and sentinel-lymph-node mapping followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy. 18 surgeons from ten centres (tertiary academic and community non-academic) in the USA participated in the trial. Negative sentinel lymph nodes (by haematoxylin and eosin staining on sections) were ultra-staged with immunohistochemistry for cytokeratin. The primary endpoint, sensitivity of the sentinel-lymph-node-based detection of metastatic disease, was defined as the proportion of patients with node-positive disease with successful sentinel-lymph-node mapping who had metastatic disease correctly identified in the sentinel lymph node. Patients who had mapping of at least one sentinel lymph node were included in the primary analysis (per protocol). All patients who received study intervention (injection of dye), regardless of mapping result, were included as part of the assessment of mapping and in the safety analysis in an intention-to-treat manner. The trial was registered with ClinicalTrials.gov, number NCT01673022 and is completed and closed. Between Aug 1, 2012, and Oct 20, 2015, 385 patients were enrolled. Sentinel-lymph-node mapping with complete pelvic lymphadenectomy was done in 340 patients and para-aortic lymphadenectomy was done in 196 (58%) of these patients. 293 (86%) patients had successful mapping of at least one sentinel lymph node. 41 (12%) patients had positive nodes, 36 of whom had at least one mapped sentinel lymph node. Nodal metastases were identified in the sentinel lymph nodes of 35 (97%) of these 36 patients, yielding a sensitivity to detect node-positive disease of 97·2% (95% CI 85·0-100), and a negative predictive value of 99·6% (97·9-100). The most common grade 3-4 adverse events or serious adverse events were postoperative neurological disorders (4 patients) and postoperative respiratory distress or failure (4 patients). 22 patients had serious adverse events, with one related to the study intervention: a ureteral injury incurred during sentinel-lymph-node dissection. Sentinel lymph nodes identified with indocyanine green have a high degree of diagnostic accuracy in detecting endometrial cancer metastases and can safely replace lymphadenectomy in the staging of endometrial cancer. Sentinel lymph node biopsy will not identify metastases in 3% of patients with node-positive disease, but has the potential to expose fewer patients to the morbidity of a complete lymphadenectomy. Indiana University Health, Indiana University Health Simon Cancer Center, and the Indiana University Department of Obstetrics and Gynecology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Management of well-differentiated thyroid cancer in 2010: perspectives of a head and neck surgical oncologist.

PubMed

Urken, Mark L

2010-01-01

To review the terminology and controversy regarding the performance of prophylactic lymph node dissection for patients without evidence suggestive of pathologic adenopathy. Terminology of lymph node levels in the neck and chest, and the issues regarding lymph node dissection, are reviewed. In addition, differences between lymph nodes are reviewed and discussed. Management of lymph nodes in this disease process has become the most contentious aspect of surgical decision-making due to the ambiguity of their prognostic significance and the prevalence of nodal metastases in very early primary tumors. Performance of prophylactic central compartment node dissection is not technically any more difficult than therapeutic node dissection when clinically significant nodes are encountered. It is therefore reasonable to consider this technique as an important adjunct to a total thyroidectomy for the purpose of enhanced disease staging, prevention of nodal recurrence, and avoidance of having to re-enter the previously operated central compartment. A recent study is reviewed and discussed in detail. The literature regarding the prognostic significance of extracapsular spread in lymph nodes is also presented. Morphologic characteristics of metastatic lymph nodes in thyroid cancer vary greatly. However, the reporting of these differences is lacking. The presence of extracapsular extension in a lymph node has prognostic significance. The clinician should be aware of these variations and the impact that they may have on recurrence risk and disease-specific survival.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience

PubMed Central

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R.; Chagpar, Anees B.

2017-01-01

Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1–15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient. PMID:28492062

Lymphatic Leak Occurring After Surgical Lymph Node Dissection: A Preliminary Study Assessing the Feasibility and Outcome of Lymphatic Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baek, Yoolim; Won, Je Hwan; Kong, Tae-Wook

PurposeTo analyze imaging findings of lymphatic leakage associated with surgical lymph node dissection on lymphangiography and assess the outcome of lymphatic embolization.Materials and MethodsThis retrospective study comprised 21 consecutive patients who were referred for lymphatic intervention between March 2014 and April 2015 due to postsurgical lymphatic leaks. Lymphangiography was performed through inguinal lymph nodes to identify the leak. When a leak was found, lymphatic embolization was performed by fine-needle injection of N-butyl cyanoacrylate into the site of leakage or into an inflow lymphatic vessel or into a pelvic lymph node located below the leakage. Electronic medical records and imaging studiesmore » were reviewed to assess the outcome.ResultLymphangiography revealed single or multiple leaks in all but one patient. Lymphatic embolization was performed in 20 patients with leaks. Including the patient who did not undergo embolization, 17 patients (81.0 %) showed initial response to treatment. Three patients underwent repeated embolization with successful results. The overall success rate was 95.2 %. The mean duration of hospitalization after lymphatic intervention was 5.9 days. During a mean follow-up period of 11 months, two patients developed localized swelling in the groin following lipiodol injection. There were no complications related to lymphatic embolization. Three patients were found to have developed small, asymptomatic lymphoceles on CT or MRI that did not require further treatment.ConclusionLymphangiography is useful for detecting lymphatic leakage occurring after lymph node dissection. Furthermore, lymphatic embolization is feasible, effective, and safe for managing leaks demonstrated on lymphangiography.« less

The pattern of lymphatic metastasis of breast cancer and its influence on the delineation of radiation fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Jinming; Li Gong; Li Jianbin

2005-03-01

Purpose: The delineation of radiation fields should cover the clinical target volume (CTV) and minimally irradiate the surrounding normal tissues and organs. This study was designed to explore the pattern of lymphatic metastasis of breast cancer and indications for radiotherapy after radical or modified radical mastectomy and to discuss the rational delineation of radiation fields. Methods and materials: Between September 1980 and December 2003, 78 breast cancer patients receiving extended radical mastectomy in the Margottini model and 61 cases with complete data were analyzed to investigate the internal mammary lymphatic metastatic status. Between March 1988 and December 1988, 46 patientsmore » with clinical negative supraclavicular nodes received radical mastectomy plus supraclavicular lymph node dissection. The supraclavicular lymph nodes and axillary lymph nodes were labeled as S and levels I, II, or III, respectively, and examined pathologically. Between January 1996 and April 1999, 412 patients who had radical or modified radical mastectomy underwent the pathologic examination of axillary or levels I, II, or III nodes. Results: The incidence of internal mammary lymph node metastasis was 24.6%. It was 36.7% for the patients with positive axillary lymph nodes and 12.9% for the patients with negative axillary lymph nodes. All the metastatic internal mammary lymph nodes were located at the first, second, and third intercostal spaces. Skipping metastasis of the supraclavicular and axillary lymph nodes was observed in 3.8% and 8.1% of patients, respectively. Conclusions: According to our data, we suggest that the radiation field for internal mammary lymph nodes should exclude the fourth and fifth intercostal spaces, which may help to reduce the radiation damage to heart. It is unnecessary to irradiate the supraclavicular lymph nodes for the patients with negative axillary level III nodes, even with positive level I and level II nodes.« less

Impact of same day vs day before pre-operative lymphoscintigraphy for sentinel lymph node biopsy for early breast cancer (local Australian experience).

PubMed

Huang, Yang Yang; Maurel, Amelie; Hamza, Saud; Jackson, Lee; Al-Ogaili, Zeyad

2018-06-01

To assess the impact of delayed vs immediate pre-operative lymphoscintigraphy (LSG) for sentinel lymph node biopsy in a single Australian tertiary breast cancer centre. Retrospective cohort study analysing patients with breast cancer or DCIS who underwent lumpectomy or mastectomy with pre-operative LSG and intra-operative sentinel lymph node biopsy from January 2015 to June 2016. A total of 182 LSG were performed. Group A patients had day before pre-operative LSG mapping (n = 79) and Group B had LSG mapping on the day of surgery (n = 103). The overall LSG localisation rate was 97.3% and no statistical difference was detected between the two groups. The overall sentinel lymph node biopsies (SLN) were identified in 99.6% of patients. The number of nodes excised was slightly higher in Group A (1.90 vs 1.72); however, this was not statistically significant. In addition, the number of nodes on histopathology and the incidence of second echelon nodal detection were also similar between the two groups without statistical significance. In conclusion, the 2-day LSG protocol had no impact on overall SLNB and LSG detection rates although slightly higher second tier nodes but this did not translate to any difference between the number of harvest nodes between the two groups. The 2-day LSG allows for greater flexibility in theatre planning and more efficient use of theatre time. We recommend a dose of 40 Mbq of Tc99 m pertechnetate-labelled colloid be given day prior to surgery within a 24-hour timeframe. © 2017 The Royal Australian and New Zealand College of Radiologists.

A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection.

PubMed

Nguyen, Daniel P; Huber, Philipp M; Metzger, Tobias A; Genitsch, Vera; Schudel, Hans H; Thalmann, George N

2016-11-01

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND. Copyright © 2016. Published by Elsevier B.V.

FDG uptake in cervical lymph nodes in children without head and neck cancer.

PubMed

Vali, Reza; Bakari, Alaa A; Marie, Eman; Kousha, Mahnaz; Charron, Martin; Shammas, Amer

2017-06-01

Reactive cervical lymphadenopathy is common in children and may demonstrate increased 18 F-fluoro-deoxyglucose ( 18 F-FDG) uptake on positron emission tomography/computed tomography (PET/CT). We sought to evaluate the frequency and significance of 18 F-FDG uptake by neck lymph nodes in children with no history of head and neck cancer. The charts of 244 patients (114 female, mean age: 10.4 years) with a variety of tumors such as lymphoma and post-transplant lymphoproliferative diseases (PTLD), but no head and neck cancers, who had undergone 18 F-FDG PET/CT were reviewed retrospectively. Using the maximum standardized uptake value (SUVmax), increased 18 F-FDG uptake by neck lymph nodes was recorded and compared with the final diagnosis based on follow-up studies or biopsy results. Neck lymph node uptake was identified in 70/244 (28.6%) of the patients. In 38 patients, the lymph nodes were benign. In eight patients, the lymph nodes were malignant (seven PTLD and one lymphoma). In 24 patients, we were not able to confirm the final diagnosis. Seven out of the eight malignant lymph nodes were positive for PTLD. The mean SUVmax was significantly higher in malignant lesions (4.2) compared with benign lesions (2.1) (P = 0.00049). 18 F-FDG uptake in neck lymph nodes is common in children and is frequently due to reactive lymph nodes, especially when the SUVmax is <3.2. The frequency of malignant cervical lymph nodes is higher in PTLD patients compared with other groups.

Correlation of cytologic and histopathologic findings with perinodal echogenicity of abdominal lymph nodes in dogs and cats.

PubMed

Davé, Aditya C; Zekas, Lisa J; Auld, Danelle M

2017-07-01

Abdominal lymphadenopathy in dogs and cats is routinely investigated with ultrasound. As the determination between benign and neoplastic etiologies of lymphadenopathy affects patient management, specific sonographic characteristics associated with both benign and neoplastic lymph nodes have been suggested. However, a significant overlap between these characteristics exists, necessitating a cytologic or histopathologic diagnosis in most instances. The objectives of this retrospective, cross-sectional study were to evaluate whether echogenicity of perinodal fat could be a discriminator between benign and neoplastic abdominal lymphadenopathy and to assess if additional sonographic features associated with malignancy could be identified in lymph nodes with hyperechoic perinodal fat. Small animal patients (257 dogs and 117 cats) with sonographic evidence of abdominal lymphadenopathy and a cytological or histopathological diagnosis were evaluated for differences in the proportions of sonographic features between benign and neoplastic groups. Greater maximum long axis diameter (in dogs and cats) and a greater number of abnormal lymph nodes (in cats) were associated with malignancy in lymph nodes with hyperechoic perinodal fat. Canine lymph nodes with round cell neoplasia were significantly more likely to have hyperechoic perinodal fat. Lymph nodes affected with other neoplasia or with lymphadenitis were equally likely to have normal or hyperechoic perinodal fat. Reactive lymph nodes were significantly less likely to have hyperechoic perinodal fat in both species. These results suggest that though echogenicity of perinodal fat is a nonspecific finding, abdominal lymph nodes with hyperechoic perinodal fat are less likely to be reactive and sampling of these lymph nodes may be indicated. © 2017 American College of Veterinary Radiology.

Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.

PubMed

Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Persson, Jan

2018-03-01

To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer. Copyright © 2017. Published by Elsevier Inc.

[The related factors of head and neck mocosal melanoma with lymph node metastasis].

PubMed

Yin, G F; Guo, W; Chen, X H; Huang, Z G

2017-12-05

Objective: To investigate the related factors of mucosal melanoma of head and neck with lymph node metastasis for early diagnosis and further treatments. Method: A retrospective analysis of 117 cases of head and neck mucosal malignant melanoma patients which received surgical treatment was performed. Eleven cases of patients with pathologically confirmed lymph node metastasis and 33 cases without lymph node metastasis (1∶3) were randomly selected to analyze. The related factors of lymph node metastasis of head and neck mucosal melanoma patients including age, gender, whether the existence of recurrence, bone invasion, lesion location were analyzed. The single factor and logistic regression analysis were performed, P <0.05 difference was statistically significant. Result: The lymph node metastasis rate of head and neck mucosal melanoma was 9.40%(11/117), the single factor analysis showed that there were 3 factors to be associated with lymph node metastasis, which was recurrence ( P =0.0000), bone invasion ( P =0.001), primary position ( P =0.007). Recurrence ( P =0.021) was a risk factor for lymph node metastasis according to the Logistic regression analysis, and the impact of bone invasion ( P =0.487) and primary location ( P =0.367) remained to be further explored. Conclusion: The patients of head and neck mucosal melanoma with the presence of recurrent usually accompanied by a further progression of the disease, such as lymph node metastasis, so for recurrent patients should pay special attention to the situation of lymph node and choose the reasonable treatment. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Immunotherapeutic effects of chitin in comparison with chitosan against Leishmania major infection.

PubMed

Hoseini, Mostafa Haji Molla; Moradi, Maryam; Alimohammadian, Mohammad Hossein; Shahgoli, Vahid Khaze; Darabi, Hayedeh; Rostami, Ali

2016-04-01

Chitin and chitosan microparticles (MPs) are important immune system stimulators. The aim of this study was to evaluate the protective effects of these compounds in comparison with each other against Leishmania infection in BALB/c mice infected with Leishmania major (L. major). Female BALB/c mice were injected subcutaneously with 2×10(5) promastigotes. Chitin and/or chitosan MPs (<40 μm) were subcutaneously injected in the BALB/c mice with two-day intervals until two weeks. Mice in all groups were sacrificed at 12 weeks post-infection. Enumeration of viable parasites was performed using limiting dilution assay. Furthermore, the animals (5 mice/group) were sacrificed two weeks post-infection. The lymph node cells were isolated and the effects of the chitinous MPs on the proliferation and production of cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were determined. The mean sizes of lesions were significantly smaller in chitin (0.6±0.12 mm) and chitosan treated groups (1.2±0.8 mm) than in the control group (6.2±1.7 mm) (P<0.05). The parasite load in the lymph nodes of the treated mice was significantly lower than that in the lymph nodes of controls (1.31×10(6) vs 8.24×10(7) parasite/lymph node [P=0.032] and 7.49×10(6) vs 8.24×10(7) parasite/lymph node [P=0.05] for chitin and chitosan MPs treatment, respectively). We found that chitinous MPs induced cell proliferation and that chitin but not chitosan increased TNF-α and IL-10 production. Chitin appears that it has more effect than chitosan against leishmaniasis. The current study revealed that chitinous MPs had significant activity against L. major and could be considered as new therapeutic modality in leishmaniasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Phleum pratense pollen starch granules induce humoral and cell-mediated immune responses in a rat model of allergy.

PubMed

Motta, A; Peltre, G; Dormans, J A M A; Withagen, C E T; Lacroix, G; Bois, F; Steerenberg, P A

2004-02-01

Timothy grass (Phleum pratense) pollen allergens are an important cause of allergic symptoms. However, pollen grains are too large to penetrate the deeper airways. Grass pollen is known to release allergen-bearing starch granules (SG) upon contact with water. These granules can create an inhalable allergenic aerosol capable of triggering an early asthmatic response and are implicated in thunderstorm-associated asthma. We studied the humoral (IgE) and bronchial lymph node cells reactivities to SG from timothy grass pollen in pollen-sensitized rats. Brown-Norway rats were sensitized (day 0) and challenged (day 21) intratracheally with intact pollen and kept immunized by pollen intranasal instillation by 4 weeks intervals during 3 months. Blood and bronchial lymph nodes were collected 7 days after the last intranasal challenge. SG were purified from fresh timothy grass pollen using 5 microm mesh filters. To determine the humoral response (IgE) to SG, we developed an original ELISA inhibition test, based on competition between pollen allergens and purified SG. The cell-mediated response to SG in the bronchial lymph node cells was determined by measuring the uptake of [3H]thymidine in a proliferation assay. An antibody response to SG was induced, and purified SG were able to inhibit the IgE ELISA absorbance by 45%. Pollen extract and intact pollen gave inhibitions of 55% and 52%, respectively. A cell-mediated response was also found, as pollen extract, intact pollen and SG triggered proliferation of bronchial lymph node cells. It was confirmed that timothy grass pollen contains allergen-loaded SG, which are released upon contact with water. These granules were shown to be recognized by pollen-sensitized rats sera and to trigger lymph node cell proliferation in these rats. These data provide new arguments supporting the implication of grass pollen SG in allergic asthma.

Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse

PubMed Central

Kerjaschki, Dontscho; Bago-Horvath, Zsuzsanna; Rudas, Margaretha; Sexl, Veronika; Schneckenleithner, Christine; Wolbank, Susanne; Bartel, Gregor; Krieger, Sigurd; Kalt, Romana; Hantusch, Brigitte; Keller, Thomas; Nagy-Bojarszky, Katalin; Huttary, Nicole; Raab, Ingrid; Lackner, Karin; Krautgasser, Katharina; Schachner, Helga; Kaserer, Klaus; Rezar, Sandra; Madlener, Sybille; Vonach, Caroline; Davidovits, Agnes; Nosaka, Hitonari; Hämmerle, Monika; Viola, Katharina; Dolznig, Helmut; Schreiber, Martin; Nader, Alexander; Mikulits, Wolfgang; Gnant, Michael; Hirakawa, Satoshi; Detmar, Michael; Alitalo, Kari; Nijman, Sebastian; Offner, Felix; Maier, Thorsten J.; Steinhilber, Dieter; Krupitza, Georg

2011-01-01

In individuals with mammary carcinoma, the most relevant prognostic predictor of distant organ metastasis and clinical outcome is the status of axillary lymph node metastasis. Metastases form initially in axillary sentinel lymph nodes and progress via connecting lymphatic vessels into postsentinel lymph nodes. However, the mechanisms of consecutive lymph node colonization are unknown. Through the analysis of human mammary carcinomas and their matching axillary lymph nodes, we show here that intrametastatic lymphatic vessels and bulk tumor cell invasion into these vessels highly correlate with formation of postsentinel metastasis. In an in vitro model of tumor bulk invasion, human mammary carcinoma cells caused circular defects in lymphatic endothelial monolayers. These circular defects were highly reminiscent of defects of the lymphovascular walls at sites of tumor invasion in vivo and were primarily generated by the tumor-derived arachidonic acid metabolite 12S-HETE following 15-lipoxygenase-1 (ALOX15) catalysis. Accordingly, pharmacological inhibition and shRNA knockdown of ALOX15 each repressed formation of circular defects in vitro. Importantly, ALOX15 knockdown antagonized formation of lymph node metastasis in xenografted tumors. Furthermore, expression of lipoxygenase in human sentinel lymph node metastases correlated inversely with metastasis-free survival. These results provide evidence that lipoxygenase serves as a mediator of tumor cell invasion into lymphatic vessels and formation of lymph node metastasis in ductal mammary carcinomas. PMID:21540548

Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients.

PubMed

Lind, Guro E; Guriby, Marianne; Ahlquist, Terje; Hussain, Israr; Jeanmougin, Marine; Søreide, Kjetil; Kørner, Hartwig; Lothe, Ragnhild A; Nordgård, Oddmund

2017-01-01

Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage ( P  = 8.2E-17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P  = 3.0E-4; time to recurrence P  = 3.1E-4), although not significant. The same trend was observed in multivariate analyses ( P  = 1.4E-1 and P  = 6.7E-2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I-II) colon cancer patients who experienced relapse. Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.

Use of High Frequency Ultrasound to Monitor Cervical Lymph Node Alterations in Mice

PubMed Central

Walk, Elyse L.; McLaughlin, Sarah; Coad, James; Weed, Scott A.

2014-01-01

Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO) and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular) lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA) biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl). Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy. PMID:24955984

Use of high frequency ultrasound to monitor cervical lymph node alterations in mice.

PubMed

Walk, Elyse L; McLaughlin, Sarah; Coad, James; Weed, Scott A

2014-01-01

Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO) and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular) lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA) biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl). Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy.

Magnetic Resonance Lymphography Findings in Patients With Biochemical Recurrence After Prostatectomy and the Relation With the Stephenson Nomogram

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Debats, Oscar A.; Roach, Mack

2012-12-01

Purpose: To estimate the occurrence of positive lymph nodes on magnetic resonance lymphography (MRL) in patients with a prostate-specific antigen (PSA) recurrence after prostatectomy and to investigate the relation between score on the Stephenson nomogram and lymph node involvement on MRL. Methods and Materials: Sixty-five candidates for salvage radiation therapy were referred for an MRL to determine their lymph node status. Clinical and histopathologic features were recorded. For 49 patients, data were complete to calculate the Stephenson nomogram score. Receiver operating characteristic (ROC) analysis was performed to determine how well this nomogram related to the MRL result. Analysis was donemore » for the whole group and separately for patients with a PSA <1.0 ng/mL to determine the situation in candidates for early salvage radiation therapy, and for patients without pathologic lymph nodes at initial lymph node dissection. Results: MRL detected positive lymph nodes in 47 patients. ROC analysis for the Stephenson nomogram yielded an area under the curve (AUC) of 0.78 (95% confidence interval, 0.61-0.93). Of 29 patients with a PSA <1.0 ng/mL, 18 had a positive MRL. Of 37 patients without lymph node involvement at initial lymph node dissection, 25 had a positive MRL. ROC analysis for the Stephenson nomogram showed AUCs of 0.84 and 0.74, respectively, for these latter groups. Conclusion: MRL detected positive lymph nodes in 72% of candidates for salvage radiation therapy, in 62% of candidates for early salvage radiation therapy, and in 68% of initially node-negative patients. The Stephenson nomogram showed a good correlation with the MRL result and may thus be useful for identifying patients with a PSA recurrence who are at high risk for lymph node involvement.« less

Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

PubMed

White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John

2014-05-01

The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.

Lymphatic drainage patterns of oral maxillary tumors: Approachable locations of sentinel lymph nodes mainly at the cervical neck level.

PubMed

Boeve, Koos; Schepman, Kees-Pieter; Vegt, Bert van der; Schuuring, Ed; Roodenburg, Jan L; Brouwers, Adrienne H; Witjes, Max J

2017-03-01

There is debate if the lymphatic drainage pattern of oral maxillary cancer is to the retropharyngeal lymph nodes or to the cervical lymph nodes. Insight in drainage patterns is important for the indication for neck treatment. The purpose of this study was to identify the lymphatic drainage pattern of oral maxillary cancer via preoperative lymphoscintigraphy. Eleven consecutive patients with oral maxillary cancer treated in our center between December 1, 2012, and April 22, 2016 were studied. Sentinel lymph nodes identified by preoperative lymphoscintigraphy after injection of 99m Tc-nanocolloid and by intraoperative detection using a γ-probe, were surgically removed and histopathologically examined. In 10 patients, sentinel lymph nodes were detected and harvested at cervical levels I, II, or III in the neck. In 2 patients, a parapharyngeal sentinel lymph node was detected. One of the harvested sentinel lymph nodes (1/19) was tumor positive. This study suggests the likelihood of 73% of exclusively cervical level I to III sentinel lymph nodes in oral maxillary cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 486-491, 2017. © 2016 Wiley Periodicals, Inc.

Retention of Ag-specific memory CD4+ T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

PubMed

Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

2017-05-01

Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4 + T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4 + T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4 + T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4 + T-cell populations are generated in peripheral lymph nodes following immunisation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical relevance of sentinel lymph node status examined with conventional histology and molecular biology.

PubMed

Micciolo, Rocco; Boi, Sebastiana; Paoli, Loredana; Cristofolini, Paolo; Girlando, Salvatore; Dalla Palma, Paolo; Cristofolini, Mario

2009-01-01

The presence of nodal metastases in patients with primary cutaneous melanoma adversely affects the biological behavior and is related to a poor prognosis. The role of sentinel lymph node biopsy is still debated. The aim of this study was to evaluate the prognostic role of sentinel lymph node biopsy with respect to disease-free period and overall survival. Patients with invasive cutaneous melanoma who underwent sentinel lymph node biopsy in the Santa Chiara Hospital of Trento between October 1997 and December 2002 were evaluated. The lymph nodes were examined with conventional histology, S100 and tyrosinase in immunohistochemistry, and tyrosinase in molecular biology. There were 144 patients with 198 sentinel lymph nodes. A significant association was found in conventional histology with Clark level and Breslow thickness. The prognostic role of sentinel lymph node status was independent of the other considered variables. However, no significant association was found with the molecular biology test. A significant excess of positive results at molecular biology was found. Sentinel lymph node biopsy is an important independent prognostic factor for invasive cutaneous melanoma, but only when evaluated with conventional histology. As a result of this study, we stopped performing the tyrosinase test in molecular biology.

Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer

PubMed Central

Kikuchi, Satoru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Hashimoto, Yuuri; Kuroda, Shinji; Nishizaki, Masahiko; Nagasaka, Takeshi; Shirakawa, Yasuhiro; Kagawa, Shunsuke; Urata, Yasuo; Hoffman, Robert M; Fujiwara, Toshiyoshi

2015-01-01

Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients. PMID:25523761

[Application of central lymph node dissection to surgical operation for clinical stage n0 papillary thyroid carcinoma].

PubMed

Hu, Wei; Shi, Jun-Yi; Sheng, Yuan; Ll, Li

2008-03-01

The treatment for papillary thyroid carcinoma (PTC) without cervical lymph node metastasis (cN0) is controversial. This study was to explore a suitable method to dissect cervical lymph nodes for stage cN0 PTC patients. Eighty-four stage cN0 PTC patients, diagnosed by B ultrasound or cervical MRI from 2005--2006, were randomly divided into two groups. Thyroidectomy and ipsilateral central lymph node dissection were performed in Group A, while only thyroidectomy was performed in Group B. Each group contained 42 patients. Both groups took thyroxin tablets after operation. An average of 3 lymph nodes were found in each case of Group A, and the lymph node metastasis rate was 47.62%. The occurrence rates of complications were not significantly different between the two groups (P<0.05). Thyroidectomy plus ipsilateral central lymph node dissection is recommended for the treatment of stage cN0 PTC. It can also avoid damage of recurrent laryngeal nerve in re-dissection.

[Identification of cervical lymph node micrometastasis of tongue cancer by color Doppler and MRI].

PubMed

Fan, Sufeng; Zhang, Quan; Li, Qiuli; Wang, Lina; Zheng, Lie; Liu, Longzhong

2014-01-01

To assess the values of color Doppler and magnetic resonance imaging (MRI) in the identification of cervical lymph node micrometastasis of tongue cancer. Totally 96 cases of tongue cancer with impalpable neck lymph node was examined with color Doppler and MRI within one week before surgery. Chi-square test was used to assess if the presence of regional lymph node micrometastasis, histopathological analysis as a golden standard lymph node micrometastasis. For the diagnosis of cervical lymph node micrometastasis, color Doppler was significantly better than MRI in sensitivity (72.5% vs 50.0%, P = 0.039) and the accuracy (78.1% vs 64.6%, P = 0.038), but no significant difference in the specificity (82.1% vs 75.0%, P = 0.357), the positive predictive value (74.4% vs 58.8%, P = 0.159) and the negative predictive value (80.7% vs 67.7%, P = 0.108). Color Doppler is better than MRI in the sensitivity and accuracy for the diagnosis of cervical lymph node micrometastasis of tongue cancer.

Perigastric lymph node metastasis from papillary thyroid carcinoma in a patient with early gastric cancer: the first case report.

PubMed

Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok

2014-09-01

Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.

Zipper-interacting protein kinase promotes epithelial-mesenchymal transition, invasion and metastasis through AKT and NF-κB signaling and is associated with metastasis and poor prognosis in gastric cancer patients

PubMed Central

Wang, Zhu; Wang, Dong; Zhang, Longjuan; Su, Qiao; Lai, Yingrong; Li, Bin; Luo, Zexing; Chen, Xu; Chen, Yu; Huang, Xiaohui; Ma, Jieyi; Wang, Wenjian; Bi, Jiong; Guan, Xinyuan

2015-01-01

Zipper-interacting Protein Kinase (ZIPK) belongs to the death-associated protein kinase family. ZIPK has been characterized as a tumor suppressor in various tumors, including gastric cancer. On the other hand, ZIPK also promotes cell survival. In this study, both in vitro and in vivo assays indicated that ZIPK promoted cell growth, proliferation, migration, invasion, tumor formation and metastasis in nude mice. ZIPK induced epithelial-mesenchymal transition (EMT) with increasing expression of β-catenin, mesenchymal markers, Snail and Slug, and with decreasing expression of E-cadherin. Furthermore, ZIPK activated the AKT/IκB/NF-κB pathway, which can promote EMT and metastasis. Additionally, ZIPK expression was detected in human primary gastric cancer and their matched metastatic lymph node samples by immunohistochemistry. Increased expression of ZIPK in lymph node metastases was significantly associated with stage VI and abdominal organ invasion. Survival analysis revealed that patients with increased ZIPK expression in metastatic lymph nodes had poor disease-specific survival. Taken together, our study reveals that ZIPK is a pro-oncogenic factor, which promotes cancer metastasis. PMID:25831050

Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women With Squamous Cell Carcinoma of the Vulva: A Gynecologic Oncology Group Study

PubMed Central

Levenback, Charles F.; Ali, Shamshad; Coleman, Robert L.; Gold, Michael A.; Fowler, Jeffrey M.; Judson, Patricia L.; Bell, Maria C.; De Geest, Koen; Spirtos, Nick M.; Potkul, Ronald K.; Leitao, Mario M.; Bakkum-Gamez, Jamie N.; Rossi, Emma C.; Lentz, Samuel S.; Burke, James J.; Van Le, Linda; Trimble, Cornelia L.

2012-01-01

Purpose To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. Patients and Methods Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. Results In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). Conclusion Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva. PMID:22753905

Sentinel Lymph Node Evaluation in Women with Cervical Cancer

PubMed Central

Holman, Laura L.; Levenback, Charles F.; Frumovitz, Michael

2014-01-01

Lymph node status is the most important prognosticator of survival among women with early stage cervical cancer. This means that many cervical cancer patients will undergo pelvic lymphadenectomy as part of their treatment. Unfortunately, this procedure is associated with significant morbidity. Utilizing the sentinel lymph node technique for women with cervical cancer has the potential to decrease this morbidity. Multiple studies have suggested that sentinel lymph node mapping in these patients is feasible with excellent detection rates and sensitivity. This review examines the current body of literature regarding sentinel lymph node biopsy among women with cervical cancer. PMID:24407177

Cervical lymph node metastases in squamous cell carcinoma of tongue and floor of mouth.

PubMed

Ehsan-ul-Haq, Muhammad; Warraich, Riaz Ahmed; Abid, Hina; Sajid, Malik Ali Hassan

2011-01-01

Oral squamous cell carcinoma has high chances of cervical lymph node metastasis. This case series describes the distribution of cervical lymph nodes in 50 cases of squamous cell carcinoma of tongue and floor of mouth. The mean age was 47.28±10.5 years. Thirty positive metastatic lymph nodes were found; 90% occurring at level I-II mostly in T4 size but also in T1 and T2 cases. The distribution of involved lymph nodes in oral cancer affects the neck dissection extent and is, therefore, an important pre-operative feature.

Lymph node biopsy

MedlinePlus

... Performed The test is used to diagnose cancer, sarcoidosis, or an infection (such as tuberculosis): When you ... of lymph nodes and other organs and tissues ( sarcoidosis ) Risks Lymph node biopsy may result in any ...

Impact of prognostic factors for postmastectomy radiation therapy of breast cancer patients

NASA Astrophysics Data System (ADS)

Simonov, K. A.; Startseva, Zh. A.; Slonimskaya, E. M.; Velikaya, V. V.

2017-09-01

The study included 196 breast cancer patients with stages T1-3N0-3M0. The comprehensive therapy for breast cancer included surgical operation, chemotherapy, and radiotherapy. Multivariate analysis showed that multifocality growth of tumor (p = 0.004), high grade III (p = 0.008), two metastatic lymph nodes (p = 0.02) were associated with an increased risk of regional node failure in the patients with one to three positive lymph nodes. The prognostic models describing the probability of local recurrences of breast cancer were developed for individualization of the radiation therapy tactics. Postmastectomy radiation therapy in the patients with high-risk breast cancer treated with modified radical mastectomy improves locoregional control, breast cancer-specific survival, does not increase late toxicity.

Tumor implantation model for rapid testing of lymphatic dye uptake from paw to node in small animals

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

2015-03-01

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue - used in the sentinel lymph node procedure - in normal and tumor-bearing animals, and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

Utilization of sentinel lymph node biopsy for uterine cancer.

PubMed

Wright, Jason D; Cham, Stephanie; Chen, Ling; Burke, William M; Hou, June Y; Tergas, Ana I; Desai, Vrunda; Hu, Jim C; Ananth, Cande V; Neugut, Alfred I; Hershman, Dawn L

2017-06-01

To limit the potential short and long-term morbidity of lymphadenectomy, sentinel lymph node biopsy has been proposed for endometrial cancer. The principle of sentinel lymph node biopsy relies on removal of a small number of lymph nodes that are the first drainage basins from a tumor and thus the most likely to harbor tumor cells. While the procedure may reduce morbidity, efficacy data are limited and little is known about how commonly the procedure is performed. We examined the patterns and predictors of use of sentinel lymph node biopsy and outcomes of the procedure in women with endometrial cancer who underwent hysterectomy. We used the Perspective database to identify women with uterine cancer who underwent hysterectomy from 2011 through 2015. Billing and charge codes were used to classify women as having undergone lymphadenectomy, sentinel lymph node biopsy, or no nodal assessment. Multivariable models were used to examine clinical, demographic, and hospital characteristics with use of sentinel lymph node biopsy. Length of stay and cost were compared among the different methods of nodal assessment. Among 28,362 patients, 9327 (32.9%) did not undergo nodal assessment, 17,669 (62.3%) underwent lymphadenectomy, and 1366 (4.8%) underwent sentinel lymph node biopsy. Sentinel lymph node biopsy was performed in 1.3% (95% confidence interval, 1.0-1.6%) of abdominal hysterectomies, 3.4% (95% confidence interval, 2.7-4.1%) of laparoscopic hysterectomies, and 7.5% (95% confidence interval, 7.0-8.0%) of robotic-assisted hysterectomies. In a multivariable model, more recent year of surgery was associated with performance of sentinel lymph node biopsy. Compared to abdominal hysterectomy, those undergoing laparoscopic (adjusted risk ratio, 2.45; 95% confidence interval, 1.89-3.18) and robotic-assisted (adjusted risk ratio, 2.69; 95% confidence interval, 2.19-3.30) hysterectomy were more likely to undergo sentinel lymph node biopsy. Among women who underwent minimally invasive hysterectomy, length of stay and cost were lower for sentinel lymph node biopsy compared to lymphadenectomy. The use of sentinel lymph node biopsy for endometrial cancer increased from 2011 through 2015. The increased use was most notable in women who underwent a robotic-assisted hysterectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Relapsed cervicomediastinal lymph node carcinoma with an unknown primary site treated with TS-1 alone: a case report.

PubMed

Yajima, Toshiki; Onozato, Ryoichi; Shitara, Yoshinori; Mogi, Akira; Tanaka, Shigebumi; Kuwano, Hiroyuki

2013-12-27

Cervicomediastinal lymph node carcinoma with an unknown primary site is quite rare, and useful treatment of these diseases has not been established. We report here the case of a patient successfully treated with TS-1 alone after the relapse of cervicomediastinal lymph node carcinoma with an unknown primary site. A 62-year-old man was referred to our hospital because of cervicomediastinal lymph node swelling and high serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen. Fluorodeoxyglucose-positron emission tomography/computed tomography revealed an accumulation of fluorodeoxyglucose in the left supraclavicular lymph nodes, mediastinal lymph nodes, and the pelvic cavity. Colonoscopy revealed rectal cancer, which was diagnosed by biopsy as a tubular adenocarcinoma. Because metastases from rectal cancer to the cervicomediastinal lymph nodes are rare, the patient underwent thoracoscopic mediastinal lymphadenectomy. A biopsy specimen from the paraaortic lymph nodes demonstrated papillary adenocarcinoma that was pathologically different from the rectal cancer; therefore, a diagnosis of mediastinal carcinoma with an unknown primary site was established. The patient underwent low anterior resection of the rectum for the rectal cancer, and no abdominal lymph node metastasis (pMP, N0/stage I) was found. Although radiotherapy was performed for the cervicomediastinal lymph nodes, the mediastinal carcinoma relapsed after 6 months. Because the patient desired oral chemotherapy on an outpatient basis, TS-1 was administered at a dosage of 80 mg/day for 2 weeks, followed by a 1-week rest. TS-1 treatment resulted in a decrease in the size of the cervicomediastinal lymph nodes, and the serum tumor marker levels decreased to normal after the fourth course. The patient continued TS-1 treatment without adverse events and is currently alive without recurrence or identification of the primary site at the 32nd month after TS-1 treatment. This is the first reported case of relapsed cervicomediastinal lymph node carcinoma with an unknown primary site treated by TS-1 alone. TS-1 treatment for the carcinoma with an unknown primary site may be useful in patients who are not candidates for systemic platinum-based chemotherapy.

Association between expression of MMP-7 and MMP-9 and pelvic lymph node and para-aortic lymph node metastasis in early cervical cancer.

PubMed

Guo, Hui; Dai, Yifei; Wang, Anna; Wang, Chunyan; Sun, Lili; Wang, Zheng

2018-05-16

To investigate the association of matrix metalloproteinase (MMP)-7 and MMP-9 with pelvic lymph node and para-aortic lymph node metastasis in early cervical cancer. A total of 137 patients with early cervical cancer (Stage Ia2-IIa2) were recruited from the Department of Gynecology and Obstetrics, Tumor Hospital of Liaoning Province from January 2009 to May 2014. We evaluated the expression of MMP-7 and MMP-9 by immunohistochemistry and their association with the clinicopathological parameters such as pelvic, common iliac and para-aortic lymph node metastasis. Spearman correlation was performed to analyze the correlation between MMP-7 and MMP-9 in cervical cancer. Finally, the areas under the receiver operating characteristic curve (ROC) of MMP-7 and MMP-9 in pelvic lymph node metastasis were assessed. MMP-7 expression was significantly higher in patients with adenocarcinomas and adenosquamous carcinomas (P = 0.014), vascular cancer embolus (P = 0.041), pelvic lymph node metastasis (P = 0.000) and a higher level of Ki-67 (P = 0.000). MMP-9 expression was significantly associated with vascular cancer embolus (P = 0.003), depth of stromal invasion (P = 0.001), pelvic lymph node metastasis (P = 0.003), common iliac lymph node metastasis (P = 0.001) and para-aortic lymph nodes metastasis (P = 0.004). Coexpression of MMP-7 and MMP-9 was significantly associated with vascular cancer embolus (P < 0.001), higher expression of Ki-67 (P < 0.001) and pelvic lymph node metastasis (P < 0.001). Spearman correlation analysis indicated a positive correlation between MMP-7 and MMP-9 (r = 0.263, P = 0.002). Areas under the ROC of MMP-7 and MMP-9 were 0.707 and 0.646, respectively. MMP-7 and MMP-9 expressions were associated with lymph node metastasis in patients with early cervical cancers, suggesting a positive correlation of MMP-7 and MMP-9 with invasive potential in early cervical cancers. © 2018 Japan Society of Obstetrics and Gynecology.

In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

PubMed

Andersen, Helene Schou; Bennedsen, Astrid Louise Bjørn; Burgdorf, Stefan Kobbelgaard; Eriksen, Jens Ravn; Eiholm, Susanne; Toxværd, Anders; Riis, Lene Buhl; Rosenberg, Jacob; Gögenur, Ismail

2017-07-01

Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

Sentinel Node Detection in Head and Neck Malignancies: Innovations in Radioguided Surgery

PubMed Central

Vermeeren, L.; Klop, W. M. C.; van den Brekel, M. W. M.; Balm, A. J. M.; Nieweg, O. E.; Valdés Olmos, R. A.

2009-01-01

Sentinel node mapping is becoming a routine procedure for staging of various malignancies, because it can determine lymph node status more precisely. Due to anatomical problems, localizing sentinel nodes in the head and neck region on the basis of conventional images can be difficult. New diagnostic tools can provide better visualization of sentinel nodes. In an attempt to keep up with possible scientific progress, this article reviews new and innovative tools for sentinel node localization in this specific area. The overview comprises a short introduction of the sentinel node procedure as well as indications in the head and neck region. Then the results of SPECT/CT for sentinel node detection are described. Finally, a portable gamma camera to enable intraoperative real-time imaging with improved sentinel node detection is described. PMID:20016804

Splenic hilar lymph node metastasis independently predicts poor survival for patients with gastric cancers in the upper and/or the middle third of the stomach.

PubMed

Zhu, Guo-Lian; Sun, Zhe; Wang, Zhen-Ning; Xu, Ying-Ying; Huang, Bao-Jun; Xu, Yan; Zhu, Zhi; Xu, Hui-Mian

2012-06-15

Effectiveness of splenectomy for advanced gastric cancers occupying the upper and/or the middle third of the stomach is still in debate. The aim of the present study is to elucidate the impact of splenectomy on patient survival by investigating the pathological characteristics and prognostic significance of splenic hilar lymph node metastasis. Clinicopathologic and prognostic data of 265 patients with gastric cancer in the upper and/or the middle third of the stomach who underwent the operation of en bloc resection of primary cancer and D2/D3 lymphadenectomy combined with splenectomy were retrospectively reviewed. Multivariate analysis revealed pT category, pN category, and distant lymph node metastasis independently correlated with the presence of splenic hilar lymph node metastasis. Prognoses of patients with positive splenic hilar lymph nodes were significantly poorer than that of patients with negative splenic hilar lymph nodes for the entire study population and for those who underwent R0 resection, but not for those who underwent R1-2 resection. There was no significant difference in survival between patients who underwent R0 resection with positive splenic hilar lymph nodes and those who underwent R1-2 resection. Splenic hilar lymph node metastasis was one of independent indicators predicting worse prognosis and the presence of distant metastasis after surgery. Subset analysis according to the TNM stage revealed there were significant differences in survival between patients with and without splenic hilar lymph node metastasis. Splenic hilar lymph node metastasis should be considered as one of incurable factors. Consequently, the efficiency of splenectomy aiming at prolonging survival for patients with high risk of splenic hilar lymph nodes metastasis should be questioned, although resection of invasive organs form gastric cancers has been recommended if R0 surgery could be achieved. Copyright © 2011 Wiley Periodicals, Inc.

Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology or valid indicators of patient outcome?

PubMed

Lahat, G; Lubezky, N; Gerstenhaber, F; Nizri, E; Gysi, M; Rozenek, M; Goichman, Y; Nachmany, I; Nakache, R; Wolf, I; Klausner, J M

2016-09-29

We evaluated the prognostic significance and universal validity of the total number of evaluated lymph nodes (ELN), number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in a relatively large and homogenous cohort of surgically treated pancreatic ductal adenocarcinoma (PDAC) patients. Prospectively accrued data were retrospectively analyzed for 282 PDAC patients who had pancreaticoduodenectomy (PD) at our institution. Long-term survival was analyzed according to the ELN, PLN, LNR, and LODDS. Of these patients, 168 patients (59.5 %) had LN metastasis (N1). Mean ELN and PLN were 13.5 and 1.6, respectively. LN positivity correlated with a greater number of evaluated lymph nodes; positive lymph nodes were identified in 61.4 % of the patients with ELN ≥ 13 compared with 44.9 % of the patients with ELN < 13 (p = 0.014). Median overall survival (OS) and 5-year OS rate were higher in N0 than in N1 patients, 22.4 vs. 18.7 months and 35 vs. 11 %, respectively (p = 0.008). Mean LNR was 0.12; 91 patients (54.1 %) had LNR < 0.3. Among the N1 patients, median OS was comparable in those with LNR ≥ 0.3 vs. LNR < 0.3 (16.7 vs. 14.1 months, p = 0.950). Neither LODDS nor various ELN and PLN cutoff values provided more discriminative information within the group of N1 patients. Our data confirms that lymph node positivity strongly reflects PDAC biology and thus patient outcome. While a higher number of evaluated lymph nodes may provide a more accurate nodal staging, it does not have any prognostic value among N1 patients. Similarly, PLN, LNR, and LODDS had limited prognostic relevance.

Axillary Lymph Node Evaluation Utilizing Convolutional Neural Networks Using MRI Dataset.

PubMed

Ha, Richard; Chang, Peter; Karcich, Jenika; Mutasa, Simukayi; Fardanesh, Reza; Wynn, Ralph T; Liu, Michael Z; Jambawalikar, Sachin

2018-04-25

The aim of this study is to evaluate the role of convolutional neural network (CNN) in predicting axillary lymph node metastasis, using a breast MRI dataset. An institutional review board (IRB)-approved retrospective review of our database from 1/2013 to 6/2016 identified 275 axillary lymph nodes for this study. Biopsy-proven 133 metastatic axillary lymph nodes and 142 negative control lymph nodes were identified based on benign biopsies (100) and from healthy MRI screening patients (42) with at least 3 years of negative follow-up. For each breast MRI, axillary lymph node was identified on first T1 post contrast dynamic images and underwent 3D segmentation using an open source software platform 3D Slicer. A 32 × 32 patch was then extracted from the center slice of the segmented tumor data. A CNN was designed for lymph node prediction based on each of these cropped images. The CNN consisted of seven convolutional layers and max-pooling layers with 50% dropout applied in the linear layer. In addition, data augmentation and L2 regularization were performed to limit overfitting. Training was implemented using the Adam optimizer, an algorithm for first-order gradient-based optimization of stochastic objective functions, based on adaptive estimates of lower-order moments. Code for this study was written in Python using the TensorFlow module (1.0.0). Experiments and CNN training were done on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. Two class axillary lymph node metastasis prediction models were evaluated. For each lymph node, a final softmax score threshold of 0.5 was used for classification. Based on this, CNN achieved a mean five-fold cross-validation accuracy of 84.3%. It is feasible for current deep CNN architectures to be trained to predict likelihood of axillary lymph node metastasis. Larger dataset will likely improve our prediction model and can potentially be a non-invasive alternative to core needle biopsy and even sentinel lymph node evaluation.

Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsunuma, Ryoichi, E-mail: r-matsunuma@nifty.com; First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka; Oguchi, Masahiko

2012-07-01

Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and lymore » status. Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.« less

Accurate evaluation of axillary sentinel lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid in breast cancer: a preliminary clinical trial.

PubMed

Matsuzawa, Fumihiko; Omoto, Kiyoka; Einama, Takahiro; Abe, Hironori; Suzuki, Takashi; Hamaguchi, Jun; Kaga, Terumi; Sato, Mami; Oomura, Masako; Takata, Yumiko; Fujibe, Ayako; Takeda, Chie; Tamura, Etsuya; Taketomi, Akinobu; Kyuno, Kenichi

2015-01-01

Breast cancer is the most common type of cancer in women. The 5-year survival rate in patients with breast cancer ranges from 74 to 82 %. Sentinel lymph node biopsy has become an alternative to axillary lymph node dissection for nodal staging. We evaluated the detection of the sentinel lymph node and metastasis of the lymph node using contrast enhanced ultrasonography with Sonazoid. Between December 2013 and May 2014, 32 patients with operable breast cancer were enrolled in this study. We evaluated the detection of axillary sentinel lymph nodes and the evaluation of axillary lymph nodes metastasis using contrast enhanced computed tomography, color Doppler ultrasonography and contrast enhanced ultrasonography with Sonazoid. All the sentinel lymph nodes were identified, and the sentinel lymph nodes detected by contrast enhanced ultrasonography with Sonazoid corresponded with those detected by computed tomography lymphography and indigo carmine method. The detection of metastasis based on contrast enhanced computed tomography were sensitivity 20.0 %, specificity 88.2 %, PPV 60.0 %, NPV 55.6 %, accuracy 56.3 %. Based on color Doppler ultrasonography, the results were sensitivity 36.4 %, specificity 95.2 %, PPV 80.0 %, NPV 74.1 %, accuracy 75.0 %. Based on contrast enhanced ultrasonography with Sonazoid, the results were sensitivity 81.8 %, specificity 95.2 %, PPV 90.0 %, NPV 90.9 %, accuracy 90.6 %. The results suggested that contrast enhanced ultrasonography with Sonazoid was the most accurate among the evaluations of these modalities. In the future, we believe that our method would take the place of conventional sentinel lymph node biopsy for an axillary staging method.

Availability of sentinel lymph node biopsy for cutaneous squamous cell carcinoma.

PubMed

Maruyama, Hiroshi; Tanaka, Ryota; Fujisawa, Yasuhiro; Nakamura, Yasuhiro; Ito, Shusaku; Fujimoto, Manabu

2017-04-01

Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty-nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow-up period were included. Forty-nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false-negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post-treatment metastases. The metastasis-free and disease-specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2-T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis-free and disease-specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging. © 2016 Japanese Dermatological Association.

Prognostic Value of Occult Isolated Tumour Cells within Regional Lymph Nodes of Dogs with Malignant Mammary Tumours.

PubMed

Coleto, A F; Wilson, T M; Soares, N P; Gundim, L F; Castro, I P; Guimarães, E C; Bandarra, M B; Medeiros-Ronchi, A A

2018-01-01

Canine mammary tumours (CMTs) are the most common type of neoplasm in bitches. As in women, the presence of metastasis in regional lymph nodes is an important prognostic factor in bitches with mammary carcinomas, but the clinical significance of occult isolated tumour cells (ITCs) within lymph nodes is still undefined in this species. The effectiveness of immunohistochemistry (IHC) in identifying occult ITCs and micrometastasis (MIC) was compared with that of the conventional haematoxylin and eosin staining technique. The relationship between tumour size, histological type, histological grade and the presence of metastasis was evaluated. The overall survival (OS) of female dogs with occult mammary carcinomas and ITCs within lymph nodes was analysed. Fragments of mammary carcinoma and regional lymph nodes of 59 female dogs were also evaluated. Histological sections of mammary carcinoma and lymph node samples were studied for tumour diagnosis and lymph node samples were tested by IHC using a pan-cytokeratin antibody. It was found that 35.2% of occult ITCs and 2.8% of hidden MIC were detected when IHC was used. There was a good correlation between the size of the tumour and metastasis to the lymph nodes (P = 0.77). ITCs were observed more frequently in the medullary region (60.7%) and metastases in the cortical region (44.4%). There was no significant difference in the OS between female dogs with occult ITCs and lymph nodes without ITCs. IHC can detect occult tumour cells in lymph nodes that are negative by histopathological examination. Female dogs with nodal ITCs do not have lower survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Lymph Node Staging System for Gastric Cancer: A Hybrid Type Based on Topographic and Numeric Systems.

PubMed

Choi, Yoon Young; An, Ji Yeong; Katai, Hitoshi; Seto, Yasuyuki; Fukagawa, Takeo; Okumura, Yasuhiro; Kim, Dong Wook; Kim, Hyoung-Il; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon

2016-01-01

Although changing a lymph node staging system from an anatomically based system to a numerically based system in gastric cancer offers better prognostic performance, several problems can arise: it does not offer information on the anatomical extent of disease and cannot represent the extent of lymph node dissection. The purpose of this study was to discover an alternative lymph node staging system for gastric cancer. Data from 6025 patients who underwent gastrectomy for primary gastric cancer between January 2000 and December 2010 were reviewed. The lymph node groups were reclassified into lesser-curvature, greater-curvature, and extra-perigastric groups. Presence of any metastatic lymph node in one group was considered positive. Lymph node groups were further stratified into four (new N0-new N3) according to the number of positive lymph node groups. Survival outcomes with this new N staging were compared with those of the current TNM system. For validation, two centers in Japan (large center, n = 3443; medium center, n = 560) were invited. Even among the same pN stages, the more advanced new N stage showed worse prognosis, indicating that the anatomical extent of metastatic lymph nodes is important. The prognostic performance of the new staging system was as good as that of the current TNM system for overall advanced gastric cancer as well as lymph node-positive gastric cancer (Harrell C-index was 0.799, 0.726, and 0.703 in current TNM and 0.799, 0.727, and 0.703 in new TNM stage). Validation sets supported these outcomes. The new N staging system demonstrated prognostic performance equal to that of the current TNM system and could thus be used as an alternative.

Methylene blue intra-arterial staining of resected colorectal cancer specimens improves accuracy of nodal staging: A randomized controlled trial.

PubMed

Reima, H; Saar, H; Innos, K; Soplepmann, J

2016-11-01

Metastatic involvement of regional lymph nodes is a major prognostic factor of colorectal cancer, which influences also its treatment strategy. International consensus foresees retrieval of ≥12 lymph nodes from colorectal specimens. The aim of the study was to assess the effect of intra-arterial staining of colorectal specimens with methylene blue on lymph node harvest. A total of 266 radically operated colorectal cancer patients were randomized into the methylene blue staining and non-staining groups. In the staining group, methylene blue solution was injected into the colorectal specimen's artery after its removal. The specimens were analysed for lymph node count, diameter and metastatic involvement. The median number of lymph nodes was higher in the staining group, 27 (95% CI 23-31%), compared with the control group, 16 (95% CI 14-19, p < 0.001). The number of examined lymph-nodes was ≥12 in 86% of the cases in the staining group and in 69% of the cases in the control group (p = 0.001). In the staining group more small-diameter (≤4 mm) lymph nodes were examined (median number 20.5 vs. 10, p < 0.001). The proportion of patients with metatatic lymph nodes was 42% in the staining group and 43% in the control group (NS). Methylene blue staining improves significantly staging accuracy through finding more small-diameter lymph nodes. It enables to detect ≥12 lymph nodes in the majority of cases. We recommend routine use of this technique in all colorectal resections with curative intent. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Predictors of metastasis to lymph nodes posterior to the right recurrent laryngeal nerve in differentiated thyroid carcinoma: A prospective study.

PubMed

Liu, Ziwen; Sun, Mengqing; Xiao, Yiding; Yang, Jing; Zhang, Taiping; Zhao, Yupei

2017-07-01

To study the clinicopathological characteristics and the risk factors of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in differentiated thyroid carcinoma; and to identify the indication for LN-prRLN dissection. We treated 145 patients with differentiated thyroid carcinoma with appropriate surgical intervention. The specimens were examined by the pathologists. The right paratracheal lymph nodes were divided into two groups: anterior or posterior to right recurrent laryngeal nerve (VIa or VIp compartment, respectively). We recorded the clinical characteristics, histopathological features of the primary tumors, and lymph node metastasis of the patients. The results were statistically analyzed. There were 85 patients (58.6%) with central lymph node metastasis, of whom 61 (42.1%) had metastasis in VIa compartment; 16 patients (11.0%) had VIp subdistrict metastasis; and 25 patients had lateral lymph node metastasis. Multiplicity, larger tumor (≥1 cm), and coexistence of central lymph node metastasis, VIa compartment metastasis, and lateral lymph node metastasis were all significantly related with LN-prRLN metastasis, while sex, age, location of the tumor, and extrathyroid extension of the tumor showed no significant relation (p > 0.05). The incidence of LN-prRLN metastasis was lower than other central lymph nodes, as well as lymph nodes anterior to right recurrent laryngeal nerve. When there were multiple foci of tumors, or the tumor was larger than 1 cm, or central or lateral LN metastasis was indicated by preoperative ultrasound or confirmed by intraoperative frozen sections, it is strongly recommended that exploration and dissection of the LN-prRLN should only be performed by experienced surgeons. Copyright © 2016. Published by Elsevier Taiwan.

Optimizing treatment for children and adolescents with papillary thyroid carcinoma in post-Chernobyl exposed region: The roles of lymph node dissections in the central and lateral neck compartments.

PubMed

Fridman, Mikhail; Krasko, Olga; Lam, Alfred King-Yin

2018-06-01

There is lack of data to predict lymph node metastases in pediatric thyroid cancer. The aims are to study (1) the factors affecting the lymph node metastases in children and adolescence with papillary thyroid carcinoma in region exposed to radiation and (2) to evaluate the predictive significance of these factors for lateral compartment lymphadenectomy. Five hundred and nine patients with papillary thyroid carcinoma underwent total thyroidectomy and lymph nodes resection (central and lateral compartments of the neck) surgery during the period of 1991-2010 in Belarus were recruited. The factors related to lymph node metastases were studied in these patients. In the patients with papillary thyroid carcinoma, increase number of cancer-positive lymph nodes in the central neck compartment were associated with a risk to develop lateral nodal disease as well as bilateral nodal disease. Futhermore, positive lateral compartment nodal metastases are associated with age and gender of the patients, tumour size, minimal extra-thyroidal extension, solid architectonic, extensive desmoplasia in carcinoma, presence of psammoma bodies, extensive involvement of the thyroid and metastatic ratio index revealed after examination of the central cervical chain lymph nodes. The presence of nodal disease, degree of lymph node involvement and the distribution of lymph node metastases significantly increase the recurrence rates of patients with papillary thyroid carcinoma. To conclude, the lymph nodes metastases in young patients with papillary thyroid carcinoma in post-Chernobyl exposed region are common and the pattern could be predicted by many clinical and pathological factors. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Prognostic Value of Lymph Node Yield and Density in Head and Neck Malignancies.

PubMed

Cheraghlou, Shayan; Otremba, Michael; Kuo Yu, Phoebe; Agogo, George O; Hersey, Denise; Judson, Benjamin L

2018-06-01

Objective Studies have suggested that the lymph node yield and lymph node density from selective or elective neck dissections are predictive of patient outcomes and may be used for patient counseling, treatment planning, or quality measurement. Our objective was to systematically review the literature and conduct a meta-analysis of studies that investigated the prognostic significance of lymph node yield and/or lymph node density after neck dissection for patients with head and neck cancer. Data Sources The Ovid/Medline, Ovid/Embase, and NLM PubMed databases were systematically searched on January 23, 2017, for articles published between January 1, 1946, and January 23, 2017. Review Methods We reviewed English-language original research that included survival analysis of patients undergoing neck dissection for a head and neck malignancy stratified by lymph node yield and/or lymph node density. Study data were extracted by 2 independent researchers (S.C. and M.O.). We utilized the DerSimonian and Laird random effects model to account for heterogeneity of studies. Results Our search yielded 350 nonduplicate articles, with 23 studies included in the final synthesis. Pooled results demonstrated that increased lymph node yield was associated with a significant improvement in survival (hazard ratio, 0.833; 95% CI, 0.790-0.879). Additionally, we found that increased lymph node density was associated with poorer survival (hazard ratio, 1.916; 95% CI, 1.637-2.241). Conclusions Increased nodal yield portends improved outcomes and may be a valuable quality indicator for neck dissections, while increased lymph node density is associated with diminished survival and may be used for postsurgical counseling and planning for adjuvant therapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dinshaw, Ketayun A.; Budrukkar, Ashwini N.; Chinoy, Roshan F.

Purpose: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. Methods and Materials: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). Results: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women.more » The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age {<=}40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). Conclusion: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.« less

Predictors and Patterns of Local, Regional, and Distant Failure in Squamous Cell Carcinoma of the Vulva.

PubMed

Bogani, Giorgio; Cromi, Antonella; Serati, Maurizio; Uccella, Stefano; Donato, Violante Di; Casarin, Jvan; Naro, Edoardo Di; Ghezzi, Fabio

2017-06-01

To identify factors predicting for recurrence in vulvar cancer patients undergoing surgical treatment. We retrospectively evaluated data of consecutive patients with squamous cell vulvar cancer treated between January 1, 1990 and December 31, 2013. Basic descriptive statistics and multivariable analysis were used to design predicting models influencing outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox model. The study included 101 patients affected by vulvar cancer: 64 (63%) stage I, 12 (12%) stage II, 20 (20%) stage III, and 5 (5%) stage IV. After a mean (SD) follow-up of 37.6 (22.1) months, 21 (21%) recurrences occurred. Local, regional, and distant failures were recorded in 14 (14%), 6 (6%), and 3 (3%) patients, respectively. Five-year DFS and OS were 77% and 82%, respectively. At multivariate analysis only stromal invasion >2 mm (hazard ratio: 4.9 [95% confidence interval, 1.17-21.1]; P=0.04) and extracapsular lymph node involvement (hazard ratio: 9.0 (95% confidence interval, 1.17-69.5); P=0.03) correlated with worse DFS, although no factor independently correlated with OS. Looking at factors influencing local and regional failure, we observed that stromal invasion >2 mm was the only factor predicting for local recurrence, whereas lymph node extracapsular involvement predicted for regional recurrence. Stromal invasion >2 mm and lymph node extracapsular spread are the most important factors predicting for local and regional failure, respectively. Studies evaluating the effectiveness of adjuvant treatment in high-risk patients are warranted.

[Expression of connective tissue growth factor (CTGF), osteopontin (OPN) and clinical significances in the laryngeal squamous cell carcinoma tissues].

PubMed

Li, Youzhong; Lu, Yongde; Ceng, Yici; Yang, Xinming

2007-02-01

To study the expressions of CTGF and OPN and detect their clinical value and correlation in the laryngeal squamous cell carcinoma tissues and paracancerous tissues. SP immunohistochemical method was used for the assays of CTGF and OPN on the routinely paraffin-embedded sections of surgical operated specimens of 41 cases with laryngeal squamous cell carcinoma and 20 ones with paracancerous tissues. The positive rate of CTGF and the score were significantly lower in cancer tissues than those in paracancerous tissues (61.0% vs 90.0%, P < 0.05; 2.41 +/- 1.60 vs 4.24 +/- 1.42, P < 0.01), but those of OPN were opposite (61.0% vs 15.0%, P < 0.01; 3. 10 +/- 1.63 vs 1.12 +/- 0.84, P < 0.01). The positive rates and scores of CTGF were significantly higher in the cases without-metastasis of lymph node and clinical stage T1 than those in the ones with-metastasis of lymph node and clinical stage T3 (P < 0.01) . The positive rates and scores of OPN were significantly lower in the cases without-metastasis of lymph node, clinical stage T1 and histological grade I those that in the ones with-metastasis of lymph node, Clinical stage T3 and histological grade III (P < 0.01). The closely negative correlation was found between the score of CTGF and that of OPN. The expression of CTGF and/or OPN might be important biological markers in reflecting the progression, biological behaviors, metastatic potential and prognosis of the laryngeal squamous cell carcinoma.

The diagnostic performance of shear wave elastography for malignant cervical lymph nodes: A systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Choi, Young Jun; Baek, Jung Hwan; Lee, Jeong Hyun

2017-01-01

To evaluate the diagnostic performance of shear wave elastography for malignant cervical lymph nodes. We searched the Ovid-MEDLINE and EMBASE databases for published studies regarding the use of shear wave elastography for diagnosing malignant cervical lymph nodes. The diagnostic performance of shear wave elastography was assessed using bivariate modelling and hierarchical summary receiver operating characteristic modelling. Meta-regression analysis and subgroup analysis according to acoustic radiation force impulse imaging (ARFI) and Supersonic shear imaging (SSI) were also performed. Eight eligible studies which included a total sample size of 481 patients with 647 cervical lymph nodes, were included. Shear wave elastography showed a summary sensitivity of 81 % (95 % CI: 72-88 %) and specificity of 85 % (95 % CI: 70-93 %). The results of meta-regression analysis revealed that the prevalence of malignant lymph nodes was a significant factor affecting study heterogeneity (p < .01). According to the subgroup analysis, the summary estimates of the sensitivity and specificity did not differ between ARFI and SSI (p = .93). Shear wave elastography is an acceptable imaging modality for diagnosing malignant cervical lymph nodes. We believe that both ARFI and SSI may have a complementary role for diagnosing malignant cervical lymph nodes. • Shear wave elastography is acceptable modality for diagnosing malignant cervical lymph nodes. • Shear wave elastography demonstrated summary sensitivity of 81 % and specificity of 85 %. • ARFI and SSI have complementary roles for diagnosing malignant cervical lymph nodes.

Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldsmith, Benjamin; Baumann, Brian C.; He, Jiwei

2014-03-01

Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, andmore » external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended coverage of pelvic lymph nodes up to the level of the common iliac nodes may be warranted in subsets of patients.« less

Expression and clinical significance of matrix metalloproteinase-9 in lymphatic invasiveness and metastasis of breast cancer.

PubMed

Wu, Qiu-Wan; Yang, Qing-Mo; Huang, Yu-Fan; She, Hong-Qiang; Liang, Jing; Yang, Qiao-Lu; Zhang, Zhi-Ming

2014-01-01

Matrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear. MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated. MMP-9(+) staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05). MMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.

Advantage of using CBA/N strain mice in a non-radioisotopic modification of the local lymph node assay.

PubMed

Takeyoshi, Masahiro; Noda, Shuji; Yamasaki, Kanji; Kimber, Ian

2006-01-01

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone test method for determining the skin sensitizing potential of chemicals. It has been incorporated into the official test guidelines published by some authorities, including the OECD. To avoid the use of radioisotopes, efforts have been made recently to develop non-radioisotopic modifications of the LLNA. A non-radioisotopic modification of the LLNA was developed previously using 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA). However, the non-RI LLNA was found to be somewhat less sensitive than the standard assay. This study reports the advantage of using mice of the CBA/N strain in the non-RI LLNA to improve the sensitivity of this method. The non-RI LLNA was performed using CBA/JN and CBA/N mice exposed to one of four confirmed skin sensitizers, 2,4-dinitrochlorobenzene (DNCB), eugenol (EG), isoeugenol (IEG) or alpha-hexylcinnamic aldehyde (HCA), and to one non-sensitizer, propylene glycol (PG). The EC3 values for DNCB, IEG, EG, HCA and PG were calculated to be 0.1%, 9.6%, 40.6%, 45.5% and >50% in CBA/JN mice and 0.08%, 1.9%, 10.7%, 20.3% and >50% in CBA/N mice, respectively. The EC3 values for DNCB, IEG, EG, HCA and PG in the standard LLNA using CBA/Ca mice and radioisotopes were reported elsewhere as being 0.08%, 1.3%, 13.0%, 8.0% and >50%, respectively. The EC3 values derived from the CBA/N mice in the non-RI LLNA were nearly equivalent to the EC3 values obtained using the standard radioisotopic LLNA with CBA/Ca mice. These data suggest that the use of CBA/N mice may provide a realistic opportunity to develop a version of the LLNA that does not have a requirement for the use of radioisotopes, but which nevertheless has sensitivity approaching, or comparable to, the standard method. 2005 John Wiley & Sons, Ltd.

Metastatic eccrine porocarcinoma: report of a case and review of the literature

PubMed Central

2011-01-01

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported. We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT). EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread. PMID:21410982

Metastatic eccrine porocarcinoma: report of a case and review of the literature.

PubMed

Marone, Ugo; Caracò, Corrado; Anniciello, Anna Maria; Di Monta, Gianluca; Chiofalo, Maria Grazia; Di Cecilia, Maria Luisa; Mozzillo, Nicola

2011-03-16

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported.We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT).EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread.

Role of near-infrared fluorescence imaging in the resection of metastatic lymph nodes in an optimized orthotopic animal model of HNSCC.

PubMed

Atallah, I; Milet, C; Quatre, R; Henry, M; Reyt, E; Coll, J-L; Hurbin, A; Righini, C A

2015-12-01

To study the role of near-infrared fluorescence imaging in the detection and resection of metastatic cervical lymph nodes in head and neck cancer. CAL33 head and neck cancer cells of human origin were implanted in the oral cavity of nude mice. The mice were followed up after tumor resection to detect the development of lymph node metastases. A specific fluorescent tracer for αvβ3 integrin expressed by CAL33 cells was injected intravenously in the surviving mice between the second and the fourth month following tumor resection. A near-infrared fluorescence-imaging camera was used to detect tracer uptake in metastatic cervical lymph nodes, to guide of lymph-node resection for histological analysis. Lymph node metastases were observed in 42.8% of surviving mice between the second and the fourth month following orthotopic tumor resection. Near-infrared fluorescence imaging provided real-time intraoperative detection of clinical and subclinical lymph node metastases. These results were confirmed histologically. Near infrared fluorescence imaging provides real-time contrast between normal and malignant tissue, allowing intraoperative detection of metastatic lymph nodes. This preclinical stage is essential before testing the technique in humans. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Extracapsular extension of pelvic lymph node metastases is of prognostic value in carcinoma of the cervix uteri.

PubMed

Horn, Lars-Christian; Hentschel, Bettina; Galle, Dana; Bilek, Karl

2008-01-01

Pelvic lymph node involvement is a well-recognized prognostic factor in cervical carcinoma (CX). Limited knowledge exists about extranodal extension of the tumor outside the lymph node capsule, i.e. extracapsular spread (ECS). Two hundred fifty-six cases of surgically treated CX (FIGO stage IB1 to IIB) with pelvic lymph node involvement were evaluated regarding the occurrence of extranodal spread of the metastatic deposits outside the lymph node capsule (ECS), determined on standardized handled lymphadenectomy specimens, regarding their impact of recurrent disease and overall survival during a median follow-up time of 62 months (95% CI 51-73 months). ECS was seen in 30.9% (79/256) of the cases. The occurrence of ECS showed a significant correlation to advanced stage disease (p=0.02), the number of involved nodes (p<0.001) and the size of metastatic deposits (p<0.01). The 5-year recurrence-free survival rate in patients with ECS was significant lower compared to patients without ECS (59.7% [95% CI: 46.3%-73.2%] versus 67.2% [95% CI: 58.9%-75.5%]; (p=0.04). The 5-year overall survival rate was significant lower in patients with ECS (33.5% [95% CI: 20.6%-46.3%] vs. 60.5% [95% CI: 52.3%-68.6%]; p<0.001). In multivariate analysis, tumor stage, number of involved pelvic nodes, tumor differentiation and ECS were independent prognostic factors. The results indicate that extracapsular spread (ECS) of pelvic lymph node metastases is of prognostic impact in cervical carcinomas. A revised FIGO/TNM classification system for pelvic lymph node disease is recommended: ECS 0 = lymph node involvement without extranodal spread of the metastatic deposits and ECS 1 = lymph node involvement with extranodal spread of the metastatic deposits.

Radiotherapy on hidradenocarcinoma.

PubMed

Lalya, Issam; Hadadi, Khalid; Tazi, El Mehdi; Lalya, Ilham; Bazine, Amine; Andaloussy, Khalid; Elmarjany, Mohamed; Sifat, Hassan; Hassouni, Khalid; Kebdani, Tayeb; Mansouri, Hamid; Benjaafar, Noureddine; Elgueddari, Brahim Khalil

2011-01-01

Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment. We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity. POST OPERATIVE RADIOTHERAPY ALLOWS BETTER LOCAL CONTROL AND SHOULD BE MANDATORY WHEN HISTOLOGICAL FEATURES PREDICTIVE OF RECURRENCE ARE PRESENT: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread.

Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis.

PubMed

Huang, Xiongfeng; Wang, Jianmin; Chen, Qiao; Jiang, Jielin

2014-01-01

This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients. A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients. Methodological quality of included randomized controlled trials was assessed according to the criteria from the Cochrane Handbook for Systematic Review of Interventions (Version 5.1.0). Meta-analysis was performed using The Cochrane Collaboration's Review Manager 5.3. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence interval (CI). We included results reported from six randomized controlled trials, with a total of 1,791 patients included in the primary meta-analysis. Compared to MLNS in NSCLC patients, there was no statistically significant difference in MLND on overall survival (HR = 0.77, 95% CI 0.55 to 1.08; P = 0.13). In addition, the results indicated that local recurrence rate (RR = 0.93, 95% CI 0.68 to 1.28; P = 0.67), distant metastasis rate (RR = 0.88, 95% CI 0.74 to 1.04; P = 0.15), and total complications rate (RR = 1.10, 95% CI 0.67 to 1.79; P = 0.72) were similar, no significant difference found between the two groups. Results for overall survival, local recurrence rate, and distant metastasis rate were similar between MLND and MLNS in early stage NSCLC patients. There was no evidence that MLND increased complications compared with MLNS. Whether or not MLND is superior to MLNS for stage II-IIIA remains to be determined.

Successful resection of metachronous para-aortic, Virchow lymph node and liver metastatic recurrence of rectal cancer.

PubMed

Takeshita, Nobuyoshi; Fukunaga, Toru; Kimura, Masayuki; Sugamoto, Yuji; Tasaki, Kentaro; Hoshino, Isamu; Ota, Takumi; Maruyama, Tetsuro; Tamachi, Tomohide; Hosokawa, Takashi; Asai, Yo; Matsubara, Hisahiro

2015-11-28

A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, cSS, cN0, cH0, cP0, cM0 cStage II, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, pSS, pN3, pH0, pP1, pM1 (para-aortic lymph node, dissemination) fStage IV. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography (CT) detected an 11 mm of liver metastasis in the postero-inferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of para-aortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in para-aortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine alone and continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome (Grade 3), we managed to continue capecitabine administration with extension of interval period and dose reduction. After 2 years and 2 mo from starting capecitabine plus bevacizumab regimen, Virchow lymph nodes had slowly grown up to 17 mm. Because no recurrence had been detected besides Virchow lymph nodes for this follow up period, considering the side effects and quality of life, surgical resection was selected. We performed left supraclavicular lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer. After the fourth operation, the patient selected follow up without chemotherapy. Now we follow up her without recurrence and keep her quality of life high.

Optimization of the extent of surgical treatment in patients with stage I in cervical cancer

NASA Astrophysics Data System (ADS)

Chernyshova, A. L.; Kolomiets, L. A.; Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.

2016-08-01

The study included 26 patients with FIGO stage Ia1-Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

Elastic scattering spectroscopy findings in formalin-fixed oral squamous cell carcinoma specimens

NASA Astrophysics Data System (ADS)

Swinson, B.; Elmaaytah, M.; Jerjes, W.; Hopper, C.

2005-11-01

Oral squamous cell carcinoma (OSCC) has been shown to spread locally and infiltrate adjacent bone or via the lymphatic system to the cervical lymph nodes. This usually necessitates a surgical neck dissection and either a local or segmental resection for bone clearance. While histopathology remains the gold standard for tissue diagnosis, several new diagnostic techniques are being developed that rely on physical and biochemical changes that mirror or precede malignant changes within tissue. The aim of this study was to compare findings of Elastic Scattering Spectroscopy (ESS) with histopathology on formalin-fixed specimens of both neck lymph node dissections and de-calcified archival bone from patients with OSCC. We wished to see if this technique could be used as an adjunct or alternative to histopathology in defining cervical nodal involvement and if it could be used to identify bone resection margins positive for tumour. 130 lymph nodes were examined from 13 patients. The nodes were formalin-fixed, bivalved and examined by ESS. The intensity of the spectrum at 4 points was considered for comparison; at 360nm, 450nm, 630nm and 690nm. 341 spectra were taken from the mandibular specimens of 21 patients, of which 231 spectra were taken from histologically positive sites and the rest were normal. The nodes and bone specimens were then routinely processed with haematoxylin and eosin-stained sections, examined histopathologically, and the results compared. Using Linear Discriminant Analysis (LDA) as a statistical method, a sensitivity of 98% and a specificity of 68% was obtained for the neck nodes and a sensitivity of 87% and a specificity of 80% for the bone margins.

Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

PubMed

Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

2016-08-01

Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. © 2016 UICC.

Dendritic cells control fibroblastic reticular network tension and lymph node expansion.

PubMed

Acton, Sophie E; Farrugia, Aaron J; Astarita, Jillian L; Mourão-Sá, Diego; Jenkins, Robert P; Nye, Emma; Hooper, Steven; van Blijswijk, Janneke; Rogers, Neil C; Snelgrove, Kathryn J; Rosewell, Ian; Moita, Luis F; Stamp, Gordon; Turley, Shannon J; Sahai, Erik; Reis e Sousa, Caetano

2014-10-23

After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion. Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion--driven by lymphocyte influx and proliferation--that is the critical hallmark of adaptive immunity.

Immunoreactivities of human nonmetastatic clone 23 and p53 products are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients.

PubMed

Tee, Y T; Wang, P H; Ko, J L; Chen, G D; Chang, H; Lin, L Y

2007-01-01

To assess the relation between expressions of human nonmetastatic clone 23 (nm23-H1) and p53 in cervical cancer, their relationships with lymph node metastasis, and further to examine their predictive of lymph node metastases. nm23-H1 and p53 expression profiles were visualized by immunohistochemistry in early-stage cervical cancer specimens. Immunoreactivities of nm23-H1 and p53 were disassociated. The independent variables related with lymph node metastases were grade of cancer cell differentiation (p < 0.029) and stromal invasion (p < 0.039). Sensitivity, specificity, positive and negative predictive values, and accuracy for lymph node metastasis were calculated to be 91.7%, 13.5%, 25.6%, 83.3%, and 32.7% for nm23-H1 and 66.7%, 51.4%, 30.8%, 82.6%, and 55.1% for p53. Nm23-H1 and p53 are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients. However, stromal invasion and cell differentiation can predict lymph node metastasis.

Interlaboratory validation of the modified murine local lymph node assay based on adenosine triphosphate measurement.

PubMed

Omori, Takashi; Idehara, Kenji; Kojima, Hajime; Sozu, Takashi; Arima, Kazunori; Goto, Hirohiko; Hanada, Tomohiko; Ikarashi, Yoshiaki; Inoda, Taketo; Kanazawa, Yukiko; Kosaka, Tadashi; Maki, Eiji; Morimoto, Takashi; Shinoda, Shinsuke; Shinoda, Naoki; Takeyoshi, Masahiro; Tanaka, Masashi; Uratani, Mamoru; Usami, Masahito; Yamanaka, Atsushi; Yoneda, Tomofumi; Yoshimura, Isao; Yuasa, Atsuko

2008-01-01

The murine local lymph node assay (LLNA) is a well-established alternative to the guinea pig maximization test (GPMT) or Buehler test (BT) for the assessment of the skin sensitizing ability of drugs and chemicals. Daicel Chemical Industries Ltd. has developed a modified LLNA based on the adenosine triphosphate (ATP) content (LLNA-DA). We conducted 2 interlaboratory validation studies to evaluate the reliability and relevance of LLNA-DA. The experiment involved 17 laboratories, wherein 14 chemicals were examined under blinded conditions. In the first study, 3 chemicals were examined in 10 laboratories and the remaining 9 were examined in 3 laboratories. In the second study, 1 chemical was examined in 7 laboratories and the remaining 4 chemicals were examined in 4 laboratories. The data were expressed as the ATP content for each chemical-treated group, and the stimulation index (SI) for each chemical-treated group was determined as the increase in the ATP content relative to the concurrent vehicle control group. An SI of 3 was set as the cut-off value for exhibiting skin sensitization activity. The results of the first study obtained in the experiments conducted for the 3 chemicals that were examined in all the 10 laboratories and for 5 of the remaining 9 chemicals were sufficiently consistent with small variations in their SI values. The sensitivity, specificity, and accuracy of LLNA-DA against those of GPMT/BT were 7/8 (87.5%), 3/3 (100%), and 10/11 (90.9%), respectively. In the second study, all the 5 chemicals studied demonstrated acceptably small interlaboratory variations. In the first study, a large variation was observed for 2 chemicals; in the second study, this variation was small. It was attributed to the application of dimethylsulfoxide as the solvent for the metallic salts. In conclusion, these 2 studies provide good evidence for the reliability of the LLNA-DA.

Appraisal of within- and between-laboratory reproducibility of non-radioisotopic local lymph node assay using flow cytometry, LLNA:BrdU-FCM: comparison of OECD TG429 performance standard and statistical evaluation.

PubMed

Yang, Hyeri; Na, Jihye; Jang, Won-Hee; Jung, Mi-Sook; Jeon, Jun-Young; Heo, Yong; Yeo, Kyung-Wook; Jo, Ji-Hoon; Lim, Kyung-Min; Bae, SeungJin

2015-05-05

Mouse local lymph node assay (LLNA, OECD TG429) is an alternative test replacing conventional guinea pig tests (OECD TG406) for the skin sensitization test but the use of a radioisotopic agent, (3)H-thymidine, deters its active dissemination. New non-radioisotopic LLNA, LLNA:BrdU-FCM employs a non-radioisotopic analog, 5-bromo-2'-deoxyuridine (BrdU) and flow cytometry. For an analogous method, OECD TG429 performance standard (PS) advises that two reference compounds be tested repeatedly and ECt(threshold) values obtained must fall within acceptable ranges to prove within- and between-laboratory reproducibility. However, this criteria is somewhat arbitrary and sample size of ECt is less than 5, raising concerns about insufficient reliability. Here, we explored various statistical methods to evaluate the reproducibility of LLNA:BrdU-FCM with stimulation index (SI), the raw data for ECt calculation, produced from 3 laboratories. Descriptive statistics along with graphical representation of SI was presented. For inferential statistics, parametric and non-parametric methods were applied to test the reproducibility of SI of a concurrent positive control and the robustness of results were investigated. Descriptive statistics and graphical representation of SI alone could illustrate the within- and between-laboratory reproducibility. Inferential statistics employing parametric and nonparametric methods drew similar conclusion. While all labs passed within- and between-laboratory reproducibility criteria given by OECD TG429 PS based on ECt values, statistical evaluation based on SI values showed that only two labs succeeded in achieving within-laboratory reproducibility. For those two labs that satisfied the within-lab reproducibility, between-laboratory reproducibility could be also attained based on inferential as well as descriptive statistics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Definitive radiotherapy for primary vaginal cancer: correlation between treatment patterns and recurrence rate.

PubMed

Kanayama, Naoyuki; Isohashi, Fumiaki; Yoshioka, Yasuo; Baek, Sungjae; Chatani, Masashi; Kotsuma, Tadayuki; Tanaka, Eiichi; Yoshida, Ken; Seo, Yuji; Suzuki, Osamu; Mabuchi, Seiji; Shiki, Yasuhiko; Tatsumi, Keiji; Kimura, Tadashi; Teshima, Teruki; Ogawa, Kazuhiko

2015-03-01

The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1-169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III-IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Fluorescence imaging to study cancer burden on lymph nodes

NASA Astrophysics Data System (ADS)

D'Souza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

2015-03-01

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue along with a cancer targeting tracer, Affibody labeled with IRDYE800CW and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

PubMed

van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

2006-04-01

Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma.

PubMed

de Carvalho, Ana Carolina; Scapulatempo-Neto, Cristovam; Maia, Danielle Calheiros Campelo; Evangelista, Adriane Feijó; Morini, Mariana Andozia; Carvalho, André Lopes; Vettore, André Luiz

2015-05-09

The presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. Frequently, routine lymph node staging cannot detect occult metastases and the post-surgical histologic evaluation of resected lymph nodes is not sensitive in detecting small metastatic deposits. Molecular markers based on tissue-specific microRNA expression are alternative accurate diagnostic markers. Herein, we evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients. An initial screening compared the expression of 667 microRNAs in a discovery set comprised by metastatic and non-metastatic lymph nodes from HNSCC patients. The most differentially expressed microRNAs were validated by qRT-PCR in two independent cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. The accuracy of the markers in identifying metastatic samples was assessed through the analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve values. Seven microRNAs highly expressed in metastatic lymph nodes from the discovery set were validated in FFPE lymph node samples. MiR-203 and miR-205 identified all metastatic samples, regardless of the size of the metastatic deposit. Additionally, these markers also showed high accuracy when FNA samples were examined. The high accuracy of miR-203 and miR-205 warrant these microRNAs as diagnostic markers of neck metastases in HNSCC. These can be evaluated in entire lymph nodes and in FNA biopsies collected at different time-points such as pre-treatment samples, intraoperative sentinel node biopsy, and during patient follow-up. These markers can be useful in a clinical setting in the management of HNSCC patients from initial disease staging and therapy planning to patient surveillance.

A comparative study of digital PCR and real-time qPCR for the detection and quantification of HPV mRNA in sentinel lymph nodes of cervical cancer patients.

PubMed

Carow, Katrin; Read, Christina; Häfner, Norman; Runnebaum, Ingo B; Corner, Adam; Dürst, Matthias

2017-10-30

Qualitative analyses showed that the presence of HPV mRNA in sentinel lymph nodes of cervical cancer patients with pN0 status is associated with significantly decreased recurrence free survival. To further address the clinical potential of the strategy and to define prognostic threshold levels it is necessary to use a quantitative assay. Here, we compare two methods of quantification: digital PCR and standard quantitative PCR. Serial dilutions of 5 ng-5 pg RNA (≙ 500-0.5 cells) of the cervical cancer cell line SiHa were prepared in 5 µg RNA of the HPV-negative human keratinocyte cell line HaCaT. Clinical samples consisted of 10 sentinel lymph nodes with varying HPV transcript levels. Reverse transcription of total RNA (5 µg RNA each) was performed in 100 µl and cDNA aliquots were analyzed by qPCR and dPCR. Digital PCR was run in the RainDrop ® Digital PCR system (RainDance Technologies) using a probe-based detection of HPV E6/E7 cDNA PCR products with 11 µl template. qPCR was done using a Rotor Gene Q 5plex HRM (Qiagen) amplifying HPV E6/E7 cDNA in a SYBR Green format with 1 µl template. For the analysis of both, clinical samples and serial dilution samples, dPCR and qPCR showed comparable sensitivity. With regard to reproducibility, both methods differed considerably, especially for low template samples. Here, we found with qPCR a mean variation coefficient of 126% whereas dPCR enabled a significantly lower mean variation coefficient of 40% (p = 0.01). Generally, we saw with dPCR a substantial reduction of subsampling errors, which most likely reflects the large cDNA amounts available for analysis. Compared to real-time PCR, dPCR shows higher reliability. Thus, our HPV mRNA dPCR assay holds promise for the clinical evaluation of occult tumor cells in histologically tumor-free lymph nodes in future studies.

Surgery of the vulva in vulvar cancer.

PubMed

Micheletti, Leonardo; Preti, Mario

2014-10-01

The standard radical mutilating surgery for the treatment of invasive vulval carcinoma is, today, being replaced by a conservative and individualised approach. Surgical conservative modifications that are currently considered safe, regarding vulval lesion, are separate skin vulval-groin incisions, drawn according to the lesion diameter, and wide local radical excision or partial radical vulvectomy with 1-2 cm of clinically clear surgical margins. Regarding inguinofemoral lymph nodes management, surgical conservative modifications not compromising patient survival are omission of groin lymphadenectomy only when tumour stromal invasion is ≤ 1 mm, unilateral groin lymphadenectomy only in well-lateralised early lesions and total or radical inguinofemoral lymphadenectomy with preservation of femoral fascia when full groin resection is needed. Sentinel lymph node dissection is a promising technique but it should not be routinely employed outside referral centres. Pelvic nodes are better managed by radiation. Locally advanced vulval carcinoma can be managed by ultraradical surgery, exclusive radiotherapy or chemoradiation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lymphatic and local spread of T1 and T2 pancreatic cancer. A study of autopsy material.

PubMed Central

Nagai, H; Kuroda, A; Morioka, Y

1986-01-01

Eight autopsy cases of pancreatic cancer (duct cell adenocarcinoma) with T1 and T2 primary tumors were studied histologically to examine the exact extent of lymphatic and local spread. Six of them had microscopic metastasis in grossly negative lymph nodes near the primary tumor. In addition, four of them had a few metastatic nodes in the para-aortic region. In cases with lymphatic metastases, the extent of cancer infiltration within lymphatic vessels, nerves, and/or connective tissues was almost the same as that of lymph node metastasis. Major vascular involvement was found in four cases. There was no case in which multicentricity or marked intraductal spread of cancer cells was observed in the pancreas. It has been suggested that most of T1 and T2 pancreatic cancers have a fairly widespread microscopic extension, although extremely small T1 cancers have a very limited extension. Images FIG. 2. FIGS. 4a-c. FIGS. 5a-c. PMID:3015059

The feasibility of contralateral lower neck sparing intensity modulation radiated therapy for nasopharyngeal carcinoma patients with unilateral cervical lymph node involvement.

PubMed

Tang, Ling-Long; Tang, Xin-Ran; Li, Wen-Fei; Chen, Lei; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2017-06-01

To investigate the feasibility of contralateral lower neck sparing intensity modulation radiated therapy (IMRT) for nasopharyngeal carcinoma patients (NPC) with unilateral cervical lymph node metastasis. Retrospective review of 546 patients with unilateral cervical lymph node metastasis treated between November 2009 and February 2012 at one institution. All patients were staged using magnetic resonance imaging and received radical IMRT. Patients were classified into two groups: the inferior border of the negative neck irradiation field only covered Levels III to Va in Group 1; the inferior border covered entire neck down to Levels IV to Vb in Group 2. Median follow-up was 49.9months (range, 1.3-69.2months). Four-year overall survival (OS:89.3% vs. 88.9%, P=0.91), disease-free survival (DFS:81.7% vs. 81.0%, P=0.91), distant metastasis-free survival (DMFS:88.2% vs. 87.9%, P=0.95), local relapse-free survival (LRFS:96.7% vs. 94.7%, P=0.70) and nodal relapse-free survival (NRFS: 96.1% vs. 95.9%, P=0.94) were not significantly different between Group 1 and Group 2. Twenty-two patients developed cervical lymph node relapse; of whom 20/22 (91.0%) developed unilateral relapse within pretreatment positive neck. Only one patient developed out-of-field relapse, though this patient also relapsed within the neck irradiation field (Level II). No clinicopathological feature tested had significant prognostic value for NRFS in multivariate analysis. In the IMRT and MRI era, contralateral lower neck sparing IMRT seems to be feasible for NPC patients with unilateral cervical lymph node metastasis. Copyright © 2017. Published by Elsevier Ltd.

CT-Guided Radioactive {sup 125}I Seed Implantation Therapy of Symptomatic Retroperitoneal Lymph Node Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhongmin, E-mail: wzm0722@hotmail.com; Lu, Jian; Gong, Ju

2013-04-12

PurposeThis study explored the clinical efficacy of CT-guided radioactive {sup 125}I seed implantation in treating patients with symptomatic retroperitoneal lymph node metastases.MethodsTwenty-five patients with pathologically confirmed malignant tumors received CT-guided radioactive {sup 125}I seed implantation to treat metastatic lymph nodes. The diameter of the metastatic lymph nodes ranged from 1.5 to 4.5 cm. Treatment planning system (TPS) was used to reconstruct the three-dimensional image of the tumor and then calculate the corresponding quantity and distribution of {sup 125}I seeds.ResultsFollow-up period for this group of patients was 2–30 months, and median time was 16 months. Symptoms of refractory pain were significantly resolved postimplantationmore » (P < 0.05), and Karnofsky score rose dramatically (P < 0.05). Most patients reported pain relief 2–5 days after treatment. Follow-up imaging studies were performed 2 months later, which revealed CR in 7 patients, PR in 13 patients, SD in 3 patients, and PD in 2 patients. The overall effective rate (CR + PR) was 80 %. Median survival time was 25.5 months. Seven patients died of recurrent tumor; 16 patients died of multiorgan failure or other metastases. Two patients survived after 30 months follow-up. Two patients reported localized skin erythema 1 week postimplantation, which disappeared after topical treatment.ConclusionsCT-guided radioactive {sup 125}I seed implantation, which showed good palliative pain relief with acceptable short-term effects, has proved in our study to be a new, safe, effective, and relatively uncomplicated treatment option for symptomatic retroperitoneal metastatic lymph nodes.« less

Ultra-small superparamagnetic iron oxide mediated magnetic hyperthermia in treatment of neck lymph node metastasis in rabbit pyriform sinus VX2 carcinoma.

PubMed

Wang, Peng; Xie, Xiaofeng; Wang, Jian; Shi, Yuan; Shen, Na; Huang, Xinsheng

2015-09-01

Lymph node metastasis of rabbit VX2 pyriform sinus carcinoma can be enhanced by MR scanning after injecting ultra-small superparamagnetic iron oxide (USPIO) into the submucosa beside the tumor. The metastasis lymph node which fit in with the diagnostic criteria will be placed into the alternating magnetic field after MR scanning. Then, magnetic particles can be heated to the effective therapeutic temperature. And it evaluates the possibility of diagnosis together with therapy in cervical metastasis of pyriform sinus carcinoma. Twenty rabbits bearing VX2 tumor in pyriform sinuses were randomly divided into hyperthermia group and control group after USPIO MR scanning; each group contained 10 rabbits. The hyperthermia for the experimental group was conducted by the alternating magnetic field. After hyperthermia, the detection of apoptosis for the two groups was tested by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL), transmission electron microscopy (TEM), and the expression of Bcl-2 and Bax evaluated by immunohistochemical analysis. The apoptosis rate detected by TUNEL in hyperthermia group was 100 %, while the control group was only 20 % (p < 0.05). TEM observation showed that cell chromatin condensation and clumping, condensed cytoplasm, endoplasmic reticulum membrane fusion with loose change, and the formation of a bubble could be seen in the hyperthermia group. However, the control group showed a more complete cytoplasm and nucleus. Bcl-2 protein expression in the hyperthermia group was lower than the control group, and Bax protein expression in hyperthermia group was higher (p < 0.05). USPIO indirect lymphography could localize the metastatic lymph nodes for hyperthermia. And it could make the metastatic cervical lymph nodes apoptosis when placed into the alternating magnetic field.

A multimodal image guiding system for Navigated Ultrasound Bronchoscopy (EBUS): A human feasibility study

PubMed Central

Hofstad, Erlend Fagertun; Amundsen, Tore; Langø, Thomas; Bakeng, Janne Beate Lervik; Leira, Håkon Olav

2017-01-01

Background Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is the endoscopic method of choice for confirming lung cancer metastasis to mediastinal lymph nodes. Precision is crucial for correct staging and clinical decision-making. Navigation and multimodal imaging can potentially improve EBUS-TBNA efficiency. Aims To demonstrate the feasibility of a multimodal image guiding system using electromagnetic navigation for ultrasound bronchoschopy in humans. Methods Four patients referred for lung cancer diagnosis and staging with EBUS-TBNA were enrolled in the study. Target lymph nodes were predefined from the preoperative computed tomography (CT) images. A prototype convex probe ultrasound bronchoscope with an attached sensor for position tracking was used for EBUS-TBNA. Electromagnetic tracking of the ultrasound bronchoscope and ultrasound images allowed fusion of preoperative CT and intraoperative ultrasound in the navigation software. Navigated EBUS-TBNA was used to guide target lymph node localization and sampling. Navigation system accuracy was calculated, measured by the deviation between lymph node position in ultrasound and CT in three planes. Procedure time, diagnostic yield and adverse events were recorded. Results Preoperative CT and real-time ultrasound images were successfully fused and displayed in the navigation software during the procedures. Overall navigation accuracy (11 measurements) was 10.0 ± 3.8 mm, maximum 17.6 mm, minimum 4.5 mm. An adequate sample was obtained in 6/6 (100%) of targeted lymph nodes. No adverse events were registered. Conclusions Electromagnetic navigated EBUS-TBNA was feasible, safe and easy in this human pilot study. The clinical usefulness was clearly demonstrated. Fusion of real-time ultrasound, preoperative CT and electromagnetic navigational bronchoscopy provided a controlled guiding to level of target, intraoperative overview and procedure documentation. PMID:28182758

The posterior cervical lymph node in toxoplasmosis.

PubMed

Gray, G F; Kimball, A C; Kean, B H

1972-11-01

Posterior cervical node enlargement is characteristic of clinical toxoplasmosis in adults. Lymph node biopsies from 37 patients, who were tested for toxoplasmosis by serologic and isolation studies, were examined. A characteristic pattern of sinus histiocytosis was seen in 17 of 18 posterior cervical nodes and in only 1 of 4 lymph nodes from other sites from patients with toxoplasmosis. The characteristic pattern was not seen in posterior cervical nodes or in lymph nodes from other sites from patients with other diseases. Lymphoma obscured the characteristic changes of toxoplasmosis in the posterior cervical nodes and other nodes of 5 patients with these coexisting diseases. Organisms were seen in tissue sections in only 2 instances. T gondii was isolated from mice in 14 of 17 attempts using nodes from patients with toxoplasmosis, but from none of 8 attempts using nodes from patients with other diseases.

Computed tomographic atlas for the new international lymph node map for lung cancer: A radiation oncologist perspective.

PubMed

Lynch, Rod; Pitson, Graham; Ball, David; Claude, Line; Sarrut, David

2013-01-01

To develop a reproducible definition for each mediastinal lymph node station based on the new TNM classification for lung cancer. This paper proposes an atlas using the new international lymph node map used in the seventh edition of the TNM classification for lung cancer. Four radiation oncologists and 1 diagnostic radiologist were involved in the project to put forward a reproducible radiologic description for the lung lymph node stations. The International Association for the Study of Lung Cancer lymph node definitions for stations 1 to 11 have been described and illustrated on axial computed tomographic scan images using a certified radiotherapy planning system. This atlas will assist both diagnostic radiologists and radiation oncologists in accurately defining the lymph node stations on computed tomographic scan in patients diagnosed with lung cancer. Copyright © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Near-infrared-fluorescence imaging of lymph nodes by using liposomally formulated indocyanine green derivatives.

PubMed

Toyota, Taro; Fujito, Hiromichi; Suganami, Akiko; Ouchi, Tomoki; Ooishi, Aki; Aoki, Akira; Onoue, Kazutaka; Muraki, Yutaka; Madono, Tomoyuki; Fujinami, Masanori; Tamura, Yutaka; Hayashi, Hideki

2014-01-15

Liposomally formulated indocyanine green (LP-ICG) has drawn much attention as a highly sensitive near-infrared (NIR)-fluorescence probe for tumors or lymph nodes in vivo. We synthesized ICG derivatives tagged with alkyl chains (ICG-Cn), and we examined NIR-fluorescence imaging for lymph nodes in the lower extremities of mice by using liposomally formulated ICG-Cn (LP-ICG-Cn) as well as conventional liposomally formulated ICG (LP-ICG) and ICG. Analysis with a noninvasive preclinical NIR-fluorescence imaging system revealed that LP-ICG-Cn accumulates in only the popliteal lymph node 1h after injection into the footpad, whereas LP-ICG and ICG accumulate in the popliteal lymph node and other organs like the liver. This result indicates that LP-ICG-Cn is a useful NIR-fluorescence probe for noninvasive in vivo bioimaging, especially for the sentinel lymph node. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of quartz exposure on lung cancer types in cases of lymph node-only silicosis and lung silicosis in German uranium miners.

PubMed

Mielke, Stefan; Taeger, Dirk; Weitmann, Kerstin; Brüning, Thomas; Hoffmann, Wolfgang

2018-05-04

Inhaled crystalline quartz is a carcinogen. Analyses show differences in the distribution of lung cancer types depending on the status of silicosis. Using 2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was differentiated into cases without silicosis in lung parenchyma and its lymph nodes, with lymph node-only silicosis, or with lung silicosis including lymph node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and small-cell lung carcinoma mortality for increasing quartz exposures were estimated in a multinomial logistic regression model. The relative proportions of the lung cancer subtypes in lymph node-only silicosis were more similar to lung silicosis than without any silicosis. The results support the hypothesis that quartz-related carcinogenesis in case of lymph node-only silicosis is more similar to that in lung silicosis than in without silicosis.

Multimodal imaging of lymph nodes and tumors using glycol-chitosan-coated gold nanoparticles (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, In-Cheol; Dumani, Diego S.; Emelianov, Stanislav Y.

2017-03-01

A key step in staging cancer is the diagnosis of metastasis that spreads through lymphatic system. For this reason, researchers develop various methods of sentinel lymph node mapping that often use a radioactive tracer. This study introduces a safe, cost-effective, high-resolution, high-sensitivity, and real-time method of visualizing the sentinel lymph node: ultrasound-guided photoacoustic (US/PA) imaging augmented by a contrast agent. In this work, we use clearable gold nanoparticles covered by a biocompatible polymer (glycol chitosan) to enhance cellular uptake by macrophages abundant in lymph nodes. We incubate macrophages with glycol-chitosan-coated gold nanoparticles (0.05 mg Au/ml), and then fix them with paraformaldehyde solution for an analysis of in vitro dark-field microscopy and cell phantom. The analysis shows enhanced cellular uptake of nanoparticles by macrophages and strong photoacoustic signal from labeled cells in tissue-mimicking cell phantoms consisting gelatin solution (6 %) with silica gel (25 μm, 0.3%) and fixed macrophages. The in-vivo US/PA imaging of cervical lymph nodes in healthy mice (nu/nu, female, 5 weeks) indicates a strong photoacoustic signal from a lymph node 10 minutes post-injection (2.5 mg Au/ml, 80 μl). The signal intensity and the nanoparticle-labeled volume of tissue within the lymph node continues to increase until 4 h post-injection. Histological analysis further confirms the accumulation of gold nanoparticles within the lymph nodes. This work suggests the feasibility of molecular/cellular US/PA imaging with biocompatible gold nanoparticles as a photoacoustic contrast agent in the diagnosis of lymph-node-related diseases.

[Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ].

PubMed

Ruvalcaba-Limón, Eva; de Jesús Garduño-Raya, María; Bautista-Piña, Verónica; Trejo-Martínez, Claudia; Maffuz-Aziz, Antonio; Rodríguez-Cuevas, Sergio

2014-01-01

Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.

Discrimination of benign and malignant lymph nodes at 7.0T compared to 1.5T magnetic resonance imaging using ultrasmall particles of iron oxide: a feasibility preclinical study.

PubMed

Kinner, Sonja; Maderwald, Stefan; Albert, Juliane; Parohl, Nina; Corot, Claire; Robert, Philippe; Baba, Hideo A; Barkhausen, Jörg

2013-12-01

To investigate the feasibility and performance of 7T magnetic resonance imaging compared to 1.5T imaging to discriminate benign (normal and inflammatory changed) from tumor-bearing lymph nodes in rabbits using ultrasmall particles of iron oxide (USPIO)-based contrast agents. Six New Zealand White rabbits were inoculated with either complete Freund's adjuvant cell suspension (n = 3) to induce reactively enlarged lymph nodes or with VX2 tumor cells to produce metastatic lymph nodes (n = 3). Image acquisition was performed before and 24 hours after bolus injection of an USPIO contrast agent at 1.5T and afterward at 7T using T1-weighted and T2*-weighted sequences. Sensitivities, specificities, and negative and positive predictive values for the detection of lymph node metastases were calculated for both field strengths with histopathology serving as reference standard. Sizes of lymph nodes with no, inflammatory, and malignant changes were compared using a Mann-Whitney U-test. All 24 lymph nodes were detected at 1.5T as well as at 7T. At 1.5T, sensitivity amounted to 0.67, while specificity reached a value of 1. At the higher field strength (7T), imaging was able to reach sensitivity and specificity values of 1. No statistical differences were detected concerning lymph node sizes. Magnetic resonance lymphography with USPIO contrast agents allows for differentiation of normal and reactively enlarged lymph nodes compared to metastatic nodes. First experiments at 7T show promising results compared to 1.5T, which have to be evaluated in further trials. Copyright © 2013. Published by Elsevier Inc.

Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer.

PubMed

Johnson, Sara D; Young, M Rita I

2016-01-01

Current treatment options for head and neck squamous cell carcinoma (HNSCC) patients are often ineffective due to tumor-localized and systemic immunosuppression. Using the 4-NQO mouse model of oral carcinogenesis, this study showed that premalignant oral lesion cells produce higher levels of the immune modulator, PGE 2 , compared to HNSCC cells. Inhibiting prostaglandin production of premalignant lesion cells with the pan-cyclooxygenase inhibitor indomethacin stimulated their induction of spleen cell cytokine production. In contrast, inhibiting HNSCC prostaglandin production did not stimulate their induction of spleen cell cytokine production. Treatment of mice bearing premalignant oral lesions with indomethacin slowed progression of premalignant oral lesions to HNSCC. Flow cytometric analysis of T cells in the regional lymph nodes of lesion-bearing mice receiving indomethacin treatment showed an increase in lymph node cellularity and in the absolute number of CD8 + T cells expressing IFN-γ compared to levels in lesion-bearing mice receiving diluent control treatment. The cytokine-stimulatory effect of indomethacin treatment was not localized to regional lymph nodes but was also seen in the spleen of mice with premalignant oral lesions. Together, these data suggest that inhibiting prostaglandin production at the premalignant lesion stage boosts immune capability and improves clinical outcomes.

Localization of tritiated vitamin A in lymph nodes of the mouse: an autoradiographic study of vitamin A-storing cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirosawa, K.; Yamada, E.

1981-07-01

Localization of tritiated vitamin A in lymph nodes of the mouse was investigated by the use of light- and electron-microscopic autoradiography. Young male mice were fed a diet containing 3H-vitamin A acetate for a week. Lymph nodes were removed and prepared for autoradiography. Lipid droplets in fibroblast-like cells showed high concentrations of radioactivity. These cells were distributed around lymphatic sinuses and blood vessels. The cells can, therefore, be classified as ''vitamin A-storing cells'' according to criteria proposed earlier by Yamada and Hirosawa (1976). Control animals from the same litter were maintained on ordinary laboratory food for the same period andmore » examined by electron microscopy. Lipid-droplet-containing cells were found in the same areas as in the experimental animals but in fewer numbers. This suggests that the increased number of vitamin A-containing lipid droplets is due to hypervitaminosis A in the experimental animals. The presence of some cells containing these droplets in the control animals would imply that even under normal feeding conditions the animals ingested excess amounts of vitamin A, which was retained in lipid droplets. The stored vitamin A probably participates in metabolic processes such as the formation of glycoproteins in ground substance.« less