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Sample records for melanoma sentinel lymph

  1. 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

  2. Sentinel lymph node biopsy for conjunctival malignant melanoma: surgical techniques

    PubMed Central

    Wainstein, Alberto JA; Drummond-Lage, Ana P; Kansaon, Milhem JM; Bretas, Gustavo O; Almeida, Rodrigo F; Gloria, Ana LF; Figueiredo, Ana RP

    2015-01-01

    Background The purpose of this report is to examine the viability and safety of preoperative lymphoscintigraphy and radio guided sentinel lymph node (SLN) biopsy for conjunctival melanoma, and to identify the best technique to perform this procedure. Methods Three patients diagnosed with malignant melanoma of the conjunctiva underwent lymphoscintigraphy and SLN biopsy using a dual technique comprising isosulfan blue dye and technetium Tc 99m sulfur colloid. Each patient was anesthetized and the conjunctival melanoma was excised. SLNs were localized by a gamma probe, identified according to radioactivity and sentinel blue printing, and dissected, along with drainage of the associated lymphatic basins. The SLNs were evaluated by a pathologist using hematoxylin-eosin staining following serial sectioning and immunohistochemistry using a triple melanoma cocktail (S-100, Melan-A, and HMB-45 antigens). Results Two SLNs were stained in the jugular chain during preoperative lymphoscintigraphy in the first patient, two SLNs were identified in the preauricular and submandibular areas in the second patient, and two SLNs were identified in the submandibular and parotid areas in the third patient. All lymph nodes identified by lymphoscintigraphy were dissected and identified at surgery with 100% accuracy in all three patients. All SLNs were histologically and immunohistochemically negative. Patients had good cosmetic and functional results, and maintained their visual acuity and ocular motility. Conclusion Patients with conjunctival melanoma can undergo preoperative lymphoscintigraphy and SLN biopsy safely using radioactive technetium and isosulfan blue dye. PMID:25565762

  3. Sentinel lymph node biopsy in paediatric melanoma. A case series.

    PubMed

    Sánchez Aguilar, M; Álvarez Pérez, R M; García Gómez, F J; Fernández Ortega, P; Borrego Dorado, I

    2015-01-01

    The incidence of melanoma in children is uncommon, being particularly rare in children under 10 years-old. However, this disease is increasing by a mean of 2% per year. As in adults, the lymph node status is the most important prognostic factor, crucial to performing the selective sentinel lymph node biopsy (SLNB). We report 3 cases of paediatric patients of 3, 4 and 8 years-old, in which SLNB was performed for malignant melanoma. Paediatric age implies greater technical difficulty to the scintigraphy scan due to poor patient cooperation, with mild sedation required in some cases, and only being able to acquire planar images in other cases. SPECT/CT was only performed in the oldest patient. In our cases, SLNB was useful for selecting the least invasive surgery in order to reduce morbidity. PMID:25595513

  4. Nodal Basin Recurrence After Sentinel Lymph Node Biopsy for Melanoma

    PubMed Central

    Kretschmer, Lutz; Bertsch, Hans Peter; Zapf, Antonia; Mitteldorf, Christina; Satzger, Imke; Thoms, Kai-Martin; Völker, Bernward; Schön, Michael Peter; Gutzmer, Ralf; Starz, Hans

    2015-01-01

    Abstract The objective of this study was to analyze different types of nodal basin recurrence after sentinel lymph node biopsy (SLNB) for melanoma. Patients and Methods: Kaplan–Meier estimates and the Cox proportional hazards model were used to study 2653 patients from 3 German melanoma centers retrospectively. The estimated 5-year negative predictive value of SLNB was 96.4%. The estimated false-negative (FN) rates after 1, 2, 3, 5, and 10 years were 2.5%, 4.6%, 6.4%, 8.7%, and 12.6%, respectively. Independent factors associated with false negativity were older age, fewer SLNs excised, and head or neck location of the primary tumor. Compared with SLN-positive patients, the FNs had a significantly lower survival. In SLN-positive patients undergoing completion lymphadenectomy (CLND), the 5-year nodal basin recurrence rate was 18.3%. The recurrence rates for axilla, groin, and neck were 17.2%, 15.5%, and 44.1%, respectively. Significant factors predicting local relapse after CLND were older age, head, or neck location of the primary tumor, ulceration, deeper penetration of the metastasis into the SLN, tumor-positive CLND, and >2 lymph node metastases. All kinds of nodal relapse were associated with a higher prevalence of in-transit metastases. The FN rate after SLNB steadily increases over the observation period and should, therefore, be estimated by the Kaplan–Meier method. False-negativity is associated with fewer SLNs excised. The beneficial effect of CLND on nodal basin disease control varies considerably across different risk groups. This should be kept in mind about SLN-positive patients when individual decisions on prophylactic CLND are taken. PMID:26356697

  5. Sentinel lymph node mapping in melanoma in the twenty-first century.

    PubMed

    Doepker, Matthew P; Zager, Jonathan S

    2015-04-01

    The incidence of melanoma is increasing faster than any other cancer. The status of the regional nodal basin remains the most important prognostic factor. Sentinel lymph node biopsy (SLNB) is recommended for staging in patients diagnosed with intermediate-thickness melanoma (1.01-4.0 mm). SLNB is considered somewhat controversial, especially when used to stage thin (1 mm), thick (>4 mm), or desmoplastic melanoma. This article reviews the current literature regarding SLNB in thin, intermediate, thick, and desmoplastic melanoma. Data supporting the use of newer radiopharmaceuticals in sentinel lymph node mapping along with newer imaging modalities are also reviewed. PMID:25769710

  6. Current status of sentinel lymph node biopsy in patients with melanoma.

    PubMed

    Nieweg, O E

    2014-10-01

    The sentinel node is defined as a lymph node on a direct lymphatic drainage pathway from the primary tumour. The sentinel node biopsy is an invasive and potentially complex diagnostic test that requires considerable skill and experience from nuclear medicine physicians, surgeons and pathologists involved in the process. The procedure provides important staging information. The tumour bearing status of a regional lymph node basin is the most important prognostic factor for patients with a clinically localised melanoma. The recently published final report of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) shows that sentinel node biopsy with subsequent regional node dissection improves the survival rate in patients with nodal metastases from an intermediate Breslow thickness melanoma (1.23.5 mm). The false negative rate is substantial but can be limited by experience, a meticulous technique and close cooperation of the specialists involved. The surgical procurement of the sentinel nodes is associated with minor morbidity. Sentinel node biopsy is now part of the standard work-up in patients with intermediate thickness melanoma and can be considered in patients with a thinner or thicker melanoma. New lymph node tracers and innovative imaging techniques are likely to improve the sensitivity of the procedure further. Now that the results of MSLT-1 are available, the next question is whether sentinel node-positive patients require further surgery. This issue is addressed by EORTCs Minitub study and the MSLT-2. Until these studies yield results, regional node dissection is recommended for patients with sentinel node metastases. PMID:25340862

  7. Sentinel lymph-node biopsy after previous wide local excision for melanoma

    PubMed Central

    McCready, David R.; Ghazarian, Danny M.; Hershkop, Marlon S.; Walker, Janet A.; Ambus, Ulo; Quirt, Ian C.

    2001-01-01

    Objective To document experience with sentinel lymph-node biopsy in patients who have already undergone a wide local excision for melanoma because in many centres previous wide excision has been a contraindication for sentinel lymph-node biopsy. Design A prospective cohort study. Setting A tertiary care academic cancer centre. Patients One hundred patients who presented with cutaneous melanoma (depth >1 mm or Clark level IV) after having undergone wide local excision of the primary lesion that was not situated in the head or neck. The follow-up was 3 years. Interventions Sentinel lymph-node biopsy. Patients with truncal melanoma had preoperative lymphoscintigraphy to document the nodal basins at risk. Technetium-99m sulfur colloid (0.5–1 mCi in 0.5 mL) was injected intradermally around the scar, and the sentinel lymph node was excised with the aid of a hand-held gamma detector. Outcome measures Accuracy of the biopsy and false-negative rates in this setting. Results Of the 100 patients, 44 had truncal and 56 had extremity lesions. The average tumour depth was 3.47 mm and 3.07 mm respectively. Thirty-one patients had a sentinel lymph node positive for melanoma metastasis. Biopsies were positive for melanoma in 18 (41%) truncal lesions and 13 (23%) extremity lesions. There were 3 (9%) false-negative sentinel lymph-node biopsies as diagnosed by clinically evident nodal disease subsequently appearing in the nodal basin subjected to biopsy. Two occurred in patients after large rotation flap closures of truncal lesions. The third patient had a subungual melanoma of the great toe. No disease was found in the 2 nodes dissected. Two of the 3 false-negative biopsy results were obtained before serial sections and immunohistochemical staining were used to examine the sentinel lymph nodes. Conclusions Sentinel lymph-node biopsies can successfully identify clinically occult nodal metastases in patients who have had previous wide local excision of a melanoma, but the false

  8. Sentinel lymph node biopsy in melanoma: final results of MSLT-I.

    PubMed

    Durham, Alison B; Wong, Sandra L

    2014-05-01

    In 1994 an international randomized controlled clinical trial, MSLT-I, opened to study the utility of sentinel lymph node biopsy (SLNB) for patients with clinically localized melanoma. This trial compared outcomes of patients treated with wide local excision (WLE) and SLNB (followed by immediate completion lymph node dissection [CLND] for those with a positive sentinel node [SN]) with outcomes of patients treated with WLE alone and CLND upon the development of clinically apparent disease. In February 2014 the final analysis of long-term outcomes data was published. Importantly, these data showed that the rates of nodal positivity were the same between the two arms of the trial. Although no difference in 10-year melanoma-specific survival was noted between the two arms, this was not entirely surprising as the overall rate of nodal disease within the trial was 20.8%, meaning that 79.2% of patients could not derive a benefit from SLNB. Subset analysis was performed to determine the impact of early intervention for those patients most likely to have a benefit from early detection. This analysis showed that for patients with nodal disease and intermediate-thickness melanoma (defined as 1.2-3.5-mm Breslow depth), early treatment following positive SLNB was associated with improved 10-year distant disease-free survival and improved 10-year melanoma-specific survival. PMID:24947251

  9. Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

    PubMed Central

    Meves, Alexander; Nikolova, Ekaterina; Heim, Joel B.; Squirewell, Edwin J.; Cappel, Mark A.; Pittelkow, Mark R.; Otley, Clark C.; Behrendt, Nille; Saunte, Ditte M.; Lock-Andersen, Jorgen; Schenck, Louis A.; Weaver, Amy L.; Suman, Vera J.

    2015-01-01

    Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis. PMID:26150443

  10. Characterization of the Microenvironment in Positive and Negative Sentinel Lymph Nodes from Melanoma Patients

    PubMed Central

    Messaoudene, Meriem; Périer, Aurélie; Fregni, Giulia; Neves, Emmanuelle; Zitvogel, Laurence; Cremer, Isabelle; Chanal, Johan; Sastre-Garau, Xavier; Deschamps, Lydia; Marinho, Eduardo; Larousserie, Frederique; Maubec, Eve; Avril, Marie-Françoise; Caignard, Anne

    2015-01-01

    Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found. In addition, in stage III melanoma patients, we identified a new subset of mature NK cells in macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune cell subsets in a series of sentinel lymph nodes (SLN). First, we show that NKp46+ NK cells infiltrate primary cutaneous melanoma. Their numbers were related to age of patients and not to Breslow thickness. Then, a series of patients with tumor-negative or -positive sentinel lymph nodes matched for Breslow thickness of the cutaneous melanoma was constituted. We investigated the distribution of macrophages (CD68), endothelial cells, NK cells, granzyme B positive (GrzB+) cells and CD8+ T cells in the SLN. Negative SLN (SLN-) were characterized by frequent adipose involution and follicular hyperplasia compared to positive SLN (SLN+). High densities of macrophages and endothelial cells (CD34), prominent in SLN+, infiltrate SLN and may reflect a tumor favorable microenvironment. Few but similar numbers of NK and GrzB+ cells were found in SLN- and SLN+: NK cells and GrzB+ cells were not correlated. Numerous CD8+ T cells infiltrated SLN with a trend for higher numbers in SLN-. Moreover, CD8+ T cells and GrzB+ cells correlated in SLN- not in SLN+. We also observed that the numbers of CD8+ T cells negatively correlated with endothelial cells in SLN-. The numbers of NK, GrzB+ or CD8+ T cells had no significant impact on overall survival. However, we found that the 5 year-relapse rate was higher in SLN with higher numbers of NK cells. PMID:26218530

  11. 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

  12. Meta-Analysis of Sentinel Lymph Node Positivity in Thin Melanoma (≤ 1 mm)

    PubMed Central

    Warycha, Melanie A.; Zakrzewski, Jan; Ni, Quanhong; Shapiro, Richard L.; Berman, Russell S.; Pavlick, Anna C.; Polsky, David; Mazumdar, Madhu; Osman, Iman

    2014-01-01

    Background Despite the lack of an established survival benefit of sentinel lymph node (SLN) biopsy, this technique has been increasingly applied in the staging of thin (≤1 mm) melanoma patients, without clear evidence to support this recommendation. We performed a meta-analysis to estimate the risk, potential predictors, and outcome of SLN positivity in this group of patients. Methods MEDLINE, EMBASE, and Cochrane databases were searched for rates of SLN positivity in patients with thin melanoma. The methodological quality of included studies was assessed using the MINORS criteria. Heterogeneity was assessed using Cochran’s Q-statistic, and publication bias was examined through funnel plot and Begg and Mazumdar’s method. Overall SLN positivity in thin melanoma patients was estimated using DerSimonial-Laird random effect method. Results 34 studies comprising 3,651 patients met inclusion criteria. The pooled SLN positivity rate was 5.6%. Significant heterogeneity among studies was detected (p=0.005). There was no statistical evidence of publication bias (p=0.21). 18 studies reported select clinical and histopathologic data limited to SLN positive patients (n=113). Among the tumors from these patients, 6.1% were ulcerated, 31.5% showed regression, and 47.5% were Clark’s level IV/V. Only 4 melanoma-related deaths were reported. Conclusion Relatively few patients with thin melanoma have a positive SLN. There are no clinical or histopathologic criteria which can reliably identify thin melanoma patients who might benefit from this intervention. Given the increasing diagnosis of thin melanoma, in addition to the cost and potential morbidity of this procedure, alternative strategies to identify patients at risk for nodal disease are needed. PMID:19117354

  13. Sentinel lymph node mapping in melanoma: the issue of false-negative findings.

    PubMed

    Manca, Gianpiero; Rubello, Domenico; Romanini, Antonella; Boni, Giuseppe; Chiacchio, Serena; Tredici, Manuel; Mazzarri, Sara; Duce, Valerio; Colletti, Patrick M; Volterrani, Duccio; Mariani, Giuliano

    2014-07-01

    Management of cutaneous melanoma has changed after introduction in the clinical routine of sentinel lymph node biopsy (SLNB) for nodal staging. By defining the nodal basin status, SLNB provides a powerful prognostic information. Nevertheless, some debate still surrounds the accuracy of this procedure in terms of false-negative rate. Several large-scale studies have reported a relatively high false-negative rate (5.6%-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. In this review, we identified all the technical aspects that the nuclear medicine physician, the surgeon, and the pathologist should take into account to improve accuracy of the procedure and minimize the false-negative rate. In particular, SPECT/CT imaging detects more SLNs than those found by planar lymphoscintigraphy. Furthermore, the nuclear medicine community should reach a consensus on the radioactive counting rate threshold to better guide the surgeon in identifying the lymph nodes with the highest likelihood of housing metastases ("true biologic SLNs"). Analysis of the harvested SLNs by conventional techniques is also a further potential source for error. More accurate SLN analysis (eg, molecular analysis by reverse transcriptase-polymerase chain reaction) and more extensive SLN sampling identify more positive nodes, thus reducing the false-negative rate.The clinical factors identifying patients at higher-risk local recurrence after a negative SLNB include older age at diagnosis, deeper lesions, histological ulceration, and head-neck anatomic location of the primary lesion.The clinical impact of a false-negative SLNB on the prognosis of melanoma patients remains controversial, because the majority of studies have failed to demonstrate overall statistically significant disadvantage in melanoma-specific survival for false-negative SLNB patients compared with true-positive SLNB patients.When new more effective

  14. Increased Angiogenesis and Lymphangiogenesis in Metastatic Sentinel Lymph Nodes Is Associated With Nonsentinel Lymph Node Involvement and Distant Metastasis in Patients With Melanoma.

    PubMed

    Pastushenko, Ievgenia; Van den Eynden, Gert G; Vicente-Arregui, Sandra; Prieto-Torres, Lucia; Alvarez-Alegret, Ramiro; Querol, Ignacio; Dirix, Luc Y; Carapeto, Francisco J; Vermeulen, Peter B; Van Laere, Steven J

    2016-05-01

    Lymph node angio- and lymphangio-genesis have been shown to play an important role in the premetastatic niche of sentinel lymph nodes. In the current study we have investigated the association of angio- and lympangio-genesis related parameters in metastatic sentinel lymph nodes of patients with melanoma with the presence of nonsentinel and distant organ metastasis. Peritumoral and intratumoral relative blood and lymphatic vessel areas (evaluated by Chalkley method), blood and lymphatic microvessel densities, and the rates of blood and lymphatic vessel proliferation were assessed in primary tumors and sentinel lymph node metastasis of 44 patients with melanoma using CD34/Ki-67 and D240/Ki-67 immunohistochemical double staining. Primary melanoma exhibited significantly higher rate of lymphatic proliferation compared with its lymph node metastasis (P < 0.05), while lymph node metastasis showed significantly higher rate of blood vessel proliferation (P < 0.05). Using multivariate logistic regression model, the rate of peritumoral lymphatic proliferation was inversely associated with positive nonsentinel lymph node status (P < 0.05), whereas the rate of intratumoral blood vessel proliferation was associated with distant organ metastasis (P < 0.05). Using multivariate Cox regression analysis, the rate of intratumoral blood vessel proliferation was also inversely associated with overall survival of patients with melanoma (P < 0.05). PMID:26909582

  15. [Sentinel lymph node procedure in melanoma patients: a staging procedure, not a therapy].

    PubMed

    van Akkooi, Alexander C J; Kukutsch, Nicole A; Soetekouw, Patricia M M B

    2014-01-01

    The definitive results of the MSLT-1 study in melanoma patients were published recently. The sentinel lymph node (SLN) procedure shows no survival benefit compared with observation. The authors reported, however, that there was a survival benefit with "biopsy management" of patients. This statement is based on subgroup analyses that we find to be incorrect for three reasons: (a) patients with a false negative SLN were incorrectly left out of consideration; (b) accelerated failure time latent subgroup analysis is an unproven statistical hypothesis, which was developed on interim data from the MSLT-1 study, and therefore cannot be used as validation; (c) there is a significant difference in terms of the percentage of patients with affected lymph nodes between the SLN group and the observation group. This excess of "prognostic false positive" patients would have incorrectly falsely improved the survival of the SLN group. We concluded that the SLN procedure does not give a survival benefit and that its role in melanoma patients should be for staging purposes and not for therapeutic purposes. PMID:25370949

  16. Clark Level Risk Stratifies Patients with Mitogenic Thin Melanomas for Sentinel Lymph Node Biopsy

    PubMed Central

    Bartlett, Edmund K.; Gimotty, Phyllis A.; Sinnamon, Andrew J.; Wachtel, Heather; Roses, Robert E.; Schuchter, Lynn; Xu, Xiaowei; Elder, David E.; Ming, Michael; Elenitsas, Rosalie; Guerry, DuPont; Kelz, Rachel R.; Czerniecki, Brian J.; Fraker, Douglas L.; Karakousis, Giorgos C.

    2014-01-01

    Background The role for sentinel lymph node biopsy (SLNB) in patients with thin melanoma (≤1mm) remains controversial. We examined a large cohort of patients with thin melanoma to better define predictors of SLN positivity. Methods Between 1995-2011, 781 patients with thin primary melanoma and evaluable clinicopathologic data underwent SLNB at our institution. Predictors of SLN positivity were determined using univariate and multivariate regression analyses, and patients were risk-stratified using a classification and regression tree (CART) analysis. Results In the study cohort (n=781), 29 patients (3.7%) had nodal metastases. In the univariate analysis, mitotic rate (OR=8.11, p=0.005), Clark level (OR=4.04, p=0.003), and thickness (OR=3.33, p=0.011) were significantly associated with SLN positivity. In the multivariate analysis, MR (OR=7.01) and level IV-V (OR=3.45) remained significant predictors of SLN positivity. CART analysis initially stratified lesions by mitotic rate; non-mitogenic lesions (n=273) had a 0.7% SLN positivity rate versus 5.6% in mitogenic lesions (n=425). Mitogenic lesions were further stratified by Clark level; patients with level II-III had a 2.9% SLN positivity rate (n=205) versus 8.2% with level IV-V (n=220). With median follow up of 6.3 years, 5 SLN negative patients developed nodal recurrence and 4 SLN positive patients died of disease. Conclusion SLN positivity is low in patients with thin melanoma (3.7%) and exceedingly so in non-mitogenic lesions (0.7%). Appreciable rates of SLN positivity can be identified in patients with mitogenic lesions, particularly with concurrent level IV-V regardless of thickness. These factors may guide appropriate selection of patients with thin melanoma for SLNB. PMID:24121883

  17. Sentinel Lymph Node Detection Using Laser-Assisted Indocyanine Green Dye Lymphangiography in Patients with Melanoma

    PubMed Central

    Jain, Vikalp; Phillips, Brett T.

    2013-01-01

    Introduction. Sentinel lymph node (SLN) biopsy is a vital component of staging and management of multiple cancers. The current gold standard utilizes technetium 99 (tech99) and a blue dye to detect regional nodes. While the success rate is typically over 90%, these two methods can be inconclusive or inconvenient for both patient and surgeon. We evaluated a new technique using laser-assisted ICG dye lymphangiography to identify SLN. Methods. In this retrospective analysis, we identified patients with melanoma who were candidates for SLN biopsy. In addition to tech99 and methylene blue, patients received a dermal injection of indocyanine green (ICG). The infrared signal was detected with the SPY machine (Novadaq), and nodes positive by any method were excised. Results. A total of 15 patients were evaluated, with 40 SLNs removed. Four patients were found to have nodal metastases on final pathology. 100% of these 4 nodes were identified by ICG, while only 75% (3/4) were positive for tech99 and/or methylene blue. Furthermore, none of the nodes missed by ICG (4/40) had malignant cells. Conclusion. ICG dye lymphangiography is a reasonable alternative for locating SLNs in patients with melanoma. Prospective studies are needed to better ascertain the full functionality of this technique. PMID:24382997

  18. Sentinel lymph-node biopsy for melanoma of the trunk and extremities: the McGill experience

    PubMed Central

    Tremblay, Francine; Loutfi, Antoine; Shibata, Henry; Meterissian, Sarkis

    2001-01-01

    Objective To determine the effectiveness of sentinel lymph-node (SLN) biopsy for melanoma of the trunk and extremities. Design Case series review. Setting Royal Victoria Hospital, a Canadian university hospital. Patients Thirty-six patients (18 women and 18 men) seen between October 1996 and December 1998 with melanoma 1 mm or more in thickness with clinically negative lymph-node basins. Follow-up was 396 days. Interventions SLN biopsy. Technetium-99m filtered sulfur colloid (0.5 mCi) was injected intradermally around the melanoma or the excision scar 10 to 15 minutes before the surgical skin preparation. The identification of the SLN(s) was done with a hand-held gamma probe. Local anesthesia was used mostly for inguinal SLN biopsy whereas general anesthesia was usually required for axillary SLN biopsy. Preoperative lymphoscintigraphy was used only for trunk melanomas. Outcome measures Morbidity, successful identification of the sentinel node and locoregional recurrence. Results The mean age of patients at diagnosis was 53.4 years (range from 22–76 yr). The melanomas were distributed between the lower extremities (20 patients), upper extremities (8 patients) and trunk (8 patients). The mean Breslow thickness was 2.35 mm (range from 1–8 mm). Lymphoscintigraphy accurately localized the lymph-node drainage basin for trunk melanomas. In 1 patient the SLN could not be identified because the radiocolloid failed to migrate (failure rate 2.8%). The average number of SLNs removed was 1.97. Eight patients (22%) had sentinel nodes positive for malignant disease. The postoperative complication rate was 8.5%. Seven of 8 patients with positive SLNs underwent a complete node dissection (1 patient refused). Of the completion dissections only 2 patients had positive non-SLNs. All patients with positive nodes received interferon alpha-2b as adjuvant treatment. At follow-up, 34 patients are alive with no evidence of disease, 1 patient with a positive SLN is alive with distant

  19. Prognostic significance of drainage to pelvic nodes at sentinel lymph node mapping in patients with extremity melanoma.

    PubMed

    Karakousis, Giorgos C; Pandit-Taskar, Neeta; Hsu, Meier; Panageas, Katherine; Atherton, Sonny; Ariyan, Charlotte; Brady, Mary S

    2013-02-01

    Patients undergoing sentinel lymph node (SLN) mapping for lower extremity melanoma may have drainage to pelvic nodes (DPN) in addition to superficial inguinal nodes. These nodes are not sampled routinely at SLN biopsy. Factors predicting DPN and its prognostic significance were assessed in a large cohort of patients undergoing an SLN biopsy. Three hundred and twenty five patients with single primary melanomas of the lower extremity or buttocks who underwent SLN mapping were identified from our prospective melanoma database (December 1995-October 2008). Associations of clinical and pathologic factors with DPN and time to melanoma recurrence (TTR) were analyzed by logistic and Cox regression, respectively. DPN was common, occurring in 23% of cases. Increased Breslow's thickness (P=0.007) and age (P=0.01) were associated with DPN by multivariate analysis. Patients with DPN were not more likely to have a positive SLN; however, SLN- patients with DPN showed a shorter TTR (P=0.02) in a multivariable model including thickness and ulceration. With age included in the model, DPN remained marginally associated with TTR in this group (P=0.08). The pelvic recurrence rates observed were similar in recurrent patients with DPN compared with those without DPN (39% in both groups). In conclusion, DPN occurs in almost one-quarter of patients with lower extremity melanoma and is marginally associated with a shorter TTR in SLN- patients. PMID:23250048

  20. Contrast enhanced ultrasound of sentinel lymph nodes

    PubMed Central

    Cui, XinWu; Ignee, Andre; Nielsen, Michael Bachmann; Schreiber-Dietrich, Dagmar; De Molo, Chiara; Pirri, Clara; Jedrzejczyk, Maciej

    2013-01-01

    Sentinel lymph nodes are the first lymph nodes in the region that receive lymphatic drainage from a primary tumor. The detection or exclusion of sentinel lymph node micrometastases is critical in the staging of cancer, especially breast cancer and melanoma because it directly affects patient's prognosis and surgical management. Currently, intraoperative sentinel lymph node biopsies using blue dye and radioisotopes are the method of choice for the detection of sentinel lymph node with high identification rate. In contrast, conventional ultrasound is not capable of detecting sentinel lymph nodes in most cases. Contrast enhanced ultrasound with contrast specific imaging modes has been used for the evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy. The method allows for real-time analysis of all vascular phases and the visualization of intranodal focal “avascular” areas that represent necrosis or deposits of neoplastic cells. In recent years, a number of animal and human studies showed that contrast enhanced ultrasound can be also used for the detection of sentinel lymph node, and may become a potential application in clinical routine. Several contrast agents have been used in those studies, including albumin solution, hydroxyethylated starch, SonoVue®, Sonazoid® and Definity®. This review summarizes the current knowledge about the use of ultrasound techniques in detection and evaluation of sentinel lymph node. PMID:26675994

  1. Black sentinel lymph node and 'scary stickers'.

    PubMed

    Yang, Arthur S; Creagh, Terrence A

    2013-04-01

    An unusual case is presented of a young adult patient with two black-stained, radio-nucleotide tracer-active sentinel lymph nodes biopsied following her primary cutaneous melanoma treatment. This was subsequently confirmed to be secondary to cutaneous tattoos, averting the need of an elective regional node dissection. History of tattooing and tattoo removal should therefore be obtained as a routine in all melanoma patients considered for sentinel node biopsy (SLN). SLN biopsy and any subsequent completion node dissection should be strictly staged so that proper histologic diagnosis of the sentinel node is available for correct decision making and treatment. PMID:23010587

  2. Contemporary controversies and perspectives in the staging and treatment of patients with lymph node metastasis from melanoma, especially with regards positive sentinel lymph node biopsy.

    PubMed

    Pasquali, Sandro; Spillane, Andrew

    2014-09-01

    The management of melanoma lymph node metastasis particularly when detected by sentinel lymph node biopsy (SLNB) is still controversial. Results of the only randomized trial conducted to assess the therapeutic value of SLNB, the Multicenter Selective Lymphadenectomy Trial (MSLT-1), have not conclusively proven the effectiveness of this procedure but are interpreted by the authors and guidelines as indicating SLNB is standard of care. After surgery, interferon alpha had a small survival benefit and radiotherapy has limited effectiveness for patient at high-risk of regional recurrence. New drugs, including immune modulating agents and targeted therapies, already shown to be effective in patients with distant metastasis, are being evaluated in the adjuvant setting. In this regard, ensuring high quality of surgery through the identification of reliable quality assurance indicators and improving the homogeneity of prognostic stratification of patients entered onto clinical trials is paramount. Here, we review the controversial issues regarding the staging and treatment of melanoma patients with lymph node metastasis, present a summary of important and potentially practice changing ongoing research and provide a commentary on what it all means at this point in time. PMID:25023758

  3. Evaluation and localization of lymphatic drainage and sentinel lymph nodes in patients with head and neck melanomas by hybrid SPECT/CT lymphoscintigraphic imaging.

    PubMed

    Mar, Martha V; Miller, Scott A; Kim, E Edmund; Macapinlac, Homer A

    2007-03-01

    In patients with head and neck tumors, preoperative lymphoscintigraphy can be used to map lymphatic drainage patterns and identify sentinel lymph nodes. However, it is very difficult to determine the exact locations of head and neck sentinel nodes on preoperative lymphoscintigraphy without the use of anatomic landmarks. Lymph nodes in the head and neck are grouped into 7 regions, or levels, on the basis of anatomic landmarks. In patients undergoing standard lymphoscintigraphy, obtaining lateral marker images that show important anatomic landmarks can help with the localization of sentinel nodes. However, technical problems often render marker images of little or no use. Hybrid SPECT/CT lymphoscintigraphic imaging facilitates the localization of sentinel nodes by reliably showing the relationships between sentinel nodes and important anatomic structures. After reading this article, the reader should understand the lymph node level classification system for head and neck melanomas, be able to describe the technique used for the imaging of sentinel nodes in the head and neck region, and be able to demonstrate how SPECT/CT lymphoscintigraphic imaging can enable precise sentinel node localization and thus help to ensure minimal dissection. PMID:17337652

  4. Absence of Tumor-Infiltrating Lymphocyte Is a Reproducible Predictive Factor for Sentinel Lymph Node Metastasis: A Multicenter Database Study by the Brazilian Melanoma Group

    PubMed Central

    Duprat, João Pedreira; Brechtbülh, Eduard René; Costa de Sá, Bianca; Enokihara, Mauro; Fregnani, Jose Humberto; Landman, Gilles; Maia, Marcus; Riccardi, Felice; Belfort, Francisco Alberto; Wainstein, Alberto; Moredo, Luciana F.; Steck, Higino; Brandão, Miguel; Moreno, Marcelo; Miranda, Eduardo; Santos, Ivan Dunshee de Oliveira

    2016-01-01

    Aims The aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs) in sentinel lymph node (SLN) metastasis. Materials and Methods This retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL) were identified by multiple logistic regression. Results SLN metastasis was detected in 101 of 633 cases (16.1%) and in 93 of 428 patients (21.7%) when melanomas ≤ 1mm were excluded. By multiple logistic regression, the absence of TILs was as an independent risk factor of SLN metastasis (OR = 1.8; 95%CI: 1.1–3.0), in addition to Breslow index (greater than 2.00 mm), lymph vascular invasion, and presence of mitosis. Conclusion SLNB can identify patients who might benefit from immunotherapy, and the determination of predictors of SLNB positivity can help select the proper population for this type of therapy. The absence of TILs is a reproducible parameter that can predict SLNB positivity in melanoma patients, since this study was made with several centers with different dermatopathologists. PMID:26859408

  5. Elevated Serum Leptin Levels are Associated With an Increased Risk of Sentinel Lymph Node Metastasis in Cutaneous Melanoma

    PubMed Central

    Oba, Junna; Wei, Wei; Gershenwald, Jeffrey E.; Johnson, Marcella M.; Wyatt, Cynthia M.; Ellerhorst, Julie A.; Grimm, Elizabeth A.

    2016-01-01

    Abstract The metabolic hormone leptin has been implicated in the pathogenesis of various malignancies and may contribute to the high rate of cancer in obese individuals. We reported that leptin and its receptor are expressed by melanoma tumors and cell lines, and that leptin stimulates proliferation of cultured melanoma cells. Here, we tested the hypothesis that leptin contributes to early melanoma progression by assessing its association with sentinel node positivity in cutaneous melanoma patients. The study enrolled 72 patients who were scheduled to undergo lymphatic mapping and sentinel node biopsy. Fasting blood was obtained before surgery, and serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) with a “raw” (assay value) and an “adjusted” value (raw value divided by body mass index). Leptin levels and other clinicopathologic parameters were compared between sentinel node positive and negative groups. Logistic regression models were used to predict sentinel node status using leptin and other relevant clinical parameters. The raw and adjusted leptin levels were significantly higher in the 15 patients with positive sentinel nodes. These findings could not be attributed to differences in body mass indices. Univariate models revealed raw leptin, adjusted leptin, Breslow thickness, and mitotic rate as significant predictors of sentinel node status. Leptin levels and Breslow thickness remained significant in multivariate models. Survival and follow-up analysis revealed more aggressive disease in diabetic patients. Elevated serum leptin levels predict sentinel node metastasis in melanoma. Validation of this finding in larger cohorts should enable better stratification of early stage melanoma patients. PMID:26986135

  6. Predictive role of preoperative lymphoscintigraphy on the status of the sentinel lymph node in clinically node-negative patients with cutaneous melanoma.

    PubMed

    Solari, Nicola; Gipponi, Marco; Stella, Mattia; Queirolo, Paola; di Somma, Carmine; Villa, Giuseppe; Piccardo, Arnoldo; Gualco, Marina; Cardinale, Francesco; Cafiero, Ferdinando

    2009-08-01

    We reviewed our experience to assess the predictive role of preoperative lymphoscintigraphy with regard to the pathological status of sentinel lymph node (sN) in patients with cutaneous melanoma, to optimize the surgical treatment planning with regard to the use of intraoperative frozen section examination of sN. Eighty-eight patients with clinically node-negative cutaneous melanoma pT1b-T4 stage underwent preoperative lymphoscintigraphy for the lymphatic mapping of sN. A lymphoscintigraphic 'score' (from L1 to L5) was developed based on the ratio of radiotracer concentration within sN nodes as compared with the injection site. Our score allowed us to foresee that sN of patients with thick melanomas (T3 and T4) and a low preoperative score (L1-L2-L3) had a 90% expected likelihood (P<0.001) of harboring metastasis, whereas sN in patients with thin melanomas (T1b-T2) and high preoperative score (from L4 to L5) showed a 100% likelihood of being metastasis free. In conclusion, the sN is a reliable predictor of regional lymph node status in patients with cutaneous malignant melanoma. Moreover, we suggest that a low score (L1-L2-L3) associated with a thick melanoma is a good predictive factor of the positive sN involvement. This information could be useful in scheduling the intraoperative frozen-section examination with an expected benefit of a positive test in almost 90% of patients. Such patients might be selected for a 'one-stage' procedure with a more effective cost/benefit ratio and decreased hospitalization costs. PMID:19584766

  7. Lymphatic mapping of the breast: locating the sentinel lymph nodes.

    PubMed

    Uren, R F; Howman-Giles, R; Renwick, S B; Gillett, D

    2001-06-01

    When the concept of sentinel lymph node biopsy was described in patients with melanoma, researchers quickly started to use lymphatic mapping techniques in breast cancer patients in an attempt to locate the sentinel node in the axilla. We have been performing mammary lymphoscintigraphy in this role for 6 years and have now studied 159 patients. Like others, we have found that most breast cancers (93%) have lymphatic drainage that includes the axilla, and we have found an average of 1.4 axillary sentinel nodes in these patients. Surgical biopsy of the axillary sentinel nodes accurately staged the node field in 96% of patients. We have also found, however, that the pattern of lymphatic drainage from the cancer site is unpredictable; and in 49% of patients lymphatic drainage occurred across the center line of the breast to axillary or internal mammary sentinel nodes. In more than half of our patients (56%) lymphatic drainage occurred to lymph nodes outside the axilla including the internal mammary (45%), supraclavicular (13%), and interpectoral and intramammary interval nodes (12%). These nodes are also sentinel nodes, and their presence indicates that a sentinel node biopsy procedure that stages only the status of the axillary lymph nodes has the potential to understage about half the patients with breast cancer. High quality lymphoscintigraphy allows accurate mapping of peritumoral lymphatic drainage in most patients with breast cancer. It is possible that in the future accurate nodal staging in each individual will involve biopsy of all sentinel lymph nodes, regardless of their location. PMID:11376417

  8. Multicenter Selective Lymphadenectomy Trial-I confirms the central role of sentinel node biopsy in contemporary melanoma management: response to 'No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report'.

    PubMed

    Faries, M B; Cochran, A J; Elashoff, R M; Thompson, J F

    2015-03-01

    Sentinel lymph node (SLN) biopsy has become a standard procedure for many patients with melanoma and is recommended in numerous national and professional melanoma guidelines. The Multicenter Selective Lymphadenectomy Trial (MSLT-1) confirms earlier large database studies and prospective clinical trials in demonstrating the independent and unequalled prognostic value of the SLN. It also demonstrates the ability of biopsy-directed management to provide effective regional disease control with the least possible morbidity. These benefits are not in question and provide ample justification for the procedure, even without evidence of a survival benefit. However, MSLT-1 also provides strong evidence of a substantial reduction in the risk of melanoma death for patients with intermediate thickness melanomas who harbour occult nodal metastases at the time of presentation. Denying appropriately selected patients with melanoma the opportunity to undergo SLN biopsy is no longer reasonable or acceptable. PMID:25776247

  9. Application of Sentinel Lymph Node Biopsy in Cutaneous Basosquamous Carcinoma

    PubMed Central

    Kovacevic, Predrag; Visnjic, Milan; Jankovic, Dimitrije; Binic, Ivana; Jankovic, Aleksandar; Ilic, Ivan

    2011-01-01

    Basosquamous carcinoma of the skin is a relatively rare cutaneous neoplasm that has significant metastatic potential and a metastatic rate greater than that of basal cell and squamous cell carcinoma. We describe the use of lymphatic mapping and sentinel lymph node biopsy in a 63-year-old man after identification of basosquamous carcinoma. Sentinel lymph node biopsy, which is a standard tool to detect regional lymphatic metastasis in cutaneous melanoma, has been rarely employed to detect lymphatic metastasis of basosquamous carcinoma. The approach was successful in detecting a regional lymphatic metastasis of two nodal basins with minor morbidity. Sentinel lymph node biopsy may be useful for certain high-risk lesions of basosquamous carcinoma. PMID:22028558

  10. Review of the role of sentinel node biopsy in cutaneous head and neck melanoma.

    PubMed

    Roy, Jennifer M; Whitfield, Robert J; Gill, P Grantley

    2016-05-01

    Sentinel node biopsy (SNB) is recommended for selected melanoma patients in many parts of the world. This review examines the evidence surrounding the accuracy and prognostic value of SNB and completion neck dissection in head and neck melanoma. Sentinel nodes were identified in an average of 94.7% of head and neck cases compared with 95.3-100% in all melanoma cases. More false-negative sentinel nodes were found in head and neck cases. A positive sentinel node was associated with both lower disease-free survival (53.4 versus 83.2%) and overall survival (40 versus 84%). We conclude that SNB should be offered to all patients with intermediate and high-risk melanomas in the head and neck area. To date, evidence does not exist to demonstrate the safety of avoiding completion lymph node dissection in sentinel node-positive patients with head and neck melanoma. PMID:26362016

  11. 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

  12. Initial results of imaging melanoma metastasis in resected human lymph nodes using photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Jose, Jithin; Grootendorst, Diederik J.; Vijn, Thomas W.; Wouters, Michel W.; van Boven, Hester; van Leeuwen, Ton G.; Steenbergen, Wiendelt; Ruers, Theo J. M.; Manohar, Srirang

    2011-09-01

    The pathological status of the sentinel lymph node is important for accurate melanoma staging, ascertaining prognosis and planning treatment. The standard procedure involves biopsy of the node and histopathological assessment of its status. Drawbacks of this examination include a finite sampling of the node with the likelihood of missing metastases, and a significant time-lag before histopathological results are available to the surgeon. We studied the applicability of photoacoustic computed tomographic imaging as an intraoperative modality for examining the status of resected human sentinel lymph nodes. We first applied the technique to image ex vivo pig lymph nodes carrying metastases-simulating melanoma cells using multiple wavelengths. The experience gained was applied to image a suspect human lymph node. We validated the photoacoustic imaging results by comparing a reconstructed slice with a histopathological section through the node. Our results suggest that photoacoustics has the potential to develop into an intraoperative imaging method to detect melanoma metastases in sentinel lymph nodes.

  13. [Anaphylactic shock after injection of patent blue for sentinel lymph node biopsy].

    PubMed

    van der Horst, J C; de Bock, M J; Klinkenbijl, J H

    2001-10-27

    After being diagnosed with a melanoma, an 18-year-old woman developed anaphylactic shock following an intracutaneous injection of patent blue during a sentinel lymph node biopsy procedure. Intracutaneous allergy tests revealed positive reactions with patent blue (Bleu patenté V 'Guerbet') as well as with several anaesthetics and morphine. It was concluded that patent blue was the most probable causative agent for the anaphylactic reaction and that the possibility of such a reaction should be taken into consideration during sentinel node procedures. After a few days the operation was completed under epidural anaesthesia with technetium Tc 99m sulphur colloid being used to detect the sentinel node. PMID:11715597

  14. Axillary lymph node management in breast cancer with positive sentinel lymph node biopsy.

    PubMed

    Voutsadakis, Ioannis A; Spadafora, Silvana

    2015-02-10

    The surgical treatment of localized breast cancer has become progressively less aggressive over the years. The management of the axillary lymph nodes has been modified by the introduction of sentinel lymph node biopsy. Axillary dissection can be avoided in patients with sentinel lymph node negative biopsies. Based on randomized trials data, it has been proposed that no lymph node dissection should be carried out even in certain patients with sentinel lymph node positive biopsies. This commentary discusses the basis of such recommendations and cautions against a general omission of lymph node dissection in breast cancer patients with positive sentinel lymph node biopsies. Instead, an individualized approach based on axillary tumor burden and biology of the cancer should be considered. PMID:25667909

  15. [Intraoperative detection of the sentinel lymph nodes in lung cancer].

    PubMed

    Akopov, A L; Papayan, G V; Chistyakov, I V

    2015-01-01

    An analysis of the scientific data was made. It was used the literature devoted to the intraoperative visualization of the sentinel lymph nodes in patients with lung cancer. Correct detection of such lymph nodes with following pathologic investigation allowed limiting the volume of lympho-dissection in a number of patients. There is the possibility of maximal in-depth study of the sentinel lymph nodes by purposeful application of most sensible pathologic and molecular methods for detection their micrometastatic lesions. At the same time the treatment strategy and prognosis could be determined. The authors present the results of an application of dye techniques, radioactive preparation and fluorescence imaging for sentinel lymph node detection. Advantages and disadvantages of the methods are shown in the article. There are validated the prospects of technical development, study of information value of new applications and the most perspective method of fluorescence indocyanine green visualization by lymph outflow. PMID:25962306

  16. [Sentinel node in melanoma and breast cancer. Current considerations].

    PubMed

    Vidal-Sicart, S; Vilalta Solsona, A; Alonso Vargas, M I

    2015-01-01

    The main objectives of sentinel node (SN) biopsy is to avoid unnecessary lymphadenectomies and to identify the 20-25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy and increases the occult lymphatic metastases identification rate by offering the pathologist the or those lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a "road map" to guide the surgeon towards the sentinel nodes and to localize unpredictable lymphatic drainage patterns. The SPECT/CT advantages include a better SN detection rate than planar images, the ability to detect SNs in difficult to interpret studies, better SN depiction, especially in sites closer to the injection site and better anatomic localization. These advantages may result in a change in the patient's clinical management both in melanoma and breast cancer. The correct SN evaluation by pathology implies a tumoral load stratification and further prognostic implication. The use of intraoperative imaging devices allows the surgeon a better surgical approach and precise SN localization. Several studies reports the added value of such devices for more sentinel nodes excision and a complete monitoring of the whole procedure. New techniques, by using fluorescent or hybrid tracers, are currently being developed. PMID:25455506

  17. Tattoo-pigmented cervical lymph node that masqueraded as the sentinel lymph node in oral squamous cell carcinoma.

    PubMed

    Pinto, Amith; Wieshmann, Hulya; Triantafyllou, Asterios; Shaw, Richard

    2015-11-01

    We describe a case of a pigmented cervical lymph node mimicking the sentinel node during sentinel lymph node biopsy (SLNB) on a patient with oral squamous cell carcinoma (OSCC). The patient had extensive tattoos on his neck. This pigmented lymph node was not identified to be the sentinel lymph node using static and dynamic lymphoscintigraphy. Subsequent histological analysis revealed tattoo pigment within this lymph node. It is important during cervical SLNB to be aware that cutaneous tattoos can pigment lymph nodes. PMID:26188933

  18. Lymphoscintigraphy in cutaneous melanoma: a total body atlas of sentinel node mapping.

    PubMed

    Intenzo, Charles M; Kim, Sung M; Patel, Jayant I; Lin, Henry C; Kairys, John C

    2002-01-01

    Lymphoscintigraphy of malignant melanoma has been a reliable method of identifying regional lymph nodes at risk for metastases and is now considered part of the standard of care in patients with melanoma. The status of the sentinel lymph node (SLN) is predictive of the metastatic status of the corresponding regional lymph node group. Lymphatic channel mapping allows identification of the SLN, thereby making selective lymph node sampling possible. Consequently, SLN identification with lymphoscintigraphy results in both less extensive surgery and more efficient pathologic examination of the lymph node specimens. Therefore, it is imperative that radiologists and nuclear medicine physicians know which radiopharmaceuticals to use, recognize different lymphatic drainage patterns from various primary tumor sites throughout the body, use proper imaging techniques, and recognize potential pitfalls in image interpretation. PMID:12006683

  19. Sentinel Lymph Node Biopsy in Pelvic Tumors: Clinical Indications and Protocols Under Investigation.

    PubMed

    Maccauro, Marco; Lorenzoni, Alice; Crippa, Flavio; Manca, Gianpiero; Chondrogiannis, Sotirios; Giammarile, Francesco; Colletti, Patrick M; Cook, Gary J; Rubello, Domenico

    2016-06-01

    Sentinel lymph node (SLN) sampling is an attractive alternative to complete lymphadenectomy. Based on the identification and sampling of the first LN draining a primary tumor, SLN biopsy is the most accurate and the only reliable method for microscopic nodal staging for solid tumors including breast cancer and melanoma. Lymph node status in pelvic tumors remains the most important prognostic factor for recurrence and survival and a major decision criterion for adjuvant therapy. We review the clinical indications, controversies, and perspective of SLN biopsy in male and female pelvic cancers. PMID:26914577

  20. Lymphoscintigraphy in cutaneous melanoma: an updated total body atlas of sentinel node mapping.

    PubMed

    Intenzo, Charles M; Truluck, Christina A; Kushen, Medina C; Kim, Sung M; Berger, Adam; Kairys, John C

    2009-01-01

    Lymphoscintigraphy has become part of the standard of care for patients with a new or recurrent diagnosis of melanoma, in helping determine the status of regional lymph nodes. Correct identification of sentinel lymph nodes enables the surgeon to further delineate the extent of malignancy by allowing sampling of the appropriate nodal group. Performing the lymphoscintigraphy prior to the planned operation allows limited surgery with less extensive postoperative morbidity. For this reason, a thorough knowledge of the lymph node drainage patterns from the different primary tumor locations, as well as of proper lymphoscintigraphic techniques and radiopharmaceuticals, constitutes an important armamentarium in the hands of surgeons, radiologists, and nuclear medicine physicians. PMID:19605661

  1. Application of novel iron core/iron oxide shell nanoparticles to sentinel lymph node identification

    NASA Astrophysics Data System (ADS)

    Cousins, Aidan; Howard, Douglas; Henning, Anna M.; Nelson, Melanie R. M.; Tilley, Richard D.; Thierry, Benjamin

    2015-12-01

    Current `gold standard' staging of breast cancer and melanoma relies on accurate in vivo identification of the sentinel lymph node. By replacing conventional tracers (dyes and radiocolloids) with magnetic nanoparticles and using a handheld magnetometer probe for in vivo identification, it is believed the accuracy of sentinel node identification in nonsuperficial cancers can be improved due to increased spatial resolution of magnetometer probes and additional anatomical information afforded by MRI road-mapping. By using novel iron core/iron oxide shell nanoparticles, the sensitivity of sentinel node mapping via MRI can be increased due to an increased magnetic saturation compared to traditional iron oxide nanoparticles. A series of in vitro magnetic phantoms (iron core vs. iron oxide nanoparticles) were prepared to simulate magnetic particle accumulation in the sentinel lymph node. A novel handheld magnetometer probe was used to measure the relative signals of each phantom, and determine if clinical application of iron core particles can improve in vivo detection of the sentinel node compared to traditional iron oxide nanoparticles. The findings indicate that novel iron core nanoparticles above a certain size possess high magnetic saturation, but can also be produced with low coercivity and high susceptibility. While some modification to the design of handheld magnetometer probes may be required for particles with large coercivity, use of iron core particles could improve MRI and magnetometer probe detection sensitivity by up to 330 %.

  2. Multiphoton microscopy as a diagnostic tool for pathological analysis of sentinel lymph nodes

    NASA Astrophysics Data System (ADS)

    Lemiere, J.; Douady, J.; Estève, F.; Salameire, D.; Lantuejoul, S.; Lorimier, P.; Ricard, C.; van der Sanden, B.; Vial, J.-C.

    2009-02-01

    Multiphoton microscopy has shown a powerful potential for biomedical in vivo and ex vivo analysis of tissue sections and explants. Studies were carried out on several animal organs such as brain, arteries, lungs, and kidneys. One of the current challenges is to transfer to the clinic the knowledge and the methods previously developed in the labs at the preclinical level. For tumour staging, physicians often remove the lymph nodes that are localized at the proximity of the lesion. In case of breast cancer or melanoma, sentinel lymph node protocol is performed: pathologists randomly realize an extensive sampling of formol fixed nodes. However, the duration of this protocol is important and its reliability is not always satisfactory. The aim of our study was to determine if multiphoton microscopy would enable the fast imaging of lymph nodes on important depths, with or without exogenous staining. Experiments were first conducted on pig lymph nodes in order to test various dyes and to determine an appropriate protocol. The same experiments were then performed on thin slices of human lymph nodes bearing metastatic melanoma cells. We obtained relevant images with both endofluorescence plus second-harmonic generation and xanthene dyes. They show a good contrast between tumour and healthy cells. Furthermore, images of pig lymph nodes were recorded up to 120μm below the surface. This new method could then enable a faster diagnosis with higher efficiency for the patient. Experiments on thicker human lymph nodes are currently underway in order to validate these preliminary results.

  3. Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

    PubMed

    Ko, Jennifer S; Prieto, Victor G; Elson, Paul J; Vilain, Ricardo E; Pulitzer, Melissa P; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa P; Ernstoff, Marc S; Gastman, Brian R; Billings, Steven D

    2016-02-01

    Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other

  4. 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. PMID:26990817

  5. Aggressive Digital Papillary Adenocarcinoma: Case Report of a Positive Sentinel Lymph Node and Discussion of Utility of Sentinel Lymph Node Biopsy.

    PubMed

    Kempton, Steve J; Navarrete, Andrew D; Salyapongse, A Neil

    2015-07-01

    Aggressive digital papillary adenocarcinoma (ADPA) is an uncommon eccrine sweat gland tumor of the distal extremities that is associated with a high rate of local recurrence and distant metastasis. Current opinion suggests that sentinel lymph node evaluation should be done for high-risk tumors where lymph node spread is a concern. Despite documented spread to regional lymph nodes, information on sentinel lymph node status in ADPA is reported infrequently, with only 1 documented case of positive findings. We report on a case of ADPA of the right long finger where sentinel lymph node biopsy was done and positive for metastases in the axilla, resulting in a subsequent completion lymphadenectomy. To determine the benefit of sentinel lymph node biopsy in ADPA, there is a need for more cases of sentinel lymph node evaluation along with data on local recurrence and distant metastasis in those with positive and negative findings. PMID:25954845

  6. Internal mammary sentinel lymph node biopsy: abandon or persist?

    PubMed

    Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Yong-Sheng

    2016-01-01

    Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN) metastases are mostly found concomitantly with axillary lymph nodes (ALN) metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients). Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance) significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach - more systemic therapy, less loco-regional therapy - clinicians should deliberate the application of regional IMLN therapy. PMID:27390528

  7. Internal mammary sentinel lymph node biopsy: abandon or persist?

    PubMed Central

    Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Yong-Sheng

    2016-01-01

    Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN) metastases are mostly found concomitantly with axillary lymph nodes (ALN) metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients). Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance) significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach – more systemic therapy, less loco-regional therapy – clinicians should deliberate the application of regional IMLN therapy. PMID:27390528

  8. Detection of melanoma metastases in resected human lymph nodes by noninvasive multispectral photoacoustic imaging.

    PubMed

    Langhout, Gerrit Cornelis; Grootendorst, Diederik Johannes; Nieweg, Omgo Edo; Wouters, Michel Wilhelmus Jacobus Maria; van der Hage, Jos Alexander; Jose, Jithin; van Boven, Hester; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theodoor Jacques Marie

    2014-01-01

    Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy. Photoacoustic imaging can evaluate intact lymph nodes, but specificity can be hampered by other absorbers such as hemoglobin. Near infrared multispectral photoacoustic imaging is a new approach that has the potential to selectively detect melanin. The purpose of the present study is to examine the potential of multispectral photoacoustic imaging to identify melanoma metastasis in human lymph nodes. Methods. Three metastatic and nine benign lymph nodes from eight melanoma patients were scanned ex vivo using a Vevo LAZR(©) multispectral photoacoustic imager and were spectrally analyzed per pixel. The results were compared to histopathology as gold standard. Results. The nodal volume could be scanned within 20 minutes. An unmixing procedure was proposed to identify melanoma metastases with multispectral photoacoustic imaging. Ultrasound overlay enabled anatomical correlation. The penetration depth of the photoacoustic signal was up to 2 cm. Conclusion. Multispectral three-dimensional photoacoustic imaging allowed for selective identification of melanoma metastases in human lymph nodes. PMID:25028587

  9. Credentialing issues with sentinel lymph node staging for breast cancer.

    PubMed

    Tafra, L; McMasters, K M; Whitworth, P; Edwards, M J

    2000-10-01

    Sentinel lymphadenectomy (SL) is a minimally invasive approach for staging patients with breast cancer. SL, when performed in lieu of axillary dissection, is associated with less morbidity and is potentially more cost effective and more accurate than the historical axillary dissection in the detection of regional nodal metastases. The credentialing and privileging of SL, as with any surgical procedure, is by the policies of the local hospital or institution. The suggested credentialing criteria for local hospitals has been an area of controversy. Herein the authors outline the credentialing controversy and suggest criteria for the implementation of sentinel lymph node staging for breast cancer. PMID:11113433

  10. Extraordinary Lymph Drainage in Cutaneous Malignant Melanoma and the Value of Hybrid Imaging: A Case Report.

    PubMed

    Brammen, Lindsay; Nedomansky, Jakob; Haslik, Werner; Staudenherz, Anton

    2014-12-01

    In melanoma patients, preoperative lymphoscintigraphy has become a gold standard. The role of single-photon emission computed tomography (SPECT) or its combination with computed tomography (SPECT-CT) as part of the standard sentinel scintigraphy protocol has yet to be determined. A 46-year-old female patient with melanoma of the trunk received preoperative lymphoscintigraphy and subsequent surgical excision. Planar imaging displayed two hot spots in the region of the primary lesion. No other lymphatic flow pathways could be appreciated. Two focal hot spots, one dorsal to the primary lesion near the left latissimus dorsi muscle and one just lateral to the primary lesion in the subcutaneous tissue, were appreciated with SPECT-CT imaging. The primary melanoma lesion, as well as the two additional lesions, which were detected by SPECT-CT, were excised and sent for histopathological examination. While the primary lesion was a superficial spreading melanoma, the lesions appreciated in SPECT-CT revealed four sentinel lymph nodes, each of which was negative for tumor cells. Melanomas, especially of the trunk, can demonstrate multiple lymphatic drain basins in a large percentage of patients. Given that without the detailed anatomical information provided by SPECT-CT it would be very difficult to locate the diverse lymphatic drain basins and their lymph nodes, we would suggest routinely implementing SPECT-CT in the standard planar sentinel imaging protocol. PMID:26396636

  11. Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique

    PubMed Central

    Qiu, Peng-Fei; Cong, Bin-Bin; Zhao, Rong-Rong; Yang, Guo-Ren; Liu, Yan-Bing; Chen, Peng; Wang, Yong-Sheng

    2015-01-01

    Abstract Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns because of the low visualization rate of internal mammary sentinel lymph nodes (IMSLN) with the traditional radiotracer injection technique. In this study, various injection techniques were evaluated in term of the IMSLN visualization rate, and the impact of IM-SLNB on the diagnostic and prognostic value were analyzed. Clinically, axillary lymph nodes (ALN) negative patients (n = 407) were divided into group A (traditional peritumoral intraparenchymal injection) and group B (modified periareolar intraparenchymal injection). Group B was then separated into group B1 (low volume) and group B2 (high volume) according to the injection volume. Clinically, ALN-positive patients (n = 63) were managed as group B2. Internal mammary sentinel lymph node biopsy was performed for patients with IMSLN visualized. The IMSLN visualization rate was significantly higher in group B than that in group A (71.1% versus 15.5%, P < 0.001), whereas the axillary sentinel lymph nodes were reliably identified in both groups (98.9% versus 98.3%, P = 0.712). With high injection volume, group B2 was found to have higher IMSLN visualization rate than group B1 (75.1% versus 45.8%, P < 0.001). The IMSLN metastasis rate was only 8.1% (12/149) in clinically ALN-negative patients with successful IM-SLNB, and adjuvant treatment was altered in a small proportion. The IMSLN visualization rate was 69.8% (44/63) in clinically ALN-positive patients with the IMSLN metastasis rate up to 20.5% (9/44), and individual radiotherapy strategy could be guided with the IM-SLNB results. The modified injection technique (periareolar intraparenchymal, high volume, and ultrasound guidance) significantly improved the IMSLN visualization rate, making the routine IM-SLNB possible in daily practice. Internal

  12. Intraoperative mapping of sentinel lymph node metastases using a clinically translated ultrasmall silica nanoparticle.

    PubMed

    Bradbury, Michelle S; Pauliah, Mohan; Zanzonico, Pat; Wiesner, Ulrich; Patel, Snehal

    2016-07-01

    The management of regional lymph nodes in patients with melanoma has undergone a significant paradigm shift over the past several decades, transitioning from the use of more aggressive surgical approaches, such as lymph node basin dissection, to the application of minimally invasive sentinel lymph node (SLN) biopsy methods to detect the presence of nodal micrometastases. SLN biopsy has enabled reliable, highly accurate, and low-morbidity staging of regional lymph nodes in early stage melanoma as a means of guiding treatment decisions and improving patient outcomes. The accurate identification and staging of lymph nodes is an important prognostic factor, identifying those patients for whom the expected benefits of nodal resection outweigh attendant surgical risks. However, currently used standard-of-care technologies for SLN detection are associated with significant limitations. This has fueled the development of clinically promising platforms that can serve as intraoperative visualization tools to aid accurate and specific determination of tumor-bearing lymph nodes, map cancer-promoting biological properties at the cellular/molecular levels, and delineate nodes from adjacent critical structures. Among a number of promising cancer-imaging probes that might facilitate achievement of these ends is a first-in-kind ultrasmall tumor-targeting inorganic (silica) nanoparticle, designed to overcome translational challenges. The rationale driving these considerations and the application of this platform as an intraoperative treatment tool for guiding resection of cancerous lymph nodes is discussed and presented within the context of alternative imaging technologies. WIREs Nanomed Nanobiotechnol 2016, 8:535-553. doi: 10.1002/wnan.1380 For further resources related to this article, please visit the WIREs website. PMID:26663853

  13. The role of sentinel lymph-node biopsy (SLNB) in the treatment of breast cancer.

    PubMed

    Marrazzo, Antonio; Taormina, Pietra; David, Massimo; Casà, Luigi; Lo Gerfo, Domenico; Noto, Antonio; Riili, Ignazio; Ficola, Umberto; Russo, Leila

    2006-01-01

    Sentinel lymph-node biopsy is an innovative method for axillary staging in breast cancer patients, based on the concept that information about the status of the entire lymphatic drainage from a tumour site could be obtained by identification and sampling of a "sentinel node". The aim of the study was to evaluate the impact of sentinel lymph-node biopsy in the management of patients with early invasive breast carcinoma. Three hundred and forty-one patients with primary invasive breast carcinoma measuring less than 2 cm (less than 3 cm from January 2001) and clinically negative axillary nodes were recruited into the study. Sentinel lymph-nodes were positive for metastases in 108/341 cases (31.7%). Micrometastases were found in 22 patients and isolated tumour cells in 1 case. The mean number of sentinel lymph-nodes removed was 1.8 per patient. The sentinel lymph-node was the only positive node in 57 of 108 patients (52.8%). The percentage of axillary recurrence in sentinel lymph-node-negative patients was 0%. The accuracy of sentinel lymph-node biopsy for axillary staging has been confirmed in many studies. Axillary recurrences after sentinel lymph-node biopsy range from 0 to 1.6% in many series, while axillary recurrence after axillary lymph-node dissection is about 0-3%. In our experience we observed no axillary recurrences in 233 patients with sentinel lymph-node biopsy alone, with a median follow-up of 33 months, confirming the accuracy of the procedure, and sentinel lymph-node-negative patients with sentinel lymph-node biopsy alone are no more at risk for axillary recurrences than those undergoing axillary lymph-node dissection. PMID:16845865

  14. Breast cancer recurrence after sentinel lymph node biopsy

    PubMed Central

    AlSaif, Abdulaziz

    2015-01-01

    Objective: To look into the pattern of breast cancer recurrence following mastectomy, breast conservative surgery and radiotherapy or chemotherapy after SLNB at our institution. Methods: Between January 2005 and December 2014, all patients diagnosed with breast cancer with clinically negative axilla, underwent SLNB. We reviewed their medical records to identify pattern of cancer recurrence. Results: The median follow-up was 35.5 months. Eighty five patients (70.8%) had a negative sentinel lymph node (SLN) and subsequently had no further axillary treatment, one of them (1.2%) developed axillary recurrence 25 months postoperatively. Twenty five patients (20.8%) had a positive SLN (macrometastases) and subsequently had immediate axillary lymph node dissection (ALND). Ten patients (8.3%) had a positive SLN (micrometastases). In the positive SLN patients (macrometastases and micrometastases), there were two ipsilateral breast recurrences (5.7%), seen three and four years postoperatively. Also in this group, there was one (2.9%) distant metastasis to bone three years postoperatively. Conclusion: In this series, the clinical axillary false negative rate for SLNB was 1.2% which is in accordance with the published literature. This supports the use of SLNB as the sole axillary staging procedure in breast cancer patients with negative SLNB. Axillary lymph node dissection can be safely omitted in patients with micrometastases in their sentinel lymph node(s). PMID:26870109

  15. Sentinel node biopsy in melanoma using technetium-99m rhenium colloid: the London experience.

    PubMed

    Temple, C L; Scilley, C G; Engel, C J; Shum, D T; Lohmann, R C; Mattar, A G; Zabel, P L

    2000-11-01

    Nodal metastases in patients with melanoma identify a reduction of survival by 50%; however, elective lymph node dissection (ELND) has not been shown clearly to improve survival. Morton's technique of sentinel node biopsy, using preoperative lymphoscintigraphy and intraoperative blue dye, addresses elegantly the controversy regarding ELND. Sentinel node biopsy has been shown to stage the patient accurately because metastases from melanoma follow an orderly progression from the sentinel node to the remainder of the basin. Fifty-six consecutive patients with American Joint Committee on Cancer stage 1b or 2 melanoma seen at the London Health Sciences Center between July 1998 and January 2000 were enrolled prospectively to undergo sentinel node biopsy. Preoperative lymphoscintigraphy was conducted in the nuclear medicine department. A total of 10 to 15 MBq (0.27-0.41 mCi) of technetium 99m (99mTc) rhenium colloid or filtered sulfur colloid was injected intradermally around the biopsy scar. Images were obtained to localize all draining nodal basins. The location of the sentinel node was marked on the skin. The patient was taken to the operating room and anesthetized. Isosulfan blue dye was injected intradermally around the biopsy scar. A hand-held gamma probe was used intraoperatively as a guide to the first draining node. Blue-stained lymphatic channels aided in the dissection. Sentinel node localization was successful in 55 of 56 patients, for an overall success rate of 98%. Preoperative lymphoscintigraphy identified a sentinel node in an unpredictable location in 32% of patients. On average, 2.3 sentinel nodes per patient were identified on the initial scan, and 2.2 sentinel nodes per patient were recovered at surgery. Both 99mTc rhenium and filtered sulfur colloid showed no substantial differences in tracer uptake and retention in the sentinel node. Twelve patients had a positive sentinel node on routine histology, and 11 patients subsequently underwent completion

  16. Superficial and deep lymph node dissection for stage III cutaneous melanoma: clinical outcome and prognostic factors

    PubMed Central

    2013-01-01

    Background The aims of this retrospective analysis were to evaluate the effect of combined superficial and deep groin dissection on disease-free and melanoma-specific survival, and to identify the most important factors for predicting the involvement of deep nodes according to clinically or microscopically detected nodal metastases. Methods Between January 1996 and December 2005, 133 consecutive patients with groin lymph node metastases underwent superficial and deep dissection at the National Cancer Institute, Naples. Lymph node involvement was clinically evident in 84 patients and detected by sentinel node biopsy in 49 cases. Results The 5-year disease-free survival was significantly better for patients with superficial lymph node metastases than for patients with involvement of both superficial and deep lymph nodes (34.9% vs. 19.0%; P = 0.001). The 5-year melanoma-specific survival was also significantly better for patients with superficial node metastases only (55.6% vs. 33.3%; P = 0.001). Conclusions Metastasis in the deep nodes is the strongest predictor of both disease-free and melanoma-specific survival. Deep groin dissection should be considered for all patients with groin clinical nodal involvement, but might be spared in patients with a positive sentinel node. Prospective studies will clarify the issue further. PMID:23379355

  17. Photoacoustic image-guided needle biopsy of sentinel lymph nodes

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Erpelding, Todd N.; Akers, Walter J.; Maslov, Konstantin; Song, Liang; Jankovic, Ladislav; Margenthaler, Julie A.; Achilefu, Samuel; Wang, Lihong V.

    2011-03-01

    We have implemented a hand-held photoacoustic and ultrasound probe for image-guided needle biopsy using a modified clinical ultrasound array system. Pulsed laser light was delivered via bifurcated optical fiber bundles integrated with the hand-held ultrasound probe. We photoacoustically guided needle insertion into rat sentinel lymph nodes (SLNs) following accumulation of indocyanine green (ICG). Strong photoacoustic image contrast of the needle was achieved. After intradermal injection of ICG in the left forepaw, deeply positioned SLNs (beneath 2-cm thick chicken breast) were easily indentified in vivo and in real time. Further, we confirmed ICG uptake in axillary lymph nodes with in vivo and ex vivo fluorescence imaging. These results demonstrate the clinical potential of this hand-held photoacoustic system for facile identification and needle biopsy of SLNs for cancer staging and metastasis detection in humans.

  18. Update on sentinel lymph node evaluation in gynecologic malignancies

    PubMed Central

    Robison, Katina; Holman, Laura L.; Moore, Richard G.

    2016-01-01

    Purpose of review Sentinel lymph node (SLN) dissections have been shown to be sensitive for the evaluation of nodal basins for metastatic disease and are associated with decreased short-term and long-term morbidity when compared with complete lymph node dissection. There has been increasing interest in the use of SLN technology in gynecologic cancers. This review assesses the current evidence-based literature for the use of SLN dissections in gynecologic malignancies. Recent findings Recent literature continues to support the safety and feasibility of SLN biopsy for early-stage vulvar cancer with negative predictive value approaching 100% and low false-negative rates. Alternatively, for endometrial cancer most studies have reported low false-negative rates, with variable sensitivities and have reported low detection rates of the sentinel node. Studies examining the utility of SLN biopsy in early-stage cervical cancer remain promising with detection rates, sensitivities, and false-negative rates greater than 90% for stage 1B1 tumors. Summary SLN dissections have been shown to be effective and safe in certain, select vulvar cancer patients and can be considered an alternative surgical approach for these patients. For endometrial and cervical cancer, SLN dissection continues to have encouraging results and however needs further investigation. PMID:21235023

  19. [Current status and new applications of sentinel lymph node mapping in non-small cell lung cancer].

    PubMed

    Minamiya, Yoshihiro; Ogawa, Jun-Ichi

    2009-03-01

    Sentinel lymph node (SLN) mapping has become a common procedure in the treatment of breast cancer and malignant melanoma. Its primary benefit is that it enables surgeons to avoid nontherapeutic lymph node dissection and the complications that may follow. All present evidence demonstrates the existence of SLNs in non-small cell lung cancer (NSCLC). However, SLN mapping is not widely used in the treatment of NSCLC for several reasons: first, special precautions are required to minimize exposure to radioisotopes; second, it is difficult to detect a dye within anthoracotic thoracic lymph nodes; and third, major complications comparable to the arm edema seen in breast cancer or the lymphedema and nerve injury seen in melanoma are not seen with mediastinal lymph node dissection. However, if the SLN mapping procedure were simplified, it could be used to avoid nontherapeutic mediastinal lymph node dissection in NSCLC. Recently, new applications of SLN mapping have been reported, such as the detection of lymph node micrometastases and segmentectomy for NSCLC. We expect SLN mapping to become a common clinical practice in the treatment of NSCLC in the near future PMID:19348199

  20. The role of lymphoscintigraphy in the detection of lymph node drainage in melanoma.

    PubMed

    Uren, Roger F; Thompson, John F; Howman-Giles, Robert; Chung, David K V

    2006-04-01

    Lymphatic drainage of the skin cannot be predicted based on clinical guidelines developed more than 100 years ago. Approximately 30% of patients experience drainage from the skin to unexpected lymph node sites rather than those specified by these guidelines, and therefore these outdated assumptions should no longer be used to plan surgery. A possible survival benefit has been shown for the early detection and surgical removal of metastatic disease in the draining lymph nodes, and therefore, clinicians must obtain accurate lymphatic mapping for each patient who has intermediate thickness melanoma to plan appropriate surgical therapy. Lymphoscintigraphy can be used to accurately define the precise position of each true sentinel node in every patient, whether these nodes lie in a standard node field or in an unusual location. In this way, lymphoscintigraphy has a direct beneficial impact on the surgical management of patients who have melanoma. PMID:16632215

  1. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

    PubMed Central

    Liss, Michael A.; Noguchi, Jonathan; Lee, Hak J.; Vera, David R.; Kader, A. Karim

    2015-01-01

    A sentinel lymph node (SLN) is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND); its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assessed a variety of imaging techniques to identify SLNs in patients with urothelial carcinoma of the bladder. Eight studies investigated human patients while one looked at animal (dog) models. Seven studies representing 156 patients noted the negative predictive value of the SLN to predict a metastasis free state was 92% (92/100). The SLN biopsy was less accurate in metastatic patients with a positive predictive value of only 77% (43/56) with a false negative range of in individual studies of 0-19%. Clinically, positive nodes routinely do not take up the pharmaceutical agent for SLN. Therefore, SLN biopsy is a promising concept with a 92% negative predictive value; however, the false negative rates are high which may be improved by standardizing populations and indications. Novel technologies are improving the detection of SLN and may provide the surgeon with an improved ability to detect micrometastasis, guide surgery, and reduce patient morbidity. PMID:26166959

  2. First Robotic SPECT for Minimally Invasive Sentinel Lymph Node Mapping.

    PubMed

    Fuerst, Bernhard; Sprung, Julian; Pinto, Francisco; Frisch, Benjamin; Wendler, Thomas; Simon, Hervé; Mengus, Laurent; van den Berg, Nynke S; van der Poel, Henk G; van Leeuwen, Fijs W B; Navab, Nassir

    2016-03-01

    In this paper we present the usage of a drop-in gamma probe for intra-operative Single-Photon Emission Computed Tomography (SPECT) imaging in the scope of minimally invasive robot-assisted interventions. The probe is designed to be inserted and reside inside the abdominal cavity during the intervention. It is grasped during the procedure using a robotic laparoscopic gripper enabling full six degrees of freedom handling by the surgeon. We demonstrate the first deployment of the tracked probe for intra-operative in-patient robotic SPECT enabling augmented-reality image guidance. The hybrid mechanical- and image-based in-patient probe tracking is shown to have an accuracy of 0.2 mm. The overall system performance is evaluated and tested with a phantom for gynecological sentinel lymph node interventions and compared to ground-truth data yielding a mean reconstruction accuracy of 0.67 mm. PMID:26561283

  3. Compact intraoperative imaging device for sentinel lymph node mapping

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Bauer, Adam Q.; Akers, Walter; Sudlow, Gail; Liang, Kexian; Shen, Duanwen; Berezin, Mikhail; Culver, Joseph P.; Achilefu, Samuel

    2011-03-01

    We have developed a novel real-time intraoperative fluorescence imaging device that can detect near-infrared (NIR) fluorescence and map sentinel lymph nodes (SLNs). In contrast to conventional imaging systems, this device is compact, portable, and battery-operated. It is also wearable and thus allows hands-free operation of clinicians. The system directly displays the fluorescence in its goggle eyepiece, eliminating the need for a remote monitor. Using this device in murine lymphatic mapping, the SLNs stained with indocyanine green (ICG) can be readily detected. Fluorescence-guided SLN resection under the new device was performed with ease. Ex vivo examination of resected tissues also revealed high fluorescence level in the SLNs. Histology further confirmed the lymphatic nature of the resected SLNs.

  4. Nanoparticles in Sentinel Lymph Node Assessment in Breast Cancer

    PubMed Central

    Johnson, Laura; Charles-Edwards, Geoff; Douek, Michael

    2010-01-01

    The modern management of the axilla in breast cancer relies on surgery for accurate staging of disease and identifying those patients at risk who would benefit from adjuvant chemotherapy. The introduction of sentinel lymph node biopsy has revolutionized axillary surgery, but still involves a surgical procedure with associated morbidity in many patients with no axillary involvement. Nanotechnology encompasses a broad spectrum of scientific specialities, of which nanomedicine is one. The potential use of dual-purpose nanoprobes could enable imaging the axilla simultaneous identification and treatment of metastatic disease. Whilst most applications of nanomedicine are still largely in the laboratory phase, some potential applications are currently undergoing clinical evaluation for translation from the bench to the bedside. This is an exciting new area of research where scientific research may become a reality. PMID:24281206

  5. Intraoperative Imaging Guidance for Sentinel Node Biopsy in Melanoma Using a Mobile Gamma Camera

    SciTech Connect

    Dengel, Lynn T; Judy, Patricia G; Petroni, Gina R; Smolkin, Mark E; Rehm, Patrice K; Majewski, Stan; Williams, Mark B

    2011-04-01

    The objective is to evaluate the sensitivity and clinical utility of intraoperative mobile gamma camera (MGC) imaging in sentinel lymph node biopsy (SLNB) in melanoma. The false-negative rate for SLNB for melanoma is approximately 17%, for which failure to identify the sentinel lymph node (SLN) is a major cause. Intraoperative imaging may aid in detection of SLN near the primary site, in ambiguous locations, and after excision of each SLN. The present pilot study reports outcomes with a prototype MGC designed for rapid intraoperative image acquisition. We hypothesized that intraoperative use of the MGC would be feasible and that sensitivity would be at least 90%. From April to September 2008, 20 patients underwent Tc99 sulfur colloid lymphoscintigraphy, and SLNB was performed with use of a conventional fixed gamma camera (FGC), and gamma probe followed by intraoperative MGC imaging. Sensitivity was calculated for each detection method. Intraoperative logistical challenges were scored. Cases in which MGC provided clinical benefit were recorded. Sensitivity for detecting SLN basins was 97% for the FGC and 90% for the MGC. A total of 46 SLN were identified: 32 (70%) were identified as distinct hot spots by preoperative FGC imaging, 31 (67%) by preoperative MGC imaging, and 43 (93%) by MGC imaging pre- or intraoperatively. The gamma probe identified 44 (96%) independent of MGC imaging. The MGC provided defined clinical benefit as an addition to standard practice in 5 (25%) of 20 patients. Mean score for MGC logistic feasibility was 2 on a scale of 1-9 (1 = best). Intraoperative MGC imaging provides additional information when standard techniques fail or are ambiguous. Sensitivity is 90% and can be increased. This pilot study has identified ways to improve the usefulness of an MGC for intraoperative imaging, which holds promise for reducing false negatives of SLNB for melanoma.

  6. Dextran-based fluorescent nanoprobes for sentinel lymph node mapping.

    PubMed

    Dai, Tingting; Zhou, Shuyan; Yin, Chuyang; Li, Shengli; Cao, Weigang; Liu, Wei; Sun, Kang; Dou, Hongjing; Cao, Yilin; Zhou, Guangdong

    2014-09-01

    Biopsy of sentinel lymph node (SLN) has become a common practice to predict whether tumor metastasis has occurred, so proper SLN positioning tracers are highly required. Due to many drawbacks of SLN tracers currently used, developing ideal, biosafe SLN imaging agents is always an urgent issue. The current study designed a novel fluorescent nanoprobe for accurate SLN mapping. Dextran-based nanogel (DNG) was prepared through a highly efficient self-assembly assisted approach and serves as a multi-functional platform for conjugating wide spectra emitting fluorescent agents. The newly fabricated fluorescent DNG (FDNG) could be designed with optimum size and stable fluorescent intensity for specific SLN imaging. Furthermore, a long-term dynamic course in vivo (from 1 min to 72 h) revealed the satisfactory specificity, sensitivity, and stability for SLN mapping. Most importantly, both in vitro and in vivo evaluations indicated that FDNG had fine biosafety and biocompatibility with lymphatic endothelial cells. All these results supported that FDNG could be used as highly efficient molecular imaging probes for specific, sensitive, stable, non-invasive, and safe SLN mapping, which provides efficient and accurate location for SLN biopsy and thus predicts tumor metastasis as well as directs therapies. Besides, our recent studies further demonstrated that DNG could also serve as a specific and controllable drug carrier, indicating a potential application for specific therapies of various lymph-associated diseases. PMID:24957293

  7. Sentinel lymph node navigation surgery for gastric cancer: Does it really benefit the patient?

    PubMed Central

    Tani, Tohru; Sonoda, Hiromichi; Tani, Masaji

    2016-01-01

    Sentinel lymph node (SLN) navigation surgery is accepted as a standard treatment procedure for malignant melanoma and breast cancer. However, the benefit of reduced lymphadenectomy based on SLN examination remains unclear in cases of gastric cancer. Here, we review previous studies to determine whether SLN navigation surgery is beneficial for gastric cancer patients. Recently, a large-scale prospective study from the Japanese Society of Sentinel Node Navigation Surgery reported that the endoscopic dual tracer method, using a dye and radioisotope for SLN biopsy, was safe and effective when applied to cases of superficial and relatively small gastric cancers. SLN mapping with SLN basin dissection was preferred for early gastric cancer since it is minimally invasive. However, previous studies reported that limited gastrectomy and lymphadenectomy may not improve the patient’s postoperative quality of life (QOL). As a result, the benefit of SLN navigation surgery for gastric cancer patients, in terms of their QOL, is limited. Thus, endoscopic and laparoscopic limited gastrectomy combined with SLN navigation surgery has the potential to become the standard minimally invasive surgery in early gastric cancer. PMID:26973385

  8. Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

    Cancer.gov

    Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

  9. Importance of sentinel lymph nodes in colorectal cancer: a pilot study.

    PubMed

    Köksal, Hande; Bostanci, Hasan; Mentes, B Bülent

    2007-01-01

    Accurate identification of lymph nodes involved in metastases is vitally important for predicting survival, and it facilitates decision making with regard to adjuvant therapy. The study described here, which was undertaken to evaluate the role of sentinel lymph node mapping in refining the staging of colorectal cancer, was performed prospectively in 19 patients with colorectal cancer who underwent surgery from January to July 2005. Sentinel lymph node sampling was performed during each operation with isosulfan blue dye. Additional immunohistochemical staining was performed only if the sentinel nodes were negative for metastasis. In 18 of 19 patients, at least 1 sentinel node was identified. In 5 of 18 patients, sentinel nodes were positive for metastasis, and in 3 of 5, the sentinel node was the only node containing metastasis that was detected by immunohistochemical staining. In 3 patients, metastases in nonsentinel lymph nodes were detected by hematoxylin and eosin staining; these were determined to be false-negative results. Upstaging associated with sentinel lymph node mapping may reveal disease that might otherwise remain undetected by conventional methods. Patients who are upstaged may benefit from adjuvant therapies that have been shown to improve survival. PMID:17660167

  10. Current Innovations in Sentinel Lymph Node Mapping for the Staging and Treatment of Resectable Lung Cancer

    PubMed Central

    Hachey, Krista J.; Colson, Yolonda L.

    2016-01-01

    Despite surgical resectability, early stage lung cancer remains a challenge to cure. Survival outcomes are hindered by variable performance of adequate lymphadenectomy and the limitations of current pathologic nodal staging. Sentinel lymph node (SLN) mapping, a mainstay in the management of breast cancer and melanoma, permits targeted nodal sampling for efficient and accurate staging that can influence both intraoperative and adjuvant treatment decisions. Unfortunately, standard SLN identification techniques with blue dye and radiocolloid tracers have not been shown to be reproducible in lung cancer. In more recent years, intraoperative near infrared (NIR) image-guided lung SLN mapping has emerged as promising technology for the identification of the tumor-associated lymph nodes most likely to contain metastatic disease. Additionally, the clinical relevance of SLN mapping for lung cancer remains pressing, as the ability to identify micrometastatic disease in SLNs could facilitate trials to assess chemotherapeutic response and the clinical impact of occult nodal disease. This review will outline the current status of lung cancer lymphatic mapping and techniques in development that may help close the gap between translational research in this field and routine clinical practice. PMID:25527014

  11. Sentinel Lymph Node in Breast Cancer: Review Article from a Pathologist’s Point of View

    PubMed Central

    Apple, Sophia K.

    2016-01-01

    Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials. PMID:26757203

  12. Optimization of Coded Aperture Radioscintigraphy for Sentinel Lymph Node Mapping

    PubMed Central

    Fujii, Hirofumi; Idoine, John D.; Gioux, Sylvain; Accorsi, Roberto; Slochower, David R.; Lanza, Richard C.; Frangioni, John V.

    2011-01-01

    Purpose Radioscintigraphic imaging during sentinel lymph node (SLN) mapping could potentially improve localization; however, parallel-hole collimators have certain limitations. In this study, we explored the use of coded aperture (CA) collimators. Procedures Equations were derived for the six major dependent variables of CA collimators (i.e., masks) as a function of the ten major independent variables, and an optimized mask was fabricated. After validation, dual-modality CA and near-infrared (NIR) fluorescence SLN mapping was performed in pigs. Results Mask optimization required the judicious balance of competing dependent variables, resulting in sensitivity of 0.35%, XY resolution of 2.0 mm, and Z resolution of 4.2 mm at an 11.5 cm FOV. Findings in pigs suggested that NIR fluorescence imaging and CA radioscintigraphy could be complementary, but present difficult technical challenges. Conclusions This study lays the foundation for using CA collimation for SLN mapping, and also exposes several problems that require further investigation. PMID:21567254

  13. Sentinel lymph node biopsy: technique validation at the Setúbal Medical Centre, Portugal

    PubMed Central

    Ferreira, P; Baía, R; António, A; Almeida, J; Simões, J; Amaro, JC; Quintana, C; Branco, L; Rigueira, MV; Gonçalves, M; Pereira, EV; Ferreira, LM

    2009-01-01

    Aims: To evaluate the accuracy of sentinel lymph node biopsy in breast cancer patients at this institution, using combined technetium-99m (99mTc) sulphur colloid and patent blue vital dye. Methods: From March 2007 to July 2008, 50 patients with a tumour of less than 3 cm and with clinically negative axillary lymph nodes underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection (ALND). Sub-areolar 99mTc sulphur colloid injection was performed the day before surgery, and patent blue vital dye was also injected sub-areolarly at least 5 minutes before surgery. Sentinel lymph node was identified during the surgical procedure, using a gamma probe and direct vision. All sentinel nodes underwent frozen section analysis. Later haematoxylin and eosin staining and immunohistochemical analysis were performed. Finally, SLNB was compared with standard ALND for its ability to accurately reflect the final pathological status of the axillary nodes. Results: The sentinel lymph node (SLN) was identified in 48 of 50 patients (96%). The number of sentinel lymph nodes ranged from one to four (mean 1.48) and non-sentinel nodes ranged from seven to 27 (mean 14.33). Of the 48 patients with successfully identified SLNs, 29.17% (14/48) were histologically positive. Sensivity of the SLN to predict axilla was 93.75%; accuracy was 97.96%. The SLN was falsely negative in one patient—6.25% (1/16). Conclusions: The SLNB represents a major advance in the surgical treatment of breast cancer as a minimally invasive procedure predicting the axillary lymph node status. This validation study demonstrates the accuracy of the SLNB and its reasonable false negative rate when performed in our institute. It can now be used as the standard method of staging in patients with early breast cancer at this institution. PMID:22275996

  14. Diagnostic value of preoperative axillary lymph node ultrasound assessment in patients with breast cancer qualified for sentinel lymph node biopsy

    PubMed Central

    Nowak, Adam; Wiśniewska, Magdalena; Wiśniewski, Michał; Zegarski, Wojciech

    2015-01-01

    Introduction Sentinel lymph node biopsy (SLNB) is a standard procedure in the therapeutic management of patients with non-advanced breast cancer. Aim To analyse the utility of ultrasound scan (USS) examination in the process of patient qualification for SLNB and to estimate the optimal time to perform USS in the clinical preoperational assessment of axillary lymph nodes. Material and methods A prospective analysis of 702 patients with invasive breast cancer treated with SLNB between 7.03.2012 and 27.05.2013 was performed. The patients were divided into three groups: I (USS < 8 weeks before SLNB), II (USS > 8 weeks before SLNB and another one on the day before SLNB) and III (USS > 8 weeks before SLNB without perioperative USS). In these patients the percentage of metastases in the sentinel lymph node and the clinical factors influencing the diagnostic value of preoperative ultrasound scan were assessed. Results Metastatic lesions in sentinel lymph nodes were found in 154 (21.9%) patients. The highest percentage of metastases was noted in patients operated on in the second and third month from the beginning of preoperative diagnostics. None of the factors tested (size of the original tumour, histological malignancy grading, kind of preoperative diagnostics, Ki-67 value, biological type of the tumour, age) had a statistically significant influence on the diagnostic value of perioperative USS examination in the analysed time span. Conclusions The lowest percentage of metastases in the sentinel lymph node was noted in the patients qualified for SLNB who had the ultrasound performed directly before the surgical procedure (not more than 4 weeks before the surgery). PMID:26240616

  15. Handheld array-based photoacoustic probe for guiding needle biopsy of sentinel lymph nodes

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Erpelding, Todd N.; Maslov, Konstantin; Jankovic, Ladislav; Akers, Walter J.; Song, Liang; Achilefu, Samuel; Margenthaler, Julie A.; Pashley, Michael D.; Wang, Lihong V.

    2010-07-01

    By modifying a clinical ultrasound array system, we develop a novel handheld photoacoustic probe for image-guided needle biopsy. The integration of optical fiber bundles for pulsed laser light delivery enables photoacoustic image-guided insertion of a needle into rat axillary lymph nodes with accumulated indocyanine green (ICG). Strong photoacoustic contrast of the needle is achieved. After subcutaneous injection of the dye in the left forepaw, sentinel lymph nodes are easily detected, in vivo and in real time, beneath 2-cm-thick chicken breast overlaying the axillary region. ICG uptake in axillary lymph nodes is confirmed with fluorescence imaging both in vivo and ex vivo. These results demonstrate the clinical potential of this handheld photoacoustic system for facile identification and needle biopsy of sentinel lymph nodes for cancer staging and metastasis detection in humans.

  16. The Utility of Sentinel Lymph Node Biopsy in Papillary Thyroid Carcinoma with Occult Lymph Nodes

    PubMed Central

    Yan, Xingqiang; Zeng, Ruichao; Ma, Zhaosheng; Chen, Chengze; Chen, Endong; Zhang, Xiaohua; Cao, Feilin

    2015-01-01

    Background The sentinel lymph node (SLN) is defined as the first draining node from the primary lesion, and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. The aim of this study was to evaluate the clinical application of SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) with occult lymph nodes. Methods From April 2006 to October 2012, 212 consecutive PTC patients were treated with SLNB using carbon nanoparticle suspension (CNS). Then, the stained nodes defined as SLN were collected, and prophylactic central compartment neck dissection (CCND) followed by total thyroidectomy or subtotal thyroidectomy were performed. All the samples were sent for pathological examination. Results There were 78 (36.8%) SLN metastasis (SLNM)-positive cases and 134 (63.2%) SLNM-negative cases. The sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates of SLNB were 78.8%, 100%, 100%, 84.3%, 0%, and 21.2%, respectively. The PTC patients with SLNM were more likely to be male (48.2% vs. 32.7%, p = 0.039) and exhibited multifocality (52.6% vs. 33.3%, p = 0.025) and extrathyroidal extension (56.7% vs. 33.5%, p = 0.015). A greater incidence of non-SLN metastases in the central compartment was found in patients with SLNM (41/78, 52.6%) than in those without SLNM (21/134, 15.7%; p < 0.05). However, the SLNM-negative PTC patients with non-SLN metastases were more likely to be male (37.9% vs. 9.5%, p < 0.05). Conclusions The application of SLNB using CNS is technically feasible, safe, and useful, especially for male patients with co-existing multifocality and extrathyroidal extension. However, the sensitivity of SLNB must be improved and its false-negative rate reduced before it can be a routine procedure and replace prophylactic CCND. More attention should be paid to PTC patients (especially males) without SLNM for signs of non-SLN metastases. PMID:26046782

  17. Sentinel lymph nodes detection with an imaging system using Patent Blue V dye as fluorescent tracer

    NASA Astrophysics Data System (ADS)

    Tellier, F.; Steibel, J.; Chabrier, R.; Rodier, J. F.; Pourroy, G.; Poulet, P.

    2013-03-01

    Sentinel lymph node biopsy is the gold standard to detect metastatic invasion from primary breast cancer. This method can help patients avoid full axillary chain dissection, thereby decreasing the risk of morbidity. We propose an alternative to the traditional isotopic method, to detect and map the sentinel lymph nodes. Indeed, Patent Blue V is the most widely used dye in clinical routine for the visual detection of sentinel lymph nodes. A Recent study has shown the possibility of increasing the fluorescence quantum yield of Patent Blue V, when it is bound to human serum albumin. In this study we present a preclinical fluorescence imaging system to detect sentinel lymph nodes labeled with this fluorescent tracer. The setup is composed of a black and white CCD camera and two laser sources. One excitation source with a laser emitting at 635 nm and a second laser at 785 nm to illuminate the region of interest. The prototype is operated via a laptop. Preliminary experiments permitted to determine the device sensitivity in the μmol.L-1 range as regards the detection of PBV fluorescence signals. We also present a preclinical evaluation performed on Lewis rats, during which the fluorescence imaging setup detected the accumulation and fixation of the fluorescent dye on different nodes through the skin.

  18. Development of a handheld fluorescence imaging camera for intraoperative sentinel lymph node mapping

    NASA Astrophysics Data System (ADS)

    Szyc, Łukasz; Bonifer, Stefanie; Walter, Alfred; Jagemann, Uwe; Grosenick, Dirk; Macdonald, Rainer

    2015-05-01

    We present a compact fluorescence imaging system developed for real-time sentinel lymph node mapping. The device uses two near-infrared wavelengths to record fluorescence and anatomical images with a single charge-coupled device camera. Experiments on lymph node and tissue phantoms confirmed that the amount of dye in superficial lymph nodes can be better estimated due to the absorption correction procedure integrated in our device. Because of the camera head's small size and low weight, all accessible regions of tissue can be reached without the need for any adjustments.

  19. Symptomatic Lymphocele Formation After Sentinel Lymph Node Biopsy for Early Stage Cervical Cancer.

    PubMed

    Dogan, Nasuh Utku; Garagozova, Nigar; Pfiffer, Tatiana; Beier, Anna; Köhler, Christhardt; Favero, Giovanni

    2016-01-01

    In early stage cervical cancer, nodal status is the most important prognostic factor, and execution of retroperitoneal lymphadenectomy is currently an integral part of surgical therapy. Sentinel lymph node biopsy has been progressively incorporated with surgical therapy and could reduce morbidity. However, the current incidence of complications exclusively related to the procedure is unknown. We report on a 29-year-old woman affected by cervical cancer (Fédération Internationale de Gynécologie et d'Obstétrique Stage 1b1), who underwent sentinel lymph node biopsy in combination with radical vaginal trachelectomy, and who later developed a symptomatic pelvic lymphocele that required surgical therapy. Conservative procedures in the pelvic lymph nodes are not free of complications, especially with regard to the formation of symptomatic lymphoceles. This report brings to light an important discussion about the exact magnitude of the complications associated with the procedure. PMID:26260297

  20. Dendronized iron oxide colloids for imaging the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Jouhannaud, J.; Garofalo, A.; Felder-Flesch, D.; Pourroy, G.

    2015-03-01

    Various methods have been used in medicine for more than one century to explore the lymphatic system. Radioactive colloids (RuS labelled with 99mTc) or/and Vital Blue dye are injected around the primary tumour and detected by means of nuclear probe or visual colour inspection respectively. The simultaneous clinical use of both markers (dye and radionuclide) improves the sensitivity of detection close to 100%. Superparamagnetic iron oxides (SPIOs) are currently receiving much attention as strong T2 weighted magnetic resonance imaging contrast agents that can be potentially used for preoperative localization of sentinel nodes, but also for peroperative detection of sentinel node using hand-held probes. In that context, we present the elaboration of dendronized iron oxide nanoparticles elaborated at the Institute of Physics and Chemistry of Materials of Strasbourg.

  1. Inappropriate Intra-cervical Injection of Radiotracer for Sentinel Lymph Node Mapping in a Uterine Cervix Cancer Patient: Importance of Lymphoscintigraphy and Blue Dye Injection

    PubMed Central

    Kadkhodayan, Sima; Farahabadi, Elham Hosseini; Yousefi, Zohreh; Hasanzadeh, Malihe; Sadeghi, Ramin

    2014-01-01

    Herein, we report a case of sentinel lymph node mapping in a uterine cervix cancer patient, referring to the nuclear medicine department of our institute. Lymphoscintigraphy images showed inappropriate intra-cervical injection of radiotracer. Blue dye technique was applied for sentinel lymph node mapping, using intra-cervical injection of methylene blue. Two blue/cold sentinel lymph nodes, with no pathological involvement, were intra-operatively identified, and the patient was spared pelvic lymph node dissection. The present case underscores the importance of lymphoscintigraphy imaging in sentinel lymph node mapping and demonstrates the added value of blue dye injection in selected patients. It is suggested that pre-operative lymphoscintigraphy imaging be considered as an integral part of sentinel lymph node mapping in surgical oncology. Detailed results of lymphoscintigraphy images should be provided for surgeons prior to surgery, and in case the sentinel lymph nodes are not visualized, use of blue dye for sentinel node mapping should be encouraged.

  2. Inappropriate Intra-cervical Injection of Radiotracer for Sentinel Lymph Node Mapping in a Uterine Cervix Cancer Patient: Importance of Lymphoscintigraphy and Blue Dye Injection.

    PubMed

    Kadkhodayan, Sima; Farahabadi, Elham Hosseini; Yousefi, Zohreh; Hasanzadeh, Malihe; Sadeghi, Ramin

    2014-01-01

    Herein, we report a case of sentinel lymph node mapping in a uterine cervix cancer patient, referring to the nuclear medicine department of our institute. Lymphoscintigraphy images showed inappropriate intra-cervical injection of radiotracer. Blue dye technique was applied for sentinel lymph node mapping, using intra-cervical injection of methylene blue. Two blue/cold sentinel lymph nodes, with no pathological involvement, were intra-operatively identified, and the patient was spared pelvic lymph node dissection. The present case underscores the importance of lymphoscintigraphy imaging in sentinel lymph node mapping and demonstrates the added value of blue dye injection in selected patients. It is suggested that pre-operative lymphoscintigraphy imaging be considered as an integral part of sentinel lymph node mapping in surgical oncology. Detailed results of lymphoscintigraphy images should be provided for surgeons prior to surgery, and in case the sentinel lymph nodes are not visualized, use of blue dye for sentinel node mapping should be encouraged. PMID:27408871

  3. Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping.

    PubMed

    Mondal, Suman B; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P; Liang, Kexian; Som, Avik; Akers, Walter J; Fields, Ryan C; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

    2015-01-01

    The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging. PMID:26179014

  4. Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping

    PubMed Central

    B. Mondal, Suman; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P.; Liang, Kexian; Som, Avik; Akers, Walter J.; Fields, Ryan C.; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

    2015-01-01

    The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging. PMID:26179014

  5. Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping

    NASA Astrophysics Data System (ADS)

    B. Mondal, Suman; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P.; Liang, Kexian; Som, Avik; Akers, Walter J.; Fields, Ryan C.; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

    2015-07-01

    The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging.

  6. Multispectral real-time fluorescence imaging for intraoperative detection of the sentinel lymph node in gynecologic oncology.

    PubMed

    Crane, Lucia M A; Themelis, George; Buddingh, K Tim; Buddingh, Tim; Harlaar, Niels J; Pleijhuis, Rick G; Sarantopoulos, Athanasios; van der Zee, Ate G J; Ntziachristos, Vasilis; van Dam, Gooitzen M

    2010-01-01

    The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases. Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema. As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor. In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix. The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid. Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion. It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used. The aim of this video article is to demonstrate the detection of

  7. Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology

    PubMed Central

    Crane, Lucia M.A.; Themelis, George; Buddingh, K. Tim; Harlaar, Niels J.; Pleijhuis, Rick G.; Sarantopoulos, Athanasios; van der Zee, Ate G.J.; Ntziachristos, Vasilis; van Dam, Gooitzen M.

    2010-01-01

    The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema.4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor.6 In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix.7 The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid. Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion.8 It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used.9. The aim of this video article is to demonstrate the

  8. Internal Mammary Sentinel Lymph Nodes in Breast Cancer - Effects on Disease Prognosis and Therapeutic Protocols - A Case Report

    PubMed Central

    Stojanoski, Sinisa; Ristevska, Nevena; Pop-Gjorcheva, Daniela; Antevski, Borce; Petrushevska, Gordana

    2015-01-01

    BACKGROUND: The main prognostic factor in early staged breast cancer is the axillary lymph node metastatic affection. Sentinel lymph node biopsy, as a staging modality, significantly decreases surgical morbidity. The status of internal mammary lymph nodes gains an increased predictive role in grading breast carcinomas and modulation of postoperative therapeutic protocols. If positive, almost always are associated with worse disease outcome. Nevertheless, the clinical significance of internal mammary lymph node micrometastases has not been up to date precisely defined. AIM: To present a case of female patient clinically diagnosed as T1, N0, M0 (clinical TNM) ductal breast carcinoma with scintigraphic detection of internal mammary and axillary sentinel lymph nodes. METHODS: Dual method of scintigraphic sentinel lymph node detection using 99mTc-SENTI-SCINT and blue dye injection, intraoperative gamma probe detection, radioguided surgery and intraoperative ex tempore biopsy were used. CASE REPORT: We present a case of clinically T1, N0, M0 ductal breast cancer with scintigraphic detection of internal mammary and axillary sentinel lymph nodes. Intraoperative ex tempore biopsy revealed micrometastases in the internal mammary node and no metastatic involvement of the axillary sentinel lymph node. CONCLUSION: Detection of internal mammary lymph node metastases improves N (nodal) grading of breast cancer by selecting a high risk subgroup of patients that require adjuvant hormone therapy, chemotherapy and/or radiotherapy.

  9. New approach to anal cancer: Individualized therapy based on sentinel lymph node biopsy

    PubMed Central

    De Nardi, Paola; Carvello, Michele; Staudacher, Carlo

    2012-01-01

    Oncological treatment is currently directed toward a tailored therapy concept. Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity. Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy. This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter, thus replacing surgical abdominoperineal resection. Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival. Mesorectal and iliac lymph nodes are usually included in the radiation field, whereas the inclusion of inguinal regions still remains controversial because of the subsequent adverse side effects. Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation. A sentinel lymph node navigation procedure is reported here to be a feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer. Based on the results of sentinel node biopsies, a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative patients could take advantage of inguinal sparing irradiation, thus avoiding toxic side effects. PMID:23197880

  10. Hybrid Natural Orifice Transluminal Endoscopic Surgery with Sentinel Lymph Node Navigation for Deep Early Gastric Cancer in the Fundic Region

    PubMed Central

    Park, Yoon Suk; Kim, Seong Hwan; Ryu, Hee Yun; Cho, Young Kwan; Jo, Yun Ju; Son, Tae il; Hong, Young Ok

    2016-01-01

    For patients refusing surgical treatment for deep early gastric cancer, hybrid natural orifice transluminal endoscopic surgery with sentinel lymph node navigation is a potential treatment option, particularly when the anatomic location of the cancer has low probability of lymph node metastasis. We report a case of deep early gastric cancer of the fundus beyond the endoscopic submucosal dissection indication that was treated by hybrid natural orifice transluminal endoscopic surgery with sentinel lymph node navigation. In a conventional approach, a total gastrectomy would have been needed; however, the patient refused surgical intervention. In this case, since the patient showed no positivity of the sentinel lymph node on intraoperative navigation, laparoscopic basin lymph node dissection was not performed. Hybrid natural orifice transluminal endoscopic surgery might be considered for specific regions such as the safety zone where lymph node metastases are less likely to occur. PMID:27020308

  11. 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

  12. Lymphangiogenesis in breast cancer is associated with non-sentinel lymph node metastases in sentinel node positive patients

    PubMed Central

    Lv, Lin; Ma, Rui-Min; Yang, Fan; Zhang, Xiao-Hua; Huang, Du-Ping

    2015-01-01

    Axillary lymph node dissection (ALND) is not suggested in breast cancer patients with negative sentinel lymph node (SLN) biopsies, and SLN is the only positive node in 40-70% of the remaining cases. To distinguish a subgroup in which ALND would be omitted, we investigated the role of lymphangiogenesis in primary breast cancer as a risk factor for distal lymph node involvements in patients with positive SLNs. 86 patients were included in this study. The frequency of proliferative lymphatic endothelial cells (LECP%) was evaluated in each specimen after immunohistochemical double staining for D2-40 and Ki-67. Larger primary tumor size, increased number of positive SLNs, lymphatic vessel invasion and LECP% were significantly associated with non-SLN metastases in the univariate analysis, but only LECP% retained significance in the multivariate model. A positive correlation between LECP% and lymphatic vessel invasion was also revealed. Our study confirmed the important role of lymphangiogenesis in tumor spread, and suggested that LECP% is a promising predictor for additional axillary lymph node involvements. PMID:26617838

  13. Novel handheld magnetometer probe based on magnetic tunnelling junction sensors for intraoperative sentinel lymph node identification.

    PubMed

    Cousins, A; Balalis, G L; Thompson, S K; Forero Morales, D; Mohtar, A; Wedding, A B; Thierry, B

    2015-01-01

    Using magnetic tunnelling junction sensors, a novel magnetometer probe for the identification of the sentinel lymph node using magnetic tracers was developed. Probe performance was characterised in vitro and validated in a preclinical swine model. Compared to conventional gamma probes, the magnetometer probe showed excellent spatial resolution of 4.0 mm, and the potential to detect as few as 5 μg of magnetic tracer. Due to the high sensitivity of the magnetometer, all first-tier nodes were identified in the preclinical experiments, and there were no instances of false positive or false negative detection. Furthermore, these preliminary data encourage the application of the magnetometer probe for use in more complex lymphatic environments, such as in gastrointestinal cancers, where the sentinel node is often in close proximity to other non-sentinel nodes, and high spatial resolution detection is required. PMID:26038833

  14. Novel Handheld Magnetometer Probe Based on Magnetic Tunnelling Junction Sensors for Intraoperative Sentinel Lymph Node Identification

    PubMed Central

    Cousins, A.; Balalis, G. L.; Thompson, S. K.; Forero Morales, D.; Mohtar, A.; Wedding, A. B.; Thierry, B.

    2015-01-01

    Using magnetic tunnelling junction sensors, a novel magnetometer probe for the identification of the sentinel lymph node using magnetic tracers was developed. Probe performance was characterised in vitro and validated in a preclinical swine model. Compared to conventional gamma probes, the magnetometer probe showed excellent spatial resolution of 4.0 mm, and the potential to detect as few as 5 μg of magnetic tracer. Due to the high sensitivity of the magnetometer, all first-tier nodes were identified in the preclinical experiments, and there were no instances of false positive or false negative detection. Furthermore, these preliminary data encourage the application of the magnetometer probe for use in more complex lymphatic environments, such as in gastrointestinal cancers, where the sentinel node is often in close proximity to other non-sentinel nodes, and high spatial resolution detection is required. PMID:26038833

  15. In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles.

    PubMed

    Galanzha, Ekaterina I; Kokoska, Mimi S; Shashkov, Evgeny V; Kim, Jin-Woo; Tuchin, Valery V; Zharov, Vladimir P

    2009-09-01

    This report introduces a novel diagnostic and therapeutic platform for in vivo non-invasive detection and treatment of metastases in sentinel lymph nodes (SLNs) at single cell level using an integrated system of multicolor photoacoustic (PA) lymph flow cytometry, PA lymphography, absorption image cytometry, and photothermal (PT) therapy. A melanoma-bearing mouse model was used to demonstrate the capability of this platform for real-time lymphatic mapping, counting of disseminated tumor cells (DTCs) in prenodal lymphatics, and detecting metastasis in SLNs and its purging. The detection and ablation of non-pigmented breast cancer cells in SLNs was achieved by labeling them with nanoparticles. The association between DTC count and SLN metastasis progression supports lymphatic DTCs as a novel prognostic marker of metastasis. The fiber-based portable PA device may replace the conventional SLN(s) excision and histology-based staging. The earliest detection of DTCs in the lymphatic vessels before the establishment of nodal metastasis may prevent metastasis by well-timed ablation of DTCs. PMID:19743443

  16. Sentinel lymph node mapping of a breast cancer of the vulva: Case report and literature review

    PubMed Central

    Cripe, James; Eskander, Ramez; Tewari, Krishnansu

    2015-01-01

    Ectopic breast tissue is rare and typically presents as an axillary mass. Previous reports have identified ectopic breast tissue in the vulva, but malignancy is exceedingly uncommon. We present a 62 years old with locally advanced breast carcinoma arising in the vulva demonstrates the utilization of sentinel lymph node mapping to identify metastatic lymph nodes previously unable to be identified via traditional surgical exploration. Our case supports the principles of adjuvant therapy for breast cancer to be applied to ectopic breast cancer arising in the vulva. A literature review highlights common key points in similar cases to guide management. PMID:25866706

  17. Should Sentinel Lymph Node Biopsy for Patients with Early Breast Cancer Be Abandoned? Not So Fast

    PubMed Central

    Chu, Quyen D.; Peddi, Prakash

    2016-01-01

    As major advances are made in the management of early breast cancer, the role of sentinel lymph node biopsy (SLNBx) has been called into question. However, before abandoning SLNBx, a critical appraisal of its role should be done because we believe that it remains a critical component of care, especially when tailoring patient’s adjuvant therapy. This commentary provides cogent arguments in favor of SLNBx in the management of patients with early breast cancer. PMID:27398043

  18. Expression of MAGE-C1/CT7 and MAGE-C2/CT10 predicts lymph node metastasis in melanoma patients.

    PubMed

    Curioni-Fontecedro, Alessandra; Nuber, Natko; Mihic-Probst, Daniela; Seifert, Burkhardt; Soldini, Davide; Dummer, Reinhard; Knuth, Alexander; van den Broek, Maries; Moch, Holger

    2011-01-01

    MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT) antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68 (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index) in a multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis. PMID:21738656

  19. Expression of MAGE-C1/CT7 and MAGE-C2/CT10 Predicts Lymph Node Metastasis in Melanoma Patients

    PubMed Central

    Mihic-Probst, Daniela; Seifert, Burkhardt; Soldini, Davide; Dummer, Reinhard; Knuth, Alexander; van den Broek, Maries; Moch, Holger

    2011-01-01

    MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT) antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68 (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index) in a multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis. PMID:21738656

  20. Ultrasound of the sentinel node in melanoma patients: echo-free island is a discriminatory morphologic feature for node positivity.

    PubMed

    Voit, Christiane A; Oude Ophuis, Charlotte M C; Ulrich, Jens; van Akkooi, Alexander C J; Eggermont, Alexander M M

    2016-06-01

    Unlike breast and thyroid cancer, the use of ultrasound (US)-guided fine needle aspiration cytology (FNAC) for preoperative staging is limited in melanoma. New US morphology criteria have shown that US-FNAC can correctly identify 50% of all involved sentinel nodes (SN) in melanoma patients before surgical excision. The aim of this study was to examine a new criterion: the echo-free island (EFI). A total of 1000 consecutively staged melanoma patients (Breslow thickness>1 or<1 mm, but ulcerated, Clark IV/V or regressed) scheduled for SN staging underwent preoperative US. US morphology items were assessed: peripheral perfusion, loss of central echoes, balloon shape, and EFI. FNAC was performed in case of suspicious and malignant US patterns. All patients proceeded to undergo an SN biopsy or direct completion lymph node dissection (CLND) (in the case of positive FNAC). In all, 57% of the patients were men. The mean/median Breslow thickness was 2.58/1.57 mm. The mean/median follow-up was 56/53 months. SN was positive in 21%. EFI information was available in 95.3%. EFI was seen in 40 patients (4%). EFI sensitivity was 10.8%, specificity was 97.6%, positive predictive value was 50%, and negative predictive value was 80.2%. EFI was significantly correlated to peripheral perfusion (67.5%). There was no correlation to balloon shape or loss of central echoes. Five-year melanoma-specific survival of patients with EFI was significantly worse: 80% versus 92% when absent. The EFI can be useful in the early detection of SN melanoma metastasis. It is an early sign of involvement and thus associated with a decreased survival. PMID:26881876

  1. Near infrared imaging to identify sentinel lymph nodes in invasive urinary bladder cancer

    NASA Astrophysics Data System (ADS)

    Knapp, Deborah W.; Adams, Larry G.; Niles, Jacqueline D.; Lucroy, Michael D.; Ramos-Vara, Jose; Bonney, Patty L.; deGortari, Amalia E.; Frangioni, John V.

    2006-02-01

    Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

  2. 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

  3. Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.

    PubMed

    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

    2015-03-01

    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

  4. Spectral imaging as a potential tool for optical sentinel lymph node biopsies

    NASA Astrophysics Data System (ADS)

    O'Sullivan, Jack D.; Hoy, Paul R.; Rutt, Harvey N.

    2011-07-01

    Sentinel Lymph Node Biopsy (SLNB) is an increasingly standard procedure to help oncologists accurately stage cancers. It is performed as an alternative to full axillary lymph node dissection in breast cancer patients, reducing the risk of longterm health problems associated with lymph node removal. Intraoperative analysis is currently performed using touchprint cytology, which can introduce significant delay into the procedure. Spectral imaging is forming a multi-plane image where reflected intensities from a number of spectral bands are recorded at each pixel in the spatial plane. We investigate the possibility of using spectral imaging to assess sentinel lymph nodes of breast cancer patients with a view to eventually developing an optical technique that could significantly reduce the time required to perform this procedure. We investigate previously reported spectra of normal and metastatic tissue in the visible and near infrared region, using them as the basis of dummy spectral images. We analyse these images using the spectral angle map (SAM), a tool routinely used in other fields where spectral imaging is prevalent. We simulate random noise in these images in order to determine whether the SAM can discriminate between normal and metastatic pixels as the quality of the images deteriorates. We show that even in cases where noise levels are up to 20% of the maximum signal, the spectral angle map can distinguish healthy pixels from metastatic. We believe that this makes spectral imaging a good candidate for further study in the development of an optical SLNB.

  5. Portable widefield imaging device for ICG-detection of the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Govone, Angelo Biasi; Gómez-García, Pablo Aurelio; Carvalho, André Lopes; Capuzzo, Renato de Castro; Magalhães, Daniel Varela; Kurachi, Cristina

    2015-06-01

    Metastasis is one of the major cancer complications, since the malignant cells detach from the primary tumor and reaches other organs or tissues. The sentinel lymph node (SLN) is the first lymphatic structure to be affected by the malignant cells, but its location is still a great challenge for the medical team. This occurs due to the fact that the lymph nodes are located between the muscle fibers, making it visualization difficult. Seeking to aid the surgeon in the detection of the SLN, the present study aims to develop a widefield fluorescence imaging device using the indocyanine green as fluorescence marker. The system is basically composed of a 780nm illumination unit, optical components for 810nm fluorescence detection, two CCD cameras, a laptop, and dedicated software. The illumination unit has 16 diode lasers. A dichroic mirror and bandpass filters select and deliver the excitation light to the interrogated tissue, and select and deliver the fluorescence light to the camera. One camera is responsible for the acquisition of visible light and the other one for the acquisition of the ICG fluorescence. The software developed at the LabVIEW® platform generates a real time merged image where it is possible to observe the fluorescence spots, related to the lymph nodes, superimposed at the image under white light. The system was tested in a mice model, and a first patient with tongue cancer was imaged. Both results showed the potential use of the presented fluorescence imaging system assembled for sentinel lymph node detection.

  6. Evaluation of a CdTe semiconductor based compact gamma camera for sentinel lymph node imaging

    SciTech Connect

    Russo, Paolo; Curion, Assunta S.; Mettivier, Giovanni; Esposito, Michela; Aurilio, Michela; Caraco, Corradina; Aloj, Luigi; Lastoria, Secondo

    2011-03-15

    Purpose: The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. Methods: The room-temperature CdTe pixel detector (1 mm thick) has 256x256 square pixels arranged with a 55 {mu}m pitch (sensitive area 14.08x14.08 mm{sup 2}), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. Results: For {sup 99m}Tc, at 50 mm distance, a background-subtracted sensitivity of 6.5x10{sup -3} cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3x10{sup -2} cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq {sup 99m}Tc and prior localization with standard gamma camera lymphoscintigraphy. Conclusions: The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter

  7. Sentinel lymph node biopsy in clinically detected ductal carcinoma in situ

    PubMed Central

    Al-Ameer, Ahmed Yahia; Al Nefaie, Sahar; Al Johani, Badria; Anwar, Ihab; Al Tweigeri, Taher; Tulbah, Asma; Alshabanah, Mohmmed; Al Malik, Osama

    2016-01-01

    AIM: To study the indications for sentinel lymph node biopsy (SLNB) in clinically-detected ductal carcinoma in situ (CD-DCIS). METHODS: A retrospective analysis of 20 patients with an initial diagnosis of pure DCIS by an image-guided core needle biopsy (CNB) between June 2006 and June 2012 was conducted at King Faisal Specialist Hospital. The accuracy of performing SLNB in CD-DCIS, the rate of sentinel and non-sentinel nodal metastasis, and the histologic underestimation rate of invasive cancer at initial diagnosis were analyzed. The inclusion criteria were a preoperative diagnosis of pure DCIS with no evidence of invasion. We excluded any patient with evidence of microinvasion or invasion. There were two cases of mammographically detected DCIS and 18 cases of CD-DCIS. All our patients were diagnosed by an image-guided CNB except two patients who were diagnosed by fine needle aspiration (FNA). All patients underwent breast surgery, SLNB, and axillary lymph node dissection (ALND) if the SLN was positive. RESULTS: Twenty patients with an initial diagnosis of pure DCIS underwent SLNB, 2 of whom had an ALND. The mean age of the patients was 49.7 years (range, 35-70). Twelve patients (60%) were premenopausal and 8 (40%) were postmenopausal. CNB was the diagnostic procedure for 18 patients, and 2 who were diagnosed by FNA were excluded from the calculation of the underestimation rate. Two out of 20 had a positive SLNB and underwent an ALND and neither had additional non sentinel lymph node metastasis. Both the sentinel visualization rate and the intraoperative sentinel identification rate were 100%. The false negative rate was 0%. Only 2 patients had a positive SLNB (10%) and neither had additional metastasis following an ALND. After definitive surgery, 3 patients were upstaged to invasive ductal carcinoma (3/18 = 16.6%) and 3 other patients were upstaged to DCIS with microinvasion (3/18 = 16.6%). Therefore the histologic underestimation rate of invasive disease was 33

  8. Technique of sentinel lymph node biopsy and lymphatic mapping during laparoscopic colon resection for cancer

    PubMed Central

    Bianchi, PP; Andreoni, B; Rottoli, M; Celotti, S; Chiappa, A; Montorsi, M

    2007-01-01

    Background: The utility of lymph node mapping to improve staging in colon cancer is still under evaluation. Laparoscopic colectomy for colon cancer has been validated in multi-centric trials. This study assessed the feasibility and technical aspects of lymph node mapping in laparoscopic colectomy for colon cancer. Methods: A total of 42 patients with histologically proven colon cancer were studied from January 2006 to September 2007. Exclusion criteria were: advanced disease (clinical stage III), rectal cancer, previous colon resection and contraindication to laparoscopy. Lymph-nodal status was assessed preoperatively by computed tomography (CT) scan and intra-operatively with the aid of laparoscopic ultrasound. Before resection, 2–3 ml of Patent Blue V dye was injected sub-serosally around the tumour. Coloured lymph nodes were marked as sentinel (SN) with metal clips or suture and laparoscopic colectomy with lymphadenectomy completed as normal. In case of failure of the intra-operative procedure, an ex vivo SN biopsy was performed on the colectomy specimen after resection. Results: A total number of 904 lymph nodes were examined, with a median number of 22 lymph nodes harvested per patient. The SN detection rate was 100%, an ex vivo lymph node mapping was necessary in four patients. Eleven (26.2%) patients had lymph-nodal metastases and in five (45.5%) of these patients, SN was the only positive lymph node. There were two (18.2%) false-negative SN. In three cases (7.1%) with aberrant lymphatic drainage, lymphadenectomy was extended. The accuracy of SN mapping was 95.2% and negative predictive value was 93.9%. Conclusions: Laparoscopic lymphatic mapping and SN removal is feasible in laparoscopic colectomy for colon cancer. The ex vivo technique is useful as a salvage technique in case of failure of the intra-operative procedure. Prospective studies are justified to determine the real accuracy and false-negative rate of the technique. PMID:22275957

  9. [INTRAOPERATIVE DETECTION OF SENTINEL LYMPH NODES USING INFRARED IMAGING SYSTEM IN LOCAL NON-SMALL CELL CARCINOMA OF LUNG].

    PubMed

    Akopov, A L; Papayan, G V; Chistyakov, I V; Karlson, A; Gerasin, A V; Agishev, A S

    2015-01-01

    The article presents the results of the first domestic experience of intraoperative fluorescence mapping of sentinel lymph nodes in lung cancer. The research included 10 patients, who underwent surgery over the period of time from September 2013 to May 2014. After performing thoracotomy, the solution of indocyanine green (ICG) was injected using subpleural position above the tumor in 3-4 points. Fluorescence (ICG) image guided surgery was carried out by using infrared radiation (wave length 808 nm) on lung surface, root of lung, mediastinum in real time. Fluorescence lymph nodes were mapped. In case that metastatic lesions weren't revealed in sentinel lymph nodes, they weren't noted in other nodes. Method specificity consisted of 100%. Biopsy and histological study of sentinel lymph nodes mapped during fluorescence (ICG) image guided surgery could be useful for prevention of lymphodissection in patients with non-small cell carcinoma of lung. PMID:26601511

  10. How Is Melanoma Skin Cancer Diagnosed?

    MedlinePlus

    ... medicine doctor injects a small amount of a radioactive substance into the area of the melanoma. After ... one or more sentinel lymph nodes. Once the radioactive area has been marked, the patient is taken ...

  11. Initial experiences in the photoacoustic detection of melanoma metastases in resected lymph nodes

    NASA Astrophysics Data System (ADS)

    Grootendorst, D.; Jose, J.; Van der Jagt, P.; Van der Weg, W.; Nagel, K.; Wouters, M.; Van Boven, H.; Van Leeuwen, T. G.; Steenbergen, W.; Ruers, T.; Manohar, S.

    2011-03-01

    Accurate lymph node analysis is essential to determine the prognosis and treatment of patients suffering from melanoma. The initial results of a tomographic photoacoustic modality to detect melanoma metastases in resected lymph nodes are presented based on phantom models and a human lymph node. The results show melanoma metastases detection is feasible and the setup is capable of distinguishing absorbing structures down to 1 mm. In addition, the use of longer laser wavelengths could result in an image containing a higher contrast ratio. Future research shall be focused on using the melanin characteristics to improve contrast and detection possibilities.

  12. In vivo carbon nanotube-enhanced non-invasive photoacoustic mapping of the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Pramanik, Manojit; Song, Kwang Hyun; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-06-01

    Sentinel lymph node biopsy (SLNB), a less invasive alternative to axillary lymph node dissection (ALND), has become the standard of care for patients with clinically node-negative breast cancer. In SLNB, lymphatic mapping with radio-labeled sulfur colloid and/or blue dye helps identify the sentinel lymph node (SLN), which is most likely to contain metastatic breast cancer. Even though SLNB, using both methylene blue and radioactive tracers, has a high identification rate, it still relies on an invasive surgical procedure, with associated morbidity. In this study, we have demonstrated a non-invasive single-walled carbon nanotube (SWNT)-enhanced photoacoustic (PA) identification of SLN in a rat model. We have successfully imaged the SLN in vivo by PA imaging (793 nm laser source, 5 MHz ultrasonic detector) with high contrast-to-noise ratio (=89) and good resolution (~500 µm). The SWNTs also show a wideband optical absorption, generating PA signals over an excitation wavelength range of 740-820 nm. Thus, by varying the incident light wavelength to the near infrared region, where biological tissues (hemoglobin, tissue pigments, lipids and water) show low light absorption, the imaging depth is maximized. In the future, functionalization of the SWNTs with targeting groups should allow the molecular imaging of breast cancer.

  13. 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

  14. Sentinel lymph node biopsy in renal malignancy: The past, present and future

    PubMed Central

    Mahesan, Tharani; Coscione, Alberto; Ayres, Ben; Watkin, Nick

    2016-01-01

    Sentinel lymph node biopsy (SLNB) is now an established technique in penile and pelvic cancers, resulting in a lower mortality and morbidity when compared with the traditional lymph node dissection. In renal cancer however, despite some early successes for the SLNB technique, paucity of data remains a problem, thus lymph node dissection and extended lymph node dissection remain the management of choice in clinically node positive patients, with surveillance of lymph nodes in those who are clinically node negative. SLNB is a rapidly evolving technique and the introduction of new techniques such as near infra-red fluorescence optical imaging agents and positron emission tomography/computed tomography scans, may improve sensitivity. Evidence in support of this has already been recorded in bladder and prostate cancer. Although the lack of large multi-centre studies and issues around false negativity currently prevent its widespread use, with evolving techniques improving accuracy and the support of large-scale studies, SLNB does have the potential to become an integral part of staging in renal malignancy. PMID:26981443

  15. Intraoperative sentinel lymph node mapping guides laparoscopic-assisted distal gastrectomy for distal gastric cancer

    PubMed Central

    Liu, Naiqing; Niu, Zhengchuan; Niu, Wei; Peng, Cheng; Zou, Xueqing; Sun, Shuxiang; Shinichi, Obo; Shahbaz, Muhammad; Sun, Qinli; Jun, Niu

    2015-01-01

    Aims: The aim of this retrospective study is to explore the effects of sentinel lymph node (SLN) mapping guided laparoscopic-assisted distal gastrectomy (LADG) for distal gastric cancer. Methods: Two hundred patients were enrolled in this study. One hundred and one patients undergoing SLN guided LADG were designated as the SLN group. Ninety-nine patients having conventional LADG with D1 or D2 lymph node dissection were designated as the control group. Intraoperative and postoperative indicators such as the number of lymph nodes dissected, intraoperative and postoperative conditions, flow cytometry analysis of T lymphocyte subsets and natural killer (NK) cells, survival rates, recurrence rates and postoperative complications were investigated between these two groups. Results: The number of lymph nodes dissected in the SLN group was significantly lesser than that in the control group. Furthermore, in the SLN group, the patients achieved better immunization status, improved intraoperative and postoperative conditions and decreased postoperative complications. There were no significant differences were found in the positive lymph nodes detected, the distance between proximal and distal cutting edge, postoperative survival or recurrence rates. Conclusions: SLN guided LADG for gastric cancer is a safe and effective method and could achieve an equal clinical effect as traditional laparoscopic D1 or D2 radical operation with less operation trauma and better recovery. PMID:26131162

  16. [Sentinel lymph node detection in breast cancer. Experience of the Institut Curie].

    PubMed

    Nos, C; Fréneaux, P; Clough, K B

    2000-05-01

    Sentinel lymph node biopsy is a recently developed, minimally invasive technique for staging the axilla in breast cancer. This new procedure of selective lymphadenectomy has been the subject of several studies, and a consensus of opinion is starting to form to define indications and methods of identification concerning the use of this technique. At the Institut Curie since 1996, we have been using the Patenté blue dye technique and from 1998 we have used the combination of blue dye and technetium labeled sulfur colloid. This article summarizes the principales aspect of this technique. PMID:10804363

  17. Sentinel lymph node detection by an optical method using scattered photons

    PubMed Central

    Tellier, Franklin; Ravelo, Rasata; Simon, Hervé; Chabrier, Renée; Steibel, Jérôme; Poulet, Patrick

    2010-01-01

    We present a new near infrared optical probe for the sentinel lymph node detection, based on the recording of scattered photons. A two wavelengths setup was developed to improve the detection threshold of an injected dye: the Patent Blue V dye. The method used consists in modulating each laser diode at a given frequency. A Fast Fourier Transform of the recorded signal separates both components. The signal amplitudes are used to compute relative Patent Blue V concentration. Results on the probe using phantoms model and small animal experimentation exhibit a sensitivity threshold of 3.2 µmol/L, which is thirty fold better than the eye visible threshold. PMID:21258517

  18. Dual-Modality Photoacoustic and Ultrasound Imaging System for Noninvasive Sentinel Lymph Node Detection in Patients with Breast Cancer

    PubMed Central

    Garcia-Uribe, Alejandro; Erpelding, Todd N.; Krumholz, Arie; Ke, Haixin; Maslov, Konstantin; Appleton, Catherine; Margenthaler, Julie A.; Wang, Lihong V.

    2015-01-01

    The detection of regional lymph node metastases is important in cancer staging as it guides the prognosis of the patient and the strategy for treatment. Sentinel lymph node biopsy (SLNB) is an accurate, less invasive alternative to axillary lymph node dissection. The sentinel lymph node hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasonic imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer. PMID:26510774

  19. Noninvasive photoacoustic sentinel lymph node mapping using Au nanocages as a lymph node tracer in a rat model

    NASA Astrophysics Data System (ADS)

    Song, Kwang Hyun; Kim, Chulhong; Cobley, Claire M.; Xia, Younan; Wang, Lihong V.

    2009-02-01

    Sentinel lymph node biopsy (SLNB) has been widely performed and become the standard procedure for axillary staging in breast cancer patients. In current SLNB, identification of SLNs is prerequisite, and blue dye and/or radioactive colloids are clinically used for mapping. However, these methods are still intraoperative, and especially radioactive colloids based method is ionizing. As a result, SLNB is generally associated with ill side effects. In this study, we have proposed near-infrared Au nanocages as a new tracer for noninvasive and nonionizing photoacoustic (PA) SLN mapping in a rat model as a step toward clinical applications. Au nanocages have great features: biocompatibility, easy surface modification for biomarker, a tunable surface plasmon resonance (SPR) which allows for peak absorption to be optimized for the laser being used, and capsule-type drug delivery. Au nanocage-enhanced photoacoustic imaging has the potential to be adjunctive to current invasive SLNB for preoperative axillary staging in breast cancer patients.

  20. Silica-Coated Gold Nanoplates as Stable Photoacoustic Contrast Agents for Sentinel Lymph Node Imaging

    PubMed Central

    Luke, Geoffrey P.; Bashyam, Ashvin; Homan, Kimberly A.; Makhija, Suraj; Chen, Yun-Sheng; Emelianov, Stanislav Y.

    2013-01-01

    A biopsy of the first lymph node to which a tumor drains – the sentinel lymph node (SLN) – is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit high photothermal stability when exposed to pulsed and continuous wave laser irradiation. This makes them well-suited for in vivo photoacoustic imaging. Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs for SLN mapping in a mouse model where they exhibited a strong, sustained photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed that the Si-AuNPs quickly drain to the SLN gradually spreading throughout a large portion of the node. PMID:24121616

  1. Transaxillary breast augmentation: two breast cancer patients with successful sentinel lymph node diagnosis.

    PubMed

    Mottura, A Aldo; Del Castillo, René

    2007-01-01

    In recent years, some surgeons have been warned of possible problems with sentinel lymph node diagnosis (SLND) for patients who have undergone transaxillary breast augmentation (TBA), although no scientific studies support this warning. The authors report two additional cases of breast cancer in which the SLND was successfully performed for patients with previous TBA. The surgical anatomy of the axilla, the groups of lymph nodes, and a personal way of performing TBA are described. Five other reports concerning the same issue are thoroughly discussed. Four of these are clinical in vivo reports, and one is a cadaver study. The four in vivo studies and what we are reporting now clearly demonstrate that what was said regarding possible problems in the SLND after TBA was not founded on clinical research and contradicts these five clinical findings. PMID:17659414

  2. Sentinel lymph node biopsy in breast cancer: a technical and clinical appraisal.

    PubMed

    Manca, Gianpiero; Tardelli, Elisa; Rubello, Domenico; Gennaro, Marta; Marzola, Maria Cristona; Cook, Gary J; Volterrani, Duccio

    2016-06-01

    Breast cancer is the most common type of cancer diagnosed in women worldwide. Regional lymph node status is one of the strongest predictors of long-term prognosis in primary breast cancer. Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection as the standard surgical procedure for staging clinically tumor-free regional nodes in patients with early-stage breast cancer. SLNB staging considerably reduces surgical morbidity in terms of shoulder dysfunction and lymphedema, without affecting diagnostic accuracy and prognostic information. Clinicians should not recommend axillary lymph node dissection for women with early-stage breast cancer who have tumor-free findings on SLNB because there is no advantage in terms of overall survival and disease-free survival. Starting from the early 1990s, SLNB has increasingly been used in breast cancer management, but its role is still debated under many clinical circumstances. Moreover, there is still a lack of standardization of the basic technical details of the procedure that is likely to be responsible for the variability found in the false-negative rate of the procedure (5.5-16.7%). In this article, we report the aspects of SLNB that are well established, those that are still debated, and the advancements that have taken place over the last 20 years. We have provided an update on the methodology from both a technical and a clinical point of view in the light of the most recent publications. PMID:26886421

  3. The value of immunohistochemistry in sentinel lymph node histopathology in breast cancer

    PubMed Central

    Klevesath, M B; Bobrow, L G; Pinder, S E; Purushotham, A D

    2005-01-01

    The optimal protocol for the histopathological examination of sentinel lymph nodes (SLNs) in breast cancer has not been determined. The value of more detailed examination using immunohistochemistry (IHC) is controversial. A total of 476 SLNs from 216 patients were reviewed. Sentinel lymph nodes were sectioned at three levels at 100 μm intervals and stained with haematoxylin and eosin (H&E). If the H&E sections showed no evidence of metastasis, then the three serial sections were stained with a murine monoclonal anti-cytokeratin antibody (CAM 5.2). Metastatic deposits were classified as macrometastasis (>2.0 mm), micrometastasis (0.2–2.0 mm) or isolated tumour cells (ITC, <0.2 mm). Of the 216 patients, 56 (26%) had metastasis as identified by H&E. Immunohistochemistry detected metastatic deposits in a further nine patients (4%), of whom four (2%) had micrometastasis and five (2%) had ITC only. Those cases with micrometastases were all, on review, visible on the H&E sections. Immunohistochemistry detects only a small proportion of metastasis in SLNs. All metastatic deposits identified by IHC were either micrometastasis or ITC. Until the prognostic significance of these deposits has been determined, IHC may be of limited value in the histopathological examination of SLNs. PMID:15942633

  4. Optimization of a gamma imaging probe for axillary sentinel lymph mapping

    NASA Astrophysics Data System (ADS)

    Georgiou, M.; Loudos, G.; Stratos, D.; Papadimitroulas, P.; Liakou, P.; Georgoulias, P.

    2012-09-01

    Sentinel lymph node (SLN) mapping is a technique for assessing whether early-stage invasive breast cancer has metastasized, thus determining prognosis and treatment options. SLN identification is achieved using the blue-dye and radioactive colloids techniques, which are sometimes combined with lymphoscintigraphy. Furthermore, intra-operative gamma acoustic probes, as well as gamma imaging probes are used during surgery. The purpose of this study is the construction of a gamma probe for sentinel lymph node imaging and its optimization in terms of sensitivity with respect to spatial resolution. The reference probe has small field of view (2.5 × 2.5 cm2) and is based on a position sensitive photomultiplier tube (PSPMT) coupled to a pixellated CsI(Tl) scintillator. Following experimental validation, we simulated the system using the GATE Monte Carlo toolkit (GATE v6.1) and modeled various collimator geometries, in order to evaluate their performance and propose the optimal configuration. The constraints of the proposed gamma imaging probe are i) sensitivity close to 2 cps/kBq and ii) spatial resolution equal to 6 mm at 2 cm source-to-collimator distance and ~ 10 mm at 5 cm. An integrated structure that achieves those requirements is a tungsten collimator with 2 × 2 mm2square holes, 16 mm thickness, 0.15 mm septa, where each CsI(Tl) 2 × 2 × 5 mm3 crystal pixel is placed inside the collimator.

  5. Preoperative Scintigrams to Identify the Sentinel Lymph Node in Breast Cancer: a Waste of Time?

    PubMed

    Sharma, N; Pinto, A; Notghi, A; Sintler, M

    2015-12-01

    Sentinel lymph node biopsy (SLNB) remains the gold standard for assessing axillary node status in breast cancer. Preoperative scintigrams have been used to identify the sentinel lymph node (SLN); however, their use is controversial. Studies suggest they add little to successful SLN detection in theatre, immediately prior to node excision. They have been associated with high false negatives, time expense, patient dissatisfaction, and unnecessary costs. The aim of the present study was to evaluate the diagnostic accuracy of scintigrams in comparison to intraoperative SLN identification techniques. This study included all patients undergoing a SLNB for breast cancer from April 2010 to 2011. Scintigram reports, operation notes, and histology results were analyzed. Mann-Whitney U and chi-squared tests were used for statistical analysis of data. Two hundred nineteen female patients with a median age of 59.6 years (24.0-89.9 years) were included in this study. Scintigram was performed in 185 and not in 34 patients due to time constraints. Combined γ-probe and Isosulfan blue dye for SLN detection (intraoperative methods) have an identification rate of 98.2 % (p = 0.005), compared to 92.4 % (p = 0.088) from scintigrams alone. Scintigrams confer no additional advantage to the operating surgeon for successful SLN detection and excision in theatre. Intraoperative SLN identification is more accurate and reliable. Routine scintigram use is unjustified and should be withdrawn from current practice. PMID:27011606

  6. New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients

    PubMed Central

    Kohrt, Holbrook E; Olshen, Richard A; Bermas, Honnie R; Goodson, William H; Wood, Douglas J; Henry, Solomon; Rouse, Robert V; Bailey, Lisa; Philben, Vicki J; Dirbas, Frederick M; Dunn, Jocelyn J; Johnson, Denise L; Wapnir, Irene L; Carlson, Robert W; Stockdale, Frank E; Hansen, Nora M; Jeffrey, Stefanie S

    2008-01-01

    Background Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model. Methods We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University. Results 285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic

  7. Detection of Sentinel Lymph Nodes in Gynecologic Tumours by Planar Scintigraphy and SPECT/CT

    PubMed Central

    Kraft, Otakar; Havel, Martin

    2012-01-01

    Objective: Assess the role of planar lymphoscintigraphy and fusion imaging of SPECT/CT in sentinel lymph node (SLN) detection in patients with gynecologic tumours. Material and Methods: Planar scintigraphy and hybrid modality SPECT/CT were performed in 64 consecutive women with gynecologic tumours (mean age 53.6 with range 30-77 years): 36 pts with cervical cancer (Group A), 21 pts with endometrial cancer (Group B), 7 pts with vulvar carcinoma (Group C). Planar and SPECT/CT images were interpreted separately by two nuclear medicine physicians. Efficacy of these two techniques to image SLN were compared. Results: Planar scintigraphy did not image SLN in 7 patients (10.9%), SPECT/CT was negative in 4 patients (6.3%). In 35 (54.7%) patients the number of SLNs captured on SPECT/CT was higher than on planar imaging. Differences in detection of SLN between planar and SPECT/CT imaging in the group of all 64 patients are statistically significant (p<0.05). Three foci of uptake (1.7% from totally visible 177 foci on planar images) in 2 patients interpreted on planar images as hot LNs were found to be false positive non-nodal sites of uptake when further assessed on SPECT/CT. SPECT/CT showed the exact anatomical location of all visualised sentinel nodes. Conclusion: In some patients with gynecologic cancers SPECT/CT improves detection of sentinel lymph nodes. It can image nodes not visible on planar scintigrams, exclude false positive uptake and exactly localise pelvic and paraaortal SLNs. It improves anatomic localization of SLNs. Conflict of interest:None declared. PMID:23486989

  8. Use of the Sentinel Lymph Node Technique Compared to Complete Inguino-femoral Lymph Node Removal in Patients with Invasive Vulvar Cancer in Germany

    PubMed Central

    Kramer, F.; Hertel, H.; Hillemanns, P.

    2013-01-01

    In the current S2 guidelines, the standard surgical therapy for patients with vulvar cancer also includes inguino-femoral lymphadenectomy. However, in view of the severe side-effects associated with this approach such as problems with wound healing, lymphoceles and lymphoedema, the search is on for alternative treatments that could decrease treatment-associated morbidity and improve patientsʼ quality of life, particularly for node-negative patients. The sentinel lymph node technique is currently the gold standard in the treatment of unifocal breast cancer (clinically negative axilla), and studies on the use of this technique in the treatment of vulvar cancer are promising. To date, the diagnostic accuracy of this method in vulvar cancer has only been evaluated in a single, one-arm, non-randomised, multicentre study. In preparation for a multicentre study, in 2010 we surveyed 41 German hospitals to investigate how often they used the sentinel lymph node technique compared to inguino-femoral lymphadenectomy. The hospitals were grouped according to hospital size and number of patients treated for vulvar cancer. The decision criteria to determine the type of procedure performed were also investigated. Finally, the hospitals were asked whether they would be willing to participate in a prospective clinical study to evaluate the sentinel lymph node technique in patients with vulvar cancer. The majority of surgeons questioned (73 %) already had some experience with this technique in patients with vulvar cancer. In our survey, 27 % of hospitals carried out inguino-femoral lymphadenectomy, 10 % used the sentinel lymph node technique, and 63 % used both methods. In 24 % of hospitals, the standard procedure consisted of the sentinel lymph node technique supplemented by inguino-femoral lymphadenectomy. Only 20 % of the institutions surveyed in our study carried out sentinel lymph node biopsy alone in accordance with the criteria of the consensus recommendations

  9. Robotic-Assisted Fluorescence Sentinel Lymph Node Mapping Using Multi-Modal Image-Guidance in an Animal Model

    PubMed Central

    Liss, Michael A.; Stroup, Sean P.; Cand, Zhengtao Qin; Hoh, Carl; Hall, David J.; Vera, David R.; Kane, Christopher J.

    2015-01-01

    Objectives To investigate PET/CT pre-operative imaging and intraoperative detection of a fluorescent-labeled receptor-targeted radiopharmaceutical in a prostate cancer animal model. Methods Three male Beagle dogs underwent an intra-prostatic injection of fluorescent-tagged tilmanocept radio-labeled with both gallium-68 and technetium-99m. One hour after injection a pelvic PET/CT scan was performed for pre-operative sentinel lymph node (SLN) mapping. Definition of SLN was a standardized uptake value (SUV) that exceeded 5% of the lymph node with the highest SUV. Thirty-six hours later we performed robotic-assisted SLN dissection using a fluorescence-capable camera system. Fluorescent lymph nodes were clipped, the abdomen was opened, and the pelvic and retroperitoneal nodes were excised. All excised nodal packets were assayed by in vitro nuclear counting and reported as percent-of-injected dose. Results Pre-operative PET/CT imaging identified a median of three sentinel lymph nodes per animal. All sentinel lymph nodes (100%) identified by the PET/CT were fluorescent during robotic-assisted lymph node dissection. Of all fluorescent nodes visualized by the camera system, 83% (10/12) satisfied the 5%-rule defined by the PET/CT scan. The two lymph nodes that did not qualify accumulated less than 0.002% of the injected dose. Conclusions Fluorescent-labeled tilmanocept has optimal logistical properties to obtain pre-operative PET/CT and subsequent real-time intraoperative confirmation during robotic-assisted sentinel lymph node dissection. PMID:25139676

  10. Near infrared photoacoustic detection of sentinel lymph nodes with gold nanobeacons.

    PubMed

    Pan, Dipanjan; Pramanik, Manojit; Senpan, Angana; Ghosh, Soumojit; Wickline, Samuel A; Wang, Lihong V; Lanza, Gregory M

    2010-05-01

    Detection of sentinel lymph node (SLN) using photoacoustic imaging is an emerging technique for noninvasive axillary staging of breast cancer. Due to the absence of intrinsic contrast inside the lymph nodes, exogenous contrast agents are used for photoacoustic detection. In this work, we have demonstrated near infrared detection of SLN with gold nanobeacons (GNBs) providing the photoacoustic contrast in a rodent model. We found that size dictates the in vivo characteristics of these nanoparticles in SLN imaging. Larger nanobeacons with high payloads of gold were not as efficient as smaller size nanobeacons with lower payloads for this purpose. Colloidal GNBs were designed as a nanomedicine platform with "soft" nature that is amenable to bio-elimination, an essential feature for in vivo efficacy and safety. The GNBs were synthesized as lipid- or polymer-encapsulated colloidal particles incorporating tiny gold nanoparticles (2-4 nm) in three tunable sizes (90 nm, 150 nm and 290 nm). Smaller GNBs were noted trafficking through the lymphatic system and accumulating more efficiently in the lymph nodes in comparison to the bigger nanoagents. At 20 min, the GNBs reached the SLN and were no longer observed within the draining lymphatic vessel. Within 1 h post-injection, the contrast ratio of the lymph nodes with the surrounding blood vessels was 9:1. These findings were also supported by analytical measurements of the ex vivo tissue samples. Results indicate that cumulative nanoparticle deposition in lymph nodes is size dependent and that high payloads of gold, although offering greater contrast in vitro, may yield nanoagents with poor intradermal migration and lymphatic transport characteristics. PMID:20172607

  11. Experimental study of 99mTc-aluminum oxide use for sentinel lymph nodes detection

    NASA Astrophysics Data System (ADS)

    Chernov, V. I.; Sinilkin, I. G.; Zelchan, R. V.; Medvedeva, A. A.; Lyapunov, A. Yu.; Bragina, O. D.; Varlamova, N. V.; Skuridin, V. S.

    2016-08-01

    The purpose of the study was a comparative research in the possibility of using the radiopharmaceuticals 99mTc-Al2O3 and 99mTc-Nanocis for visualizing sentinel lymph nodes. The measurement of the sizes of 99mTc-Al2O3 and 99mTc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. The pharmacokinetics of 99mTc-Al2O3 and 99mTc-Nanocis was researched on 50 white male rats. The possibility of the use of 99mTc-Al2O3 and 99mTc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. The average dynamic diameter of the sol particle was 52-77 nm for 99mTc-Al2O3 and 16.7-24.5 nm for 99mTc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node in 1 hour after administration; the average uptake of 99mTc-Al2O3 was 8.6% in it, and the accumulation of 99mTc-Nanocis was significantly lower—1.8% (p < 0.05). In all study points the average uptake of 99mTc-Al2O3 in the lymph node was significantly higher than 99mTc-Nanocis accumulation. The results of dynamic scintigraphic studies in rats showed that 99mTc-Al2O3 and 99mTc-Nanocis actively accumulated into the lymphatic system. By using 99mTc-Al2O3 inguinal lymph node was determined in 5 minutes after injection and clearly visualized in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the 99mTc-Al2O3 accumulation reached a plateau in a lymph node (average 10.5%) during 2-hour study and then its accumulation remained practically at the same level, slightly increasing to 12% in 24 hours. In case of 99mTc-Nanocis inguinal lymph node was visualized in all animals for 15 min when it was accumulated on the average 1.03% of the administered dose. Plateau of 99mTc-Nanocis accumulation in the lymph node (average 2.05%) occurred after 2 hours of the study and remained almost on the same level (in average 2.3%) for 24 hours. Thus, the experimental study of a new domestic

  12. Correlation between serum levels of vascular endothelial growth factor-C and sentinel lymph node status in early breast cancer.

    PubMed

    Pérez, Diego; Rohde, Alexander; Callejón, Gonzalo; Pérez-Ruiz, Elisabeth; Rodrigo, Isabel; Rivas-Ruiz, Francisco; Ramos, Belen; Medina, Francisco; Villatoro, Rosa; Redondo, Maximino; Zarcos, Irene; Maañón, Claudio; Rueda, Antonio

    2015-12-01

    Axillary lymph nodes status is the most important prognosis factor in early breast cancer. This status is known by a selective sentinel lymph node biopsy (SLNB) and/or lymphadenectomy. Immunohistochemical studies of breast cancer tumour tissue have reported a relation between the increased expression of vascular endothelial growth factor-C (VEGF-C) and the risk of lymph node metastasis. We researched whether serum levels of VEGF-C could be a predictor factor of sentinel lymph node status in these patients. A prospective analysis was performed on serum from 174 patients with early breast cancer who underwent SLNB. The level of VEGF-C was determined by enzyme-linked immunosorbent assay. Clinical-pathologic variables were collected. Univariate analysis and multivariate logistic regression were conducted, taking SLNB positivity as the segmentation variable. The predictive value of VEGF-C was assessed using ROC curves. Of the sample group of 167 patients, 64 (38.3 %) had affected lymph node. Eighteen patients (28.1 %) presented micrometastasis; there were isolated tumour cells in 11 cases (17.2 %) and macrometastasis in 35 (54.6 %). The median value of VEGF-C was 6561.5 pg/ml. These values did not correlate with any clinical variables, and there was no association between the level of VEGF-C and SLNB status (p = 0.626). In the multivariate analysis, tumour size (p = 0.009) and the presence of vascular invasion (p < 0.001) were independently associated with sentinel lymph node affected. Serum levels of VEGF-C do not appear to predict sentinel lymph node status in patients with early breast cancer who undergo SLNB. PMID:26104766

  13. Malignant Melanoma

    PubMed Central

    Perera, Eshini; Gnaneswaran, Neiraja; Jennens, Ross; Sinclair, Rodney

    2013-01-01

    Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery), treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar. PMID:27429256

  14. Sentinel lymph nodes fluorescence detection and imaging using Patent Blue V bound to human serum albumin

    PubMed Central

    Tellier, Franklin; Steibel, Jérôme; Chabrier, Renée; Blé, François Xavier; Tubaldo, Hervé; Rasata, Ravelo; Chambron, Jacques; Duportail, Guy; Simon, Hervé; Rodier, Jean-François; Poulet, Patrick

    2012-01-01

    Patent Blue V (PBV), a dye used clinically for sentinel lymph node detection, was mixed with human serum albumin (HSA). After binding to HSA, the fluorescence quantum yield increased from 5 × 10−4 to 1.7 × 10−2, which was enough to allow fluorescence detection and imaging of its distribution. A detection threshold, evaluated in scattering test objects, lower than 2.5 nmol × L−1 was obtained, using a single-probe setup with a 5-mW incident light power. The detection sensitivity using a fluorescence imaging device was in the µmol × L−1 range, with a noncooled CCD camera. Preclinical evaluation was performed on a rat model and permitted to observe inflamed nodes on all animals. PMID:23024922

  15. Atypical Anaphylactic Reaction to Patent Blue During Sentinel Lymph Node Biopsy for Breast Cancer

    PubMed Central

    Lanitis, Sophocles; Filippakis, George; Sidhu, Virinder; Mufti, Ragheed AL; Lee, Tak H; Hadjiminas, Dimitri J

    2008-01-01

    INTRODUCTION We present an unusual case of severe anaphylaxis to Patent Blue dye with atypical clinical features during sentinel lymph node biopsy (SLNB). The medical personnel involved with sentinel node biopsies should be alert, and familiar with this unusual entity. We also present current data from the literature. CASE REPORT During a wide local excision for primary breast cancer and SLNB, and early during the operation, the patient became severely tachycardic and hypotensive without any signs of urticaria, rash, oedema, or bronchospasm. Resuscitation required the addition of noradrenaline infusion followed by an overnight admission to the intensive care unit. Raised serum tryptase levels supported the diagnosis of anaphylactic shock while skin tests showed a severe reaction to Patent Blue dye. CONCLUSIONS Severe, life-threatening anaphylaxis to Patent Blue dye may present without obvious previous exposure to the dye and without the cardinal signs of oedema, urticaria and bronchospasm making the diagnosis and management of such cases challenging. Correct diagnosis and identification of the causative factor is important and requires a specific set of laboratory tests that are not commonly requested in every-day medical practice. It is not clear from the literature whether the condition is common enough to justify pre-operative prophylactic or diagnostic measures. PMID:18492403

  16. Usefulness of sentinel lymph node biopsy for prognostic prediction in extramammary Paget's disease.

    PubMed

    Ogata, Dai; Kiyohara, Yoshio; Yoshikawa, Syusuke; Tsuchida, Tetsuya

    2016-06-01

    Complete excision of the primary lesion has long been considered the standard treatment for extramammary Paget's disease (EMPD). However, the presence of lymph node metastases has been reported as an important prognostic factor. We evaluated the association between lymph node metastasis and prognosis for EMPD using sentinel lymph node (SLN) biopsy. This retrospective study included 59 patients with histopathologically-confirmed primary EMPD. A total of 45 patients with microinvasion to the papillary dermis and deep invasion into the reticular dermis or subcutaneous tissue were included in the analysis. The survival curves of the SLN-negative group and the SLN-positive group were compared and we examined the risk factors for SLN positivity. A total of 139 SLNs were excised from one (28 patients) or both inguinal regions (31 patients). The average number of detected SLNs was 2.4. The incidence of SLN metastases was 16.9%. SLN positivity rates according to level of invasion were 0% for intraepithelial lesions, 4.1% for microinvasion, and 42.8% for dermal invasion. The five-year survival rates were 100% in the SLN-negative and 24% in the SLN-positive groups (p = 0.0001). Reticular dermis or subcutaneous tissue invasion was a significant independent risk factor for SLN positivity according to multivariate analysis. The result of SLN biopsy affected prognosis. It is extremely important to accurately ascertain the presence, i.e. the number, or absence of regional lymph node metastases in patients with EMPD. We conclude that SLN biopsy may be appropriate for cases where invasion is suspected. PMID:26985569

  17. A mini-review on factors and countermeasures associated with false-negative sentinel lymph node biopsies in breast cancer

    PubMed Central

    Han, Chao; Yang, Li

    2016-01-01

    Sentinel lymph node biopsy (SLNB) is a new surgical technique for local axillary lymph nodes (ALNs) of breast cancer. Large-scale clinical trials have confirmed that undergoing SLNB and ALN dissection (ALND) showed no significant difference for sentinel lymph node (SLN)-negative patients in terms of disease-free survival, overall survival and recurrence-free survival. However, false-negative results are still the main concern of physicians as well as patients who undergo SLNB instead of ALND. The American Society of Breast Surgeons established a task force to suggest acceptable standards for SLNB. In 2000, the task force recommended that the identification rate for SLNB be 85% or higher and the false-negative rate be 5% or lower. This review focuses on clinical factors (tumor volume, multifocal/multi-center cancers, neoadjuvant chemotherapy and skip metastasis), tracer techniques and pathological factors affecting SLNB and explores methods for reducing the false-negative rate PMID:27478323

  18. In vivo quantitative evaluation of gold nanocages' kinetics in sentinel lymph nodes by photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Cai, Xin; Li, Weiyang; Kim, Chulhong; Yuan, Yuchen; Xia, Younan; Wang, Lihong V.

    2012-02-01

    As a new class of sentinel lymph node (SLN) tracers for photoacoustic (PA) imaging, Au nanocages offer the advantages of noninvasiveness, strong optical absorption in the near-infrared region (for deep penetration), and accumulation in higher concentrations than the initial injected solution. By monitoring the amplitude changes of PA signals in an animal model, we quantified the accumulations of nanocages in SLNs over time. Based on this method, we quantitatively evaluated the kinetics of gold nanocages in SLN in terms of concentration, size, and surface modification. We could detect the SLN at an Au nanocage injection concentration of 50 pM and a dose of 100 μL in vivo. This concentration is about 40 times less than the previously reported value. We also investigated the influence of nanocages' size (50 nm and 30 nm in edge length), and the effects of surface modification (with positive, or neutral, or negative surface charges). The results are helpful to develop this AuNC-based PA imaging system for noninvasive lymph node mapping, providing valuable information about metastatic cancer staging.

  19. A dual-modality photoacoustic and ultrasound imaging system for noninvasive sentinel lymph node detection: preliminary clinical results

    NASA Astrophysics Data System (ADS)

    Erpelding, Todd N.; Garcia-Uribe, Alejandro; Krumholz, Arie; Ke, Haixin; Maslov, Konstantin; Appleton, Catherine; Margenthaler, Julie; Wang, Lihong V.

    2014-03-01

    Sentinel lymph node biopsy (SLNB) has emerged as an accurate, less invasive alternative to axillary lymph node dissection, and it has rapidly become the standard of care for patients with clinically node-negative breast cancer. The sentinel lymph node (SLN) hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first (i.e., sentinel) lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasound imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer. The system consists of a tunable dye laser pumped by a Nd:YAG laser, a commercial ultrasound imaging system (Philips iU22), and a multichannel data acquisition system which displays co-registered photoacoustic and ultrasound images in real-time. Our clinical results demonstrate that real-time photoacoustic imaging can provide sensitive and specific detection of methylene blue dye in vivo. While preliminary studies have shown that in vivo detection of SLNs by using co-registered photoacoustic and ultrasound imaging is feasible, further investigation is needed to demonstrate robust SLN detection.

  20. In vivo photoacoustic (PA) mapping of sentinel lymph nodes (SLNs) using carbon nanotubes (CNTs) as a contrast agent

    NASA Astrophysics Data System (ADS)

    Pramanik, Manojit; Song, Kwang Hyun; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-02-01

    Sentinel lymph node biopsy (SLNB), a less invasive alternative to axillary lymph node dissection (ALND), is routinely used in clinic for staging breast cancer. In SLNB, lymphatic mapping with radio-labeled sulfur colloid and/or blue dye helps identify the sentinel lymph node (SLN), which is most likely to contain metastatic breast cancer. Even though SLNB, using both methylene blue and radioactive tracers, has a high identification rate, it still relies on an invasive surgical procedure, with associated morbidity. In this study, we have demonstrated a non-invasive single-walled carbon nanotube (SWNT)-enhanced photoacoustic (PA) identification of SLN in a rat model. We have used single-walled carbon nanotubes (SWNTs) as a photoacoustic contrast agent to map non-invasively the sentinel lymph nodes (SLNs) in a rat model in vivo. We were able to identify the SLN non-invasively with high contrast to noise ratio (~90) and high resolution (~500 μm). Due to the broad photoacoustic spectrum of these nanotubes in the near infrared wavelength window we could easily choose a suitable light wavelength to maximize the imaging depth. Our results suggest that this technology could be a useful clinical tool, allowing clinicians to identify SLNs non-invasively in vivo. In the future, these contrast agents could be functionalized to do molecular photoacoustic imaging.

  1. The role of lymph node ultrasound evaluation in melanoma - review of the literature.

    PubMed

    Ungureanu, Loredana; Botar Jid, Carolina; Candrea, Elisabeta; Cosgarea, Rodica; Șenilă, Simona Corina

    2016-06-01

    Melanoma is an aggressive tumour, resistant to treatment, derived from melanocytes, with an increasing incidence in the last years in the majority of countries. The most important prognostic factor in the initial stages (I/II) is the presence of metastases at the level of lymph nodes. Ultrasound (US) is a non-invasive method, used in the pre- and post-operative node evaluation due to its high availability, the reduced cost and easy reproducibility. The US accuracy is however dependent on operator expertise. The present article proposes a presentation of the US role in the evaluation of lymph nodes in melanoma patients. PMID:27239659

  2. Metastatic malignant melanoma of the inguinal lymph node with unknown primary lesion.

    PubMed

    Eltawansy, Sherif Ali; Panasiti, Ryane; Hasanien, Samaa; Lourdusamy, Dennis; Sharon, David

    2015-01-01

    Background. Malignant melanoma could present with metastasis with unknown primary (MUP) and this happens in 2-3% according to the studies. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation. Case Report. We report a 58-year-old Caucasian male who presented with a right sided swelling in the inguinal region. Surgery was performed and biopsy showed metastatic malignant melanoma. No cutaneous lesions were identified by history or physical examination. Work up could not detect the primary lesion and patient was started on radiotherapy and immunotherapy. Conclusion. We present a case of malignant melanoma of unknown primary presenting in an unusual place which is the inguinal lymph node. Theories try to explain the pathway of development of such tumors and one of the theories mentions that it could be a spontaneous regression of the primary cutaneous lesion. Another theory is that it could be from transformation of aberrant melanocyte within the lymph node. Prognosis is postulated to be better in this case than in melanoma with a known primary. PMID:25705230

  3. Sentinel lymph node mapping in breast cancer: a critical reappraisal of the internal mammary chain issue.

    PubMed

    Manca, G; Volterrani, D; Mazzarri, S; Duce, V; Svirydenka, A; Giuliano, A; Mariani, G

    2014-06-01

    Although, like the axilla, the internal mammary nodes (IMNs) are a first-echelon nodal drainage site in breast cancer, the importance of their treatment has long been debated. Seminal randomized trials have failed to demonstrate a survival benefit from surgical IMN dissection, and several retrospective studies have shown that IMNs are rarely the first site of recurrence. However, the recent widespread adoption of sentinel lymph node (SLN) biopsy has stimulated a critical reappraisal of such early results. Furthermore, the higher proportion of screening-detected cancers, improved imaging and techniques (i.e., lymphoscintigraphy for radioguided SLN biopsy) make it possible to visualize lymphatic drainage to the IMNs. The virtually systematic application of adjuvant systemic and/or loco-regional radiotherapy encourages re-examination of the significance of IMN metastases. Moreover, randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic chemotherapy, which was not routinely administered in the earlier studies. However, the contribution from IMN treatment is unclear. Lymphoscintigraphic studies have shown that a significant proportion of breast cancers have primary drainage to the IMNs, including approximately 30% of medial tumors and 15% of lateral tumors. In the few studies where IMN biopsy was performed, 20% of sentinel IMNs were metastatic. The risk of IMN involvement is higher in patients with medial tumors and positive axillary nodes. IMN metastasis has prognostic significance, as recognized by its inclusion in the American Joint Committee on Cancer staging criteria, and seems to have similar prognostic importance as axillary nodal involvement. Although routine IMN evaluation might be indicated, it has not been routinely performed

  4. Is sentinel lymph node biopsy more accurate than axillary dissection for staging nodal involvement in breast cancer patients?

    PubMed

    Marrazzo, Antonio; Taormina, Pietra; Gebbiab, Vittorio; David, Massimo; Riili, Ignazio; Lo Gerfo, Domenico; Casà, Luigi; Noto, Antonio

    2007-01-01

    Today evaluation of axillary involvement can be routinely performed with the technique of sentinel lymph node biopsy (SLNB). One of the greatest advantages of SLNB is the nearly total absence of local postoperative complications. It is important to understand whether SLNB is better than axillary lymph-node dissection (ALND) for staging axillary nodal involvement. The aim of the study was to evaluate the axillary staging accuracy comparing three different methods: axillary dissection, sentinel node biopsy with the traditional 4-6 sections and sentinel node biopsy with complete analysis of the lymph node. 527 consecutive patients (525 females and 2 males) with invasive breast cancer < or = 3 cm and clinically negative axillary nodes were divided into 3 different groups: group A treated with axillary dissection, group B treated with sentinel nodal biopsy analysed with 4-6 sections, and group C treated with sentinel node biopsy with analysis of the entire node. All patients underwent a quadrantectomy to treat the tumor. Group differences and statistical significance were assessed by ANOVA. The percentages of N+ in group A and group B were 25.80% and 28% respectively, while in the third group it rose to 45%, or almost half the patients. The differences among the three groups were statistically significant (p = 0.02). From our analysis of the data it emerges that axillary dissection and sentinel node biopsy with analysis of 4-6 sections have the same accuracy in staging the nodal status of the axilla; analysis of the entire sentinel lymph node revealed an increased number of patients with axillary nodal involvement, proving more powerful in predicting nodal stage. SLNB with complete examination of the SLN removed can be considered the best method for axillary staging in breast cancer patients with clinical negative nodes. In our study, the percentage of metastases encountered after complete examination of SLN was 45% compared to the accuracy of axillary dissection that

  5. How Long Will I Be Blue? Prolonged Skin Staining Following Sentinel Lymph Node Biopsy Using Intradermal Patent Blue Dye

    PubMed Central

    Gumus, Metehan; Gumus, Hatice; Jones, Sue E; Jones, Peter A; Sever, Ali R; Weeks, Jennifer

    2013-01-01

    Summary Background Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. Patients and Methods 236 consecutive patients who had undergone breast conserving surgery and SLNB for breast cancer were reviewed prospectively from January 2007 to December 2009. Results Of the 236 patients, 2 had undergone bilateral surgery, and 41 had been examined in consecutive yearly reviews. Blue discoloration remained visible at the injection site after 12, 24, and > 36 months in 36.5, 23.6, and 8.6% of the patients, respectively. Conclusion The use of patent blue for identification of the sentinel lymph node in patients undergoing breast cancer surgery may result in prolonged discoloration of the skin at the injection site. PMID:24415970

  6. 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. PMID:24581865

  7. Treatment Option Overview (Melanoma)

    MedlinePlus

    ... and treatments will also be taken. Lymph node mapping and sentinel lymph node biopsy : Procedures in which ... has spread to the lymph nodes . Lymph node mapping and sentinel lymph node biopsy are done to ...

  8. Stages of Melanoma

    MedlinePlus

    ... and treatments will also be taken. Lymph node mapping and sentinel lymph node biopsy : Procedures in which ... has spread to the lymph nodes . Lymph node mapping and sentinel lymph node biopsy are done to ...

  9. Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study

    PubMed Central

    Tummers, Quirijn R J G; Boogerd, Leonora S F; de Steur, Wobbe O; Verbeek, Floris P R; Boonstra, Martin C; Handgraaf, Henricus J M; Frangioni, John V; van de Velde, Cornelis J H; Hartgrink, Henk H; Vahrmeijer, Alexander L

    2016-01-01

    AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer. METHODS: A prospective, single-institution, phase I feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 mL ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE™ NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated. RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging (mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90% (70%-99%; 95%CI), which decreased by higher pT-stage (100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4 (range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients. CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified. PMID:27053856

  10. Establishing a Sentinel Lymph Node Mapping Algorithm for the Treatment of Early Cervical Cancer

    PubMed Central

    Cormier, Beatrice; Diaz, John P.; Shih, Karin; Sampson, Rachael M.; Sonoda, Yukio; Park, Kay J.; Alektiar, Khaled; Chi, Dennis S.; Barakat, Richard R.; Abu-Rustum, Nadeem R.

    2016-01-01

    Objective To establish an algorithm that incorporates sentinel lymph node (SLN) mapping to the surgical treatment of early cervical cancer, ensuring that lymph node (LN) metastases are accurately detected but minimizing the need for complete lymphadenectomy (LND). Methods A prospectively maintained database of all patients who underwent SLN procedure followed by a complete bilateral pelvic LND for cervical cancer (FIGO stages IA1 with LVI to IIA) from 03/2003 to 09/2010 was analyzed. The surgical algorithm we evaluated included the following: 1. SLN are removed and submitted to ultrastaging; 2. Any suspicious LN is removed regardless of mapping; 3. If only unilateral mapping is noted, a contralateral side-specific pelvic LND is performed (including inter-iliac nodes); 4. Parametrectomy en bloc with primary tumor resection is done in all cases. We retrospectively applied the algorithm to determine how it would have performed. Results One hundred twenty-two patients were included. Median SLN count was 3 and median total LN count was 20. At least one SLN was identified in 93% of cases (114/122), while optimal (bilateral) mapping was achieved in 75% (91/122). SLN correctly diagnosed 21 of 25 patients with nodal spread. When the algorithm was applied, all pts with LN metastasis were detected and bilateral pelvic LND could have been spared in the 75% of cases with optimal mapping. Conclusions In the surgical treatment of early cervical cancer, the algorithm we propose allows for comprehensive detection of all patients with nodal disease and spares complete LND in the majority of cases. PMID:21570713

  11. Discordance of Intraoperative Frozen Section Analysis with Definitive Histology of Sentinel Lymph Nodes in Breast Cancer Surgery: Complementary Axillary Lymph Node Dissection is Irrelevant for Subsequent Systemic Therapy

    PubMed Central

    Geertsema, D.; Gobardhan, P. D.; Madsen, E. V. E.; Albregts, M.; van Gorp, J.; de Hooge, P.

    2010-01-01

    Background In breast cancer surgery, intraoperative frozen section (FS) analysis of sentinel lymph nodes (SLNs) enables axillary lymph node dissection (ALND) during the same operative procedure. In case of discordance between a “negative” FS analysis and definitive histology, an ALND as a second operation is advocated since additional lymph node metastases may be present. The clinical implications of the subsequent ALND in these patients were evaluated. Materials and Methods Between November 2000 and May 2008, 879 consecutive breast cancer patients underwent surgery including sentinel lymph node biopsy (SLNB) with intraoperative FS analysis of 2 central cuts from axillary SLNs. Following fixation and serial sectioning, SLNs were further examined postoperatively with hematoxylin and eosin (H&E) and immunohistochemical techniques. For patients with a discordant FS examination, the effect of the pathology findings of the subsequent ALND specimen on subsequent nonsurgical therapy were evaluated. Results FS analysis detected axillary metastases in the SLN(s) in 200 patients (23%), while the definitive pathology examination detected metastases in SLNs in another 151 patients (17%). A complementary ALND was performed in 108 of the 151 patients with discordant FS. Additional tumor positive axillary lymph nodes were found in 17 patients (16%), leading to “upstaging” in 7 (6%). Subsequent nonsurgical treatment was adjusted in 4 patients (4%): all 4 had more extensive locoregional radiotherapy; no patient received additional hormonal and/or chemotherapy. Conclusion Discordance between intraoperative FS analysis and definitive histology of SLNs is common. In this selection of patients, a substantial proportion had additional lymph node metastases, but postsurgical treatment was rarely adjusted based on the findings of the complementary ALND. PMID:20422461

  12. Significance of Matrix Metalloproteinase 9 Expression as Supporting Marker to Cytokeratin 19 mRNA in Sentinel Lymph Nodes in Breast Cancer Patients

    PubMed Central

    Murawski, Marek; Woźniak, Marta; Duś-Szachniewicz, Kamila; Kołodziej, Paweł; Rzeszutko, Marta; Ziółkowski, Piotr

    2016-01-01

    One-step nucleic acid amplification (OSNA) detects and quantifies, with the use of a polymerase chain reaction, the presence of cytokeratin 19 mRNA in sentinel lymph nodes. The main advantage of the OSNA assay is the avoidance of second surgery in case of positive sentinel lymph node diagnosis. The objective of this study was to evaluate the significance of matrix metalloproteinase 9 expression by immunohistochemistry as supporting marker to cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer patients and to relate this expression with clinicopathological data. This study was conducted on fresh sentinel lymph nodes obtained from 40 patients with tumors classified as carcinoma of no special type. The presence of metastatic cells in the slices of lymph nodes was evaluated by immunohistochemistry using antibodies for CK19 and MMP-9. Expression of CK19 and MMP-9 in lymph nodes was also confirmed by means of Western blot analysis. Results indicated that the strongest correlation with CK19 mRNA was displayed by MMP-9, CK19 (by immunohistochemistry, IHC), and nodal metastases (p < 0.001). Higher histological grading also positively correlated with CK19 mRNA, however that correlation was less significant. Since MMP-9 shows very strong correlation with CK19 mRNA in breast carcinoma of no special type metastases, expression of MMP-9 in sentinel lymph nodes should be considered as useful method whenever OSNA analysis is not available. PMID:27110764

  13. Scanning elastic scattering spectroscopy detects metastatic breast cancer in sentinel lymph nodes

    NASA Astrophysics Data System (ADS)

    Austwick, Martin R.; Clark, Benjamin; Mosse, Charles A.; Johnson, Kristie; Chicken, D. Wayne; Somasundaram, Santosh K.; Calabro, Katherine W.; Zhu, Ying; Falzon, Mary; Kocjan, Gabrijela; Fearn, Tom; Bown, Stephen G.; Bigio, Irving J.; Keshtgar, Mohammed R. S.

    2010-07-01

    A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20×20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.

  14. Breast Lymphatic Mapping and Sentinel Lymph Node Biopsy: State of the Art: 2015.

    PubMed

    Reintgen, Michael; Kerivan, Lauren; Reintgen, Eric; Swaninathan, Santosh; Reintgen, Douglas

    2016-06-01

    Lymphatic mapping with sentinel lymph node biopsy (SLNB) was introduced in the 1990s as a method to stage the nodal axilla in women with breast cancer. Very quickly the technique became the standard of care because pathologic staging was more accurate and sensitive and the surgical procedure resulted in low morbidity. SLNB has continued to evolve, and the applications in breast cancer have been expanded. A review of the published data was performed to update the lymphatic mapping technique and identify key issues and trends in the application of SLNB in women with breast cancer in 2015. The importance of axillary staging continues to effect the surgical treatment of patients with breast cancer. Originally described for patients with invasive cancer, the technique now plays an important role in staging women with ductal carcinoma in situ or recurrent breast cancer and patients with advanced breast cancer who are receiving neoadjuvant chemotherapy. Histologic examinations have incorporated multiple sectioning and immunostains. The morbidity has been low, and techniques for limiting lymphedema are being introduced. Lymphatic mapping will continue to play an important role in the treatment of women with breast cancer. The SLNB will evolve by eliminating the need for radioactivity in the operating room, and the technique will become more accurate and used in expanded indications by incorporating preoperative imaging and intraoperative guidance procedures. PMID:26952594

  15. Laparoscopic sentinel lymph node mapping after cervical injection of indocyanine green for endometrial cancer – preliminary report

    PubMed Central

    Reinholz-Jaskolska, Malgorzata; Bidzinski, Mariusz

    2015-01-01

    Introduction Endometrial cancer (EC) has an increasing incidence worldwide, with lymph node metastases as the main prognostic factor. Systemic lymphadenectomy is connected with elevated morbidity. Sentinel lymph node (SLN) biopsy is intended to avoid extensive lymphadenectomy and provide significant oncologic information. Aim To evaluate the accuracy of laparoscopic SLN biopsy guided by indocyanine green (ICG) injection into the cervix in EC patients and to develop ideas to improve this method. The optimal time from dye injection to lymph node visualization was assessed. Material and methods This retrospective study was conducted between July 2014 and March 2015 in a group of 9 women with EC, at low and intermediate risk of recurrence, scheduled for total laparoscopic hysterectomy and pelvic lymphadenectomy. All patients underwent cervical ICG injection and SLN biopsy, followed by surgery. Pelvic lymph nodes were located using an ICG endoscopic camera. Results The following data were collected: There were 9 patients with endometrial cancer at low and intermediate risk of recurrence. Median patient age was 59 years, median body mass index (BMI) 28 kg/m2, endometrioid adenocarcinoma in 9 cases, grading: G1 – 1 patient, G2 – 8 patients. No intraoperative or postoperative complications were noted. Median time from ICG injection and SLN detection during surgery was 25 min. There were no lymph nodes metastasis, all identified by the SLN protocol using ICG injection. Conclusions Sentinel lymph node mapping can play a significant role in lymph node assessment and staging in early-stage EC patients with low risk of recurrence according to the ESMO classification. The use of SLN mapping in EC is much needed and the therapeutic benefit is high. PMID:26649087

  16. Clinical usefulness of intradermal fluorescein and patent blue violet dyes for sentinel lymph node identification in dogs.

    PubMed

    Wells, S; Bennett, A; Walsh, P; Owens, S; Peauroi, J

    2006-06-01

    The first lymph node receiving drainage from a specific anatomic region is referred to as the sentinel lymph node (SLN). This study sought to evaluate the intradermal use of two dyes, patent blue violet (PBV) and fluorescein (FL), for SLN mapping in the dog. Multiple intradermal injections were performed in five healthy dogs using two dyes, PBV in 0.9% NaCl and FL in solutions of 0.9% NaCl and 6% hetastarch. Skin flaps were raised and followed to the first area of discrete stain uptake. Areas of uptake were identified as lymph nodes grossly and by cytology. Identification of a SLN for each area of intradermal injection was accomplished for 98% of the injection sites. Intradermal injections of both PBV and FL dyes produce readily visible staining of lymphatic vessels and SLNs in healthy dogs and are sufficient to allow ready identification of these structures during postmortem dissection. PMID:19754821

  17. Locoregional treatment of early breast cancer with isolated tumor cells or micrometastases on sentinel lymph node biopsy

    PubMed Central

    Tallet, Agnès; Lambaudie, Eric; Cohen, Monique; Minsat, Mathieu; Bannier, Marie; Resbeut, Michel; Houvenaeghel, Gilles

    2016-01-01

    The advent of sentinel lymph-node technique has led to a shift in lymph-node staging, due to the emergence of new entities namely micrometastases (pN1mi) and isolated tumor cells [pN0(i+)]. The prognostic significance of this low positivity in axillary lymph nodes is currently debated, as is, therefore its management. This article provides updates evidence-based medicine data to take into account for treatment decision-making in this setting, discussing the locoregional treatment in pN0(i+) and pN1mi patients (completion axillary dissection, axillary irradiation with or without regional nodes irradiation, or observation), according to systemic treatment, with the goal to help physicians in their daily practice. PMID:27081647

  18. Quantitative Molecular Analysis of Sentinel Lymph Node May Be Predictive of Axillary Node Status in Breast Cancer Classified by Molecular Subtypes

    PubMed Central

    Buglioni, Simonetta; Di Filippo, Franco; Terrenato, Irene; Casini, Beatrice; Gallo, Enzo; Marandino, Ferdinando; Maini, Carlo L.; Pasqualoni, Rossella; Botti, Claudio; Di Filippo, Simona; Pescarmona, Edoardo; Mottolese, Marcella

    2013-01-01

    To determine the performance of intraoperative one-step nucleic acid amplification (OSNA) assay in detecting sentinel lymph node metastases compared to postoperative histology taking into account breast cancer molecular classification and to evaluate whether the level of cytokeratin 19 mRNA copy number may be useful in predicting the likelihood of a positive axillary lymph node dissection. OSNA assay was performed in a prospective series of 903 consecutive sentinel lymph nodes from 709 breast cancer patients using 2 alternate slices of each sentinel lymph node. The remaining 2 slices were investigated by histology. Cytokeratin 19 mRNA copy number, which distinguishes negative cases (<250 copies), micrometastases (+, ≥250≤5000 copies) and macrometastases (++, >5000 copies), was compared to axillary lymph node dissection status and to the biological tumor profile. Concordance between OSNA and histopathology was 95%, specificity 95% and sensitivity 93%. Multiple Corresponce Analysis and logistic regression evidenced that positive axillary lymph node dissection was significantly associated with a higher cytokeratin 19 mRNA copy number (>5000; p<0.0001), HER2 subtype (p = 0.007) and lymphovascular invasion (p<0.0001). Conversely, breast cancer patients with cytokeratin 19 mRNA copy number <2000 mostly presented a luminal subtype and a negative axillary lymph node dissection. We confirmed that OSNA assay can provide standardized and reproducible results and that it represents a fast and quantitative tool for intraoperative evaluation of sentinel lymph node. Omission of axillary lymph node dissection could be proposed in patients presenting a sentinel lymph node with a cytokeratin 19 mRNA copy number <2000 and a Luminal tumor phenotype. PMID:23533593

  19. Detection of MAGE-A3 in breast cancer patients’ sentinel lymph nodes

    PubMed Central

    Wascher, R A; Bostick, P J; Huynh, K T; Turner, R; Qi, K; Giuliano, A E; Hoon, D S B

    2001-01-01

    The detection of occult metastatic breast cancer cells by RT-PCR is limited by the poor specificity of most tumour mRNA markers. MAGE-A3 is a highly specific tumour mRNA marker that is not expressed in non-cancer cells. This study assesses MAGE-A3 mRNA as a molecular marker for the detection of tumour cells in the sentinel lymph nodes (SLN) of breast cancer patients. Serial frozen sections of SLN (n= 121) were obtained from 77 AJCC (American Joint Committee on Cancer) Stage I–IIIA breast cancer patients. MAGE-A3 mRNA analysis of SLN was performed by RT-PCR and Southern blot analysis. Tumour cells were detected in 48 of 121 (40%) SLN from 77 patients by H&E or IHC staining, and 35 of 77 (45%) patients, overall, had histopathologically (H&E and/or IHC) positive SLN. Among histopathologically negative SLN, 28 of 73 (38%) SLN were MAGE-A3 mRNA positive by RT-PCR. Overall, 41 of 77 (53%) patients and 50 of 121 (41%) SLN were positive for MAGE-A3. MAGE-A3 mRNA expression in the SLN occurred more frequently with infiltrating lobular carcinoma (P< 0.001) than with infiltrating ductal carcinoma, adding further evidence of possible phenotypic differences between these 2 subtypes of breast cancer. Due to its high specificity, MAGE-A3 mRNA is a potentially useful marker for detecting breast cancer cells in the SLN. One half of breast tumours expressed MAGE-A3 mRNA, which has important potential implications for antigen-specific targeted immunotherapy. © 2001 Cancer Research Campaign PMID:11720472

  20. Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer

    PubMed Central

    Schaafsma, Boudewijn E.; Verbeek, Floris P.R.; Rietbergen, Daphne D.D.; van der Hiel, Bernies; van der Vorst, Joost R.; Liefers, Gerrit-Jan; Frangioni, John V.; van de Velde, Cornelis J.H.; van Leeuwen, Fijs W.B.; Vahrmeijer, Alexander L.

    2013-01-01

    Background Combining radioactive colloids and a near-infrared (NIR) fluorophore permit preoperative planning and intraoperative localization of deeply located sentinel lymph nodes (SLNs) with direct optical guidance by a single lymphatic tracer. The aim of this clinical trial was to evaluate and optimize a hybrid NIR fluorescence and radioactive tracer for SLN detection in breast cancer patients. Method Patients with breast cancer undergoing SLN biopsy were enrolled. The day before surgery, indocyanine green (ICG)-99mTc-Nanocolloid was injected periareolarly and a lymphoscintigram was acquired. Directly before surgery, blue dye was injected. Intraoperative SLN localization was performed by a gamma probe and the Mini-FLARETM NIR fluorescence imaging system. Patients were divided into two dose groups, with one group receiving twice the particle density of ICG and nanocolloid, but the same dose of radioactive 99mTechnetium. Results Thirty-two patients were enrolled in the trial. At least one SLN was identified pre- and intraoperatively. All 48 axillary SLNs could be detected by gamma tracing and NIR fluorescence imaging, but only 42 of them stained blue. NIR fluorescence permitted detection of lymphatic vessels draining to the SLN up to 29 hours after injection. Increasing the particle density by two-fold did not yield a difference in fluorescence intensity, median 255 (range 98 – 542) vs. median 284 (90 – 921; P = 0.590), or signal- to- background ratio, median 5.4 (range 3.0 – 15.4) vs. median 4.9 (3.5 – 16.3; P = 1.000), of the SLN. Conclusion The hybrid NIR fluorescence and radioactive tracer ICG-99mTc-Nanocolloid permitted accurate pre- and intraoperative detection of the SLNs in patients with breast cancer. PMID:23696463

  1. Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience

    PubMed Central

    Verbeek, Floris P.R.; Troyan, Susan L.; Mieog, J. Sven D.; Liefers, Gerrit-Jan; Moffitt, Lorissa A.; Rosenberg, Mireille; Hirshfield-Bartek, Judith; Gioux, Sylvain; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.; Frangioni, John V.

    2014-01-01

    NIR fluorescence imaging using indocyanine green (ICG) has the potential to improve the SLN procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 ml of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of near-infrared (NIR) fluorescence for sentinel lymph node (SLN) mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using 99Technetium-colloid in all subjects and patent blue in 27 (28%) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99%) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean = 1.9, range = 1–5) were resected: 100% NIR fluorescent, 88% radioactive, and 78% (of 40 nodes) blue. In 2 of 95 subjects (2.1%), SLNs containing macrometastases were found only by NIR fluorescence, and in 1 patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies. PMID:24337507

  2. Sentinel lymph node biopsy can be omitted in DCIS patients treated with breast conserving therapy.

    PubMed

    van Roozendaal, L M; Goorts, B; Klinkert, M; Keymeulen, K B M I; De Vries, B; Strobbe, L J A; Wauters, C A P; van Riet, Y E; Degreef, E; Rutgers, E J T; Wesseling, J; Smidt, M L

    2016-04-01

    Breast cancer guidelines advise sentinel lymph node biopsy (SLNB) in patients with ductal carcinoma in situ (DCIS) on core biopsy at high risk of invasive cancer or in case of mastectomy. This study investigates the incidence of SLNB and SLN metastases and the relevance of indications in guidelines and literature to perform SLNB in order to validate whether SLNB is justified in patients with DCIS on core biopsy in current era. Clinically node negative patients diagnosed from 2004 to 2013 with only DCIS on core needle biopsy were selected from a national database. Incidence of SLN biopsy and metastases was calculated. With Fisher exact tests correlation between SLNB indications and actual presence of SLN metastases was studied. Further, underestimation rate for invasive cancer and correlation with SLN metastases was analysed. 910 patients were included. SLNB was performed in 471 patients (51.8 %): 94.5 % had pN0, 3.0 % pN1mi and 2.5 % pN1. Patients undergoing mastectomy had 7 % SLN metastases versus 3.5 % for breast conserving surgery (BCS) (p = 0.107). The only factors correlating to SLN metastases were smaller core needle size (p = 0.01) and invasive cancer (p < 0.001). Invasive cancer was detected in 16.7 % by histopathology with 15.6 % SLN metastases versus only 2 % in pure DCIS. SLNB showed metastases in 5.5 % of patients; 3.5 % in case of BCS (any histopathology) and 2 % when pure DCIS was found at definitive histopathology (BCS and mastectomy). Consequently, SLNB should no longer be performed in patients diagnosed with DCIS on core biopsy undergoing BCS. If definitive histopathology shows invasive cancer, SLNB can still be considered after initial surgery. PMID:27083179

  3. Desmoplastic melanoma of the eyelid and conjunctival melanoma in neurofibromatosis type 1: a clinical pathological correlation.

    PubMed

    Rubinstein, Tal J; Plesec, Thomas P; Singh, Arun D

    2015-01-01

    A 56-year-old woman with neurofibromatosis type 1 (NF1) presented with a left upper eyelid amelanotic nodule with adjacent eyelid margin hyperpigmentation. Physical examination additionally revealed primary acquired melanosis (PAM) on the palpebral conjunctiva of the same eyelid. Full thickness eyelid excision and conjunctival map biopsy identified desmoplastic melanoma of the eyelid in addition to invasive conjunctival melanoma and conjunctival melanoma in situ. Sentinel lymph node biopsy was negative for metastasis. She was treated with surgical excision for the eyelid melanoma and topical mitomycin C for the conjunctival melanoma. We discuss the rare entity of desmoplastic melanoma of the eyelid and its possible association with NF1. PMID:25233828

  4. A dual-reporter fluorescent imaging approach can be used to estimate sentinel lymph node tumor burden

    NASA Astrophysics Data System (ADS)

    Tichauer, Kenneth M.; Samkoe, Kimberley S.; Gunn, Jason R.; Govindan, Ramesh; Viswanathan, Aravind; Hoopes, P. Jack; Hasan, Tayyaba; Kaufman, Peter A.; Pogue, Brian W.

    2013-03-01

    The presence of metastatic tumor cells in tumor-draining lymph nodes is an important indicator for cancer staging and therapy. Current clinical approaches of assessing lymph node tumor burden require invasive surgery that can be associated with nerve damage and other complications. In this study, a dual-reporter fluorescence molecular imaging approach, previously validated for quantifying targeted reporter binding in various human tumor xenographs, was assessed as a means of quantifying tumor burden in metastatic disease in mice. The utility of the dual-reporter imaging approach to measure tumor burden in sentinel lymph nodes was investigated in a bioluminescent human breast cancer xenograph model in 18 female nude mice. Once the presence of tumor in the lymph node was confirmed by bioluminescent imaging, fluorescently labeled anti-EGFR antibody and an untargeted antibody (labeled with a different fluorophore) were injected intradermally, proximal to the lymph node, and the uptake of the two reporters was imaged simultaneously with a with a flat-panel fluorescent scanner. Preliminary results demonstrated a statistically significant correlation between the dual-reporter measured tumor burden and the bioluminescent measure of tumor burden.

  5. TOPICAL REVIEW (Non-targeted) radioactive/fluorescent nanoparticles and their potential in combined pre- and intraoperative imaging during sentinel lymph node resection

    NASA Astrophysics Data System (ADS)

    Buckle, Tessa; Chin, Patrick T. K.; van Leeuwen, Fijs W. B.

    2010-12-01

    One clinical precedent for the use of nanosized imaging agents is the localization of the tumor draining sentinel lymph nodes. In this application, radiocolloids such as 99mTc-NanoColl are currently used to plan the surgical procedure and to provide acoustic guidance during the intervention. Additional injections of dyes are common to provide optical surgical guidance. Bimodal imaging agents, which are both radioactive and fluorescent, have the potential to be used for both surgical planning and intraoperative fluorescence guidance towards the sentinel lymph nodes. This review provides an overview of the radioactive, fluorescent, and size properties of (non-targeted) bimodal nanoparticles, and their (potential) value in sentinel lymph node detection.

  6. Treatment Options by Stage (Melanoma)

    MedlinePlus

    ... and treatments will also be taken. Lymph node mapping and sentinel lymph node biopsy : Procedures in which ... has spread to the lymph nodes . Lymph node mapping and sentinel lymph node biopsy are done to ...

  7. Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

    NASA Astrophysics Data System (ADS)

    Qin, Zhengtao

    Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

  8. Sentinel lymph node detection in breast cancer patients using surgical navigation system based on fluorescence molecular imaging technology

    NASA Astrophysics Data System (ADS)

    Chi, Chongwei; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Tian, Jie

    2015-03-01

    Introduction: Precision and personalization treatments are expected to be effective methods for early stage cancer studies. Breast cancer is a major threat to women's health and sentinel lymph node biopsy (SLNB) is an effective method to realize precision and personalized treatment for axillary lymph node (ALN) negative patients. In this study, we developed a surgical navigation system (SNS) based on optical molecular imaging technology for the precise detection of the sentinel lymph node (SLN) in breast cancer patients. This approach helps surgeons in precise positioning during surgery. Methods: The SNS was mainly based on the technology of optical molecular imaging. A novel optical path has been designed in our hardware system and a feature-matching algorithm has been devised to achieve rapid fluorescence and color image registration fusion. Ten in vivo studies of SLN detection in rabbits using indocyanine green (ICG) and blue dye were executed for system evaluation and 8 breast cancer patients accepted the combination method for therapy. Results: The detection rate of the combination method was 100% and an average of 2.6 SLNs was found in all patients. Our results showed that the method of using SNS to detect SLN has the potential to promote its application. Conclusion: The advantage of this system is the real-time tracing of lymph flow in a one-step procedure. The results demonstrated the feasibility of the system for providing accurate location and reliable treatment for surgeons. Our approach delivers valuable information and facilitates more detailed exploration for image-guided surgery research.

  9. Sentinel Lymph Node Navigation Surgery for Early Gastric Cancer: Is It a Safe Procedure in Countries with Non-Endemic Gastric Cancer Levels? A Preliminary Experience

    PubMed Central

    Dos Santos, Elizabeth Gomes; Victer, Felipe Carvalho; Neves, Marcelo Soares; Pinto, Márcia Ferreira; Carvalho, Carlos Eduardo De Souza

    2016-01-01

    Purpose Early diagnosis of gastric cancer is still the exception in Western countries. In the East, as in Japan and Korea, this disease is an endemic disorder. More conservative surgical procedures are frequently performed in early gastric cancer cases in these countries where sentinel lymph node navigation surgery is becoming a safe option for some patients. This study aims to evaluate preliminary outcomes of patients with early gastric cancer who underwent sentinel node navigation surgeries in Brazil, a country with non-endemic gastric cancer levels. Materials and Methods From September 2008 to March 2014, 14 out of 205 gastric cancer patients underwent sentinel lymph node navigation surgeries, which were performed using intraoperative, endoscopic, and peritumoral injection of patent blue dye. Results Antrectomies with Billroth I gastroduodenostomies were performed in seven patients with distal tumors. The other seven patients underwent wedge resections. Sentinel basin resections were performed in four patients, and lymphadenectomies were extended to stations 7, 8, and 9 in the other 10. Two patients received false-negative results from sentinel node biopsies, and one of those patients had micrometastasis. There was one postoperative death from liver failure in a cirrhotic patient. Another cirrhotic patient died after two years without recurrence of gastric cancer, also from liver failure. All other patients were followed-up for 13 to 79 months with no evidence of recurrence. Conclusions Sentinel lymph node navigation surgery appears to be a safe procedure in a country with non-endemic levels of gastric cancer. PMID:27104022

  10. 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

  11. γ-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph Nodes, Binds to the Mannose Receptor (CD206)

    PubMed Central

    Azad, Abul K.; Rajaram, Murugesan V. S.; Metz, Wendy L.; Cope, Frederick O.; Blue, Michael S.; Vera, David R.

    2015-01-01

    γ-Tilmanocept (99mTc-labeled-tilmanocept or [99mTc]-tilmanocept) is the first mannose-containing, receptor-directed, radiolabeled tracer for the highly sensitive imaging of sentinel lymph nodes in solid tumor staging. To elucidate the mannose-binding receptor that retains tilmanocept in this microenvironment, human macrophages were used that have high expression of the C-type lectin mannose receptor (MR; CD206). Cy3-labeled tilmanocept exhibited high specificity binding to macrophages that was nearly abolished in competitive inhibition experiments. Furthermore, Cy3-tilmanocept binding was markedly reduced on macrophages deficient in the MR by small interfering RNA treatment and was increased on MR-transfected HEK 293 cells. Finally, confocal microscopy revealed colocalization of Cy3-tilmanocept with the macrophage membrane MR and binding of labeled tilmanocept to MR+ cells (macrophages and/or dendritic cells) in human sentinel lymph node tissues. Together these data provide strong evidence that CD206 is a major binding receptor for γ-tilmanocept. Identification of CD206 as the γ-tilmanocept–binding receptor enables opportunities for designing receptor-targeted advanced imaging agents and therapeutics for cancer and other diseases. PMID:26202986

  12. Current concepts of metastasis in melanoma

    PubMed Central

    Zbytek, Blazej; Carlson, J Andrew; Granese, Jacqueline; Ross, Jeffrey; Mihm, Martin C; Slominski, Andrzej

    2008-01-01

    The main cause of death in melanoma patients is widespread metastases. Staging of melanoma is based on the primary tumor thickness, ulceration, lymph node and distant metastases. Metastases develop in regional lymph nodes, as satellite or in-transit lesions, or in distant organs. Lymph flow and chemotaxis is responsible for the homing of melanoma cells to different sites. Standard pathologic evaluation of sentinel lymph nodes fails to find occult melanoma in a significant proportion of cases. Detection of small numbers of malignant melanoma cells in these and other sites, such as adjacent to the primary site, bone marrow or the systemic circulation, may be enhanced by immunohistochemistry, reverse transcription PCR, evaluation of lymphatic vessel invasion and proteomics. In the organs to which melanoma cells metastasize, extravasation of melanoma cells is regulated by adhesion molecules, matrix metalloproteases, chemokines and growth factors. Melanoma cells may travel along external vessel lattices. After settling in the metastatic sites, melanoma cells develop mechanisms that protect them against the attack of the immune system. It is thought that one of the reasons why melanoma cells are especially resistant to killing is the fact that melanocytes (cells from which melanoma cells derive) are resistant to such noxious factors as ultraviolet light and reactive oxygen species. Targeted melanoma therapies are, so far, largely unsuccessful, and new ones, such as adjuvant inhibition of melanogenesis, are under development. PMID:19649148

  13. The use of 99mTc-Al2O3 for detection of sentinel lymph nodes in breast cancer

    NASA Astrophysics Data System (ADS)

    Sinilkin, I.; Chernov, V.; Medvedeva, A.; Zeltchan, R.; Slonimskaya, E.; Doroshenko, A.; Varlamova, N.; Skuridin, V.

    2016-08-01

    Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n = 34) were injected with radioactive 99mTc-Al2O3, and Group II patients (n = 30) received 99mTc-labeled phytate colloid. A total of 37 SLNs were detected in Group I patients. The number of identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. 18 hours after 99mTc-Al2O3 injection, the percentage of its accumulation in the SLN was 7-11% (of the counts in the injection site) by SPECT and 17-31% by gamma probe detection. In Group II SLNs were detected in 27 patients. 18 hours after injection of the phytate colloid the percentage of its accumulation in the SLN was 1.5-2% out of the counts in the injection site by SPECT and 4-7% by gamma probe. The new radiopharmaceutical based on the 99mTc-Al2O3 demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. The sensitivity and specificity of 99mTc-Al2O3 were 100% for both SPECT and intraoperative gamma probe identification.

  14. P16 protein expression in primary cutaneous melanoma with positive and negative lymph node biopsies: Particular aspects of a study performed at the Hospital de Clinicas de Porto Alegre, Brazil

    PubMed Central

    Fauri, JAC; Ricardi, F; Diehl, ES; Cartell, A; Furian, R; Bakos, L; Edelweiss, MI

    2011-01-01

    BACKGROUND: Cutaneous melanoma dermal invasion, identified through measurement of maximum tumour thickness and sentinel lymph node (SLN) biopsy, is important to establish melanoma prognosis and progression. P16 protein expression has been shown to be a predictive factor for melanoma evolution and prognosis. OBJECTIVE: To investigate p16 protein expression in cutaneous melanomas with and without SLN metastasis. PATIENTS AND METHODS: Sixty-seven paraffin-embedded cutaneous melanoma specimens of patients who had undergone SLN investigation were evaluated from 1995 to 2007. SLN biopsy was negative for metastasis in 34 of these patients (controls); in the remaining 33 patients, SLN biopsy was positive (cases). The expression of p16 protein in the primary tumour was measured using an immunohistochemical assay. The samples were classified according to their nuclear expression. RESULTS: P16 nuclear expression was absent in 14 cases and in 15 controls; P=0.812. There was no statistically significant difference in p16 nuclear expression between cases and controls. CONCLUSIONS: The present study does not support the findings of other studies that suggest p16 protein expression is important in the prognosis of cutaneous melanoma. PMID:22942654

  15. Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma.

    PubMed

    Saito, Yoichi; Ohnishi, Koji; Miyashita, Azusa; Nakahara, Satoshi; Fujiwara, Yukio; Horlad, Hasita; Motoshima, Takanobu; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu; Takeya, Motohiro; Komohara, Yoshihiro

    2015-12-01

    CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggest that CD169(+) macrophages in lymph nodes have properties in preventing cancers. In order to determine the significance of CD169(+) macrophages in patients with malignant melanoma, we evaluated tissue samples from 93 patients to investigate CD169 expression in regional lymph nodes (RLN) and determine the relationship of this expression with overall survival and various clinicopathologic factors. Higher densities of CD169(+) cells were significantly associated with longer overall survival (P = 0.001). A multivariate analysis showed that the density of CD169(+) cells was an independent prognostic factor, with higher densities correlating with higher density of CD8(+) cytotoxic T cells within tumor sites. High CD169 expression in macrophages could be stimulated by IFNα in vitro, and in RLNs, IFNα-producing macrophages and CD303(+) plasmacytoid dendritic cells were identified surrounding CD169(+) macrophages. These data suggest that IFNα-stimulated CD169(+) macrophages in RLNs are closely involved in T-cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant melanoma. PMID:26297710

  16. A quantitative reverse transcription-PCR assay for rapid, automated analysis of breast cancer sentinel lymph nodes.

    PubMed

    Hughes, Steven J; Xi, Liqiang; Gooding, William E; Cole, David J; Mitas, Michael; Metcalf, John; Bhargava, Rohit; Dabbs, David; Ching, Jesus; Kozma, Lynn; McMillan, William; Godfrey, Tony E

    2009-11-01

    We have previously reported that a quantitative reverse transcription (QRT)-PCR assay accurately analyzes sentinel lymph nodes (SLNs) from breast cancer patients. The aim of this study was to assess a completely automated, cartridge-based version of the assay for accuracy, predictive value, and reproducibility. The triplex (two markers + control) QRT-PCR assay was incorporated into a single-use cartridge for point-of-care use on the GeneXpert system. Three academic centers participated equally. Twenty-nine positive lymph nodes and 30 negative lymph nodes were analyzed to establish classification rules. SLNs from 120 patients were subsequently analyzed by QRT-PCR and histology (including immunohistochemistry), and the predetermined decision rules were used to classify the SLNs; 112 SLN specimens produced an informative result by both QRT-PCR and histology. By histological analysis, 21 SLNs were positive and 91 SLNs were negative for metastasis. QRT-PCR characterization produced a classification with 100% sensitivity, 97.8% specificity, and 98.2% accuracy compared with histology (91.3% positive predictive value and 100% negative predictive value). Interlaboratory reproducibility analyses demonstrated that a 95% prediction interval for a new measurement (DeltaCt) ranged between 0.403 and 0.956. This fully automated QRT-PCR assay accurately characterizes breast cancer SLNs for the presence of metastasis. Furthermore, the assay is not dependent on subjective interpretation, is reproducible across three clinical environments, and is rapid enough to allow intraoperative decision making. PMID:19797614

  17. Sentinel lymph node biopsy revisited: ultrasound-guided photoacoustic detection of micrometastases using molecularly targeted plasmonic nanosensors

    PubMed Central

    Luke, Geoffrey P.; Myers, Jeffrey N.; Emelianov, Stanislav Y.; Sokolov, Konstantin V.

    2014-01-01

    Metastases rather than primary tumors are responsible for killing most cancer patients. Cancer cells often invade regional lymph nodes (LN) before colonizing other parts of the body. However, due to the low sensitivity and specificity of current imaging methods to detect localized nodal spread, an invasive surgical procedure - sentinel lymph node biopsy - is generally employed to identify metastatic cancer cells. Here we introduce a new approach for more sensitive in vivo detection of lymph node micrometastases, based on the use of ultrasound-guided spectroscopic photoacoustic (sPA) imaging of molecularly-activated plasmonic nanosensors (MAPS). Using a metastatic murine model of oral squamous cell carcinoma, we showed that MAPS targeted to the EGFR shifted their optical absorption spectrum to the red-near-infrared region after specific interactions with nodal metastatic cells, enabling their non-invasive detection by sPA. Notably, LN metastases as small as 50 μm were detected at centimeter-depth range with high sensitivity and specificity. Large sPA signals appeared in metastatic LN within 30 minutes of MAPS injection, in support of the clinical utility of this method. Our findings offer a rapid and effective tool to non-invasively identify micrometastases as an alternate to sentinal node biopsy analysis. PMID:25106426

  18. Diagnostic Performance of Indocyanine Green-Guided Sentinel Lymph Node Biopsy in Breast Cancer: A Meta-Analysis

    PubMed Central

    Zhou, Yidong; Mao, Feng; Lin, Yan; Guan, Jinghong; Sun, Qiang

    2016-01-01

    Background The diagnostic performance of indocyanine green (ICG) fluorescence-guided sentinel lymph node biopsy (SLNB) for the presence of metastases in breast cancer remains unclear. Objective We performed a meta-analysis to investigate the diagnostic performance of ICG-guided SLNB. Methods Eligible studies were identified from searches of the databases PubMed and EMBASE up to September 2015. Studies that reported the detection rate of ICG fluorescence-guided SLNB with full axillary lymph node dissection and histological or immunohistochemical examinations were included. A meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, false negative rate, diagnostic odds ratio (DOR) and a summary receiver operator characteristic curve (SROC). Results Nineteen published studies were included to generate a pooled detection rate, comprising 2594 patients. The pooled detection rate was 0.98 (95% confidence interval [CI], 0.96–0.99). Six studies finally met the criteria for meta-analysis, which yielded a pooled sensitivity of 0.92 (95% CI, 0.85–0.96), specificity 1 (95% CI, 0.97–1), and DOR 311.47 (95% CI, 84.11–1153.39). The area under the SROC was 0.9758. No publication bias was found. Conclusion ICG fluorescence-guided SLNB is viable for detection of lymph node metastases in breast cancer. Large-scale randomized multi-center trials are necessary to confirm our results. PMID:27280407

  19. The Study of 99mTc-Aluminum Oxide Using for Sentinel Lymph Nodes Detection in Experiment

    NASA Astrophysics Data System (ADS)

    Medvedeva, A. A.; Sinilkin, I. G.; Zelchan, R. V.; Chernov, V. I.; Lyapunov, A. Yu.; Bragina, O. D.; Varlamova, N. V.; Skuridin, V. S.; Dergilev, A. P.

    2016-06-01

    The purpose of the study was a comparative research of the possibility of using the radiopharmaceuticals 99mTc-Al2O3 and 99mTc-Nanocis for visualizing sentinel lymph nodes in the experiment. Measurement of the sizes of 99mTc-Al2O3 and 99mTc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. Pharmacokinetics of 99mTc-Al2O3 and 99mTc-Nanocis was researched on 50 white male rats. The possibility of the use of 99mTc-Al2O3 and 99mTc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. Average dynamic diameter of the sol particle was 52-77 nm for 99mTc-Al2O3 and 16.7-24.5 nm for 99mTc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node - at 1 hour after administration the average uptake of 99mTc-Al2O3 was 8.6% in it and the accumulation of 99mTc-Nanocis was significantly lower - 1,8% (p <0,05). In all study point average uptake of 99mTc-Al2O3 in the lymph node was significantly higher 99mTc-Nanocis accumulation. The results dynamic scintigraphic studies in rats showed that 99mTc-Al2O3 and 99mTc-Nanocis actively accumulated into the lymphatic system. By using 99mTc-Al2O3 inguinal lymph node was determined in 5 minutes after injection and clearly visualize in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the 99mTc-Al2O3 accumulation reaches a plateau in a lymph node (average 10.5%) for 2 hour study and then its accumulation remains practically at the same level, slightly increasing to 12% at 24 hours. In the case of 99mTc-Nanocis inguinal lymph node visualized in all animals for 15 minutes when it was accumulated on the average 1.03% of the administered dose. Plateau of 99mTc-Nanocis accumulation in the lymph node (average 2.05%) occurred at 2 hour of the study and remained almost on the same level (in average 2.3%) to 24 hours. Thus, the experimental study of a new domestic radiopharmaceutical showed

  20. One-step nucleic acid amplification assay for intraoperative prediction of advanced axillary lymph node metastases in breast cancer patients with sentinel lymph node metastasis

    PubMed Central

    KUBOTA, MICHIYO; KOMOIKE, YOSHIFUMI; HAMADA, MIKA; SHINZAKI, WATARU; AZUMI, TATSUYA; HASHIMOTO, YUKIHIKO; IMOTO, SHIGERU; TAKEYAMA, YOSHIFUMI; OKUNO, KIYOTAKA

    2016-01-01

    The one-step nucleic acid amplification (OSNA) assay is used to semiquantitatively measure the cytokeratin (CK)19 mRNA copy numbers of each sentinel lymph node (SLN) in breast cancer patients. The aim of the present study was to evaluate whether the diagnosis of ≥4 LN metastases is possible using the OSNA assay intraoperatively. Between May, 2010 and December, 2014, a total of 134 patients who underwent axillary lymph node dissection (ALND) of positive SLNs were analyzed. The total tumor load (TTL) was defined as the total CK19 mRNA copies of all positive SLNs. The correlation between TTL and ≥4 LN metastases was evaluated. Of the 134 patients, 31 (23.1%) had ≥4 LN metastases. TTL ≥5.4×104 copies/µl evaluated by receiver operator characteristic curve analysis was examined along with other clinicopathological variables. In the multivariate analysis, only TTL ≥5.4×104 copies/µl was correlated with ≥4 LN metastases (odds ratio = 2.95, 95% confidence interval: 1.17–7.97, P=0.022). Therefore, TTL assessed by the OSNA assay has the potential to be a predictor of ≥4 LN metastases and it may be useful for the selection of patients with positive SLNs in whom ALND may be safely omitted. PMID:26893855

  1. Sentinel lymph node biopsy using indigo carmine blue dye and the validity of '10% rule' and '4 nodes rule'.

    PubMed

    Nagao, Tomoya; Kinoshita, Takayuki; Hojo, Takashi; Kurihara, Hiroaki; Tsuda, Hitoshi

    2012-08-01

    This is the study which assessed sentinel lymph node biopsy (SNB) using indigo carmine blue dye and the validity of the '10% rule' and '4 nodes rule'. Patients (302) were performed SNB using the combined radioisotope (RI)/indigo carmine dye method. Excised SLNs were confirmed whether they were stained and numbered in order of RI count and the percentage of radioactivity as compared to the hottest node was calculated. The relationship between histological diagnosis, dyeing and RI count was assessed. All the patients were detected SLN. Positive nodes were identified in 84 (27.8%) patients and were identified up to the third degree of hottest. All the hottest positive nodes were stained by indigo carmine. From the results, removing the three most radioactive SLNs identified all cases of nodal metastasis without complications. These stopping rules were valid and useful under indigo carmine use too. PMID:22119457

  2. In vivo non-ionizing photoacoustic mapping of sentinel lymph nodes and bladders with ICG-enhanced carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Koo, Jasung; Jeon, Mansik; Oh, Yunok; Kang, Hyun Wook; Kim, Jeehyun; Kim, Chulhong; Oh, Junghwan

    2012-12-01

    We demonstrate the feasibility of mapping a sentinel lymph node (SLN) and urinary bladder by using modified single-walled carbon nanotubes (SWNTs) as a nonionizing photoacoustic (PA) contrast agent. To improve the PA sensitivity, indocyanine green (ICG) was conjugated with SWNTs and the optical absorption of SWNTs-ICG was enhanced by approximately four times compared to that of plain SWNTs at a concentration of 0.3 µM. In vivo PA imaging results showed that the SLN and bladder were clearly visualized due to accumulation of SWNTs-ICG. This implies that the SWNTs-ICG could be potentially utilized to identify SLNs in breast cancer patients and tracking vesicoureteral reflux in combination with PA imaging.

  3. Sentinel lymph node biopsy in T1/T2 squamous cell carcinomas of the tongue: A prospective study

    PubMed Central

    SAGHEB, KEYVAN; SAGHEB, KAWE; RAHIMI-NEDJAT, ROMAN; TAYLOR, KATHY; AL-NAWAS, BILAL; WALTER, CHRISTIAN

    2016-01-01

    Commonly used staging procedures often cannot predict the absence of cervical metastases (CM) in squamous cell carcinomas (SCCs) of the oral cavity. Due to the high incidence of occult CM in numerous N0 cases in the clinic, an elective neck dissection (ND) is performed. The sentinel lymph node biopsy (SNB) is a common concept in the modern surgical therapy of malignancies. The present study evaluates the applicability of this concept for T1/T2-SCC of the tongue. In a prospective clinical study, 10 consecutive patients with T1/T2-SCC of the tongue and cN0 necks, were enrolled. Following sentinel lymph node (SLN) scintigraphy, all patients underwent SNB with a γ-probe and a subsequent ND. SNB specimens were compared with histopathological assessments of surgical specimens from the ND. A total of 5 female and 5 male patients (mean age, 52 years; women, 62 years; men, 42 years), with a median follow-up time of 33.5 months (range, 10–40 months), were treated. All patients presented with detectable SLNs. In 7 cases, the SLN(s) and the residual ND were negative for CM. In 3 cases, the SLN(s) were positive without further CM in the other neck nodes. Furthermore, 1 patient showed additional CMs after 10 months in the contralateral neck and lung metastasis after 18 months, but none at the time of the initial treatment. The concept of an SNB appears to be applicable to the management of the cN0 neck in small SCC of the tongue. The role of SNB in the management of SCC requires further investigation by prospective trials with larger patient numbers. PMID:26870253

  4. Malignant potential of cells isolated from lymph node or brain metastases of melanoma patients and implications for prognosis.

    PubMed

    Zhang, R D; Price, J E; Schackert, G; Itoh, K; Fidler, I J

    1991-04-15

    We studied the correlation between the formation of brain metastasis and the malignant growth potential of seven human melanoma cell lines, isolated from lymph node metastases (A375-SM, TXM-1, DM-4) or from brain metastases (TXM-13, TXM-18, TXM-34, TXM-40), and the potential of three variants of the mouse K-1735 melanoma. Growth rates in different concentrations of fetal bovine serum and colony-forming efficiency in semisolid agarose were measured, and the tumorigenicity and metastatic ability were determined in nude mice (for the human melanoma cell lines) or in C3H/HeN mice (for the K-1735 variants). The ability to form brain metastasis was tested by injection of cells into the carotid artery. A high colony-forming efficiency in agarose, especially at concentrations of agarose greater than 0.6%, corresponded with high tumor take rates, rapid tumor growth rates, and metastatic colonization of the lungs of the recipient mice. For the human melanomas, the lymph node metastasis-derived cells were more tumorigenic and metastatic than the brain metastasis-derived cells. In the K-1735 mouse melanoma, the tumorigenic and metastatic behavior of the cells after i.v. and s.c. injection corresponded with growth in agarose cultures. However, for growth in the brain after intracarotid injection, the different melanoma cell lines showed similar frequencies of tumor take, regardless of tumorigenicity in other sites of the recipient mice, although mice given injections of brain metastasis-derived cells survived longer than mice given injections of lymph node metastasis (human melanoma) or lung metastasis (K-1735 M-2)-derived cell lines. The results from the human and mouse melanoma cell lines show that the brain metastasis-derived cell lines were not more malignant than the lymph node or lung metastasis-derived cells. These data imply that the production of brain metastasis is not always the final stage of a metastatic cascade. PMID:1826230

  5. Sentinel lymph node biopsy in a patient with ruptured poly implant prothese (PIP) implants: A case report

    PubMed Central

    Tafazal, H.; Basu, N.N.; Jewkes, A.

    2014-01-01

    Introduction Around 400,000 silicone gel breast implants produced by the French company poly implant prothese (PIP) were used worldwide. Following revelations that the company were using non- medical grade silicone for the production of their implants there has been growing concern over the increased rupture rate of these implants and the implications this may have on patients. Presentation of Case We report the case of a 57-year old lady with ruptured bilateral cosmetic PIP breast implants in whom a right breast lesion was detected on screening mammograms. Biopsies demonstrated a grade 1 tubular carcinoma. Histology from the sentinel lymph node biopsy showed axillary silicone granulomas but no evidence of metastatic disease. Discussion To our knowledge, this is the first reported case to describe SLNB in the presence of ruptured PIP implants, although SLNB in ruptured non-PIP implants has been previously described. Conclusion We conclude that SLNB can be utilised even in the context of concurrent PIP implant rupture and the presence of silicone granulomas in the axillary lymph nodes. PMID:25460455

  6. Melanoma of the Hand: Current Practice and New Frontiers

    PubMed Central

    Turner, John Brad; Rinker, Brian

    2014-01-01

    Melanoma of the hand represents a complicated clinical entity. Anatomic features of the hand create challenges in successful management of melanoma not encountered elsewhere in the body. The objectives of this article are to outline current standards for managing melanoma of the hand including diagnosis, surgical, and chemotherapeutic management. Particular emphasis will be placed on currently debated topics of the role of sentinel lymph node biopsy, the role of Mohs micrographic surgery, tissue sparing management of subungual melanoma, and the consideration of melanoma of the hand as a distinct entity based on clinical and molecular studies.

  7. The Impact on Post-surgical Treatment of Sentinel Lymph Node Biopsy of Internal Mammary Lymph Nodes in Patients with Breast Cancer

    PubMed Central

    Madsen, EVE; Gobardhan, PD; Bongers, V; Albregts, M; Burgmans, JPJ; De Hooge, P; Van Gorp, J

    2007-01-01

    Background Since the introduction of the sentinel lymph node (SLN) biopsy in breast cancer patients there is a renewed interest in lymphatic drainage to the internal mammary (IM) chain nodes. We evaluated the frequency of lymphatic drainage to the IM chain, the rate of SLNs that contain metastases and the clinical implications of IM LN metastases. Methods Between June 1999 and April 2005 506 consecutive patients underwent SLN biopsy as a staging procedure for clinically T1-2N0 breast cancer. In all patients preoperative lymphoscintigraphy was combined with the intraoperative use of a gammaprobe. In patients with IM SLNs visualized on lymphoscintigraphy, LNs were extirpated through an intercostal parasternal incision. Results SLNs were visualized by preoperative lymphoscintigraphy in 99% of all patients (502/506): axillary SLNs in 499 patients (99%), ipsilateral IM LNs in 109 patients (22%). In 85 patients with visualized IM SLNs the IM nodes could be removed (78%). In 20 of the latter 85 patients IM SLNs contained metastases (24%). IM metastases were associated with axillary LN metastases (P < 0.001). In 17 patients IM metastases led to extension of the radiotherapy field, while additional (adjuvant) systemic therapy was given in six patients. Conclusion SLNs in the IM chain are common in breast cancer patients and can be extirpated in the majority of these patients. The proportion of patients in whom radiotherapeutic treatment was adjusted due to IM LN metastases was substantial. We advocate retrieval of IM SLNs when visualized by preoperative lymphoscintigraphy. PMID:17253106

  8. B-Mode Ultrasound Imaging, Doppler Imaging, and Real-Time Elastography in Cutaneous Malignant Melanoma and Lymph Node Metastases

    PubMed Central

    Uematsu, Takayoshi; Kasami, Masako; Kiyohara, Yoshio

    2013-01-01

    Examination by ultrasonography (US) is a rapid, sensitive, cost-effective, and even portable technique for confirming the presence of tumors. However, US is not routinely used worldwide for the diagnostic work-up of cutaneous malignant melanoma. High-resolution US using a 6–14 MHz or 5–13 MHz linear transducer enables the preoperative assessment of tumor size and thickness. Compared with physical examination, US is also very effective in the early detection of lymph node metastases. It can be easily repeated for the follow-up of cutaneous malignant melanoma and lymph node metastases. Ultrasonographic appearance of some lymph nodes may overlap, thus producing diagnostic pitfalls. In such cases with overlapping findings, Doppler imaging and elastography may additionally facilitate the evaluation of cutaneous malignant melanoma and lymph node metastases. US-guided fine needle aspiration cytology (FNAC) finally helps to confirm ultrasonographic results, thus improving the specificity and sensitivity in difficult situations in which US alone gives unclear results in lymph node assessment.

  9. Imaging methods for the local lymphatic system of the axilla in early breast cancer in patients qualified for sentinel lymph node biopsy

    PubMed Central

    Kurylcio, Andrzej; Polkowski, Wojciech; Zegarski, Wojciech

    2016-01-01

    Breast cancer is the most common malignancy in women in well-developed countries. Despite a constant increase in its incidence, the percentage of patients diagnosed with the disease in the non-invasive stage is also rising. This allows more frequently for the use of breast-preserving surgical techniques, involving the breast and the regional lymphatic system. According to current guidelines of expert panels and research societies, the recommended method of identifying the sentinel lymph node is the use of an isotope marker with a dye (a combined isotope and dye method). Cooperation with a nuclear medicine unit is essential (performing a preoperative lymphoscintigraphic scan to identify the lymphatic drainage basin and sentinel lymph node). In the case of smaller centers treating breast cancer, it can be associated with a number of difficulties, including organizational ones, and also increasing general treatment costs. A possible solution to these problems is to use alternative techniques of visualizing the sentinel lymph node, which do not require a radiotracer. In this paper we discuss the currently available methods of mapping the lymphatic system of the axillary region in patients with early breast cancer. The review is limited to reporting on methods of proven (based on clinical research) high diagnostic value. PMID:27095960

  10. Imaging methods for the local lymphatic system of the axilla in early breast cancer in patients qualified for sentinel lymph node biopsy.

    PubMed

    Nowikiewicz, Tomasz; Kurylcio, Andrzej; Polkowski, Wojciech; Zegarski, Wojciech

    2016-03-01

    Breast cancer is the most common malignancy in women in well-developed countries. Despite a constant increase in its incidence, the percentage of patients diagnosed with the disease in the non-invasive stage is also rising. This allows more frequently for the use of breast-preserving surgical techniques, involving the breast and the regional lymphatic system. According to current guidelines of expert panels and research societies, the recommended method of identifying the sentinel lymph node is the use of an isotope marker with a dye (a combined isotope and dye method). Cooperation with a nuclear medicine unit is essential (performing a preoperative lymphoscintigraphic scan to identify the lymphatic drainage basin and sentinel lymph node). In the case of smaller centers treating breast cancer, it can be associated with a number of difficulties, including organizational ones, and also increasing general treatment costs. A possible solution to these problems is to use alternative techniques of visualizing the sentinel lymph node, which do not require a radiotracer. In this paper we discuss the currently available methods of mapping the lymphatic system of the axillary region in patients with early breast cancer. The review is limited to reporting on methods of proven (based on clinical research) high diagnostic value. PMID:27095960

  11. Sentinel lymph node biopsy reduces the incidence of secondary neck metastasis in patients with oral squamous cell carcinoma

    PubMed Central

    HIRAKI, AKIMITSU; FUKUMA, DAIKI; NAGATA, MASASHI; SHIRAISHI, SHINYA; KAWAHARA, KENTA; MATSUOKA, YUICHIRO; NAKAGAWA, YOSHIHIRO; YOSHIDA, RYOJI; TANAKA, TAKUYA; YOSHITAKE, YOSHIHIRO; SHINOHARA, MASANORI; YAMASHITA, YASUYUKI; NAKAYAMA, HIDEKI

    2016-01-01

    It has recently been established that sentinel node biopsy (SNB) is an applicable and feasible procedure for the prediction of neck lymph node status in patients with early oral squamous cell carcinoma (OSCC) who are clinically negative for neck metastasis (cN0). The aim of this study was to retrospectively compare excision followed by watchful waiting with excision and SNB, in order to determine the effectiveness of SNB. A total of 125 patients with cN0 early OSCC were divided into two groups, namely the excision alone (n=78) and excision with SNB (n=47) groups. The clinical data of these two groups between 2006 and 2013 were analyzed. In the excision with SNB group, the negative predictive value and false-negative rate of SNB were 94% (30/32) and 18% (2/11), respectively. Secondary neck metastasis, also known as delayed neck metastasis, occurred in 24.2% of the patients in the excision alone group and 4.9% of the patients in the excision with SNB group. The 5-year overall survival (OS) rates were 84.0 and 97.5% in the excision alone and excision with SNB groups, respectively. Significant differences were found in the rate of secondary neck metastasis and OS between the two groups. SNB may be effective in the detection of occult neck lymph node metastasis, with a reduction in the incidence of secondary neck metastasis and improvements in the 5-year OS in patients with early-stage (stage I/II) oral cancer. PMID:27330766

  12. A Rapid, Fully Automated, Molecular-Based Assay Accurately Analyzes Sentinel Lymph Nodes for the Presence of Metastatic Breast Cancer

    PubMed Central

    Hughes, Steven J.; Xi, Liqiang; Raja, Siva; Gooding, William; Cole, David J.; Gillanders, William E.; Mikhitarian, Keidi; McCarty, Kenneth; Silver, Susan; Ching, Jesus; McMillan, William; Luketich, James D.; Godfrey, Tony E.

    2006-01-01

    Objective: To develop a fully automated, rapid, molecular-based assay that accurately and objectively evaluates sentinel lymph nodes (SLN) from breast cancer patients. Summary Background Data: Intraoperative analysis for the presence of metastatic cancer in SLNs from breast cancer patients lacks sensitivity. Even with immunohistochemical staining (IHC) and time-consuming review, alarming discordance in the interpretation of SLN has been observed. Methods: A total of 43 potential markers were evaluated for the ability to accurately characterize lymph node specimens from breast cancer patients as compared with complete histologic analysis including IHC. Selected markers then underwent external validation on 90 independent SLN specimens using rapid, multiplex quantitative reverse transcription-polymerase chain reaction (QRT-PCR) assays. Finally, 18 SLNs were analyzed using a completely automated RNA isolation, reverse transcription, and quantitative PCR instrument (GeneXpert). Results: Following analysis of potential markers, promising markers were evaluated to establish relative level of expression cutoff values that maximized classification accuracy. A validation set of 90 SLNs from breast cancer patients was prospectively characterized using 4 markers individually or in combinations, and the results compared with histologic analysis. A 2-marker assay was found to be 97.8% accurate (94% sensitive, 100% specific) compared with histologic analysis. The fully automated GeneXpert instrument produced comparable and reproducible results in less than 35 minutes. Conclusions: A rapid, fully automated QRT-PCR assay definitively characterizes breast cancer SLN with accuracy equal to conventional pathology. This approach is superior to intraoperative SLN analysis and can provide standardized, objective results to assist in pathologic diagnosis. PMID:16495705

  13. A self-assembled multimodal complex for combined pre- and intraoperative imaging of the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Buckle, Tessa; van Leeuwen, Anne C.; Chin, Patrick T. K.; Janssen, Hans; Muller, Sara H.; Jonkers, Jos; van Leeuwen, Fijs W. B.

    2010-09-01

    Specific removal of the sentinel lymph node (SLN) during breast cancer surgery presents physicians with the opportunity to detect early metastatic disease. To increase the accuracy of intraoperative SLN detection, new methods with higher sensitivity and specificity are required. We have quantitatively compared conventional preoperative lymphoscintigraphy with albumin radiocolloids (99mTc-NanoColl) with optical intraoperative guidance using the near infrared dye indocyanine green (ICG) in an orthotopic mouse model for metastatic breast cancer. Furthermore, we have applied a self-assembled multimodal complex, in which ICG is non-covalently bound to the albumin radiocolloid, to attain identical dynamics of the radioactive and optical components. The SLN specificity of the multimodal complex is similar to conventional lymphoscintigraphy, while the fluorescent signal-to-noise ratio is improved by 86% compared to ICG alone. In addition, the multimodal complex permits scintigraphic validation of the fluorescent findings. The multimodal ICG-99mTc-NanoColl complex can be used both for lymphoscintigraphy by preoperative single photon emission computed tomography/computed tomography and for surgical navigation by intraoperative fluorescence imaging.

  14. Navigation surgery for intraoperative sentinel lymph node detection using Indocyanine green (ICG) fluorescence real-time imaging in breast cancer.

    PubMed

    Toh, U; Iwakuma, N; Mishima, M; Okabe, M; Nakagawa, S; Akagi, Y

    2015-09-01

    A new sensitive fluorescence imaging system was developed for the real-time identification of sentinel lymph nodes (SLNs) in patients with early breast cancer. The purpose of this study was to evaluate the utility of a color charge-coupled device camera system for the intraoperative detection of SLNs and to determine its clinical efficacy and sensitivity in patients with operable breast cancer. We assessed a total of 168 patients diagnosed with or suspected of having early-stage breast cancer without metastasis in SLNs. The intraoperative detection of SLNs was performed using the conventional Indigo Carmine dye (indigotindisulfonate sodium) technique combined with a new Indocyanine green (ICG) imaging system (HyperEye Medical System: HEMS, MIZUHO IKAKOGYO, Japan) to map SLNs, in which the lymphatic vessels and SLNs were visualized transcutaneously with illuminating ICG fluorescence. Between January 2012 and May 2013, SLNs were successfully identified in all 168 patients (detection rate: 100%). By histopathology, the sensitivity was 93.8% for the detection of the metastatic involvement of SLNs (15 of 16 nodal-positive patients). After a median follow-up of 30.5 months, none of the patients presented with axillary recurrence. These results suggest that the HEMS imaging system is a feasible and effective method for the detection of SLNs in breast cancer. Furthermore, the HEMS device permitted the transcutaneous visualization of lymphatic vessels under light conditions, thus facilitating the identification and detection of SLNs without affecting the surgical procedure, together with a high sensitivity and specificity. PMID:26267663

  15. Factors associated with involvement of four or more axillary nodes for sentinel lymph node-positive patients

    SciTech Connect

    Katz, Angela . E-mail: abkatz@partners.org; Niemierko, Andrzej; Gage, Irene; Evans, Sheila; Shaffer, Margaret; Smith, Frederick P.; Taghian, Alphonse; Magnant, Colette

    2006-05-01

    Purpose: Sentinel lymph node-positive (SLN+) patients who are unlikely to have 4 or more involved axillary nodes might be treated with less extensive regional nodal radiation. The purpose of this study was to define possible predictors of having 4 or more involved axillary nodes. Methods and Materials: The records of 224 patients with breast cancer and 1 to 3 involved SLNs, who underwent completion axillary dissection without neoadjuvant chemotherapy or hormonal therapy were reviewed. Factors associated with the presence of 4 or more involved axillary nodes (SLNs plus non-SLNs) were evaluated by Pearson chi-square test of association and by simple and multiple logistic-regression analysis. Results: Of 224 patients, 42 had involvement of 4 or more axillary nodes. On univariate analysis, the presence of 4 or more involved axillary nodes was positively associated with increased tumor size, lobular histology, lymphovascular space invasion (LVSI), increased number of involved SLNs, decreased number of uninvolved SLNs, and increased size of SLN metastasis. On multivariate analysis, the presence of 4 or more involved axillary nodes was associated with LVSI, increased number of involved SLNs, increased size of SLN metastasis, and lobular histology. Conclusions: Patients with 1 or more involved SLN, LVSI, or SLN macrometastasis should be treated to the supraclavicular fossa/axillary apex if they do not undergo completion axillary dissection. Other SLN+ patients might be adequately treated with less extensive radiation fields.

  16. A near-infrared fluorescence-based surgical navigation system imaging software for sentinel lymph node detection

    NASA Astrophysics Data System (ADS)

    Ye, Jinzuo; Chi, Chongwei; Zhang, Shuang; Ma, Xibo; Tian, Jie

    2014-02-01

    Sentinel lymph node (SLN) in vivo detection is vital in breast cancer surgery. A new near-infrared fluorescence-based surgical navigation system (SNS) imaging software, which has been developed by our research group, is presented for SLN detection surgery in this paper. The software is based on the fluorescence-based surgical navigation hardware system (SNHS) which has been developed in our lab, and is designed specifically for intraoperative imaging and postoperative data analysis. The surgical navigation imaging software consists of the following software modules, which mainly include the control module, the image grabbing module, the real-time display module, the data saving module and the image processing module. And some algorithms have been designed to achieve the performance of the software, for example, the image registration algorithm based on correlation matching. Some of the key features of the software include: setting the control parameters of the SNS; acquiring, display and storing the intraoperative imaging data in real-time automatically; analysis and processing of the saved image data. The developed software has been used to successfully detect the SLNs in 21 cases of breast cancer patients. In the near future, we plan to improve the software performance and it will be extensively used for clinical purpose.

  17. Cervical conization and sentinel lymph node mapping in the treatment of stage I cervical cancer: is less enough?

    PubMed Central

    Andikyan, Vaagn; Khoury-Collado, Fady; Denesopolis, John; Park, Kay J.; Hussein, Yaser R.; Brown, Carol L.; Sonoda, Yukio; Chi, Dennis S.; Barakat, Richard R.; Abu-Rustum, Nadeem R.

    2016-01-01

    Objective To determine the feasibility of cervical conization and sentinel lymph node (SLN) mapping as a fertility-sparing strategy to treat stage I cervical cancer and estimate the tumor margin status needed to achieve no residual carcinoma in the cervix. Methods We identified all patients who desired fertility-preservation and underwent SLN mapping with cervical conization for stage I cervical cancer from 9/2005–8/2012. Relevant demographic, clinical, and pathological information was collected. Results Ten patients were identified. Median age was 28 years (range,18–36). None of the patients had a grossly visible tumor. The initial diagnosis of invasive carcinoma was made either on a loop electrosurgical excision procedure (LEEP) or cone biopsy. All patients underwent preoperative radiologic evaluation (MRI and PET-CT). None of the patients had evidence of gross tumor or suspicion of lymph node metastasis on imaging. Stage distribution included: IA1 with lymphovascular invasion, 7(70%); and microscopic IB1, 3(30%). Histology included: squamous cell carcinoma, 8(80%); adenocarcinoma, 1(10%); and clear cell carcinoma, 1(10%). Nine patients underwent repeat cervical conization with SLN mapping, and 1 patient underwent post-conization cervical biopsies and SLN mapping. None of the patients had residual tumor identified on the final specimen. The median distance from the invasive carcinoma to the endocervical margin was 2.25mm, and the distance from the invasive carcinoma to the ectocervical margin was 1.9mm. All collected lymph nodes were negative for metastasis. After a median follow-up of 17 months (range,1–83), none of the patients were diagnosed with recurrent disease and 3 patients (30%) achieved pregnancy. Conclusion Cervical conization and SLN mapping appears to be an acceptable treatment strategy for selected patients with small-volume stage I cervical cancer. Tumor clearance of ≥2mm appears to correlate well with no residual on repeat conization. A

  18. Synthesis and evaluation of Cy5.5-Rit tracer for specific near-infrared fluorescence imaging of sentinel lymph node.

    PubMed

    Li, Nan; Zhu, Hua; Li, Yan; Wang, Jing; Yang, Zhi

    2016-09-01

    Sentinel lymph nodes biopsy (SLNB) is a critically important technique to determine the metastatic status of primary breast cancer. Here we reported the new use of a conjugate, Cy5.5-Rituximab (Cy5.5-Rit), which is specific toward the CD20 receptor, as an imaging agent for non-invasive near-infrared fluorescence (NIRF) imaging of sentinel lymph nodes (SLN). The conjugate, Cy5.5-Rit, was synthesized with the ratio of dye to Rituximab close to 1.0. Both gel electrophoresis and mass spectrometry analysis confirmed the molecular integrity of Cy5.5-Rit. For in vivo NIRF imaging, the conjugate stayed in SLN as long as 9days post injection. The in vivo imaging results of SLN targeting were also confirmed by in vitro HE stain. In addition, the direct fluorescence signal of dissected lymph node demonstrated that Cy5.5-Rit binds to the surface of lymph node cells. All of these results showed that the conjugate Cy5.5-Rit has potential for non-invasive optical imaging of SLN. PMID:27497982

  19. Lymphatic Invasion as a Prognostic Biomarker in Primary Cutaneous Melanoma

    PubMed Central

    Xu, Xiaowei; Gimotty, Phyllis A.; Guerry, DuPont; Karakousis, Giorgos; Elder, David E.

    2016-01-01

    Melanoma has a propensity for lymph node metastasis. However, the incidence of lymphatic invasion detected by histology alone in primary melanoma is disproportionately low in comparison to the incidence of positive sentinel lymph nodes (SLN). With the discovery of lymphatic endothelial cell markers, such as podoplanin and LYVE-1, lymphatic vessels can be reliably detected in formalin-fixed paraffin-embedded (FFPE) tissues. There is a now consensus that lymphatic invasion detected by immunohistochemical stains in primary melanoma is much more common than previously reported by histological examination alone. Immunohistochemical stains show that lymphangiogenesis and lymphatic invasion in primary melanoma may occur intratumorally or peritumorally, and lymphatic invasion is common across the range of tumor thicknesses in primary vertical growth phase (VGP) melanomas. A number of studies have shown that lymphatic invasion in primary melanoma is associated with a positive sentinel lymph node biopsy and a worse clinical outcome. Although not currently a part of the standard of care for staging of melanoma, the detection of lymphatic invasion in primary melanoma using immunohistochemical markers may be helpful in planning of therapy in some cases and may find a routine role in primary melanoma microscopic attributes in future. PMID:24258984

  20. Non-invasive Photoacoustic and Fluorescence Sentinel Lymph Node Identification using Dye-loaded Perfluorocarbon Nanoparticles

    PubMed Central

    Akers, Walter J.; Kim, Chulhong; Berezin, Mikhail; Guo, Kevin; Fuhrhop, Ralph; Lanza, Gregory M.; Fischer, Georg M.; Daltrozzo, Ewald; Zumbusch, Andreas; Cai, Xin; Wang, Lihong V.; Achilefu, Samuel

    2010-01-01

    The contrast mechanisms used for photoacoustic tomography (PAT) and fluorescence imaging differ in subtle but significant ways. Design of contrast agents for each or both modalities requires an understanding of the spectral characteristics as well as intra- and intermolecular interactions that occur during formulation. We found that fluorescence quenching that occurs in the formulation of near infrared (NIR) fluorescent dyes in nanoparticles results in enhanced contrast for PAT. The ability of the new PAT method to utilize strongly absorbing chromophores for signal generation allowed us to convert a highly fluorescent dye into an exceptionally high PA contrast material. Spectroscopic characterization of the developed NIR dye-loaded perfluorocarbon-based nanoparticles for combined fluorescence and PA imaging revealed distinct dye-dependent photophysical behavior. We demonstrate that the enhanced contrast allows detection of regional lymph nodes of rats in vivo with time-domain optical and photoacoustic imaging methods. The results further show that the use of fluorescence lifetime (FLT) imaging, which is less dependent on fluorescence intensity, provides a strategic approach to bridge the disparate contrast reporting mechanisms of fluorescence and PA imaging methods. PMID:21171567

  1. Melanoma exosome induction of endothelial cell GM-CSF in pre-metastatic lymph nodes may result in different M1 and M2 macrophage mediated angiogenic processes.

    PubMed

    Hood, Joshua L

    2016-09-01

    Angiogenesis is a key process in the preparation of lymph nodes for melanoma metastasis. Granulocyte macrophage colony stimulating factor (GM-CSF) induces hypoxia inducible factor 1 alpha (HIF-1α) in M1 or HIF-2α in M2 polarized macrophages. HIF-1α promotes neoangiogenesis while HIF-2α facilitates morphogenic normalization of neovasculature. Melanoma exosomes induce GM-CSF expression by endothelial cells in vitro and HIF-1α expression in pre-metastatic lymph nodes in vivo. This suggest a relationship between melanoma exosome induced endothelial GM-CSF and macrophage mediated angiogenesis in lymph nodes. Theoretically, induction of endothelial cell derived GM-CSF by melanoma exosomes mediates different angiogenic functions in pre-metastatic lymph nodes depending on subcapsular sinus (SCS) macrophage polarity. To explore this hypothesis, experiments utilizing melanoma exosomes in a lymph node model are outlined. Despite their opposing immune functions, indirect melanoma exosome stimulation of M1 or M2 SCS macrophages via endothelial derived GM-CSF in lymph nodes may induce different although complementary pro-tumor angiogenic processes. PMID:27515216

  2. Rapid Molecular Detection of Metastatic Head and Neck Squamous Cell Carcinoma as an Intraoperative Adjunct to Sentinel Lymph Node Biopsy

    PubMed Central

    Ferris, Robert L.; Stefanika, Patrick; Xi, Liqiang; Gooding, William; Seethala, Raja R.; Godfrey, Tony E.

    2012-01-01

    Objectives Clinical staging of early head and neck squamous cell carcinoma (SCCHN) is often inaccurate, leading to elective neck dissection to detect the 30% of patients with micrometastatic disease. Sentinel node biopsy (SNB) accurately stages the regional lymphatics, but intraoperative pathology is only moderately sensitive and final pathology takes several days to complete. To facilitate immediate neck dissection where necessary, we have identified several promising marker genes of SCCHN metastasis and developed a rapid, accurate and automated quantitative real time PCR (qRT-PCR) assay for intraoperative use. Design Prospective tissue collection, retrospective pathologic correlation with qRT-PCR Methods From a 40-gene marker screen, we quantified expression of 11 potential tumor genes using a test set of primary tumors (n=32), metastatic (n=19), and benign (n=10) lymph nodes. Eight patients’ paired primary tumor and metastatic nodes were included. A validation set of 442 grossly tumor-negative nodes was evaluated for expression of the most promising markers, comparing metastasis detection by qRT-PCR with pathologic analysis (H&E and immunohistochemistry). A novel multiplexed, automated, single-tube qRT-PCR assay was used to analyze over 100 lymph nodes using a two marker, 35-minute assay to determine its negative predictive value (NPV). Results Based on expression of 11 tumor-associated genes from the marker screen, the two most promising markers of SCCHN metastasis in the test set, pemphigus vulgaris antigen (PVA) and tumor-associated calcium signal transducer 1 (TACSTD1), also known as epithelial cell adhesion molecule (EpCAM), were selected. Development of a multiplexed qRT-PCR assay for the detection of metastasis compared favorably with pathologic analysis in the additional 442 node set. A rapid, multiplexed assay using PVA and TACSTD1 demonstrated excellent reproducibility, linearity, and accuracy (~96% NPV) for identifying positive (n=40) and negative

  3. Resection of Sentinel Lymph Nodes by an Extraperitoneal Minilaparoscopic Approach Using Indocyanine Green for Uterine Malignancies: A Preclinical Comparative Study.

    PubMed

    Ferreira, Hélder; Nogueira-Silva, Cristina; Miranda, Alice; Correia-Pinto, Jorge

    2016-08-01

    Background The sentinel lymph node (SLN) concept might minimize surgical aggressiveness in cervical and endometrial malignancies. The aim of the study was to test the feasibility and reliability of minilaparoscopic extraperitoneal SLN excision after indocyanine green (ICG) cervical injection using a high-definition near infrared (NIR) imaging system in an in vivo porcine model. The same procedure was performed using conventional laparoscopic instruments and both outcomes were compared. Methods Twenty-four animals were equally and randomly divided into a minilaparoscopic group (group A) and a 5-mm conventional laparoscopic group (group B). A high-definition NIR imaging system and a 30° ICG endoscope were used. First, ICG (0.5 mL) was injected in the paracervical region. The SLN coloring time was recorded. An extraperitoneal approach to the SLN was executed with the same CO2 retropneumoperitoneum pressures (10 mm Hg). In both groups, the times for SLN localization and excision, as well as complications, were registered. Finally, a laparotomy was then done to evaluate whether any stained SLN still remained. The same surgical team performed all experiments. Results SLNs were identified and extraperitoneally excised in all animals without major complications. The SLN localization varied between animals from external iliac to preaortic regions. The surgical times were shorter with minilaparoscopy (39.3 ± 13 minutes) than with conventional 5-mm instruments (51.3 ± 14.17 minutes; P = .042). In group B, one stained SLN remained and was only detected by laparotomy. Conclusions We confirmed the feasibility and reliability of extraperitoneal minilaparoscopic approach for identification, dissection, and excision of SLN using an NIR imaging system and ICG. PMID:26637497

  4. Self-illuminating quantum dots for highly sensitive in vivo real-time luminescent mapping of sentinel lymph nodes.

    PubMed

    Wu, Qiang; Chu, Maoquan

    2012-01-01

    Quantum dots (QDs) show promise as novel nanomaterials for sentinel lymph node (SLN) mapping through their use in noninvasive in vivo fluorescence imaging, and they have provided remarkable results. However, in vivo fluorescence imaging has limitations mainly reflected in the strong autofluorescence and low deepness of tissue penetration associated with this technique. Here, we report on the use of self-illuminating 3-mercaptopropionic acid-capped CdTe/CdS QDs for mouse axillary SLN mapping by bioluminescence resonance energy transfer, which was found to overcome these limitations [corrected]. We used CdTe/CdS QDs synthesized in aqueous solution to conjugate a mutant of the bioluminescent protein, Renilla reniformis luciferase. The nanobioconjugates obtained had an average hydrodynamic diameter of 19 nm, and their luminescence catalyzed by the substrate (coelenterazine) could penetrate into at least 20 mm of hairless pigskin, which could be observed using an in vivo imaging system equipped with a 700 nm emission filter. Conversely, the fluorescence of the nanobioconjugates penetrated no more than 10 mm of pigskin and was observed with a strong background. When 80 μL of the nanobioconjugates (containing about 0.5 μmol/L of QDs) and 5 μL of coelenterazine (1 μg/μL) were intradermally injected into a mouse paw, the axillary SLN could be imaged in real time without external excitation, and little background interference was detected. Furthermore, the decayed luminescence of QD-Luc8 in SLNs could be recovered after being intradermally reinjected with the coelenterazine. Our data showed that using self-illuminating QDs, as opposed to fluorescence QDs, has greatly enhanced sensitivity in SLN mapping, and that the SLN could be identified synchronously by the luminescence and fluorescence of the self-illuminating QDs. PMID:22848169

  5. Frozen section evaluation of breast carcinoma sentinel lymph nodes: a retrospective review of 1,940 cases.

    PubMed

    Poling, Justin S; Tsangaris, Theodore N; Argani, Pedram; Cimino-Mathews, Ashley

    2014-11-01

    Many sentinel lymph node biopsies (SLNBs) are evaluated intraoperatively by frozen section, which may impact the need for further axillary dissection (AD). However, the need for AD in patients with small metastases has been recently called into question, meaning that frozen SLNB may be unnecessary. Furthermore, frozen section can compromise tissue for further study. At our institution, we grossly evaluate all SLNB and freeze half of the node. Here, we evaluate the frozen SLNB discrepancy rate using this method, focusing on cause of discrepancy and need for further surgery. We reviewed surgical pathology records for all breast cancer resections with frozen section of SLNB examined from 2003 to 2012. For cases with a frozen section discrepancy, we compiled clinicopathologic data. In total, 1,940 cases involved frozen section evaluation of SLNB. In 95 cases (4.9% of total cases, 23.8% of positive node cases), the SLNB was called negative on frozen but positive on final examination (false negatives). The majority of missed metastases are isolated tumor cells or micrometastases. A trend was observed toward fewer patients receiving completion AD after a discrepant frozen SLNB in the later years of the study. The protocol of freezing half of a SLNB is a reasonable method, with results similar to or better than other studies. The main adverse outcome is the need for separate AD; however, additional positive nodes are uncommon. The trend of fewer patients getting additional AD after a discrepant frozen SLNB suggests that clinicians may be using this information differently recently. PMID:25318925

  6. Image-Guided Sentinel Lymph Node Mapping and Nanotechnology-Based Nodal Treatment in Lung Cancer using Invisible Near-Infrared Fluorescent Light

    PubMed Central

    Khullar, Onkar; Frangioni, John V.; Colson, Yolonda L.

    2011-01-01

    Current methods for sentinel lymph node (SLN) mapping and nodal treatment in lung cancer remain inadequate for routine clinical use. Here we discuss the potential for using the combination of invisible near-infrared (NIR) fluorescent light and nanotechnology for these applications. NIR fluorescence imaging has recently received significant attention for in vivo imaging applications because of its low tissue autofluorescence, high photon penetration into living tissue, and high signal-to-background ratio. Our large animal in vivo studies have been able to successfully identify sentinel lymph nodes in lung tissue and several clinical studies have examined the use of NIR fluorescence imaging systems for SLN mapping in breast and gastric cancer. Promising new nanoparticle technologies, when combined with NIR fluorescence imaging, offer the potential for image-guided treatment of lymph nodes at high risk for tumor recurrence. This review provides a theoretical and empirical framework for developing the next-generation of diagnostic and therapeutic agents for lung cancer. PMID:20226343

  7. Deep venous thromboembolism in patients undergoing inguinal lymph node dissection for melanoma

    SciTech Connect

    Arbeit, J.M.; Lowry, S.F.; Line, B.R.

    1981-11-01

    Deep venous thromboembolism (DVT) was studied in 44 patients with clinical Stage I, II, and III melanoma undergoing staging and therapeutic inguinal lymph node dissection. The ability of two noninvasive methods of surveillance, the phleborheograph (PRG) and the /sup 125/I fibrinogen scan to detect deep venous thrombosis was determined by comparison with prospective bilateral lower extremity venograms. In addition, the therapeutic impact, both beneficial and detrimental, of low dose heparin, 5000 units administered subcutaneously two hours prior to and every eight hours after operation was determined in a double blind study. The sensitivity of the PRG and /sup 125/I fibrinogen scan were both 20%. There were five deep venous thrombi, and two pulmonary emboli for a combined incidence of DVT of 13.6% for the entire patient population. However, there was no significant difference in the incidence of DVT between the two groups. The heparin-treated patients had an increased total volume (796 +/- 516 versus 388 +/- 208 ml; p < 0.05), and duration of wound drainage (9 +/- 4 versus 13 +/- 6 days; p < 0.05).

  8. Deep venous thromboembolism in patients undergoing inguinal lymph node dissection for melanoma

    SciTech Connect

    Arbeit, J.M.; Lowry, S.F.; Line, B.R.; Jones, D.C.; Brennan, M.F.

    1981-01-01

    Deep venous thromboembolism (DVT) was studied in 44 patients with clinical Stage I, II, and III melanoma undergoing staging and therapeutic inguinal lymph node dissection. The ability of two noninvasive methods of surveillance, the phleborheograph (PRG) and the /sup 125/I fibrinogen scan to detect deep venous thrombosis was determined by comparison with prospective bilateral lower extremity venograms. In addition, the therapeutic impact, both beneficial and detrimental, of low dose heparin, 5000 units administered subcutaneously two hours prior to and every eight hours after operation was determined in a double blind study. The sensitivity of the PRG and /sup 125/I fibrinogen scan were both 20%. There were five deep venous thrombi, and two pulmonary emboli for a combined incidence of DVT of 13.6% for the entire patient population. However, there was no significant difference in the incidence of DVT between the two groups. The heparin-treated patients had an increased total volume (796 +/- 516 versus 388 +/- 208 ml; p less than 0.05), and duration of wound drainage (9 +/- 4 versus 13 +/- 6 days; p less than 0.05).

  9. Melanoma

    MedlinePlus

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  10. Feasibility and optimal dosage of indocyanine green fluorescence for sentinel lymph node detection using robotic single-site instrumentation: preclinical study.

    PubMed

    Levinson, Kimberly L; Mahdi, Haider; Escobar, Pedro F

    2013-01-01

    The present study was performed to determine the optimal dosage of indocyanine green (ICG) to accurately differentiate the sentinel node from surrounding tissue and then to test this dosage using novel single-port robotic instrumentation. The study was performed in healthy female pigs. After induction of anesthesia, all pigs underwent exploratory laparotomy, dissection of the bladder, and colpotomy to reveal the cervical os. With use of a 21-gauge needle, 0.5 mL normal saline solution was injected at the 3- and 9-o'clock positions as control. Four concentrations of ICG were constituted for doses of 1000, 500, 250, and 175 μg per 0.5 mL. ICG was then injected at the 3- and 9-o'clock positions on the cervix. The SPY camera was used to track ICG into the sentinel nodes and to quantify the intensity of light emitted. SPY technology uses an intensity scale of 1 to 256; this scale was used to determine the difference in intensity between the sentinel node and surrounding tissues. The optimal dosage was tested using single-port robotic instrumentation with the same injection techniques. A sentinel node was identified at all doses except 175 μg, at which ICG stayed in the cervix and vasculature only. For both the 500- and 250-μg doses, the sentinel node was identified before reaching maximum intensity. At maximum intensity, the difference between the surrounding tissue and the node was 207 (251 vs 44) for the 500-μg dose and 159 (251 vs 92) for the 250-μg dose. Sentinel lymph node (SLN) biopsy was successfully performed using single-port robotic technology with both the 250- and 500-μg doses. For SLN detection, the dose of ICG is related to the ability to differentiate the sentinel node from the surrounding tissue. An ICG dose of 250 to 500 μg enables identification of a SLN with more distinction from the surrounding tissues, and this procedure is feasible using single-port robotics instrumentation. PMID:24034538

  11. The interplay between hospital and surgeon factors and the use of sentinel lymph node biopsy for breast cancer

    PubMed Central

    Yen, Tina W.F.; Li, Jianing; Sparapani, Rodney A.; Laud, Purushuttom W.; Nattinger, Ann B.

    2016-01-01

    Abstract Background: Several surgeon characteristics are associated with the use of sentinel lymph node biopsy (SLNB) for breast cancer. No studies have systematically examined the relative contribution of both surgeon and hospital factors on receipt of SLNB. Objective: To evaluate the relationship between surgeon and hospital characteristics, including a novel claims-based classification of hospital commitment to cancer care (HC), and receipt of SLNB for breast cancer, a marker of quality care. Data Sources/Study Design: Observational prospective survey study was performed in a population-based cohort of Medicare beneficiaries who underwent incident invasive breast cancer surgery, linked to Medicare claims, state tumor registries, American Hospital Association Annual Survey Database, and American Medical Association Physician Masterfile. Multiple logistic regression models determined surgeon and hospital characteristics that were predictors of SLNB. Results: Of the 1703 women treated at 471 different hospitals by 947 different surgeons, 65% underwent an initial SLNB. Eleven percent of hospitals were high-volume and 58% had a high commitment to cancer care. In separate adjusted models, both high HC (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.12–2.10) and high hospital volume (HV, OR 1.90, 95% CI 1.28–2.79) were associated with SLNB. Adding surgeon factors to a model including both HV and HC minimally modified the effect of high HC (OR 1.34, 95% CI 0.95–1.88) but significantly weakened the effect of high HV (OR 1.25, 95% CI 0.82–1.90). Surgeon characteristics (higher volume and percentage of breast cancer cases) remained strong independent predictors of SLNB, even when controlling for various hospital characteristics. Conclusions: Hospital factors are associated with receipt of SLNB but surgeon factors have a stronger association. Since regionalization of breast cancer care in the U.S. is unlikely to occur, efforts to improve the surgical care and

  12. 12-Chemokine Gene Signature Identifies Lymph Node-like Structures in Melanoma: Potential for Patient Selection for Immunotherapy?

    NASA Astrophysics Data System (ADS)

    Messina, Jane L.; Fenstermacher, David A.; Eschrich, Steven; Qu, Xiaotao; Berglund, Anders E.; Lloyd, Mark C.; Schell, Michael J.; Sondak, Vernon K.; Weber, Jeffrey S.; Mulé, James J.

    2012-10-01

    We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20+ B cell follicles with prominent areas of CD3+ T cells (both CD4+ and CD8+ subsets). CD86+, but not FoxP3+, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.

  13. 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. PMID:26552923

  14. Localization of the sentinel lymph node in breast cancer: prospective comparison of vital staining and radioactive tracing methods.

    PubMed

    Marrazzo, Antonio; Taormina, Pietra; Noto, Antonio; Cardinale, Giovanni; Casà, Luigi; Mercadante, Sebastiano; Lo Gerfo, Domenico; David, Massimo

    2004-01-01

    The aim of the study was to evaluate possible differences in accuracy between the radioactive tracing and vital staining method in the search for sentinel nodes in patients with breast cancer. From January 1999 to December 2000, 102 patients with T1 N0 breast carcinoma were recruited into the study for localization of sentinel nodes with vital blue dye staining and radioactive tracing and were then submitted to lumpectomy and axillary dissection. For the two methods, we estimated the percentage of sentinel nodes localized, the false-negative rate, the predictive negative and positive value and the accuracy. The vital blue dye staining method permitted localization of the sentinel node in 73% of patients with a false-negative rate of 8%, a predictive negative value of 92% and 92% accuracy. The radioactive tracing method permitted localization of the sentinel node in 97% cases with a false-negative rate of 0%, a predictive negative value of 100% and 100% accuracy (P<0.0005). The method that offers the better results is radioactive tracing. Currently, many authors use both techniques, since, in common practice, staining helps to identify the sentinel node with the probe. PMID:15553432

  15. Sentinel Lymph Node Biopsy

    MedlinePlus

    ... therapy , or both), and 82 percent had external-beam radiation therapy to the affected breast. The researchers ... treated with surgery, adjuvant systemic therapy, and external-beam radiation therapy. Subsequently, the American College of Surgeons ...

  16. Economic Costs Avoided by Diagnosing Melanoma Six Months Earlier Justify >100 Benign Biopsies.

    PubMed

    Aires, Daniel J; Wick, Jo; Shaath, Tarek S; Rajpara, Anand N; Patel, Vikas; Badawi, Ahmed H; Li, Cicy; Fraga, Garth R; Doolittle, Gary; Liu, Deede Y

    2016-05-01

    New melanoma drugs bring enormous benefits but do so at significant costs. Because melanoma grows deeper and deadlier over time, deeper lesions are costlier due to increased sentinel lymph node biopsy, chemotherapy, and disease-associated income loss. Prior studies have justified pigmented lesion biopsies on a "value per life" basis; by contrast we sought to assess how many biopsies are justified per melanoma found on a purely economic basis. We modeled how melanomas in the United States would behave if diagnosis were delayed by 6 months, eg, not biopsied, only observed until the next surveillance visit. Economic loss from delayed biopsy is the obverse of economic benefit of performing biopsy earlier. Growth rates were based on Liu et al. The results of this study can be applied to all patients presenting to dermatologists with pigmented skin lesions suspicious for melanoma. In-situ melanomas were excluded because no studies to date have modeled growth rates analogous to those for invasive melanoma. We assume conservatively that all melanomas not biopsied initially will be biopsied and treated 6 months later. Major modeled costs are (1) increased sentinel lymph node biopsy, (2) increased chemotherapy for metastatic lesions using increased 5-yr death as metastasis marker, and (3) income loss per melanoma death at $413,370 as previously published. Costs avoided by diagnosing melanoma earlier justify 170 biopsies per melanoma found. Efforts to penalize "unnecessary" biopsies may be economically counterproductive.

    J Drugs Dermatol. 2016;15(5):527-532. PMID:27168261

  17. The first experience of using of 99mTc-Al2O3 for detection of sentinel lymph nodes in breast cancer

    NASA Astrophysics Data System (ADS)

    Doroshenko, A.; Chernov, V.; Medvedeva, A.; Zeltchan, R.; Slonimskaya, E.; Varlamova, N.; Skuridin, V.; Dergilev, A.; Sinilkin, I.

    2016-06-01

    Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. Materials and methods. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n=34) were injected with radioactive 99mTc-Al203, and Group II patients (n=30) received 99mTc-labeled phytate colloid. Results. A total of 37 SLNs were detected in Group I patients. The number of identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. At 18 hours after 99mTc-Al203 injection, the percentage of its accumulation in the SLN was 7-11% (of the counts in the injection site) by SPECT and 17-31% by gamma probe detection. In Group II patients, SLNs were detected in 27 patients. At 18 hours after injection of the phytate colloid, the percentage of its accumulation in the SLN was 1.5-2% out of the counts in the injection site by SPECT and 4-7% by gamma probe. Conclusion. The new radiopharmaceutical based on the 99mTc - Al203 demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. Sensitivity and specificity of 99mTc - Al203 were 100% for both SPECT and intraoperative gamma probe identification.

  18. Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis.

    PubMed

    Nottegar, A; Veronese, N; Senthil, M; Roumen, R M; Stubbs, B; Choi, A H; Verheuvel, N C; Solmi, M; Pea, A; Capelli, P; Fassan, M; Sergi, G; Manzato, E; Maruzzo, M; Bagante, F; Koç, M; Eryilmaz, M A; Bria, E; Carbognin, L; Bonetti, F; Barbareschi, M; Luchini, C

    2016-07-01

    Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging. PMID:27005805

  19. Increasing the Efficacy of SLNB in Cases of Malignant Melanoma Located in Close Proximity to the Lymphatic Basin

    PubMed Central

    Bogdanov-Berezovsky, Alexander; Pagkalos, Vasileios A.; Silberstein, Eldad; Xanthinaki, Arsinoi A.; Krieger, Yuval

    2014-01-01

    Background. Being predictive of the entire nodal bed, sentinel lymph node biopsy (SLNB) is invaluable in the surgical management of melanoma. Although the concept is simple, sentinel lymph node (SLN) identification and removal can be technically challenging. Methods. A total of 102 consecutive patients have undergone SLNB in the Division of Plastic and Reconstructive Surgery of Soroka University Medical Center from 2009 to 2012. Patients have undergone SLNB using a radioactive tracer and blue stain in order to identify the SLN. Although SLNB usually precedes the wide excision of melanoma, primary lesions in close proximity (<10 cm) to the lymph basin require wide excision before beginning the SLN quest. Results. All pathology reports confirmed the excision of lymph nodes. Conclusions. When treating MM in close proximity to the lymph basin, changing the sequence of the SLNB procedure seems to increase the efficacy of the method. PMID:24660067

  20. Hybrid Modality Fusion of Planar Scintigrams and CT Topograms to Localize Sentinel Lymph Nodes in Breast Lymphoscintigraphy: Technical Description and Phantom Studies

    PubMed Central

    Dickinson, Renée L.; Erwin, William D.; Stevens, Donna M.; Bidaut, Luc M.; Mar, Martha V.; Macapinlac, Homer A.; Wendt, Richard E.

    2011-01-01

    Lymphoscintigraphy is a nuclear medicine procedure that is used to detect sentinel lymph nodes (SLNs). This project sought to investigate fusion of planar scintigrams with CT topograms as a means of improving the anatomic reference for the SLN localization. Heretofore, the most common lymphoscintigraphy localization method has been backlighting with a 57Co sheet source. Currently, the most precise method of localization through hybrid SPECT/CT increases the patient absorbed dose by a factor of 34 to 585 (depending on the specific CT technique factors) over the conventional 57Co backlighting. The new approach described herein also uses a SPECT/CT scanner, which provides mechanically aligned planar scintigram and CT topogram data sets, but only increases the dose by a factor of two over that from 57Co backlighting. Planar nuclear medicine image fusion with CT topograms has been proven feasible and offers a clinically suitable compromise between improved anatomic details and minimally increased radiation dose. PMID:21490727

  1. International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

    PubMed

    Meretoja, Tuomo J; Audisio, R A; Heikkilä, P S; Bori, R; Sejben, I; Regitnig, P; Luschin-Ebengreuth, G; Zgajnar, J; Perhavec, A; Gazic, B; Lázár, G; Takács, T; Kővári, B; Saidan, Z A; Nadeem, R M; Castellano, I; Sapino, A; Bianchi, S; Vezzosi, V; Barranger, E; Lousquy, R; Arisio, R; Foschini, M P; Imoto, S; Kamma, H; Tvedskov, T F; Jensen, M-B; Cserni, G; Leidenius, M H K

    2013-04-01

    Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use. PMID:23558360

  2. High nevus counts confer a favorable prognosis in melanoma patients.

    PubMed

    Ribero, Simone; Davies, John R; Requena, Celia; Carrera, Cristina; Glass, Daniel; Rull, Ramon; Vidal-Sicart, Sergi; Vilalta, Antonio; Alos, Lucia; Soriano, Virtudes; Quaglino, Pietro; Traves, Victor; Newton-Bishop, Julia A; Nagore, Eduardo; Malvehy, Josep; Puig, Susana; Bataille, Veronique

    2015-10-01

    A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi. PMID:25809795

  3. Fast 18F Labeling of a Near-Infrared Fluorophore Enables Positron Emission Tomography and Optical Imaging of Sentinel Lymph Nodes

    PubMed Central

    2010-01-01

    We combine a novel boronate trap for F− with a near-infrared fluorophore into a single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). Our first application of this generic tag is to label Lymphoseek (tilmanocept), an agent designed for receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates 18F− in a single, aqueous step, targets mouse SLN rapidly (1 h) with reduced distal lymph node accumulation, permits PET or scintigraphic imaging of SLN, and enables NIRF-guided excision and histological verification even after 18F decay. This embodiment is superior to current SLN mapping agents such as nontargeted [99mTc]sulfur colloids and Isosulfan Blue, as well as the phase III targeted ligand [99mTc]SPECT Lymphoseek counterpart, species that are visible by SPECT or visible absorbance separately. Facile incorporation of 18F into a NIRF probe should promote many synergistic PET and NIRF combinations. PMID:20873712

  4. Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model.

    PubMed

    Song, Kwang Hyun; Kim, Chulhong; Cobley, Claire M; Xia, Younan; Wang, Lihong V

    2009-01-01

    This work demonstrated the use of Au nanocages as a new class of lymph node tracers for noninvasive photoacoustic (PA) imaging of a sentinel lymph node (SLN). Current SLN mapping methods based on blue dye and/or nanometer-sized radioactive colloid injection are intraoperative due to the need for visual detection of the blue dye and low spatial resolution of Geiger counters in detecting radioactive colloids. Compared to the current methods, PA mapping based on Au nanocages shows a number of attractive features: noninvasiveness, strong optical absorption in the near-infrared region (for deep penetration), and the accumulation of Au nanocages with a higher concentration than the initial solution for the injection. In an animal model, these features allowed us to identify SLNs containing Au nanocages as deep as 33 mm below the skin surface with good contrast. Most importantly, compared to methylene blue Au nanocages can be easily bioconjugated with antibodies for targeting specific receptors, potentially eliminating the need for invasive axillary staging procedures in addition to providing noninvasive SLN mapping. PMID:19072058

  5. Comparative Study of the One-step Nucleic Acid Amplification Assay and Conventional Histological Examination for the Detection of Breast Cancer Sentinel Lymph Node Metastases.

    PubMed

    Terada, Mizuho; Niikura, Naoki; Tsuda, Banri; Masuda, Shinobu; Kumaki, Nobue; Tang, Xiaoyan; Okamura, Takuho; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka

    2014-09-01

    Intraoperative sentinel lymph node (SLN) biopsy is widely used in patients with early-stage breast cancer and is conventionally performed using hematoxylin and eosin-based histological examination. The one-step nucleic acid amplification (OSNA) assay is a molecular diagnostic tool and a semi-automated lymph node examination method. The purpose of this study was to compare the performance of the OSNA assay and conventional histological examination with frozen sections (FSs) by using 111 SLN biopsy samples from 89 patients at the Tokai University Hospital. The SLN samples were split into 3 slices: the middle slice was used for FS histological examination and the other slices were used for the OSNA assay. The McNemar test was used to compare the differences in the sensitivity and specificity between the OSNA assay and FS histological examination. The sensitivity of the OSNA assay (97.1%) was less than that of FS histological examination (100%), but this difference was not statistically significant (P = 0.125). The specificity of both the methods was identical (96.9%). Despite previously published results suggesting that the OSNA assay is as reliable as histological examinations, our results indicate that this assay often fails to detect micrometastases or isolated tumor cells in SLNs. PMID:25248427

  6. Melanoma

    MedlinePlus

    ... to other parts of the body very quickly. Melanoma treatment can cause side effects, including pain, nausea, and ... Livingstone; 2013:chap 69. National Cancer Institute: PDQ Melanoma Treatment. Bethesda, MD: National Cancer Institute. Last modified March ...

  7. Predicting Likelihood of Having Four or More Positive Nodes in Patient With Sentinel Lymph Node-Positive Breast Cancer: A Nomogram Validation Study

    SciTech Connect

    Unal, Bulent; Gur, Akif Serhat; Beriwal, Sushil; Tang Gong; Johnson, Ronald; Ahrendt, Gretchen; Bonaventura, Marguerite; Soran, Atilla

    2009-11-15

    Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The area under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.

  8. Sentinel node techniques in cancer of the vulva.

    PubMed

    de Hullu, Joanne A; van der Zee, Ate G J

    2003-02-01

    The sentinel lymph node procedure, with the combined technique (preoperative lymphoscintigraphy with (99m)Technetium-labeled Nanocolloid and Patente Blue V ), is a promising staging technique for patients with vulvar cancer. The clinical implementation of the sentinel lymph node procedure and the role of additional histopathologic techniques of the sentinel lymph nodes are under investigation. PMID:12521546

  9. Size Control of (99m)Tc-tin Colloid Using PVP and Buffer Solution for Sentinel Lymph Node Detection.

    PubMed

    Kim, Eun-Mi; Lim, Seok Tae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2015-06-01

    Colloidal particle size is an important characteristic that allows mapping sentinel nodes in lymphoscintigraphy. This investigation aimed to introduce different ways of making a (99m)Tc-tin colloid with a size of tens of nanometers. All agents, tin fluoride, sodium fluoride, poloxamer-188, and polyvinylpyrrolidone (PVP), were mixed and labeled with (99m)Tc. Either phosphate or sodium bicarbonate buffers were used to adjust the pH levels. When the buffers were added, the size of the colloids increased. However, as the PVP continued to increase, the size of the colloids was controlled to within tens of nanometers. In all samples, phosphate buffer added PVP (30 mg) stabilized tin colloid ((99m)Tc-PPTC-30) and sodium bicarbonate solution added PVP (50 mg) stabilized tin colloid ((99m)Tc-BPTC-50) were chosen for in vitro and in vivo studies. (99m)Tc-BPTC-50 (<20 nm) was primarily located in bone marrow and was then secreted through the kidneys, and (99m)Tc-PPTC-30 (>100 nm) mainly accumulated in the liver. When a rabbit was given a toe injection, the node uptake of (99m)Tc-PPTC-30 decreased over time, while (99m)Tc-BPTC-50 increased. Therefore, (99m)Tc-BPTC-50 could be a good candidate radiopharmaceutical for sentinel node detection. The significance of this study is that nano-sized tin colloid can be made very easily and quickly by PVP. PMID:26028937

  10. Principles of Melanoma Staging.

    PubMed

    Boland, Genevieve M; Gershenwald, Jeffrey E

    2016-01-01

    Although now commonplace in contemporary cancer care, the systematic approach to classification of disease-specific cancers into a formalized staging system is a relatively modern concept. Overall, the goals of cancer staging are to characterize the status of cancer at a specific moment in time, risk stratify, facilitate prognostication, and inform clinical decision making. The revisions to the American Joint Committee on Cancer (AJCC) melanoma staging system over time reflect changes in our understanding of the biology of the disease. Since the 1st edition, where tumor thickness was defined anatomically by its relationship to the reticular or papillary dermis (Clark level) as well as tumor thickness (Breslow thickness), there have been significant strides in our use of clinicopathological variables to stratify low- versus high-risk patients. Management of the regional nodal basin has also changed dramatically over time, impacted by techniques such as lymphatic mapping and sentinel lymph node biopsy (SLNB) and changes in pathological evaluation of the regional lymph nodes. Additionally, stratification of distant metastases has evolved as survival outcomes have been shown to vary based upon anatomic site of metastases and serum lactate dehydrogenase levels. The variables in use in the current (7th edition) AJCC staging system are surrogate markers of biology with validated impact of survival outcomes. Going forward, it is likely that these and additional clinicopathological factors will be integrated with molecular and other correlates of melanoma tumor biology to further refine and personalize melanoma staging. PMID:26601861

  11. Analysis of EpCAM positive cells isolated from sentinel lymph nodes of breast cancer patients identifies subpopulations of cells with distinct transcription profiles

    PubMed Central

    2011-01-01

    Introduction The presence of tumor cells in the axillary lymph nodes is the most important prognostic factor in early stage breast cancer. However, the optimal method for sentinel lymph node (SLN) examination is still sought and currently many different protocols are employed. To examine two approaches for tumor cell detection we performed, in sequence, immunomagnetic enrichment and RT-PCR analysis on SLN samples from early stage breast cancer patients. This allowed us to compare findings based on the expression of cell surface proteins with those based on detection of intracellular transcripts. Methods Enrichment of EpCAM and Mucin 1 expressing cells from fresh SLN samples was achieved using magnetic beads coated with the appropriate antibodies. All resulting cell fractions were analyzed by RT-PCR using four chosen breast epithelial markers (hMAM, AGR2, SBEM, TFF1). Gene expression was further analyzed using RT-PCR arrays and markers for epithelial to mesenchymal transition (EMT). Results Both EpCAM and Mucin 1 enriched for the epithelial-marker expressing cells. However, EpCAM-IMS identified epithelial cells in 71 SLNs, whereas only 35 samples were positive with RT-PCR targeting breast epithelial transcripts. Further analysis of EpCAM positive but RT-PCR negative cell fractions showed that they had increased expression of MMPs, repressors of E-cadherin, SPARC and vimentin, all transcripts associated with the process of epithelial to mesenchymal transition. Conclusions The EpCAM IMS-assay detected tumor cells with epithelial and mesenchymal-like characteristics, thus proving to be a more robust marker than pure epithelial derived biomarkers. This finding has clinical implications, as most methods for SLN analysis today rely on the detection of epithelial transcripts or proteins. PMID:21816090

  12. Minimally Invasive Electro-Magnetic Navigational Bronchoscopy-Integrated Near-Infrared-Guided Sentinel Lymph Node Mapping in the Porcine Lung

    PubMed Central

    Wada, Hironobu; Hirohashi, Kentaro; Anayama, Takashi; Nakajima, Takahiro; Kato, Tatsuya; Chan, Harley H. L.; Qiu, Jimmy; Daly, Michael; Weersink, Robert; Jaffray, David A.; Irish, Jonathan C.; Waddell, Thomas K.; Keshavjee, Shaf; Yoshino, Ichiro; Yasufuku, Kazuhiro

    2015-01-01

    Background The use of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) for sentinel lymph node (SN) mapping has been investigated in lung cancer; however, this has not been fully adapted for minimally invasive surgery (MIS). The aim of our study was to develop a minimally invasive SN mapping integrating pre-operative electro-magnetic navigational bronchoscopy (ENB)-guided transbronchial ICG injection and intraoperative NIR thoracoscopic imaging. Methods A NIR thoracoscope was used to visualize ICG fluorescence. ICG solutions in a 96-well plate and ex vivo porcine lungs were examined to optimize ICG concentrations and injection volumes. Transbronchial ICG injection (n=4) was assessed in comparison to a traditional transpleural approach (n=3), where after thoracotomy an ICG solution (100μL at 100μg/mL) was injected into the porcine right upper lobe for SN identification. For further translation into clinical use, transbronchial ICG injection prior to thoracotomy followed by NIR thoracoscopic imaging was validated (n=3). ENB was used for accurate targeting in two pigs with a pseudo-tumor. Results The ICG fluorescence at 10 μg/mL was the brightest among various concentrations, unchanged by the distance between the thoracoscope and ICG solutions. Injected ICG of no more than 500μL showed a localized fluorescence area. All 7 pigs showed a bright paratracheal lymph node within 15 minutes post-injection, with persistent fluorescence for 60 minutes. The antecedent transbronchial ICG injection succeeded in SN identification in all 3 cases at the first thoracoscopic inspection within 20 minutes post-injection. The ENB system allowed accurate ICG injection surrounding the pseudo-tumors. Conclusions ENB-guided ICG injection followed by NIR thoracoscopy was technically feasible for SN mapping in the porcine lung. This promising platform may be translated into human clinical trials and is suited for MIS. PMID:25993006

  13. Multimodal Surgical Guidance during Sentinel Node Biopsy for Melanoma: Combined Gamma Tracing and Fluorescence Imaging of the Sentinel Node through Use of the Hybrid Tracer Indocyanine Green-(99m)Tc-Nanocolloid.

    PubMed

    van den Berg, Nynke S; Brouwer, Oscar R; Schaafsma, Boudewijn E; Mathéron, Hanna M; Klop, W Martin C; Balm, Alfons J M; van Tinteren, Harm; Nieweg, Omgo E; van Leeuwen, Fijs W B; Valdés Olmos, Renato A

    2015-05-01

    Purpose To evaluate the hybrid approach in a large population of patients with melanoma in the head and neck, on the trunk, or on an extremity who were scheduled for sentinel node (SN) biopsy. Materials and Methods This prospective study was approved by the institutional review board. Between March 2010 and March 2013, 104 patients with a melanoma, including 48 women (average age, 54.3 years; range, 18.5-87.4 years) and 56 men (average age, 55.2 years; range, 22.4-77.4 years) (P = .76) were enrolled after obtaining written informed consent. Following intradermal hybrid tracer administration, lymphoscintigraphy and single photon emission computed tomography/computed tomography were performed. Blue dye was intradermally injected prior to the start of the surgical operation (excluding patients with a facial melanoma). Intraoperatively, SNs were initially pursued by using gamma tracing followed by fluorescence imaging (FI) and, when applicable, blue-dye detection. A portable gamma camera was used to confirm SN removal. Collected data included number and location of the preoperatively and intraoperatively identified SNs and the intraoperative number of SNs that were radioactive, fluorescent, and blue. A two-sample test for equality of proportions was performed to evaluate differences in intraoperative SN visualization through FI and blue-dye detection. Results Preoperative imaging revealed 2.4 SNs (range, 1-6) per patient. Intraoperatively, 93.8% (286 of 305) of the SNs were radioactive, 96.7% (295 of 305) of the SNs were fluorescent, while only 61.7% (116 of 188) of the SNs stained blue (P < .0001). FI was of value for identification of near-injection-site SNs (two patients), SNs located in complex anatomic areas (head and neck [28 patients]), and SNs that failed to accumulate blue dye (19 patients). Conclusion The hybrid tracer enables both preoperative SN mapping and intraoperative SN identification in melanoma patients. In the setup of this study, optical

  14. [The validity of the sentinel node concept in gastrointestinal cancers].

    PubMed

    Kitagawa, Y; Fujii, H; Mukai, M; Ando, N; Kubota, T; Ikeda, T; Ohgami, M; Watanabe, M; Otani, Y; Ozawa, S; Hasegawa, H; Furukawa, T; Nakahara, T; Kubo, A; Kumai, K; Kitajima, M

    2000-03-01

    Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers. PMID:10774000

  15. The use of 99mTc-Al2O3 for detection of sentinel lymph nodes in cervical cancer patients

    NASA Astrophysics Data System (ADS)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-06-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3- based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (TlaNxMx- T2bNxMx) treated at the Tomsk Cancer Research Institute. At 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 were injected peritumorally, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3(the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac, obturator, presacral and retrosacral regions (they amounted to 14%, respectively),and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  16. The first experience of using 99mTc-Al2O3-based radiopharmaceutical for the detection of sentinel lymph nodes in cervical cancer patients

    NASA Astrophysics Data System (ADS)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-08-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3-based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (T1aNxMx-T2bNxMx) treated at the Tomsk Cancer Research Institute. In the 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 in peritumoral injected, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3 (the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac (14%), obturator (14%), presacral and retrosacral regions (14%), and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  17. Near-Infrared Sentinel Lymph Node Mapping With Indocyanine Green Using the VITOM II ICG Exoscope for Open Surgery for Gynecologic Malignancies.

    PubMed

    Buda, Alessandro; Dell'Anna, Tiziana; Vecchione, Francesca; Verri, Debora; Di Martino, Giampaolo; Milani, Rodolfo

    2016-01-01

    Sentinel lymph node (SLN) mapping is emerging as an effective method for surgical staging of different gynecologic malignancies. Near-infrared (NIR) technology using a fluorescent dye such as indocyanine green (ICG) represents an interesting and feasible method for SLN mapping even in traditional open surgeries by applying video telescope operating microscope (VITOM) system technology. We report our preliminary experience in 12 women who underwent surgical nodal staging for early-stage vulvar and uterine or cervical cancer. Surgical and pathological outcomes are described, and the VITOM II ICG system's intraoperative image quality, handling and docking, and teaching value are assessed. The general impression of the surgical staff was that the VITOM II system is easy to use, and that the image quality of the anatomic structures is impressive. Traditional open SLN mapping with ICG appears to be easy to perform and reproducible, providing a new tool in the management of patients with gynecologic malignancies. Moreover, we believe that this technology has great potential as an operative teaching and learning modality for trainers for open surgical cases. Additional studies involving the VITOM system with a large sample size of patients are needed to confirm these promising results. PMID:26921484

  18. Validation of Contrast Enhanced Ultrasound Technique to Wire Localization of Sentinel Lymph Node in Patients with Early Breast Cancer.

    PubMed

    Esfehani, Maryam H; Yazdankhah-Kenari, Adel; Omranipour, Ramesh; Mahmoudzadeh, Habib Allah; Shahriaran, Shahriar; Zafarghandi, Mohammad Reza; Amoli, Hadi Ahmadi

    2015-12-01

    Axillary staging is one of the primary steps in management of Breast cancer patients. Current standard methods including blue dye and radicolloid have limitations and disadvantages. In this study, the feasibility of visualization of lymph node pathways and localization of SLN with the help of CEUS was assessed. 50 patients with early breast cancer diagnosis underwent CEUS and wire localization, methylenblue dye, and isotope scan methods for SLN detection. The pathology findings of the wired SLN were compared with those obtained from, methylenblue dye, and isotope scan methods. Lymph node wiring was successfully performed in 48 patients.Radio-isotope technique detected SLN in all 50 patients while blue-dye succeeded in 48. Sensitivity of CEUS to detect SLN compared with radio-isotope and blue dye methods was 96 % and 100 %, respectively. Considering costs and facilities required to perform radio-isotope technique and complications of blue dye we may accept CEUS with the help of micro-bubble contrasts as a viable alternative. However, more studies with larger sample volumes, using various drugs, and including non-selective population are warranted to better clarify feasibility and accuracy of this technique in comparison with current methods. PMID:27065663

  19. Enrichment of CD56dimKIR+CD57+ highly cytotoxic NK cells in tumor infiltrated lymph nodes of melanoma patients

    PubMed Central

    Mortarini, Roberta; Anichini, Andrea; Garofalo, Cinzia; Tallerico, Rossana; Santinami, Mario; Gulletta, Elio; Ietto, Caterina; Galgani, Mario; Matarese, Giuseppe; Bifulco, Maurizio; Ferrone, Soldano; Colucci, Francesco; Moretta, Alessandro; Kärre, Klas; Carbone, Ennio

    2014-01-01

    An important checkpoint in the progression of melanoma is the metastasis to lymph nodes. Here, to investigate the role of lymph node NK cells in disease progression, we analyze frequency, phenotype and functions of NK cells from tumor-infiltrated (TILN) and tumor-free ipsilateral lymph nodes (TFLN) of the same patients. We show an expansion of CD56dimCD57dimCD69+CCR7+KIR+ NK cells in TILN. TILN NK cells display robust cytotoxic activity against autologous melanoma cells. In the blood of metastatic melanoma patients the frequency of NK cells expressing the receptors for CXCL8 receptor is increased compared to healthy subjects, and blood NK cells also express the receptors for CCL2 and IL6. These factors are produced in high amount in TILN and in vitro switch the phenotype of blood NK cells from healthy donors to the phenotype associated with TILN. Our data suggest that the microenvironment of TILN generates and/or recruits a particularly effective NK cell subset. PMID:25472612

  20. Intravital and Whole-Organ Imaging Reveals Capture of Melanoma-Derived Antigen by Lymph Node Subcapsular Macrophages Leading to Widespread Deposition on Follicular Dendritic Cells

    PubMed Central

    Moalli, Federica; Proulx, Steven T.; Schwendener, Reto; Detmar, Michael; Schlapbach, Christoph; Stein, Jens V.

    2015-01-01

    Aberrant antigens expressed by tumor cells, such as in melanoma, are often associated with humoral immune responses, which may in turn influence tumor progression. Despite recent data showing the central role of adaptive immune responses on cancer spread or control, it remains poorly understood where and how tumor-derived antigen (TDA) induces a humoral immune response in tumor-bearing hosts. Based on our observation of TDA accumulation in B cell areas of lymph nodes (LNs) from melanoma patients, we developed a pre-metastatic B16.F10 melanoma model expressing a fluorescent fusion protein, tandem dimer tomato, as a surrogate TDA. Using intravital two-photon microscopy (2PM) and whole-mount 3D LN imaging of tumor-draining LNs in immunocompetent mice, we report an unexpectedly widespread accumulation of TDA on follicular dendritic cells (FDCs), which were dynamically scanned by circulating B cells. Furthermore, 2PM imaging identified macrophages located in the subcapsular sinus of tumor-draining LNs to capture subcellular TDA-containing particles arriving in afferent lymph. As a consequence, depletion of macrophages or genetic ablation of B cells and FDCs resulted in dramatically reduced TDA capture in tumor-draining LNs. In sum, we identified a major pathway for the induction of humoral responses in a melanoma model, which may be exploitable to manipulate anti-TDA antibody production during cancer immunotherapy. PMID:25821451

  1. Intravital and whole-organ imaging reveals capture of melanoma-derived antigen by lymph node subcapsular macrophages leading to widespread deposition on follicular dendritic cells.

    PubMed

    Moalli, Federica; Proulx, Steven T; Schwendener, Reto; Detmar, Michael; Schlapbach, Christoph; Stein, Jens V

    2015-01-01

    Aberrant antigens expressed by tumor cells, such as in melanoma, are often associated with humoral immune responses, which may in turn influence tumor progression. Despite recent data showing the central role of adaptive immune responses on cancer spread or control, it remains poorly understood where and how tumor-derived antigen (TDA) induces a humoral immune response in tumor-bearing hosts. Based on our observation of TDA accumulation in B cell areas of lymph nodes (LNs) from melanoma patients, we developed a pre-metastatic B16.F10 melanoma model expressing a fluorescent fusion protein, tandem dimer tomato, as a surrogate TDA. Using intravital two-photon microscopy (2PM) and whole-mount 3D LN imaging of tumor-draining LNs in immunocompetent mice, we report an unexpectedly widespread accumulation of TDA on follicular dendritic cells (FDCs), which were dynamically scanned by circulating B cells. Furthermore, 2PM imaging identified macrophages located in the subcapsular sinus of tumor-draining LNs to capture subcellular TDA-containing particles arriving in afferent lymph. As a consequence, depletion of macrophages or genetic ablation of B cells and FDCs resulted in dramatically reduced TDA capture in tumor-draining LNs. In sum, we identified a major pathway for the induction of humoral responses in a melanoma model, which may be exploitable to manipulate anti-TDA antibody production during cancer immunotherapy. PMID:25821451

  2. Lymph Node Micrometastases and In-Transit Metastases from Melanoma: In Vivo Detection with Multispectral Optoacoustic Imaging in a Mouse Model.

    PubMed

    Neuschmelting, Volker; Lockau, Hannah; Ntziachristos, Vasilis; Grimm, Jan; Kircher, Moritz F

    2016-07-01

    Purpose To study whether multispectral optoacoustic tomography (MSOT) can serve as a label-free imaging modality for the detection of lymph node micrometastases and in-transit metastases from melanoma on the basis of the intrinsic contrast of melanin in comparison to fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Materials and Methods The study was approved by the institutional animal care and use committee. Sequential MSOT was performed in a mouse B16F10 melanoma limb lymph node metastasis model (n = 13) to survey the development of macro-, micro- and in-transit metastases (metastases that are in transit from the primary tumor site to the local nodal basin) in vivo. The in vitro limit of detection was assessed in a B16F10 cell phantom. Signal specificity was determined on the basis of a simultaneous lymphadenitis (n = 4) and 4T1 breast cancer lymph metastasis (n = 2) model. MSOT was compared with intravenous FDG PET/CT. The diagnosis was assessed with histologic examination. Differences in the signal ratio (metastatic node to contralateral limb) between the two modalities were determined with the two-tailed paired t test. Results The mean signal ratios acquired with MSOT in micrometastases (2.5 ± 0.3, n = 6) and in-transit metastases (8.3 ± 5.8, n = 4) were higher than those obtained with FDG PET/CT (1.1 ± 0.5 [P < .01] and 1.3 ± 0.6 [P < .05], respectively). MSOT was able to help differentiate even small melanoma lymph node metastases from the other lymphadenopathies (P < .05 for both) in vivo, whereas FDG PET/CT could not (P > .1 for both). In vitro, the limit of detection was at an approximate cell density of five cells per microliter (P < .01). Conclusion MSOT enabled detection of melanoma lymph node micrometastases and in-transit metastases undetectable with FDG PET/CT and helped differentiate melanoma metastasis from other lymphadenopathies. (©) RSNA, 2016 Online supplemental material is available for

  3. Imaging of Lymph Node Micrometastases Using an Oncolytic Herpes Virus and [18F]FEAU PET

    PubMed Central

    Brader, Peter; Kelly, Kaitlyn; Gang, Sheng; Shah, Jatin P.; Wong, Richard J.; Hricak, Hedvig; Blasberg, Ronald G.; Fong, Yuman; Gil, Ziv

    2009-01-01

    Background In patients with melanoma, knowledge of regional lymph node status provides important information on outlook. Since lymph node status can influence treatment, surgery for sentinel lymph node (SLN) biopsy became a standard staging procedure for these patients. Current imaging modalities have a limited sensitivity for detection of micrometastases in lymph nodes and, therefore, there is a need for a better technique that can accurately identify occult SLN metastases. Methodology/Principal Findings B16-F10 murine melanoma cells were infected with replication-competent herpes simplex virus (HSV) NV1023. The presence of tumor-targeting and reporter-expressing virus was assessed by [18F]-2′-fluoro-2′-deoxy-1-β-D-β-arabinofuranosyl-5-ethyluracil ([18F]FEAU) positron emission tomography (PET) and confirmed by histochemical assays. An animal foot pad model of melanoma lymph node metastasis was established. Mice received intratumoral injections of NV1023, and 48 hours later were imaged after i.v. injection of [18F]FEAU. NV1023 successfully infected and provided high levels of lacZ transgene expression in melanoma cells. Intratumoral injection of NV1023 resulted in viral trafficking to melanoma cells that had metastasized to popliteal and inguinal lymph nodes. Presence of virus-infected tumor cells was successfully imaged with [18F]FEAU-PET, that identified 8 out of 8 tumor-positive nodes. There was no overlap between radioactivity levels (lymph node to surrounding tissue ratio) of tumor-positive and tumor-negative lymph nodes. Conclusion/Significance A new approach for imaging SLN metastases using NV1023 and [18F]FEAU-PET was successful in a murine model. Similar studies could be translated to the clinic and improve the staging and management of patients with melanoma. PMID:19274083

  4. Value of staging squamous cell carcinoma of the anal margin and canal using the sentinel lymph node procedure: an update of the series and a review of the literature

    PubMed Central

    Mistrangelo, D M; Bellò, M; Cassoni, P; Milanesi, E; Racca, P; Munoz, F; Fora, G; Rondi, N; Gilbo, N; Senetta, R; Ricardi, U; Morino, M

    2013-01-01

    Background: Inguinal metastases in patients affected by anal cancer are an independent prognostic factor for local failure and overall mortality. Since 2001, sentinel lymph node biopsy was applied in these patients. This original study reports an update of personal and previous published series, which were compared with Literature to value the incidence of inguinal metastases T-stage related and the overall incidence of false negative inguinal metastases at sentinel node. Methods: In all, 63 patients diagnosed with anal cancer submitted to inguinal sentinel node. Furthermore a research in the Pub Med database was performed to find papers regarding this technique. Results: In our series, detection rate was 98.4%. Inguinal metastases were evidentiated in 13 patients (20.6%). Our median follow-up was 35 months. In our series, no false negative nodes were observed. Conclusion: Sentinel node technique in the detection of inguinal metastases in patients affected by anal cancer should be considered as a standard of care. It is indicated for all T stages in order to select patients to be submitted to inguinal radiotherapy, avoiding related morbidity in negative ones. An overall 3.7% rate of false negative must be considered acceptable. PMID:23329231

  5. Melanin nanoparticles derived from a homology of medicine and food for sentinel lymph node mapping and photothermal in vivo cancer therapy.

    PubMed

    Chu, Maoquan; Hai, Wangxi; Zhang, Zheyu; Wo, Fangjie; Wu, Qiang; Zhang, Zefei; Shao, Yuxiang; Zhang, Ding; Jin, Lu; Shi, Donglu

    2016-06-01

    The use of non-toxic or low toxicity materials exhibiting dual functionality for use in sentinel lymph node (SLN) mapping and cancer therapy has attracted considerable attention during the past two decades. Herein, we report that the natural black sesame melanin (BSM) extracted from black sesame seeds (Sesamum indicum L.) shows exciting potential for SLN mapping and cancer photothermal therapy. Aqueous solutions of BSM under neutral and alkaline conditions can assemble into sheet-like nanoparticles ranging from 20 to 200 nm in size. The BSM nanoparticles were encapsulated by liposomes to improve their water solubility and the encapsulated and bare BSM nanoparticles were both non-toxic to cells. Furthermore, the liposome-encapsulated BSM nanoparticles (liposome-BSM) did not exhibit any long-term toxicity in mice. The liposome-BSM nanoparticles were subsequently used to passively target healthy and tumor-bearing mice SLNs, which were identified by the black color of the nanoparticles. BSM also strongly absorbed light in the near-infrared (NIR) range, which was rapidly converted to heat energy. Human esophagus carcinoma cells (Eca-109) were killed efficiently by liposome-BSM nanocomposites upon NIR laser irradiation. Furthermore, mouse tumor tissues grown from Eca-109 cells were seriously damaged by the photothermal effects of the liposome-BSM nanocomposites, with significant tumor growth suppression compared with controls. Given that BSM is a safe and nutritious biomaterial that can be easily obtained from black sesame seed, the results presented herein represent an important development in the use of natural biomaterials for clinical SLN mapping and cancer therapy. PMID:27031812

  6. The FLARE™ Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping

    PubMed Central

    Troyan, Susan L.; Kianzad, Vida; Gibbs-Strauss, Summer L.; Gioux, Sylvain; Matsui, Aya; Oketokoun, Rafiou; Ngo, Long; Khamene, Ali; Azar, Fred; Frangioni, John V.

    2009-01-01

    Background Invisible NIR fluorescent light can provide high sensitivity, high-resolution, and real-time image-guidance during oncologic surgery, but imaging systems that are presently available do not display this invisible light in the context of surgical anatomy. The FLARE™ imaging system overcomes this major obstacle. Methods Color video was acquired simultaneously, and in real-time, along with two independent channels of NIR fluorescence. Grayscale NIR fluorescence images were converted to visible “pseudo-colors” and overlaid onto the color video image. Yorkshire pigs weighing 35 kg (n = 5) were used for final pre-clinical validation of the imaging system. A 6-patient pilot study was conducted in women undergoing sentinel lymph node (SLN) mapping for breast cancer. Subjects received 99mTc-sulfur colloid lymphoscintigraphy. In addition, 12.5 µg of indocyanine green (ICG) diluted in human serum albumin (HSA) was used as an NIR fluorescent lymphatic tracer. Results The FLARE™ system permitted facile positioning in the operating room. NIR light did not change the look of the surgical field. Simultaneous pan-lymphatic and SLN mapping was demonstrated in swine using clinically available NIR fluorophores and the dual NIR capabilities of the system. In the pilot clinical trial, a total of 9 SLNs were identified by 99mTc-lymphoscintigraphy and 9 SLNs were identified by NIR fluorescence, although results differed in two patients. No adverse events were encountered. Conclusions We describe the successful clinical translation of a new NIR fluorescence imaging system for image-guided oncologic surgery. PMID:19582506

  7. Metastasis Detection in Sentinel Lymph Nodes: Comparison of a Limited Widely Spaced (NSABP protocol B-32) and a Comprehensive Narrowly Spaced Paraffin Block Sectioning Strategy

    PubMed Central

    Weaver, Donald L.; Le, U. Phuong; Dupuis, Stacey L.; Weaver, Katherine A. E.; Harlow, Seth P.; Ashikaga, Takamaru; Krag, David N.

    2009-01-01

    The NSABP B-32 trial is examining whether patients with initially negative sentinel lymph nodes (SLNs) who have occult metastases detected on deeper levels and cytokeratin immunohistochemistry (CK-IHC) stains are at risk for regional or distant metastases. The experimental B-32 protocol was designed to detect metastases larger than 1.0 mm by examining sections approximately 0.5 and 1.0 mm deeper into the paraffin blocks (2 levels; wide spacing). This pilot quality assurance study compares detection rates to a comprehensive protocol designed to detect metastases larger than 0.2 mm (multilevel; narrow spacing). All SLNs were sectioned grossly at close to 2.0 mm and all sections embedded in paraffin blocks. For clinical treatment, a single H&E section was examined from each block. For 54 cases with 1–5 SLNs and all SLNs negative, additional CK-IHC sections were evaluated every 0.18 mm through the block until no tissue remained. 20 of 176 (11.4%) blocks harbored occult metastases; the B-32 protocol detected metastases in 11 blocks (6.3%) and 9 additional blocks (5.1%) with metastases were detected on sections that would not have been evaluated (p=0.002; correlated proportions). Median number of levels examined per block on the comprehensive protocol was 11 (range 3–26); the B-32 protocol was fixed at 2 levels (median 2; range 1–2). Median thickness of node sections in the block was 2.1 mm (range 0.7–4.8 mm) and the modal thickness was 2.3 mm. Although more comprehensive sectioning of SLNs detects additional micrometastases, the data suggest diminishing returns and reduced cost effectiveness for the comprehensive strategy. PMID:19730364

  8. The magic of numbers: malignant melanoma between science and pseudoscience.

    PubMed

    Weyers, Wolfgang

    2011-06-01

    In 2009, a new system for staging and classification of malignant melanoma has been proposed by the American Joint Committee on Cancer (AJCC). The AJCC recommends that staging of primary melanoma be based on 3 criteria, namely, thickness, ulceration, and mitotic rate, the latter substituting Clark levels in the previous classification. In melanomas measuring ≤1 mm in thickness, ulceration or finding of single mitotic figure in the dermis defines stage T1b. According to the AJCC, sentinel lymph node dissection should be considered for those melanomas because of a significantly impaired prognosis. As with other prognostic parameters, however, assessment of mitotic rate, with one mitotic figure being the cutoff point, is highly unreliable, and statistics based on such data lack validity. Despite the large database being employed, they may be pseudoscience rather than science. PMID:21478727

  9. Melanoma

    MedlinePlus

    ... have melanoma that has spread. Help the patient’s immune system fight the cancer Ipilimumab (Yervoy®), which was FDA ... How ipilimumab works : This drug helps the patient’s immune system to recognize, target, and attack cancer cells. Healthy ...

  10. Feasibility of preoperative 125I seed-guided tumoural tracer injection using freehand SPECT for sentinel lymph node mapping in non-palpable breast cancer

    PubMed Central

    2014-01-01

    Background This study was designed to explore the feasibility of replacing the conventional peri-/intratumoural ultrasound (US)-guided technetium-99m albumin nanocolloid (99mTc-nanocolloid) administration by an injection of the same tracer guided by a freehand single-photon emission computed tomography (SPECT) device in patients with non-palpable breast cancer with an iodine-125 (125I) seed as tumour marker, who are scheduled for a sentinel lymph node biopsy (SLNB). This approach aimed to decrease the workload of the radiology department, avoiding a second US-guided procedure. Methods In ten patients, the implanted 125I seed was primarily localised using freehand SPECT and subsequently verified by conventional US in order to inject the 99mTc-nanocolloid. The following 34 patients were injected using only freehand SPECT localisation. In these patients, additional SPECT/CT was acquired to measure the distance between the 99mTc-nanocolloid injection depot and the 125I seed. In retrospect, a group of 21 patients with US-guided 99mTc-nanocolloid administrations was included as a control group. Results The depth difference measured by US and freehand SPECT in ten patients was 1.6 ± 1.6 mm. In the following 36 125I seeds (34 patients), the average difference between the 125I seed and the centre of the 99mTc-nanocolloid injection depot was 10.9 ± 6.8 mm. In the retrospective study, the average distance between the 125I seed and the centre of the 99mTc-nanocolloid injection depot as measured in SPECT/CT was 9.7 ± 6.5 mm and was not significantly different compared to the freehand SPECT-guided group (two-sample Student's t test, p = 0.52). Conclusion We conclude that using freehand SPECT for 99mTc-nanocolloid administration in patients with non-palpable breast cancer with previously implanted 125I seed is feasible. This technique may improve daily clinical logistics, reducing the workload of the radiology department. PMID:24949282